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ACS disagrees with CDC on HPV vaccination in adults
The ACS has endorsed two recommendations made by the CDC’s Advisory Committee on Immunization Practices, but the ACS does not agree with a third recommendation for older adults.
The ACIP recommends shared clinical decision-making regarding human papillomavirus (HPV) vaccination in some adults aged 27-45 years who are not adequately vaccinated. The ACS does not endorse this recommendation “because of the low effectiveness and low cancer prevention potential of vaccination in this age group, the burden of decision-making on patients and clinicians, and the lack of sufficient guidance on the selection of individuals who might benefit,” wrote Debbie Saslow, PhD, of the ACS’s section on human papillomavirus and gynecologic cancers, and colleagues.
Dr. Saslow and colleagues detailed the ACS recommendations in CA: A Cancer Journal for Clinicians.
The HPV vaccine protects against the virus that can cause cervical, oropharyngeal, anal, vaginal, vulvar, and penile cancers. For younger people, the ACIP recommends routine HPV vaccination of boys and girls aged 9-12 years and catch-up vaccination in everyone up to age 26 who has not been fully immunized against HPV.
The ACS endorses both of these recommendations. It also advises clinicians to tell patients aged 22-26 years who haven’t received the HPV vaccine or completed the series that the vaccine is less effective at reducing the risk of cancer at older ages.
After the Food and Drug Administration approved the HPV vaccine for adults aged 27-45 years, the ACIP updated its recommendations to state that routine catch-up vaccination is not recommended for anyone aged over 26 years. However, the ACIP recommended that these older adults talk with their providers about the risks and benefits of the vaccine to determine whether to get it.
The ACS subsequently conducted a methodological review of the ACIP’s recommendations and published its own adapted guidance, stating that the ACS does not endorse the shared decision-making. Administering the HPV vaccine to adults aged over 26 years would only prevent an estimated 0.5% of additional cancer cases, 0.4% additional cases of cervical precancer, and 0.3% additional cases of genital warts over the next 100 years, compared with vaccination under age 26.
“In addition to the low effectiveness and low cancer prevention potential of vaccination in this age group, other considerations included the burden of decision-making on patients and clinicians and the lack of sufficient guidance on the selection of individuals who might benefit,” according to the guidance. The ACS also expressed concern that these provider-patient discussions could interfere with the public health goal of increasing HPV vaccination in younger people.
HPV vaccination rates have lagged substantially behind other routinely recommended childhood vaccinations. Just over half (51%) of U.S. teens aged 13-17 years were up to date with HPV vaccination, and 68% had received one dose of the vaccine in 2018, according to the National Immunization Survey.
It’s very uncommon for a professional medical organization to not endorse recommendations from the CDC, particularly with vaccines, according to Robert A. Bednarczyk, PhD, an assistant professor of public health at Emory University, Atlanta, who specializes in HPV vaccination research but was not involved with the ACS statement or the ACIP recommendations.
“Often, for vaccination recommendations, there is a harmonization between health care provider organizations, such as the American Academy of Pediatrics, American Academy of Family Physicians, etc., when new vaccination schedules are released,” Dr. Bednarczyk said.
He acknowledged the ACS’s reasons for not endorsing the ACIP’s HPV recommendations in older adults: the burden of shared decision-making given the communication issues, the vaccine’s lower effectiveness in this population, and the ongoing HPV vaccine shortage.
But Dr. Bednarczyk also pointed out that the ACIP’s recommendation opens the door to these discussions when they may actually be needed, such as in adults at greater risk for HPV. He cited data suggesting that, in 2015, divorces occurred in 24 out of 1,000 married people aged 25-39 years and 21 out of 1,000 people aged 40-49.
“When you consider these marriages that end, in addition to marriages that end when one spouse dies, there is a potential for individuals who previously had a low risk of HPV acquisition now entering into new potential sexual relationships,” Dr. Bednarczyk said. “Additionally, it has been estimated that approximately 4% of the U.S. population are in open or consensually nonmonogamous relationships, where exposure to more sexual partners may increase their risk for HPV. These are just some examples of where conversations with health care providers, and shared clinical decision-making, can help with a targeted reduction of HPV risk.”
The ACIP recommendation regarding adults aged 27-45 years also provides people in this age group with insurance coverage for the HPV vaccine if they choose to get it, Dr. Bednarczyk pointed out. Insurance companies may not be required to cover HPV vaccination in people aged over 26 years without the CDC’s recommendation, even if it’s not for routine immunization.
Dr. Bednarczyk agreed, however, with how the ACS adapted the CDC’s recommendation for routine vaccination in youth. The CDC’s routine recommendation is at ages 11-12 but can begin at 9 years, according to the ACIP. The ACS guidance qualifies this statement to place more emphasis on encouraging the vaccine earlier.
“Routine HPV vaccination between ages 9-12 is expected to achieve higher on-time vaccination rates, resulting in increased numbers of cancers prevented,” according to the ACS. “Health care providers are encouraged to start offering the HPV vaccine at age 9 or 10.”
Dr. Bednarczyk pointed to some of his past research finding low proportions of teens fully vaccinated against HPV by age 13 years (J Infect Dis. 2019 Jul 31;220[5]:730-4). Therefore, “any efforts to encourage vaccination, including starting the series at ages 9-10 years may help,” he said.
He also agreed that there may be diminished effectiveness with vaccinating adults aged 22-26, “but this should also be considered relative to an individual’s risk of acquiring HPV.”
While an HPV vaccine shortage is a major concern and HPV vaccination efforts should remain most focused on young teens, adults should not necessarily be neglected, Dr. Bednarczyk noted.
“Given how common HPV infection is in the population, open discussion between patients and health care providers can help identify those adults for whom HPV vaccination can be effective,” he said.
The development of the ACS guideline was supported by ACS operational funds. The ACS has received an independent educational grant from Merck Sharp & Dohme for a project intended to increase HPV vaccination rates. Dr. Saslow is the principal investigator for a cooperative agreement between the ACS and the CDC to support the National HPV Vaccination Roundtable and is coprincipal investigator of a cooperative agreement between the ACS and CDC to support initiatives to increase HPV vaccination. The remaining authors and Dr. Bednarczyk reported no relevant disclosures.
SOURCE: Saslow D et al. CA Cancer J Clin. 2020 Jul 8. doi: 10.3322/caac.21616.
The ACS has endorsed two recommendations made by the CDC’s Advisory Committee on Immunization Practices, but the ACS does not agree with a third recommendation for older adults.
The ACIP recommends shared clinical decision-making regarding human papillomavirus (HPV) vaccination in some adults aged 27-45 years who are not adequately vaccinated. The ACS does not endorse this recommendation “because of the low effectiveness and low cancer prevention potential of vaccination in this age group, the burden of decision-making on patients and clinicians, and the lack of sufficient guidance on the selection of individuals who might benefit,” wrote Debbie Saslow, PhD, of the ACS’s section on human papillomavirus and gynecologic cancers, and colleagues.
Dr. Saslow and colleagues detailed the ACS recommendations in CA: A Cancer Journal for Clinicians.
The HPV vaccine protects against the virus that can cause cervical, oropharyngeal, anal, vaginal, vulvar, and penile cancers. For younger people, the ACIP recommends routine HPV vaccination of boys and girls aged 9-12 years and catch-up vaccination in everyone up to age 26 who has not been fully immunized against HPV.
The ACS endorses both of these recommendations. It also advises clinicians to tell patients aged 22-26 years who haven’t received the HPV vaccine or completed the series that the vaccine is less effective at reducing the risk of cancer at older ages.
After the Food and Drug Administration approved the HPV vaccine for adults aged 27-45 years, the ACIP updated its recommendations to state that routine catch-up vaccination is not recommended for anyone aged over 26 years. However, the ACIP recommended that these older adults talk with their providers about the risks and benefits of the vaccine to determine whether to get it.
The ACS subsequently conducted a methodological review of the ACIP’s recommendations and published its own adapted guidance, stating that the ACS does not endorse the shared decision-making. Administering the HPV vaccine to adults aged over 26 years would only prevent an estimated 0.5% of additional cancer cases, 0.4% additional cases of cervical precancer, and 0.3% additional cases of genital warts over the next 100 years, compared with vaccination under age 26.
“In addition to the low effectiveness and low cancer prevention potential of vaccination in this age group, other considerations included the burden of decision-making on patients and clinicians and the lack of sufficient guidance on the selection of individuals who might benefit,” according to the guidance. The ACS also expressed concern that these provider-patient discussions could interfere with the public health goal of increasing HPV vaccination in younger people.
HPV vaccination rates have lagged substantially behind other routinely recommended childhood vaccinations. Just over half (51%) of U.S. teens aged 13-17 years were up to date with HPV vaccination, and 68% had received one dose of the vaccine in 2018, according to the National Immunization Survey.
It’s very uncommon for a professional medical organization to not endorse recommendations from the CDC, particularly with vaccines, according to Robert A. Bednarczyk, PhD, an assistant professor of public health at Emory University, Atlanta, who specializes in HPV vaccination research but was not involved with the ACS statement or the ACIP recommendations.
“Often, for vaccination recommendations, there is a harmonization between health care provider organizations, such as the American Academy of Pediatrics, American Academy of Family Physicians, etc., when new vaccination schedules are released,” Dr. Bednarczyk said.
He acknowledged the ACS’s reasons for not endorsing the ACIP’s HPV recommendations in older adults: the burden of shared decision-making given the communication issues, the vaccine’s lower effectiveness in this population, and the ongoing HPV vaccine shortage.
But Dr. Bednarczyk also pointed out that the ACIP’s recommendation opens the door to these discussions when they may actually be needed, such as in adults at greater risk for HPV. He cited data suggesting that, in 2015, divorces occurred in 24 out of 1,000 married people aged 25-39 years and 21 out of 1,000 people aged 40-49.
“When you consider these marriages that end, in addition to marriages that end when one spouse dies, there is a potential for individuals who previously had a low risk of HPV acquisition now entering into new potential sexual relationships,” Dr. Bednarczyk said. “Additionally, it has been estimated that approximately 4% of the U.S. population are in open or consensually nonmonogamous relationships, where exposure to more sexual partners may increase their risk for HPV. These are just some examples of where conversations with health care providers, and shared clinical decision-making, can help with a targeted reduction of HPV risk.”
The ACIP recommendation regarding adults aged 27-45 years also provides people in this age group with insurance coverage for the HPV vaccine if they choose to get it, Dr. Bednarczyk pointed out. Insurance companies may not be required to cover HPV vaccination in people aged over 26 years without the CDC’s recommendation, even if it’s not for routine immunization.
Dr. Bednarczyk agreed, however, with how the ACS adapted the CDC’s recommendation for routine vaccination in youth. The CDC’s routine recommendation is at ages 11-12 but can begin at 9 years, according to the ACIP. The ACS guidance qualifies this statement to place more emphasis on encouraging the vaccine earlier.
“Routine HPV vaccination between ages 9-12 is expected to achieve higher on-time vaccination rates, resulting in increased numbers of cancers prevented,” according to the ACS. “Health care providers are encouraged to start offering the HPV vaccine at age 9 or 10.”
Dr. Bednarczyk pointed to some of his past research finding low proportions of teens fully vaccinated against HPV by age 13 years (J Infect Dis. 2019 Jul 31;220[5]:730-4). Therefore, “any efforts to encourage vaccination, including starting the series at ages 9-10 years may help,” he said.
He also agreed that there may be diminished effectiveness with vaccinating adults aged 22-26, “but this should also be considered relative to an individual’s risk of acquiring HPV.”
While an HPV vaccine shortage is a major concern and HPV vaccination efforts should remain most focused on young teens, adults should not necessarily be neglected, Dr. Bednarczyk noted.
“Given how common HPV infection is in the population, open discussion between patients and health care providers can help identify those adults for whom HPV vaccination can be effective,” he said.
The development of the ACS guideline was supported by ACS operational funds. The ACS has received an independent educational grant from Merck Sharp & Dohme for a project intended to increase HPV vaccination rates. Dr. Saslow is the principal investigator for a cooperative agreement between the ACS and the CDC to support the National HPV Vaccination Roundtable and is coprincipal investigator of a cooperative agreement between the ACS and CDC to support initiatives to increase HPV vaccination. The remaining authors and Dr. Bednarczyk reported no relevant disclosures.
SOURCE: Saslow D et al. CA Cancer J Clin. 2020 Jul 8. doi: 10.3322/caac.21616.
The ACS has endorsed two recommendations made by the CDC’s Advisory Committee on Immunization Practices, but the ACS does not agree with a third recommendation for older adults.
The ACIP recommends shared clinical decision-making regarding human papillomavirus (HPV) vaccination in some adults aged 27-45 years who are not adequately vaccinated. The ACS does not endorse this recommendation “because of the low effectiveness and low cancer prevention potential of vaccination in this age group, the burden of decision-making on patients and clinicians, and the lack of sufficient guidance on the selection of individuals who might benefit,” wrote Debbie Saslow, PhD, of the ACS’s section on human papillomavirus and gynecologic cancers, and colleagues.
Dr. Saslow and colleagues detailed the ACS recommendations in CA: A Cancer Journal for Clinicians.
The HPV vaccine protects against the virus that can cause cervical, oropharyngeal, anal, vaginal, vulvar, and penile cancers. For younger people, the ACIP recommends routine HPV vaccination of boys and girls aged 9-12 years and catch-up vaccination in everyone up to age 26 who has not been fully immunized against HPV.
The ACS endorses both of these recommendations. It also advises clinicians to tell patients aged 22-26 years who haven’t received the HPV vaccine or completed the series that the vaccine is less effective at reducing the risk of cancer at older ages.
After the Food and Drug Administration approved the HPV vaccine for adults aged 27-45 years, the ACIP updated its recommendations to state that routine catch-up vaccination is not recommended for anyone aged over 26 years. However, the ACIP recommended that these older adults talk with their providers about the risks and benefits of the vaccine to determine whether to get it.
The ACS subsequently conducted a methodological review of the ACIP’s recommendations and published its own adapted guidance, stating that the ACS does not endorse the shared decision-making. Administering the HPV vaccine to adults aged over 26 years would only prevent an estimated 0.5% of additional cancer cases, 0.4% additional cases of cervical precancer, and 0.3% additional cases of genital warts over the next 100 years, compared with vaccination under age 26.
“In addition to the low effectiveness and low cancer prevention potential of vaccination in this age group, other considerations included the burden of decision-making on patients and clinicians and the lack of sufficient guidance on the selection of individuals who might benefit,” according to the guidance. The ACS also expressed concern that these provider-patient discussions could interfere with the public health goal of increasing HPV vaccination in younger people.
HPV vaccination rates have lagged substantially behind other routinely recommended childhood vaccinations. Just over half (51%) of U.S. teens aged 13-17 years were up to date with HPV vaccination, and 68% had received one dose of the vaccine in 2018, according to the National Immunization Survey.
It’s very uncommon for a professional medical organization to not endorse recommendations from the CDC, particularly with vaccines, according to Robert A. Bednarczyk, PhD, an assistant professor of public health at Emory University, Atlanta, who specializes in HPV vaccination research but was not involved with the ACS statement or the ACIP recommendations.
“Often, for vaccination recommendations, there is a harmonization between health care provider organizations, such as the American Academy of Pediatrics, American Academy of Family Physicians, etc., when new vaccination schedules are released,” Dr. Bednarczyk said.
He acknowledged the ACS’s reasons for not endorsing the ACIP’s HPV recommendations in older adults: the burden of shared decision-making given the communication issues, the vaccine’s lower effectiveness in this population, and the ongoing HPV vaccine shortage.
But Dr. Bednarczyk also pointed out that the ACIP’s recommendation opens the door to these discussions when they may actually be needed, such as in adults at greater risk for HPV. He cited data suggesting that, in 2015, divorces occurred in 24 out of 1,000 married people aged 25-39 years and 21 out of 1,000 people aged 40-49.
“When you consider these marriages that end, in addition to marriages that end when one spouse dies, there is a potential for individuals who previously had a low risk of HPV acquisition now entering into new potential sexual relationships,” Dr. Bednarczyk said. “Additionally, it has been estimated that approximately 4% of the U.S. population are in open or consensually nonmonogamous relationships, where exposure to more sexual partners may increase their risk for HPV. These are just some examples of where conversations with health care providers, and shared clinical decision-making, can help with a targeted reduction of HPV risk.”
The ACIP recommendation regarding adults aged 27-45 years also provides people in this age group with insurance coverage for the HPV vaccine if they choose to get it, Dr. Bednarczyk pointed out. Insurance companies may not be required to cover HPV vaccination in people aged over 26 years without the CDC’s recommendation, even if it’s not for routine immunization.
Dr. Bednarczyk agreed, however, with how the ACS adapted the CDC’s recommendation for routine vaccination in youth. The CDC’s routine recommendation is at ages 11-12 but can begin at 9 years, according to the ACIP. The ACS guidance qualifies this statement to place more emphasis on encouraging the vaccine earlier.
“Routine HPV vaccination between ages 9-12 is expected to achieve higher on-time vaccination rates, resulting in increased numbers of cancers prevented,” according to the ACS. “Health care providers are encouraged to start offering the HPV vaccine at age 9 or 10.”
Dr. Bednarczyk pointed to some of his past research finding low proportions of teens fully vaccinated against HPV by age 13 years (J Infect Dis. 2019 Jul 31;220[5]:730-4). Therefore, “any efforts to encourage vaccination, including starting the series at ages 9-10 years may help,” he said.
He also agreed that there may be diminished effectiveness with vaccinating adults aged 22-26, “but this should also be considered relative to an individual’s risk of acquiring HPV.”
While an HPV vaccine shortage is a major concern and HPV vaccination efforts should remain most focused on young teens, adults should not necessarily be neglected, Dr. Bednarczyk noted.
“Given how common HPV infection is in the population, open discussion between patients and health care providers can help identify those adults for whom HPV vaccination can be effective,” he said.
The development of the ACS guideline was supported by ACS operational funds. The ACS has received an independent educational grant from Merck Sharp & Dohme for a project intended to increase HPV vaccination rates. Dr. Saslow is the principal investigator for a cooperative agreement between the ACS and the CDC to support the National HPV Vaccination Roundtable and is coprincipal investigator of a cooperative agreement between the ACS and CDC to support initiatives to increase HPV vaccination. The remaining authors and Dr. Bednarczyk reported no relevant disclosures.
SOURCE: Saslow D et al. CA Cancer J Clin. 2020 Jul 8. doi: 10.3322/caac.21616.
FROM CA: A CANCER JOURNAL FOR CLINICIANS
P-tau217 differentiates Alzheimer’s disease from other neurodegenerative conditions
new research suggests.
Results from a large multinational study showed that the level of P-tau217 in blood collected during life was an accurate predictor of tau brain changes seen in brain tissue after death. In addition, increasing blood P-tau217 levels can be detected in some individuals up to 20 years before the average age of onset of the early cognitive decline that signals Alzheimer’s disease, researchers reported.
“While there is still more work to be done, this biomarker has the potential to have a transformational impact on research, treatment, prevention, and therapy development, and in the clinical setting,” said senior author Eric M. Reiman, MD, executive director of Banner Alzheimer’s Institute in Phoenix.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and simultaneously published online July 28 in JAMA.
Three cohorts
The international team of researchers evaluated the P-tau217 blood test in 1,402 adults from three cohorts. The first cohort was made up of 81 individuals in the Arizona (Banner Sun Health Research Institute) Brain Donation program and included clinical, blood, and neuropathologic data. The second cohort included 699 individuals in the Swedish BioFINDER-2 study and provided clinical, brain imaging, cerebrospinal fluid (CSF), and blood data. The third cohort was made up of 522 participants from the Columbian autosomal-dominant Alzheimer’s disease kindred, including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers.
In the Arizona cohort, plasma P-tau217 discriminated neuropathologically defined Alzheimer’s disease from non-Alzheimer’s disease (area under the curve, 0.89; 95% CI, 0.81-0.97) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P < .05).
In the Swedish BioFINDER-2 cohort, the discriminative accuracy of plasma P-tau217 for clinical Alzheimer’s disease dementia versus other neurodegenerative diseases was 96% (AUC, 0.96; 95% CI, 0.93-0.98).
This was significantly higher than plasma P-tau181, plasma NfL, and MRI measures (AUC range, 0.50-0.81; P < .001), but was not significantly different than CSF P-tau217, CSF P-tau181, and tau-PET (AUC range, 0.90-0.99; P > .15).
In the Colombian cohort, plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers than noncarriers starting at around age 25 years, which is 20 years prior to the estimated onset of mild cognitive impairment among mutation carriers.
Additionally, plasma P-tau217 levels correlated with cerebral tau tangles, and discriminated abnormal versus normal tau-PET scans with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF Abeta42:Abeta40 ratio, and MRI measures.
The blood test “opens the possibility of early diagnosis of Alzheimer’s disease before the dementia stage, which is very important for clinical trials evaluating novel therapies that might stop or slow down the disease process,” presenting author Oskar Hansson, MD, PhD, of Lund (Sweden) University, said in a statement.
Further research is now needed to optimize the P-tau217 blood test, validate the findings in unselected and diverse populations, and determine its potential role in the clinic, the investigators noted.
Potential game changer?
Commenting on the study, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, noted his enthusiasm for the test. “This tau blood test will be a real game changer, advancing clinical care and research,” said Dr. Fillit, who was not involved in the research.
“This is a real breakthrough: a simple and accessible blood test that can diagnose Alzheimer’s disease better than the more costly and invasive methods currently available like PET scans and cerebrospinal fluid biomarkers,” he said.
The P-tau217 blood test “is like the equivalent of the cholesterol test for heart disease, but for Alzheimer’s disease,” Dr. Fillit added.
As previously reported, another study presented at AAIC 2020 compared P-tau217 with P-tau181 to determine which could best identify individuals with Alzheimer’s disease. Results showed that, although the two biomarkers were similar overall, P-tau217 had a slight edge in terms of accuracy.
The study by Reiman et al. was funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Alzheimer Foundation. Dr. Hansson reported receiving grants from Roche, Biogen, and Pfizer, and receiving nonfinancial support from GE Healthcare, AVID Radiopharmaceuticals, and Euroimmun. Dr. Reiman has received grants from Roche/Roche Diagnostics and received personal fees from Alkahest, Alzheon, Aural Analytics, Denali, Green Valley, MagQ, Takeda/Zinfandel, and United Neuroscience. He is also a cofounder of AlzPath, which aims to further develop P-tau217 and fluid biomarkers; holds a patent owned by Banner Health for a strategy to use biomarkers to accelerate evaluation of Alzheimer prevention therapies; and is a principal investigator of prevention trials that include research agreements with Genentech/Roche and Novartis/Amgen, PET studies that include research agreements with Avid/Lilly, and several National Institute of Health–supported research studies. Dr. Fillit reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Results from a large multinational study showed that the level of P-tau217 in blood collected during life was an accurate predictor of tau brain changes seen in brain tissue after death. In addition, increasing blood P-tau217 levels can be detected in some individuals up to 20 years before the average age of onset of the early cognitive decline that signals Alzheimer’s disease, researchers reported.
“While there is still more work to be done, this biomarker has the potential to have a transformational impact on research, treatment, prevention, and therapy development, and in the clinical setting,” said senior author Eric M. Reiman, MD, executive director of Banner Alzheimer’s Institute in Phoenix.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and simultaneously published online July 28 in JAMA.
Three cohorts
The international team of researchers evaluated the P-tau217 blood test in 1,402 adults from three cohorts. The first cohort was made up of 81 individuals in the Arizona (Banner Sun Health Research Institute) Brain Donation program and included clinical, blood, and neuropathologic data. The second cohort included 699 individuals in the Swedish BioFINDER-2 study and provided clinical, brain imaging, cerebrospinal fluid (CSF), and blood data. The third cohort was made up of 522 participants from the Columbian autosomal-dominant Alzheimer’s disease kindred, including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers.
In the Arizona cohort, plasma P-tau217 discriminated neuropathologically defined Alzheimer’s disease from non-Alzheimer’s disease (area under the curve, 0.89; 95% CI, 0.81-0.97) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P < .05).
In the Swedish BioFINDER-2 cohort, the discriminative accuracy of plasma P-tau217 for clinical Alzheimer’s disease dementia versus other neurodegenerative diseases was 96% (AUC, 0.96; 95% CI, 0.93-0.98).
This was significantly higher than plasma P-tau181, plasma NfL, and MRI measures (AUC range, 0.50-0.81; P < .001), but was not significantly different than CSF P-tau217, CSF P-tau181, and tau-PET (AUC range, 0.90-0.99; P > .15).
In the Colombian cohort, plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers than noncarriers starting at around age 25 years, which is 20 years prior to the estimated onset of mild cognitive impairment among mutation carriers.
Additionally, plasma P-tau217 levels correlated with cerebral tau tangles, and discriminated abnormal versus normal tau-PET scans with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF Abeta42:Abeta40 ratio, and MRI measures.
The blood test “opens the possibility of early diagnosis of Alzheimer’s disease before the dementia stage, which is very important for clinical trials evaluating novel therapies that might stop or slow down the disease process,” presenting author Oskar Hansson, MD, PhD, of Lund (Sweden) University, said in a statement.
Further research is now needed to optimize the P-tau217 blood test, validate the findings in unselected and diverse populations, and determine its potential role in the clinic, the investigators noted.
Potential game changer?
Commenting on the study, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, noted his enthusiasm for the test. “This tau blood test will be a real game changer, advancing clinical care and research,” said Dr. Fillit, who was not involved in the research.
“This is a real breakthrough: a simple and accessible blood test that can diagnose Alzheimer’s disease better than the more costly and invasive methods currently available like PET scans and cerebrospinal fluid biomarkers,” he said.
The P-tau217 blood test “is like the equivalent of the cholesterol test for heart disease, but for Alzheimer’s disease,” Dr. Fillit added.
As previously reported, another study presented at AAIC 2020 compared P-tau217 with P-tau181 to determine which could best identify individuals with Alzheimer’s disease. Results showed that, although the two biomarkers were similar overall, P-tau217 had a slight edge in terms of accuracy.
The study by Reiman et al. was funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Alzheimer Foundation. Dr. Hansson reported receiving grants from Roche, Biogen, and Pfizer, and receiving nonfinancial support from GE Healthcare, AVID Radiopharmaceuticals, and Euroimmun. Dr. Reiman has received grants from Roche/Roche Diagnostics and received personal fees from Alkahest, Alzheon, Aural Analytics, Denali, Green Valley, MagQ, Takeda/Zinfandel, and United Neuroscience. He is also a cofounder of AlzPath, which aims to further develop P-tau217 and fluid biomarkers; holds a patent owned by Banner Health for a strategy to use biomarkers to accelerate evaluation of Alzheimer prevention therapies; and is a principal investigator of prevention trials that include research agreements with Genentech/Roche and Novartis/Amgen, PET studies that include research agreements with Avid/Lilly, and several National Institute of Health–supported research studies. Dr. Fillit reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
new research suggests.
Results from a large multinational study showed that the level of P-tau217 in blood collected during life was an accurate predictor of tau brain changes seen in brain tissue after death. In addition, increasing blood P-tau217 levels can be detected in some individuals up to 20 years before the average age of onset of the early cognitive decline that signals Alzheimer’s disease, researchers reported.
“While there is still more work to be done, this biomarker has the potential to have a transformational impact on research, treatment, prevention, and therapy development, and in the clinical setting,” said senior author Eric M. Reiman, MD, executive director of Banner Alzheimer’s Institute in Phoenix.
The findings were presented at the virtual annual meeting of the Alzheimer’s Association International Conference and simultaneously published online July 28 in JAMA.
Three cohorts
The international team of researchers evaluated the P-tau217 blood test in 1,402 adults from three cohorts. The first cohort was made up of 81 individuals in the Arizona (Banner Sun Health Research Institute) Brain Donation program and included clinical, blood, and neuropathologic data. The second cohort included 699 individuals in the Swedish BioFINDER-2 study and provided clinical, brain imaging, cerebrospinal fluid (CSF), and blood data. The third cohort was made up of 522 participants from the Columbian autosomal-dominant Alzheimer’s disease kindred, including 365 PSEN1 E280A mutation carriers and 257 mutation noncarriers.
In the Arizona cohort, plasma P-tau217 discriminated neuropathologically defined Alzheimer’s disease from non-Alzheimer’s disease (area under the curve, 0.89; 95% CI, 0.81-0.97) with significantly higher accuracy than plasma P-tau181 and neurofilament light chain (NfL) (AUC range, 0.50-0.72; P < .05).
In the Swedish BioFINDER-2 cohort, the discriminative accuracy of plasma P-tau217 for clinical Alzheimer’s disease dementia versus other neurodegenerative diseases was 96% (AUC, 0.96; 95% CI, 0.93-0.98).
This was significantly higher than plasma P-tau181, plasma NfL, and MRI measures (AUC range, 0.50-0.81; P < .001), but was not significantly different than CSF P-tau217, CSF P-tau181, and tau-PET (AUC range, 0.90-0.99; P > .15).
In the Colombian cohort, plasma P-tau217 levels were significantly greater among PSEN1 mutation carriers than noncarriers starting at around age 25 years, which is 20 years prior to the estimated onset of mild cognitive impairment among mutation carriers.
Additionally, plasma P-tau217 levels correlated with cerebral tau tangles, and discriminated abnormal versus normal tau-PET scans with significantly higher accuracy than plasma P-tau181, plasma NfL, CSF P-tau181, CSF Abeta42:Abeta40 ratio, and MRI measures.
The blood test “opens the possibility of early diagnosis of Alzheimer’s disease before the dementia stage, which is very important for clinical trials evaluating novel therapies that might stop or slow down the disease process,” presenting author Oskar Hansson, MD, PhD, of Lund (Sweden) University, said in a statement.
Further research is now needed to optimize the P-tau217 blood test, validate the findings in unselected and diverse populations, and determine its potential role in the clinic, the investigators noted.
Potential game changer?
Commenting on the study, Howard Fillit, MD, founding executive director and chief science officer of the Alzheimer’s Drug Discovery Foundation, noted his enthusiasm for the test. “This tau blood test will be a real game changer, advancing clinical care and research,” said Dr. Fillit, who was not involved in the research.
“This is a real breakthrough: a simple and accessible blood test that can diagnose Alzheimer’s disease better than the more costly and invasive methods currently available like PET scans and cerebrospinal fluid biomarkers,” he said.
The P-tau217 blood test “is like the equivalent of the cholesterol test for heart disease, but for Alzheimer’s disease,” Dr. Fillit added.
As previously reported, another study presented at AAIC 2020 compared P-tau217 with P-tau181 to determine which could best identify individuals with Alzheimer’s disease. Results showed that, although the two biomarkers were similar overall, P-tau217 had a slight edge in terms of accuracy.
The study by Reiman et al. was funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, and the Swedish Alzheimer Foundation. Dr. Hansson reported receiving grants from Roche, Biogen, and Pfizer, and receiving nonfinancial support from GE Healthcare, AVID Radiopharmaceuticals, and Euroimmun. Dr. Reiman has received grants from Roche/Roche Diagnostics and received personal fees from Alkahest, Alzheon, Aural Analytics, Denali, Green Valley, MagQ, Takeda/Zinfandel, and United Neuroscience. He is also a cofounder of AlzPath, which aims to further develop P-tau217 and fluid biomarkers; holds a patent owned by Banner Health for a strategy to use biomarkers to accelerate evaluation of Alzheimer prevention therapies; and is a principal investigator of prevention trials that include research agreements with Genentech/Roche and Novartis/Amgen, PET studies that include research agreements with Avid/Lilly, and several National Institute of Health–supported research studies. Dr. Fillit reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM AAIC 2020
Urine screen as part of triple test improves ID of adrenal cancer
A strategy that includes a urine steroid test along with imaging characteristics and tumor size criteria can significantly improve the challenging diagnosis of adrenocortical cancer, helping to avoid unnecessary, and often unsuccessful, further imaging and even surgery, new research shows.
“A triple-test strategy of tumor diameter, imaging characteristics, and urine steroid metabolomics improves detection of adrenocortical carcinoma, which could shorten time to surgery for patients with ... carcinoma and help to avoid unnecessary surgery in patients with benign tumors,” the authors say in research published online July 23 in The Lancet Diabetes & Endocrinology.
The triple-test strategy can be expected to make its way into international guidelines, notes joint lead author Irina Bancos, MD, an associate professor of endocrinology at the Mayo Clinic, Rochester, Minn., in a press statement issued by the University of Birmingham (England), which also had a number of researchers involved in the study.
“The findings of this study will feed into the next international guidelines on the management of adrenal tumors and the implementation of the new test will hopefully improve the overall outlook for patients diagnosed with adrenal tumors,” Dr. Bancos emphasized.
More imaging has led to detection of more adrenal tumors
Advances in CT and MRI imaging have increased the ability to detect adrenal incidentalomas, which are now picked up on about 5% of scans, and the widespread use of imaging has compounded the prevalence of such findings, particularly in older people.
Adrenocortical carcinomas represent only about 2%-12% of adrenal incidentalomas, but the prognosis is very poor, and early detection and surgery can improve outcomes, so findings of any adrenal tumor typically trigger additional multimodal imaging to rule out malignancy.
Evidence is lacking on the accuracy of imaging in determining whether such masses are truly cancerous, or benign, and such procedures add costs, as well as expose patients to radiation that may ultimately have no benefit. However, a previous proof-of-concept study from the same authors did show that the presence of excess adrenal steroid hormones in the urine is a key indicator of adrenal tumors, and other research has supported the findings.
All three tests together give best predictive value: EURINE-ACT
To further validate this work, the authors conducted the EURINE-ACT trial, a prospective 14-center study that is the first of its kind to evaluate the efficacy of a screening strategy for adrenocortical carcinoma that combines urine steroid profiling with tumor size and imaging characteristics.
The study of 2,017 participants with newly diagnosed adrenal masses, recruited from January 2011 to July 2016 from specialist centers in 11 different countries, assessed the diagnostic accuracy of three components: maximum tumor diameter (≥4 cm vs. <4 cm), imaging characteristics (positive vs. negative), and urine steroid metabolomics (low, medium, or high risk of adrenocortical carcinoma), separately and in combination.
Of the patients, 98 (4.9%) had adrenocortical carcinoma confirmed clinically, histopathologically, or biochemically.
Tumors with diameters of 4 cm or larger were identified in 488 patients (24.2%) and were observed in the vast majority of patients with adrenocortical carcinoma (96 of 98), for a positive predictive value (PPV) of 19.7%.
Likewise, the PPV for imaging characteristics was 19.7%. However, increasing the unenhanced CT tumor attenuation threshold to 20 Hounsfield units (HU) from the recommended 10 HU increased specificity for adrenocortical carcinoma (80.0% vs. 64.0%) while maintaining sensitivity (99.0% vs. 100.0%).
Comparatively, a urine steroid metabolomics result suggesting a high risk of adrenocortical carcinoma had a PPV of 34.6%.
A total of 106 patients (5.3%) met the criteria for all three measures, and the PPV for all three was 76.4%.
Using the criteria, 70 patients (3.5%) were classified as being at moderate risk of adrenocortical carcinoma and 1,841 (91.3%) at low risk, for a negative predictive value (NPV) of 99.7%.
“Use of radiation-free, noninvasive urine steroid metabolomics has a higher PPV than two standard imaging tests, and best performance was seen with the combination of all three tests,” the authors state.
Limit urine test to patients with larger tumors
They note that the use of the combined diagnostic strategy would have led to additional imaging in only 488 (24.2%) of the study’s 2,017 patients, compared with the 2,737 scans that were actually conducted before reaching a diagnostic decision.
“Implementation of urine steroid metabolomics in the routine diagnostic assessment of newly discovered adrenal masses could reduce the number of imaging procedures required to diagnose adrenocortical carcinoma and avoid unnecessary surgery of benign adrenal tumors, potentially yielding beneficial effects with respect to patient burden and health care costs,” they stress.
And regarding imaging parameters, “we also showed that using a cutoff of 20 HU for unenhanced CT tumor attenuation increases the accuracy of imaging characteristic assessment for exclusion of adrenocortical carcinoma, compared with the currently recommended cutoff of 10 HU, which has immediate implications for clinical practice,” they emphasize.
In an accompanying editorial, Adina F. Turcu, MD, of the division of metabolism, endocrinology, and diabetes, University of Michigan, Ann Arbor, and Axel K. Walch, MD, of the Helmholtz Zentrum München–German Research Centre for Environmental Health, agree. “The introduction of urine steroid metabolomics into routine clinical practice would provide major advantages,” they state.
However, they point out that, although the overall negative predictive value of the test was excellent, the specificity was weak.
“Thus, urine steroid metabolomics should be limited to patients who have adrenal nodules larger than 4 cm and have qualitative imaging characteristics suggestive of malignancy,” say Dr. Turcu and Dr. Walch.
The EURINE-ACT study results suggest this subgroup would represent roughly only 12% of all patients with adrenal incidentalomas, they add.
Issues that remain to be addressed with regard to the implementation of the screening strategy include how to best respond to patients who are classified as having intermediate or moderate risk of malignancy, and whether the diagnostic value of steroid metabolomics could be refined by adding analytes or parameters, the editorialists conclude.
The study was funded by the European Commission, U.K. Medical Research Council, Wellcome Trust, U.K. National Institute for Health Research, U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.
A version of this article originally appeared on Medscape.com.
A strategy that includes a urine steroid test along with imaging characteristics and tumor size criteria can significantly improve the challenging diagnosis of adrenocortical cancer, helping to avoid unnecessary, and often unsuccessful, further imaging and even surgery, new research shows.
“A triple-test strategy of tumor diameter, imaging characteristics, and urine steroid metabolomics improves detection of adrenocortical carcinoma, which could shorten time to surgery for patients with ... carcinoma and help to avoid unnecessary surgery in patients with benign tumors,” the authors say in research published online July 23 in The Lancet Diabetes & Endocrinology.
The triple-test strategy can be expected to make its way into international guidelines, notes joint lead author Irina Bancos, MD, an associate professor of endocrinology at the Mayo Clinic, Rochester, Minn., in a press statement issued by the University of Birmingham (England), which also had a number of researchers involved in the study.
“The findings of this study will feed into the next international guidelines on the management of adrenal tumors and the implementation of the new test will hopefully improve the overall outlook for patients diagnosed with adrenal tumors,” Dr. Bancos emphasized.
More imaging has led to detection of more adrenal tumors
Advances in CT and MRI imaging have increased the ability to detect adrenal incidentalomas, which are now picked up on about 5% of scans, and the widespread use of imaging has compounded the prevalence of such findings, particularly in older people.
Adrenocortical carcinomas represent only about 2%-12% of adrenal incidentalomas, but the prognosis is very poor, and early detection and surgery can improve outcomes, so findings of any adrenal tumor typically trigger additional multimodal imaging to rule out malignancy.
Evidence is lacking on the accuracy of imaging in determining whether such masses are truly cancerous, or benign, and such procedures add costs, as well as expose patients to radiation that may ultimately have no benefit. However, a previous proof-of-concept study from the same authors did show that the presence of excess adrenal steroid hormones in the urine is a key indicator of adrenal tumors, and other research has supported the findings.
All three tests together give best predictive value: EURINE-ACT
To further validate this work, the authors conducted the EURINE-ACT trial, a prospective 14-center study that is the first of its kind to evaluate the efficacy of a screening strategy for adrenocortical carcinoma that combines urine steroid profiling with tumor size and imaging characteristics.
The study of 2,017 participants with newly diagnosed adrenal masses, recruited from January 2011 to July 2016 from specialist centers in 11 different countries, assessed the diagnostic accuracy of three components: maximum tumor diameter (≥4 cm vs. <4 cm), imaging characteristics (positive vs. negative), and urine steroid metabolomics (low, medium, or high risk of adrenocortical carcinoma), separately and in combination.
Of the patients, 98 (4.9%) had adrenocortical carcinoma confirmed clinically, histopathologically, or biochemically.
Tumors with diameters of 4 cm or larger were identified in 488 patients (24.2%) and were observed in the vast majority of patients with adrenocortical carcinoma (96 of 98), for a positive predictive value (PPV) of 19.7%.
Likewise, the PPV for imaging characteristics was 19.7%. However, increasing the unenhanced CT tumor attenuation threshold to 20 Hounsfield units (HU) from the recommended 10 HU increased specificity for adrenocortical carcinoma (80.0% vs. 64.0%) while maintaining sensitivity (99.0% vs. 100.0%).
Comparatively, a urine steroid metabolomics result suggesting a high risk of adrenocortical carcinoma had a PPV of 34.6%.
A total of 106 patients (5.3%) met the criteria for all three measures, and the PPV for all three was 76.4%.
Using the criteria, 70 patients (3.5%) were classified as being at moderate risk of adrenocortical carcinoma and 1,841 (91.3%) at low risk, for a negative predictive value (NPV) of 99.7%.
“Use of radiation-free, noninvasive urine steroid metabolomics has a higher PPV than two standard imaging tests, and best performance was seen with the combination of all three tests,” the authors state.
Limit urine test to patients with larger tumors
They note that the use of the combined diagnostic strategy would have led to additional imaging in only 488 (24.2%) of the study’s 2,017 patients, compared with the 2,737 scans that were actually conducted before reaching a diagnostic decision.
“Implementation of urine steroid metabolomics in the routine diagnostic assessment of newly discovered adrenal masses could reduce the number of imaging procedures required to diagnose adrenocortical carcinoma and avoid unnecessary surgery of benign adrenal tumors, potentially yielding beneficial effects with respect to patient burden and health care costs,” they stress.
And regarding imaging parameters, “we also showed that using a cutoff of 20 HU for unenhanced CT tumor attenuation increases the accuracy of imaging characteristic assessment for exclusion of adrenocortical carcinoma, compared with the currently recommended cutoff of 10 HU, which has immediate implications for clinical practice,” they emphasize.
In an accompanying editorial, Adina F. Turcu, MD, of the division of metabolism, endocrinology, and diabetes, University of Michigan, Ann Arbor, and Axel K. Walch, MD, of the Helmholtz Zentrum München–German Research Centre for Environmental Health, agree. “The introduction of urine steroid metabolomics into routine clinical practice would provide major advantages,” they state.
However, they point out that, although the overall negative predictive value of the test was excellent, the specificity was weak.
“Thus, urine steroid metabolomics should be limited to patients who have adrenal nodules larger than 4 cm and have qualitative imaging characteristics suggestive of malignancy,” say Dr. Turcu and Dr. Walch.
The EURINE-ACT study results suggest this subgroup would represent roughly only 12% of all patients with adrenal incidentalomas, they add.
Issues that remain to be addressed with regard to the implementation of the screening strategy include how to best respond to patients who are classified as having intermediate or moderate risk of malignancy, and whether the diagnostic value of steroid metabolomics could be refined by adding analytes or parameters, the editorialists conclude.
The study was funded by the European Commission, U.K. Medical Research Council, Wellcome Trust, U.K. National Institute for Health Research, U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.
A version of this article originally appeared on Medscape.com.
A strategy that includes a urine steroid test along with imaging characteristics and tumor size criteria can significantly improve the challenging diagnosis of adrenocortical cancer, helping to avoid unnecessary, and often unsuccessful, further imaging and even surgery, new research shows.
“A triple-test strategy of tumor diameter, imaging characteristics, and urine steroid metabolomics improves detection of adrenocortical carcinoma, which could shorten time to surgery for patients with ... carcinoma and help to avoid unnecessary surgery in patients with benign tumors,” the authors say in research published online July 23 in The Lancet Diabetes & Endocrinology.
The triple-test strategy can be expected to make its way into international guidelines, notes joint lead author Irina Bancos, MD, an associate professor of endocrinology at the Mayo Clinic, Rochester, Minn., in a press statement issued by the University of Birmingham (England), which also had a number of researchers involved in the study.
“The findings of this study will feed into the next international guidelines on the management of adrenal tumors and the implementation of the new test will hopefully improve the overall outlook for patients diagnosed with adrenal tumors,” Dr. Bancos emphasized.
More imaging has led to detection of more adrenal tumors
Advances in CT and MRI imaging have increased the ability to detect adrenal incidentalomas, which are now picked up on about 5% of scans, and the widespread use of imaging has compounded the prevalence of such findings, particularly in older people.
Adrenocortical carcinomas represent only about 2%-12% of adrenal incidentalomas, but the prognosis is very poor, and early detection and surgery can improve outcomes, so findings of any adrenal tumor typically trigger additional multimodal imaging to rule out malignancy.
Evidence is lacking on the accuracy of imaging in determining whether such masses are truly cancerous, or benign, and such procedures add costs, as well as expose patients to radiation that may ultimately have no benefit. However, a previous proof-of-concept study from the same authors did show that the presence of excess adrenal steroid hormones in the urine is a key indicator of adrenal tumors, and other research has supported the findings.
All three tests together give best predictive value: EURINE-ACT
To further validate this work, the authors conducted the EURINE-ACT trial, a prospective 14-center study that is the first of its kind to evaluate the efficacy of a screening strategy for adrenocortical carcinoma that combines urine steroid profiling with tumor size and imaging characteristics.
The study of 2,017 participants with newly diagnosed adrenal masses, recruited from January 2011 to July 2016 from specialist centers in 11 different countries, assessed the diagnostic accuracy of three components: maximum tumor diameter (≥4 cm vs. <4 cm), imaging characteristics (positive vs. negative), and urine steroid metabolomics (low, medium, or high risk of adrenocortical carcinoma), separately and in combination.
Of the patients, 98 (4.9%) had adrenocortical carcinoma confirmed clinically, histopathologically, or biochemically.
Tumors with diameters of 4 cm or larger were identified in 488 patients (24.2%) and were observed in the vast majority of patients with adrenocortical carcinoma (96 of 98), for a positive predictive value (PPV) of 19.7%.
Likewise, the PPV for imaging characteristics was 19.7%. However, increasing the unenhanced CT tumor attenuation threshold to 20 Hounsfield units (HU) from the recommended 10 HU increased specificity for adrenocortical carcinoma (80.0% vs. 64.0%) while maintaining sensitivity (99.0% vs. 100.0%).
Comparatively, a urine steroid metabolomics result suggesting a high risk of adrenocortical carcinoma had a PPV of 34.6%.
A total of 106 patients (5.3%) met the criteria for all three measures, and the PPV for all three was 76.4%.
Using the criteria, 70 patients (3.5%) were classified as being at moderate risk of adrenocortical carcinoma and 1,841 (91.3%) at low risk, for a negative predictive value (NPV) of 99.7%.
“Use of radiation-free, noninvasive urine steroid metabolomics has a higher PPV than two standard imaging tests, and best performance was seen with the combination of all three tests,” the authors state.
Limit urine test to patients with larger tumors
They note that the use of the combined diagnostic strategy would have led to additional imaging in only 488 (24.2%) of the study’s 2,017 patients, compared with the 2,737 scans that were actually conducted before reaching a diagnostic decision.
“Implementation of urine steroid metabolomics in the routine diagnostic assessment of newly discovered adrenal masses could reduce the number of imaging procedures required to diagnose adrenocortical carcinoma and avoid unnecessary surgery of benign adrenal tumors, potentially yielding beneficial effects with respect to patient burden and health care costs,” they stress.
And regarding imaging parameters, “we also showed that using a cutoff of 20 HU for unenhanced CT tumor attenuation increases the accuracy of imaging characteristic assessment for exclusion of adrenocortical carcinoma, compared with the currently recommended cutoff of 10 HU, which has immediate implications for clinical practice,” they emphasize.
In an accompanying editorial, Adina F. Turcu, MD, of the division of metabolism, endocrinology, and diabetes, University of Michigan, Ann Arbor, and Axel K. Walch, MD, of the Helmholtz Zentrum München–German Research Centre for Environmental Health, agree. “The introduction of urine steroid metabolomics into routine clinical practice would provide major advantages,” they state.
However, they point out that, although the overall negative predictive value of the test was excellent, the specificity was weak.
“Thus, urine steroid metabolomics should be limited to patients who have adrenal nodules larger than 4 cm and have qualitative imaging characteristics suggestive of malignancy,” say Dr. Turcu and Dr. Walch.
The EURINE-ACT study results suggest this subgroup would represent roughly only 12% of all patients with adrenal incidentalomas, they add.
Issues that remain to be addressed with regard to the implementation of the screening strategy include how to best respond to patients who are classified as having intermediate or moderate risk of malignancy, and whether the diagnostic value of steroid metabolomics could be refined by adding analytes or parameters, the editorialists conclude.
The study was funded by the European Commission, U.K. Medical Research Council, Wellcome Trust, U.K. National Institute for Health Research, U.S. National Institutes of Health, the Claire Khan Trust Fund at University Hospitals Birmingham Charities, and the Mayo Clinic Foundation for Medical Education and Research.
A version of this article originally appeared on Medscape.com.
Positive phase 3 top-line results for migraine prevention drug
AbbVie, the company developing the drug, has announced.
Top-line results from the ADVANCE trial, which evaluated atogepant 10, 30, and 60 mg, showed all three doses were associated with a significant reduction from baseline in mean monthly migraine days, compared with placebo.
There were also significant improvements in all six secondary endpoints with the two higher doses.
Data from the ADVANCE trial and a previous phase 2/3 trial will be the basis for regulatory submissions in the United States and other countries, AbbVie reported.
Decreased migraine days
The phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the efficacy, safety, and tolerability of oral atogepant for the prevention of migraine in those who experienced 4-14 migraine days per month.
A total of 910 patients were randomized to one of four treatment groups: 10 mg, 30 mg, or 60 mg of atogepant once daily or placebo. Efficacy analyses were based on the modified intent-to-treat population of 873 patients.
The primary endpoint was change from baseline in mean monthly migraine days during the 12-week treatment period. All atogepant dose groups met the primary endpoint and demonstrated significantly greater decreases in mean monthly migraine days, compared with placebo.
Mean monthly migraine days were reduced by 3.69 days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose of atogepant, compared with a reduction of 2.48 migraine days in the placebo group (P < .0001, all dose groups vs. placebo).
A key secondary endpoint measured the proportion of patients who achieved at least a 50% reduction in mean monthly migraine days over 12 weeks. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group, compared with 29% of the placebo group (P < .0001, all dose groups vs. placebo).
Significant improvements
Additional secondary endpoints measured during the 12-week treatment period included change from baseline in mean monthly headache days, mean monthly acute–medication use days, mean monthly performance of daily activities and physical impairment domain scores on the Activity Impairment in Migraine-Diary, and change from baseline in the Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive domain score at week 12. Treatment with the 30-mg and 60-mg doses resulted in significant improvements in all secondary endpoints, and treatment with the 10-mg dose resulted in significant improvements in four of the six secondary endpoints.
No new safety risks were observed when compared with the safety profile of atogepant observed in previous trials, AbbVie said. Serious adverse events occurred in 0.9% of patients in the atogepant 10-mg group versus 0.9% of patients in the placebo group. No patients in the atogepant 30-mg or 60-mg groups experienced a serious adverse event. The most common adverse events (reported in at least 5% of patients and at least one atogepant group and at a rate greater than placebo), across all doses versus placebo, were constipation (6.9%-7.7% vs. 0.5%), nausea (4.4%-6.1% vs. 1.8%), and upper respiratory tract infection (3.9%-5.7% vs. 4.5%).
Most cases of constipation, nausea, and upper respiratory tract infection were mild or moderate in severity and did not lead to discontinuation. There were no hepatic safety issues identified in the trial.
Full data results will be presented at an upcoming medical congress and/or published in a peer-reviewed journal, the company said.
A version of this article originally appeared on Medscape.com.
AbbVie, the company developing the drug, has announced.
Top-line results from the ADVANCE trial, which evaluated atogepant 10, 30, and 60 mg, showed all three doses were associated with a significant reduction from baseline in mean monthly migraine days, compared with placebo.
There were also significant improvements in all six secondary endpoints with the two higher doses.
Data from the ADVANCE trial and a previous phase 2/3 trial will be the basis for regulatory submissions in the United States and other countries, AbbVie reported.
Decreased migraine days
The phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the efficacy, safety, and tolerability of oral atogepant for the prevention of migraine in those who experienced 4-14 migraine days per month.
A total of 910 patients were randomized to one of four treatment groups: 10 mg, 30 mg, or 60 mg of atogepant once daily or placebo. Efficacy analyses were based on the modified intent-to-treat population of 873 patients.
The primary endpoint was change from baseline in mean monthly migraine days during the 12-week treatment period. All atogepant dose groups met the primary endpoint and demonstrated significantly greater decreases in mean monthly migraine days, compared with placebo.
Mean monthly migraine days were reduced by 3.69 days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose of atogepant, compared with a reduction of 2.48 migraine days in the placebo group (P < .0001, all dose groups vs. placebo).
A key secondary endpoint measured the proportion of patients who achieved at least a 50% reduction in mean monthly migraine days over 12 weeks. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group, compared with 29% of the placebo group (P < .0001, all dose groups vs. placebo).
Significant improvements
Additional secondary endpoints measured during the 12-week treatment period included change from baseline in mean monthly headache days, mean monthly acute–medication use days, mean monthly performance of daily activities and physical impairment domain scores on the Activity Impairment in Migraine-Diary, and change from baseline in the Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive domain score at week 12. Treatment with the 30-mg and 60-mg doses resulted in significant improvements in all secondary endpoints, and treatment with the 10-mg dose resulted in significant improvements in four of the six secondary endpoints.
No new safety risks were observed when compared with the safety profile of atogepant observed in previous trials, AbbVie said. Serious adverse events occurred in 0.9% of patients in the atogepant 10-mg group versus 0.9% of patients in the placebo group. No patients in the atogepant 30-mg or 60-mg groups experienced a serious adverse event. The most common adverse events (reported in at least 5% of patients and at least one atogepant group and at a rate greater than placebo), across all doses versus placebo, were constipation (6.9%-7.7% vs. 0.5%), nausea (4.4%-6.1% vs. 1.8%), and upper respiratory tract infection (3.9%-5.7% vs. 4.5%).
Most cases of constipation, nausea, and upper respiratory tract infection were mild or moderate in severity and did not lead to discontinuation. There were no hepatic safety issues identified in the trial.
Full data results will be presented at an upcoming medical congress and/or published in a peer-reviewed journal, the company said.
A version of this article originally appeared on Medscape.com.
AbbVie, the company developing the drug, has announced.
Top-line results from the ADVANCE trial, which evaluated atogepant 10, 30, and 60 mg, showed all three doses were associated with a significant reduction from baseline in mean monthly migraine days, compared with placebo.
There were also significant improvements in all six secondary endpoints with the two higher doses.
Data from the ADVANCE trial and a previous phase 2/3 trial will be the basis for regulatory submissions in the United States and other countries, AbbVie reported.
Decreased migraine days
The phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was designed to evaluate the efficacy, safety, and tolerability of oral atogepant for the prevention of migraine in those who experienced 4-14 migraine days per month.
A total of 910 patients were randomized to one of four treatment groups: 10 mg, 30 mg, or 60 mg of atogepant once daily or placebo. Efficacy analyses were based on the modified intent-to-treat population of 873 patients.
The primary endpoint was change from baseline in mean monthly migraine days during the 12-week treatment period. All atogepant dose groups met the primary endpoint and demonstrated significantly greater decreases in mean monthly migraine days, compared with placebo.
Mean monthly migraine days were reduced by 3.69 days with the 10-mg dose, 3.86 days with the 30-mg dose, and 4.2 days with the 60-mg dose of atogepant, compared with a reduction of 2.48 migraine days in the placebo group (P < .0001, all dose groups vs. placebo).
A key secondary endpoint measured the proportion of patients who achieved at least a 50% reduction in mean monthly migraine days over 12 weeks. This outcome occurred in 55.6% of the 10-mg atogepant group, 58.7% of the 30-mg group, and 60.8% of the 60-mg group, compared with 29% of the placebo group (P < .0001, all dose groups vs. placebo).
Significant improvements
Additional secondary endpoints measured during the 12-week treatment period included change from baseline in mean monthly headache days, mean monthly acute–medication use days, mean monthly performance of daily activities and physical impairment domain scores on the Activity Impairment in Migraine-Diary, and change from baseline in the Migraine-Specific Quality of Life Questionnaire Role Function-Restrictive domain score at week 12. Treatment with the 30-mg and 60-mg doses resulted in significant improvements in all secondary endpoints, and treatment with the 10-mg dose resulted in significant improvements in four of the six secondary endpoints.
No new safety risks were observed when compared with the safety profile of atogepant observed in previous trials, AbbVie said. Serious adverse events occurred in 0.9% of patients in the atogepant 10-mg group versus 0.9% of patients in the placebo group. No patients in the atogepant 30-mg or 60-mg groups experienced a serious adverse event. The most common adverse events (reported in at least 5% of patients and at least one atogepant group and at a rate greater than placebo), across all doses versus placebo, were constipation (6.9%-7.7% vs. 0.5%), nausea (4.4%-6.1% vs. 1.8%), and upper respiratory tract infection (3.9%-5.7% vs. 4.5%).
Most cases of constipation, nausea, and upper respiratory tract infection were mild or moderate in severity and did not lead to discontinuation. There were no hepatic safety issues identified in the trial.
Full data results will be presented at an upcoming medical congress and/or published in a peer-reviewed journal, the company said.
A version of this article originally appeared on Medscape.com.
Schizoaffective disorder: A challenging diagnosis
Mr. C, age 34, presented to the emergency department with his wife because of increasingly bizarre behavior. He reported auditory and visual hallucinations, and believed that the “mob had ordered a hit” against him. He had threatened to shoot his wife and children, which led to his arrest and being briefly jailed. In jail, he was agitated, defecated on the floor, and disrobed. His wife reported that Mr. C had a long history of bipolar disorder and had experienced his first manic episode and hospitalization at age 17. Since then, he had been treated with many different antidepressants, antipsychotics, and mood stabilizers.
Mr. C was admitted to the hospital, where he developed a catatonic syndrome that was treated with a course of electroconvulsive therapy. He was eventually stabilized with
Over the next 8 years, Mr. C was often noncompliant with medication and frequently was hospitalized for mania. His symptoms included poor sleep, grandiosity, pressured speech, racing and disorganized thoughts, increased risk-taking behavior (ie, driving at excessive speeds), and hyperreligiosity (ie, speaking with God). Mr. C also occasionally used methamphetamine, cannabis, and cocaine. Although he had responded well to treatment early in the course of his illness, as he entered his late 30s, his response was less complete, and by his 40s, Mr. C was no longer able to function independently. He eventually was prescribed a long-acting injectable antipsychotic, paliperidone palmitate, 156 mg monthly. Eventually, his family was no longer able to care for him at home, so he was admitted to a residential care facility.
In this facility, based on the long-standing nature of Mr. C’s psychotic disorder and frequency with which he presented with mania, his clinicians changed his diagnosis to schizoaffective disorder, bipolar type. It had become clear that mood symptoms comprised >50% of the total duration of his illness.
Schizoaffective disorder (SAD) often has been used as a diagnosis for patients who have an admixture of mood and psychotic symptoms whose diagnosis is uncertain. Its hallmark is the presence of symptoms of a major mood episode (either a depressive or manic episode) concurrent with symptoms characteristic of schizophrenia, such as delusions, hallucinations, or disorganized speech.1
SAD is a controversial diagnosis. There has been inadequate research regarding the epidemiology, course, etiologic factors, and treatment of this disorder. Debate continues to swirl around its conceptualization; some experts view SAD as an independent disorder, while others see SAD as either a form of schizophrenia or a mood disorder.1 In this review, we describe the classification of SAD and its features, diagnosis, and treatment.
An evolving diagnosis
The term schizoaffective was first used by Jacob Kasanin, MD, in 1933.2 He described 9 patients with “acute schizoaffective psychoses,” each of whom had an abrupt onset. The term was used in the first edition of the DSM as a subtype of schizophrenia.3 In DSM-I, the “schizo-affective type” was defined as a diagnosis for patients with a “significant admixture of schizophrenic and affective reactions.”3 Diagnostic criteria for SAD were developed for DSM-III-R, published in 1987.4 These criteria continued to evolve with subsequent editions of the DSM.
Continue to: DSM-5 provides...
DSM-5 provides a clearer separation between schizophrenia with mood symptoms, bipolar disorder, and SAD (Table5). In addition, DSM-5 shifts away from the DSM-IV diagnosis of SAD as an episode, and instead focuses more on the longitudinal course of the illness. It has been suggested that this change will likely lead to reduced rates of diagnosis of SAD.6 Despite improvements in classification, the diagnosis remains controversial (Box7-11).
Box 1
Despite improvements in classification, controversy continues to swirl around the question of whether schizoaffective disorder (SAD) represents an independent disorder that stands apart from schizophrenia and bipolar disorder, whether it is a form of schizophrenia, or whether it is a form of bipolar disorder or a depressive disorder.7,8 Other possibilities are that SAD is heterogeneous or that it represents a middle point on a spectrum that bridges mood and psychotic disorders. While the merits of each possibility are beyond the scope of this review, it is safe to say that each possibility has its proponents. For these reasons, some argue that the concept itself lacks validity and shows the pitfalls of our classification system.7
Poor diagnostic reliability is one reason for concerns about validity. Most recently, a field trial using DSM-5 criteria produced a kappa of 0.50, which is moderate,9 but earlier definitions produced relatively poor results. Wilson et al10 point out that Criterion C, which concerns duration of mood symptoms, produces a particularly low kappa. Another reason is diagnostic switching, whereby patients initially diagnosed with 1 disorder receive a different diagnosis at followup. Diagnostic switching is especially problematic for SAD. In a large meta-analysis by Santelmann et al,11 36% of patients initially diagnosed with SAD had their diagnosis changed when reassessed. This diagnostic shift tended more toward schizophrenia than bipolar disorder. In addition, more than one-half of all patients initially diagnosed with schizophrenia, bipolar disorder, or major depressive disorder were re-diagnosed with SAD when reassessed.
DSM-5 subtypes and specifiers
In DSM-5,SAD has 2 subtypes5:
- Bipolar type. The bipolar type is marked by the presence of a manic episode (major depressive episodes may also occur)
- Depressive type. The depressive type is marked by the presence of only major depressive episodes.
SAD also includes several specifiers, with the express purpose of giving clinicians greater descriptive ability. The course of SAD can be described as either “first episode,” defined as the first manifestation of the disorder, or as having “multiple episodes,” defined as a minimum of 2 episodes with 1 relapse. In addition, SAD can be described as an acute episode, in partial remission, or in full remission. The course can be described as “continuous” if it is clear that symptoms have been present for the majority of the illness with very brief subthreshold periods. The course is designated as “unspecified” when information is unavailable or lacking. The 5-point Clinician-Rated Dimensions of Psychosis Symptoms was introduced to enable clinicians to make a quantitative assessment of the psychotic symptoms, although its use is not required.
Epidemiology and gender ratio
The epidemiology of SAD has not been well studied. DSM-5 estimates that SAD is approximately one-third as common as schizophrenia, which has a lifetime prevalence of 0.5% to 0.8%.5 This is similar to an estimate by Perälä et al12 of a 0.32% lifetime prevalence based on a nationally representative sample of persons in Finland age ≥30. Scully et al13 calculated a prevalence estimate of 1.1% in a representative sample of adults in rural Ireland. Based on pooled clinical data, Keck et al14 estimated the prevalence in clinical settings at 16%, similar to the figure of 19% reported by Levinson et al15 based on data from New York State psychiatric hospitals. In clinical practice, the diagnosis of SAD is used frequently when there is diagnostic uncertainty, which potentially inflates estimates of lifetime prevalence.
The prevalence of SAD is higher in women than men, with a sex ratio of about 2:1, similar to that seen in mood disorders.13,16-19 There are an equal number of men and women with the bipolar subtype, but a female preponderance with the depressive subtype.5 The bipolar subtype is more common in younger patients, while the depressive subtype is more common in older patients. SAD is a rare diagnosis in children.20
Continue to: Course and outcome
Course and outcome
The onset of SAD typically occurs in early adulthood, but can range from childhood to senescence. Approximately one-third of patients are diagnosed before age 25, one-third between age 25 and 35, and one-third after age 35.21-23 Based on a literature review, Cheniaux et al7 concluded that that age at onset for patients with SAD is between those with schizophrenia and those with mood disorders.
The course of SAD is variable but represents a middle ground between that of schizophrenia and the mood disorders. In a 4- to 5-year follow-up,24 patients with SAD had a better overall course than patients with schizophrenia but had poorer functioning than those with bipolar mania, and much poorer than those with unipolar depression. Mood-incongruent psychotic features predict a particularly worse outcome. These findings were reaffirmed at a 10-year follow-up.25 Mood symptoms portend a better outcome than do symptoms of schizophrenia.
The lifetime suicide risk for patients with SAD is estimated at 5%, with a higher risk associated with the presence of depressive symptoms.26 One study found that women with SAD had a 17.5-year reduced life expectancy (64.1 years) compared with a reduction of 8.0 years for men (69.4 years).27
Comorbidity
Patients with SAD are commonly diagnosed with other psychiatric disorders, including anxiety disorders, obsessive-compulsive disorder, posttraumatic stress disorder, and substance use disorders.21,28,29 When compared with the general population, patients with SAD are at higher risk for coronary heart disease, stroke, obesity, and smoking, likely contributing to their decreased life expectancy.27,30 Because second-generation antipsychotics (SGAs) are often used to treat SAD, patients with SAD are at risk for metabolic syndrome and diabetes mellitus.30
Clinical assessment
Because there are no diagnostic, laboratory, or neuroimaging tests for SAD, the most important basis for making the diagnosis is the patient’s history, supplemented by collateral history from family members or friends, and medical records. Determining the percentage of time spent in a mood episode (DSM-5 Criterion C) is especially important.31 This requires the clinician to pay close attention to the temporal relationship of psychotic and mood symptoms.
Continue to: Differential diagnosis
Differential diagnosis
The differential diagnosis for SAD is broad because it includes all of the possibilities usually considered for major mood disorders and for psychotic disorders5:
- schizophrenia
- bipolar disorder with psychotic features
- major depressive disorder with psychotic features
- depressive or bipolar disorders with catatonic features
- personality disorders (especially the schizotypal, paranoid, and borderline types)
- major neurocognitive disorders in which there are mood and psychotic symptoms
- substance/medication-induced psychotic disorder
- disorders induced by medical conditions.
With schizophrenia, the duration of all episodes of a mood syndrome is brief (<50% of the total duration of the illness) relative to the duration of the psychotic symptoms. Although psychotic symptoms may occur in persons with mood disorders, they are generally not present in the absence of depression or mania, helping to set the boundary between SAD and psychotic mania or depression. As for personality disorders, the individual will not have a true psychosis, although some symptoms, such as feelings of unreality, paranoia, or magical thinking, may cause diagnostic confusion.
Medical conditions also can present with psychotic and mood symptoms and need to be ruled out. These include psychotic disorder due to another medical condition, and delirium. A thorough medical workup should be performed to rule out any possible medical causes for the symptoms.
Substance use should also be ruled out as the cause of the symptoms because many substances are associated with mood and psychotic symptoms. It is usually clear from the history, physical examination, or laboratory tests when a medication/illicit substance has initiated and maintained the disorder.
Neurologic conditions. If a neurologic condition is suspected, a neurologic evaluation may be warranted, including laboratory tests, brain imaging to identify specific anatomical abnormalities, lumbar puncture with cerebrospinal fluid analysis, and an electroencephalogram to rule out a convulsive disorder.
Continue to: Clinical symptoms
Clinical symptoms
The signs and symptoms of SAD include those typically seen in schizophrenia and the mood disorders. Thus, the patient may exhibit elated mood and/or grandiosity, or severe depression, combined with mood-incongruent psychotic features such as paranoid delusions. The symptoms may present together or in an alternating fashion, and psychotic symptoms may be mood-congruent or mood-incongruent. Mr. C’s case illustrates some of the symptoms of the disorder.
Brain imaging
Significant changes have been reported to occur in the brain structure and function in persons with SAD. Neuroimaging studies using voxel-based morphometry have shown significant reductions in gray matter volume in several areas of the brain, including the medial prefrontal cortex, insula, Rolandic operculum, parts of the temporal lobe, and the hippocampus.32-35 Amann et al32 found that patients with SAD and schizophrenia had widespread and overlapping areas of significant volume reduction, but patients with bipolar disorder did not. These studies suggest that at least from a neuroimaging standpoint, SAD is more closely related to schizophrenia than bipolar disorder, and could represent a variant of schizophrenia.
Treatment of SAD
The pharmacotherapy of SAD is mostly empirical because of the lack of randomized controlled trials. Clinicians have traditionally prescribed an antipsychotic agent along with either a mood stabilizer (eg,
Since that exhaustive review,
Patients with SAD will require maintenance treatment for ongoing symptom control. Medication that is effective for treatment of an acute episode should be considered for maintenance treatment. Both the extended-release and long-acting injectable (LAI) formulations of paliperidone have been shown to be efficacious in the maintenance treatment of patients with SAD.40 The LAI form of paliperidone significantly delayed psychotic, depressive, and manic relapses, improved clinical rating scale scores, and increased medication adherence.41,42 In an open-label study, olanzapine LAI was effective in long-term maintenance treatment, although approximately 40% of patients experienced significant weight gain.43 One concern with olanzapine is the possible occurrence of a post-injection delirium/sedation syndrome. For that reason, patients receiving olanzapine must be monitored for at least 3 hours post-injection. The paliperidone LAI does not require monitoring after injection.
Continue to: There is a single clinical trial...
There is a single clinical trial showing that patients with SAD can be successfully switched from other antipsychotics to
Other approaches
Electroconvulsive therapy (ECT) should be considered for patients with SAD who are acutely ill and have failed to respond adequately to medication. ECT is especially relevant in the setting of acute mood symptoms (ie, depressive or manic symptoms co-occurring with psychosis or in the absence of psychosis).45
As currently conceptualized, the diagnosis of SAD is made in persons having an admixture of mood and psychotic symptoms, although by definition mood symptoms must take up the majority (≥50%) of the total duration of the illness. Unfortunately, SAD has been inadequately researched due to the unreliability of its definition and concerns about its validity. The long-term course of SAD is midway between mood and psychotic disorders, and the disorder can cause significant disability.
Bottom Line
Schizoaffective disorder (SAD) is characterized by the presence of symptoms of a major mood episode (a depressive or manic episode) concurrent with symptoms of schizophrenia. The most important basis for establishing the diagnosis is the patient’s history. Determining the percentage of time spent in a mood episode is especially important. Treatment usually consists of an antipsychotic plus a mood stabilizer or antidepressant. Electroconvulsive therapy is an option for patients with SAD who do not respond well to medication.
Related Resources
- Wy TJP, Saadabadi A. Schizoaffective disorder. NCBI Bookshelf: StatPearls Publishing. Published January 2020. https://www.ncbi.nlm.nih.gov/books/NBK541012/. Updated April 15, 2020.
- Parker G. How well does the DSM-5 capture schizoaffective disorder? Can J Psychiatry. 2019;64(9):607-610.
Drug Brand Names
Aripiprazole • Abilify
Lithium • Eskalith, Lithobid
Lurasidone • Latuda
Olanzapine • Zyprexa
Olanzapine long-acting injectable • Zyprexa Relprevv
Paliperidone • Invega
Paliperidone palmitate • Invega sustenna
Valproate • Depacon
1. Miller JN, Black DW. Schizoaffective disorder: a review. Ann Clin Psychiatry. 2019;31(1):47-53.
2. Kasanin J. The acute schizoaffective psychoses. Am J Psychiatry. 1933;90:97-126.
3. Diagnostic and statistical manual of mental disorders, 1st ed. Washington, DC: American Psychiatric Association; 1952.
4. Diagnostic and statistical manual of mental disorders, 3rd ed, revision. Washington, DC: American Psychiatric Association; 1987.
5. Diagnostic and statistical manual of mental disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.
6. Malaspina D, Owen M, Heckers S, et al. Schizoaffective disorder in the DSM-5. Schizophr Res. 2013;150:21-25.
7. Cheniaux E, Landeria-Fernandez J, Telles LL, et al. Does schizoaffective disorder really exist? A systematic review of the studies that compared schizoaffective disorder with schizophrenia or mood disorders. J Affect Disord. 2008;106:209-217.
8. Kantrowitz JT, Citrome L. Schizoaffective disorder: a review of current research themes and pharmacologic management. CNS Drugs. 2011;25:317-331.
9. Regier DA, Narrow WE, Clarke DE, et al. DSM-5 field trials in the United States and Canada, Part II: test-retest reliability of selected categorical diagnoses. Am J Psychiatry. 2013;170:59-70.
10. Wilson JE, Nian H, Heckers S. The schizoaffective disorder diagnosis: a conundrum in the clinical setting. Eur Arch Psychiatry Clin Neurosci. 2014;264:29-34.
11. Santelmann H, Franklin J, Bußhoff J, Baethge C. Test-retest reliability of schizoaffective disorder compared with schizophrenia, bipolar disorder, and unipolar depression--a systematic review and meta-analysis. Bipolar Disord. 2015;17:753-768.
12. Perälä J, Suvisaari J, Saarni SI, et al. Lifetime Prevalence of psychotic and bipolar I disorders in a general population. JAMA Psychiatry. 2007;64:19-28.
13. Scully PJ, Owens JM, Kinsella A, et al. Schizophrenia, schizoaffective and bipolar disorder within an epidemiologically complete, homogeneous population in rural Ireland: small area variation in rate. Schizophr Res. 2004;67:143-155.
14. Keck PE Jr, McElroy SE, Strakowski SM, et al. Pharmacologic treatment of schizoaffective disorder. Psychopharmacol. 1994;114:529-538.
15. Levinson DF, Umapathy C, Musthaq M. Treatment of schizoaffective disorder and schizophrenia with mood symptoms. Am J Psychiatry. 1999;156:1138-1148.
16. Angst J, Felder W, Lohmeyer B. Course of schizoaffective psychoses: results of a follow-up study. Schizophr Bull. 1980;6:579-585.
17. Lenz G, Simhandl C, Thau K, et al. Temporal stability of diagnostic criteria for functional psychoses. Psychopathol. 1991;24:328-335.
18. Malhi GS, Green M, Fagiolini A, et al. Schizoaffective disorder: diagnostic issues and future recommendations. Bipolar Disord. 2008;10:215-230.
19. Marneros A, Deister A, Rohde A. Psychopathological and social status of patients with affective, schizophrenic and schizoaffective disorders after long‐term course. Acta Psychiatr Scand. 1990;82:352-358.
20. Werry JS, McClellan JM, Chard L. Childhood and adolescent schizophrenic, bipolar, and schizoaffective disorders: a clinical and outcome study. J Am Acad Child Adolesc Psychiatry. 1991;30:457-465.
21. Abrams DJ, Rojas DC, Arciniegas DB. Is schizoaffective disorder a distinct categorical diagnosis? A critical review of the literature. Neuropsychiatr Dis Treat. 2008;4:1089-1109.
22. Bromet EJ, Kotov R, Fochtmann LJ, et al. Diagnostic shifts during the decade following first admission for psychosis. Am J Psychiatry. 2011;168:1186-1194.
23. Salvatore P, Baldessarini RJ, Tohen M, et al. The McLean-Harvard First Episode Project: two-year stability of DSM-IV diagnoses in 500 first-episode psychotic disorder patients. J Clin Psychiatry. 2009;70:458-466.
24. Grossman LS, Harrow M, Goldberg JF, et al. Outcome of schizoaffective disorder at two long term follow-ups: comparisons with outcome of schizophrenia and affective disorders. Am J Psychiatry. 1991;148:1359-1365.
25. Harrow M, Grossman L, Herbener E, et al. Ten-year outcome: patients with schizoaffective disorders, schizophrenia, affective disorders and mood-incongruent psychotic symptoms. Br J Psychiatry. 2000;177:421-426.
26. Hor K, Taylor M. Review: suicide and schizophrenia: a systematic review of rates and risk factors. J Psychopharmacol. 2010;24:81-90.
27. Chang CK, Hayes RD, Perera G, et al. Life expectancy at birth for people with serious mental illness and other major disorders from a secondary mental health care case register in London. PLoS ONE. 2011;6:e19590.
28. Byerly M, Goodman W, Acholonu W, et al. Obsessive compulsive symptoms in schizophrenia: frequency and clinical features. Schizophr Res. 2005;76:309-316.
29. Strauss JL, Calhoun PS, Marx CE, et al. Comorbid posttraumatic stress disorder is associated with suicidality in male veterans with schizophrenia or schizoaffective disorder. Schizophr Res. 2006;84:165-169.
30. Fagiolini A, Goracci A. The effects of undertreated chronic medical illnesses in patients with severe mental disorders. J Clin Psychiatry. 2009;70:22-29.
31. Black DW, Grant JE. DSM-5 guidebook: the essential companion to the diagnostic and statistical manual of mental disorders, 5th edition. Washington, DC: American Psychiatric Publishing; 2014.
32. Amann BL, Canales-Rodríguez EJ, Madre M, et al. Brain structural changes in schizoaffective disorder compared to schizophrenia and bipolar disorder. Acta Psychiatr Scand. 2016;133:23-33.
33. Ivleva EI, Bidesi AS, Keshavan MS, et al. Gray matter volume as an intermediate phenotype for psychosis: Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP). Am J Psychiatry. 2013;170:1285-1296.
34. Ivleva EI, Bidesi AS, Thomas BP, et al. Brain gray matter phenotypes across the psychosis dimension. Psychiatry Res. 2012;204:13-24.
35. Radonic
36. Jäger M, Becker T, Weinmann S, et al. Treatment of schizoaffective disorder - a challenge for evidence-based psychiatry. Acta Psychiatr Scand. 2010;121:22-32.
37. Glick ID, Mankosli R, Eudicone JM, et al. The efficacy, safety, and tolerability of aripiprazole for the treatment of schizoaffective disorder: results from a pooled analysis of a sub-population of subjects from two randomized, double-blind, placebo controlled, pivotal trials. J Affect Disord. 2009;115:18-26.
38. Canuso CM, Lindenmayer JP, Kosik-Gonzalez C, et al. A randomized, double-blind, placebo controlled study of 2 dose ranges of paliperidone extended-release in the treatment of subjects with schizoaffective disorder. J Clin Psychiatry. 2010;71:587-598.
39. Canuso CM, Schooler NR, Carothers J, et al. Paliperidone extended-release in schizoaffective disorder: a randomized controlled trial comparing a flexible-dose with placebo in patients treated with and without antidepressants and/or mood stabilizers. J Clin Psychopharmacol. 2010;30:487-495.
40. Lindenmayer JP, Kaur A. Antipsychotic management of schizoaffective disorder: a review. Drugs. 2016;76:589-604.
41. Alphs L, Fu DJ, Turkoz I. Paliperidone for the treatment of schizoaffective disorder. Expert Opin Pharmacother. 2016;176:871-883.
42. Bossie CA, Turkoz I, Alphs L, et al. Paliperidone palmitate once-monthly treatment in recent onset and chronic illness patients with schizoaffective disorder. J Nerv Ment Dis. 2017;205:324-328.
43. McDonnell DP, Landry J, Detke HC. Long-term safety and efficacy of olanzapine long-acting injection in patients with schizophrenia or schizoaffective disorder: a 6-year, multinational, single-arm, open-label study. Int Clin Psychopharmacol. 2014;29:322-331.
44. McEvoy JP, Citrome L, Hernandez D, et al. Effectiveness of lurasidone in patients with schizophrenia or schizoaffective disorder switched from other antipsychotics: a randomized, 6-week, open-label study. J Clin Psychiatry. 2013;74:170-179.
45. Mankad MV, Beyer JL, Wiener RD, et al. Manual of electroconvulsive therapy. Washington, DC: American Psychiatric Publishing; 2010.
Mr. C, age 34, presented to the emergency department with his wife because of increasingly bizarre behavior. He reported auditory and visual hallucinations, and believed that the “mob had ordered a hit” against him. He had threatened to shoot his wife and children, which led to his arrest and being briefly jailed. In jail, he was agitated, defecated on the floor, and disrobed. His wife reported that Mr. C had a long history of bipolar disorder and had experienced his first manic episode and hospitalization at age 17. Since then, he had been treated with many different antidepressants, antipsychotics, and mood stabilizers.
Mr. C was admitted to the hospital, where he developed a catatonic syndrome that was treated with a course of electroconvulsive therapy. He was eventually stabilized with
Over the next 8 years, Mr. C was often noncompliant with medication and frequently was hospitalized for mania. His symptoms included poor sleep, grandiosity, pressured speech, racing and disorganized thoughts, increased risk-taking behavior (ie, driving at excessive speeds), and hyperreligiosity (ie, speaking with God). Mr. C also occasionally used methamphetamine, cannabis, and cocaine. Although he had responded well to treatment early in the course of his illness, as he entered his late 30s, his response was less complete, and by his 40s, Mr. C was no longer able to function independently. He eventually was prescribed a long-acting injectable antipsychotic, paliperidone palmitate, 156 mg monthly. Eventually, his family was no longer able to care for him at home, so he was admitted to a residential care facility.
In this facility, based on the long-standing nature of Mr. C’s psychotic disorder and frequency with which he presented with mania, his clinicians changed his diagnosis to schizoaffective disorder, bipolar type. It had become clear that mood symptoms comprised >50% of the total duration of his illness.
Schizoaffective disorder (SAD) often has been used as a diagnosis for patients who have an admixture of mood and psychotic symptoms whose diagnosis is uncertain. Its hallmark is the presence of symptoms of a major mood episode (either a depressive or manic episode) concurrent with symptoms characteristic of schizophrenia, such as delusions, hallucinations, or disorganized speech.1
SAD is a controversial diagnosis. There has been inadequate research regarding the epidemiology, course, etiologic factors, and treatment of this disorder. Debate continues to swirl around its conceptualization; some experts view SAD as an independent disorder, while others see SAD as either a form of schizophrenia or a mood disorder.1 In this review, we describe the classification of SAD and its features, diagnosis, and treatment.
An evolving diagnosis
The term schizoaffective was first used by Jacob Kasanin, MD, in 1933.2 He described 9 patients with “acute schizoaffective psychoses,” each of whom had an abrupt onset. The term was used in the first edition of the DSM as a subtype of schizophrenia.3 In DSM-I, the “schizo-affective type” was defined as a diagnosis for patients with a “significant admixture of schizophrenic and affective reactions.”3 Diagnostic criteria for SAD were developed for DSM-III-R, published in 1987.4 These criteria continued to evolve with subsequent editions of the DSM.
Continue to: DSM-5 provides...
DSM-5 provides a clearer separation between schizophrenia with mood symptoms, bipolar disorder, and SAD (Table5). In addition, DSM-5 shifts away from the DSM-IV diagnosis of SAD as an episode, and instead focuses more on the longitudinal course of the illness. It has been suggested that this change will likely lead to reduced rates of diagnosis of SAD.6 Despite improvements in classification, the diagnosis remains controversial (Box7-11).
Box 1
Despite improvements in classification, controversy continues to swirl around the question of whether schizoaffective disorder (SAD) represents an independent disorder that stands apart from schizophrenia and bipolar disorder, whether it is a form of schizophrenia, or whether it is a form of bipolar disorder or a depressive disorder.7,8 Other possibilities are that SAD is heterogeneous or that it represents a middle point on a spectrum that bridges mood and psychotic disorders. While the merits of each possibility are beyond the scope of this review, it is safe to say that each possibility has its proponents. For these reasons, some argue that the concept itself lacks validity and shows the pitfalls of our classification system.7
Poor diagnostic reliability is one reason for concerns about validity. Most recently, a field trial using DSM-5 criteria produced a kappa of 0.50, which is moderate,9 but earlier definitions produced relatively poor results. Wilson et al10 point out that Criterion C, which concerns duration of mood symptoms, produces a particularly low kappa. Another reason is diagnostic switching, whereby patients initially diagnosed with 1 disorder receive a different diagnosis at followup. Diagnostic switching is especially problematic for SAD. In a large meta-analysis by Santelmann et al,11 36% of patients initially diagnosed with SAD had their diagnosis changed when reassessed. This diagnostic shift tended more toward schizophrenia than bipolar disorder. In addition, more than one-half of all patients initially diagnosed with schizophrenia, bipolar disorder, or major depressive disorder were re-diagnosed with SAD when reassessed.
DSM-5 subtypes and specifiers
In DSM-5,SAD has 2 subtypes5:
- Bipolar type. The bipolar type is marked by the presence of a manic episode (major depressive episodes may also occur)
- Depressive type. The depressive type is marked by the presence of only major depressive episodes.
SAD also includes several specifiers, with the express purpose of giving clinicians greater descriptive ability. The course of SAD can be described as either “first episode,” defined as the first manifestation of the disorder, or as having “multiple episodes,” defined as a minimum of 2 episodes with 1 relapse. In addition, SAD can be described as an acute episode, in partial remission, or in full remission. The course can be described as “continuous” if it is clear that symptoms have been present for the majority of the illness with very brief subthreshold periods. The course is designated as “unspecified” when information is unavailable or lacking. The 5-point Clinician-Rated Dimensions of Psychosis Symptoms was introduced to enable clinicians to make a quantitative assessment of the psychotic symptoms, although its use is not required.
Epidemiology and gender ratio
The epidemiology of SAD has not been well studied. DSM-5 estimates that SAD is approximately one-third as common as schizophrenia, which has a lifetime prevalence of 0.5% to 0.8%.5 This is similar to an estimate by Perälä et al12 of a 0.32% lifetime prevalence based on a nationally representative sample of persons in Finland age ≥30. Scully et al13 calculated a prevalence estimate of 1.1% in a representative sample of adults in rural Ireland. Based on pooled clinical data, Keck et al14 estimated the prevalence in clinical settings at 16%, similar to the figure of 19% reported by Levinson et al15 based on data from New York State psychiatric hospitals. In clinical practice, the diagnosis of SAD is used frequently when there is diagnostic uncertainty, which potentially inflates estimates of lifetime prevalence.
The prevalence of SAD is higher in women than men, with a sex ratio of about 2:1, similar to that seen in mood disorders.13,16-19 There are an equal number of men and women with the bipolar subtype, but a female preponderance with the depressive subtype.5 The bipolar subtype is more common in younger patients, while the depressive subtype is more common in older patients. SAD is a rare diagnosis in children.20
Continue to: Course and outcome
Course and outcome
The onset of SAD typically occurs in early adulthood, but can range from childhood to senescence. Approximately one-third of patients are diagnosed before age 25, one-third between age 25 and 35, and one-third after age 35.21-23 Based on a literature review, Cheniaux et al7 concluded that that age at onset for patients with SAD is between those with schizophrenia and those with mood disorders.
The course of SAD is variable but represents a middle ground between that of schizophrenia and the mood disorders. In a 4- to 5-year follow-up,24 patients with SAD had a better overall course than patients with schizophrenia but had poorer functioning than those with bipolar mania, and much poorer than those with unipolar depression. Mood-incongruent psychotic features predict a particularly worse outcome. These findings were reaffirmed at a 10-year follow-up.25 Mood symptoms portend a better outcome than do symptoms of schizophrenia.
The lifetime suicide risk for patients with SAD is estimated at 5%, with a higher risk associated with the presence of depressive symptoms.26 One study found that women with SAD had a 17.5-year reduced life expectancy (64.1 years) compared with a reduction of 8.0 years for men (69.4 years).27
Comorbidity
Patients with SAD are commonly diagnosed with other psychiatric disorders, including anxiety disorders, obsessive-compulsive disorder, posttraumatic stress disorder, and substance use disorders.21,28,29 When compared with the general population, patients with SAD are at higher risk for coronary heart disease, stroke, obesity, and smoking, likely contributing to their decreased life expectancy.27,30 Because second-generation antipsychotics (SGAs) are often used to treat SAD, patients with SAD are at risk for metabolic syndrome and diabetes mellitus.30
Clinical assessment
Because there are no diagnostic, laboratory, or neuroimaging tests for SAD, the most important basis for making the diagnosis is the patient’s history, supplemented by collateral history from family members or friends, and medical records. Determining the percentage of time spent in a mood episode (DSM-5 Criterion C) is especially important.31 This requires the clinician to pay close attention to the temporal relationship of psychotic and mood symptoms.
Continue to: Differential diagnosis
Differential diagnosis
The differential diagnosis for SAD is broad because it includes all of the possibilities usually considered for major mood disorders and for psychotic disorders5:
- schizophrenia
- bipolar disorder with psychotic features
- major depressive disorder with psychotic features
- depressive or bipolar disorders with catatonic features
- personality disorders (especially the schizotypal, paranoid, and borderline types)
- major neurocognitive disorders in which there are mood and psychotic symptoms
- substance/medication-induced psychotic disorder
- disorders induced by medical conditions.
With schizophrenia, the duration of all episodes of a mood syndrome is brief (<50% of the total duration of the illness) relative to the duration of the psychotic symptoms. Although psychotic symptoms may occur in persons with mood disorders, they are generally not present in the absence of depression or mania, helping to set the boundary between SAD and psychotic mania or depression. As for personality disorders, the individual will not have a true psychosis, although some symptoms, such as feelings of unreality, paranoia, or magical thinking, may cause diagnostic confusion.
Medical conditions also can present with psychotic and mood symptoms and need to be ruled out. These include psychotic disorder due to another medical condition, and delirium. A thorough medical workup should be performed to rule out any possible medical causes for the symptoms.
Substance use should also be ruled out as the cause of the symptoms because many substances are associated with mood and psychotic symptoms. It is usually clear from the history, physical examination, or laboratory tests when a medication/illicit substance has initiated and maintained the disorder.
Neurologic conditions. If a neurologic condition is suspected, a neurologic evaluation may be warranted, including laboratory tests, brain imaging to identify specific anatomical abnormalities, lumbar puncture with cerebrospinal fluid analysis, and an electroencephalogram to rule out a convulsive disorder.
Continue to: Clinical symptoms
Clinical symptoms
The signs and symptoms of SAD include those typically seen in schizophrenia and the mood disorders. Thus, the patient may exhibit elated mood and/or grandiosity, or severe depression, combined with mood-incongruent psychotic features such as paranoid delusions. The symptoms may present together or in an alternating fashion, and psychotic symptoms may be mood-congruent or mood-incongruent. Mr. C’s case illustrates some of the symptoms of the disorder.
Brain imaging
Significant changes have been reported to occur in the brain structure and function in persons with SAD. Neuroimaging studies using voxel-based morphometry have shown significant reductions in gray matter volume in several areas of the brain, including the medial prefrontal cortex, insula, Rolandic operculum, parts of the temporal lobe, and the hippocampus.32-35 Amann et al32 found that patients with SAD and schizophrenia had widespread and overlapping areas of significant volume reduction, but patients with bipolar disorder did not. These studies suggest that at least from a neuroimaging standpoint, SAD is more closely related to schizophrenia than bipolar disorder, and could represent a variant of schizophrenia.
Treatment of SAD
The pharmacotherapy of SAD is mostly empirical because of the lack of randomized controlled trials. Clinicians have traditionally prescribed an antipsychotic agent along with either a mood stabilizer (eg,
Since that exhaustive review,
Patients with SAD will require maintenance treatment for ongoing symptom control. Medication that is effective for treatment of an acute episode should be considered for maintenance treatment. Both the extended-release and long-acting injectable (LAI) formulations of paliperidone have been shown to be efficacious in the maintenance treatment of patients with SAD.40 The LAI form of paliperidone significantly delayed psychotic, depressive, and manic relapses, improved clinical rating scale scores, and increased medication adherence.41,42 In an open-label study, olanzapine LAI was effective in long-term maintenance treatment, although approximately 40% of patients experienced significant weight gain.43 One concern with olanzapine is the possible occurrence of a post-injection delirium/sedation syndrome. For that reason, patients receiving olanzapine must be monitored for at least 3 hours post-injection. The paliperidone LAI does not require monitoring after injection.
Continue to: There is a single clinical trial...
There is a single clinical trial showing that patients with SAD can be successfully switched from other antipsychotics to
Other approaches
Electroconvulsive therapy (ECT) should be considered for patients with SAD who are acutely ill and have failed to respond adequately to medication. ECT is especially relevant in the setting of acute mood symptoms (ie, depressive or manic symptoms co-occurring with psychosis or in the absence of psychosis).45
As currently conceptualized, the diagnosis of SAD is made in persons having an admixture of mood and psychotic symptoms, although by definition mood symptoms must take up the majority (≥50%) of the total duration of the illness. Unfortunately, SAD has been inadequately researched due to the unreliability of its definition and concerns about its validity. The long-term course of SAD is midway between mood and psychotic disorders, and the disorder can cause significant disability.
Bottom Line
Schizoaffective disorder (SAD) is characterized by the presence of symptoms of a major mood episode (a depressive or manic episode) concurrent with symptoms of schizophrenia. The most important basis for establishing the diagnosis is the patient’s history. Determining the percentage of time spent in a mood episode is especially important. Treatment usually consists of an antipsychotic plus a mood stabilizer or antidepressant. Electroconvulsive therapy is an option for patients with SAD who do not respond well to medication.
Related Resources
- Wy TJP, Saadabadi A. Schizoaffective disorder. NCBI Bookshelf: StatPearls Publishing. Published January 2020. https://www.ncbi.nlm.nih.gov/books/NBK541012/. Updated April 15, 2020.
- Parker G. How well does the DSM-5 capture schizoaffective disorder? Can J Psychiatry. 2019;64(9):607-610.
Drug Brand Names
Aripiprazole • Abilify
Lithium • Eskalith, Lithobid
Lurasidone • Latuda
Olanzapine • Zyprexa
Olanzapine long-acting injectable • Zyprexa Relprevv
Paliperidone • Invega
Paliperidone palmitate • Invega sustenna
Valproate • Depacon
Mr. C, age 34, presented to the emergency department with his wife because of increasingly bizarre behavior. He reported auditory and visual hallucinations, and believed that the “mob had ordered a hit” against him. He had threatened to shoot his wife and children, which led to his arrest and being briefly jailed. In jail, he was agitated, defecated on the floor, and disrobed. His wife reported that Mr. C had a long history of bipolar disorder and had experienced his first manic episode and hospitalization at age 17. Since then, he had been treated with many different antidepressants, antipsychotics, and mood stabilizers.
Mr. C was admitted to the hospital, where he developed a catatonic syndrome that was treated with a course of electroconvulsive therapy. He was eventually stabilized with
Over the next 8 years, Mr. C was often noncompliant with medication and frequently was hospitalized for mania. His symptoms included poor sleep, grandiosity, pressured speech, racing and disorganized thoughts, increased risk-taking behavior (ie, driving at excessive speeds), and hyperreligiosity (ie, speaking with God). Mr. C also occasionally used methamphetamine, cannabis, and cocaine. Although he had responded well to treatment early in the course of his illness, as he entered his late 30s, his response was less complete, and by his 40s, Mr. C was no longer able to function independently. He eventually was prescribed a long-acting injectable antipsychotic, paliperidone palmitate, 156 mg monthly. Eventually, his family was no longer able to care for him at home, so he was admitted to a residential care facility.
In this facility, based on the long-standing nature of Mr. C’s psychotic disorder and frequency with which he presented with mania, his clinicians changed his diagnosis to schizoaffective disorder, bipolar type. It had become clear that mood symptoms comprised >50% of the total duration of his illness.
Schizoaffective disorder (SAD) often has been used as a diagnosis for patients who have an admixture of mood and psychotic symptoms whose diagnosis is uncertain. Its hallmark is the presence of symptoms of a major mood episode (either a depressive or manic episode) concurrent with symptoms characteristic of schizophrenia, such as delusions, hallucinations, or disorganized speech.1
SAD is a controversial diagnosis. There has been inadequate research regarding the epidemiology, course, etiologic factors, and treatment of this disorder. Debate continues to swirl around its conceptualization; some experts view SAD as an independent disorder, while others see SAD as either a form of schizophrenia or a mood disorder.1 In this review, we describe the classification of SAD and its features, diagnosis, and treatment.
An evolving diagnosis
The term schizoaffective was first used by Jacob Kasanin, MD, in 1933.2 He described 9 patients with “acute schizoaffective psychoses,” each of whom had an abrupt onset. The term was used in the first edition of the DSM as a subtype of schizophrenia.3 In DSM-I, the “schizo-affective type” was defined as a diagnosis for patients with a “significant admixture of schizophrenic and affective reactions.”3 Diagnostic criteria for SAD were developed for DSM-III-R, published in 1987.4 These criteria continued to evolve with subsequent editions of the DSM.
Continue to: DSM-5 provides...
DSM-5 provides a clearer separation between schizophrenia with mood symptoms, bipolar disorder, and SAD (Table5). In addition, DSM-5 shifts away from the DSM-IV diagnosis of SAD as an episode, and instead focuses more on the longitudinal course of the illness. It has been suggested that this change will likely lead to reduced rates of diagnosis of SAD.6 Despite improvements in classification, the diagnosis remains controversial (Box7-11).
Box 1
Despite improvements in classification, controversy continues to swirl around the question of whether schizoaffective disorder (SAD) represents an independent disorder that stands apart from schizophrenia and bipolar disorder, whether it is a form of schizophrenia, or whether it is a form of bipolar disorder or a depressive disorder.7,8 Other possibilities are that SAD is heterogeneous or that it represents a middle point on a spectrum that bridges mood and psychotic disorders. While the merits of each possibility are beyond the scope of this review, it is safe to say that each possibility has its proponents. For these reasons, some argue that the concept itself lacks validity and shows the pitfalls of our classification system.7
Poor diagnostic reliability is one reason for concerns about validity. Most recently, a field trial using DSM-5 criteria produced a kappa of 0.50, which is moderate,9 but earlier definitions produced relatively poor results. Wilson et al10 point out that Criterion C, which concerns duration of mood symptoms, produces a particularly low kappa. Another reason is diagnostic switching, whereby patients initially diagnosed with 1 disorder receive a different diagnosis at followup. Diagnostic switching is especially problematic for SAD. In a large meta-analysis by Santelmann et al,11 36% of patients initially diagnosed with SAD had their diagnosis changed when reassessed. This diagnostic shift tended more toward schizophrenia than bipolar disorder. In addition, more than one-half of all patients initially diagnosed with schizophrenia, bipolar disorder, or major depressive disorder were re-diagnosed with SAD when reassessed.
DSM-5 subtypes and specifiers
In DSM-5,SAD has 2 subtypes5:
- Bipolar type. The bipolar type is marked by the presence of a manic episode (major depressive episodes may also occur)
- Depressive type. The depressive type is marked by the presence of only major depressive episodes.
SAD also includes several specifiers, with the express purpose of giving clinicians greater descriptive ability. The course of SAD can be described as either “first episode,” defined as the first manifestation of the disorder, or as having “multiple episodes,” defined as a minimum of 2 episodes with 1 relapse. In addition, SAD can be described as an acute episode, in partial remission, or in full remission. The course can be described as “continuous” if it is clear that symptoms have been present for the majority of the illness with very brief subthreshold periods. The course is designated as “unspecified” when information is unavailable or lacking. The 5-point Clinician-Rated Dimensions of Psychosis Symptoms was introduced to enable clinicians to make a quantitative assessment of the psychotic symptoms, although its use is not required.
Epidemiology and gender ratio
The epidemiology of SAD has not been well studied. DSM-5 estimates that SAD is approximately one-third as common as schizophrenia, which has a lifetime prevalence of 0.5% to 0.8%.5 This is similar to an estimate by Perälä et al12 of a 0.32% lifetime prevalence based on a nationally representative sample of persons in Finland age ≥30. Scully et al13 calculated a prevalence estimate of 1.1% in a representative sample of adults in rural Ireland. Based on pooled clinical data, Keck et al14 estimated the prevalence in clinical settings at 16%, similar to the figure of 19% reported by Levinson et al15 based on data from New York State psychiatric hospitals. In clinical practice, the diagnosis of SAD is used frequently when there is diagnostic uncertainty, which potentially inflates estimates of lifetime prevalence.
The prevalence of SAD is higher in women than men, with a sex ratio of about 2:1, similar to that seen in mood disorders.13,16-19 There are an equal number of men and women with the bipolar subtype, but a female preponderance with the depressive subtype.5 The bipolar subtype is more common in younger patients, while the depressive subtype is more common in older patients. SAD is a rare diagnosis in children.20
Continue to: Course and outcome
Course and outcome
The onset of SAD typically occurs in early adulthood, but can range from childhood to senescence. Approximately one-third of patients are diagnosed before age 25, one-third between age 25 and 35, and one-third after age 35.21-23 Based on a literature review, Cheniaux et al7 concluded that that age at onset for patients with SAD is between those with schizophrenia and those with mood disorders.
The course of SAD is variable but represents a middle ground between that of schizophrenia and the mood disorders. In a 4- to 5-year follow-up,24 patients with SAD had a better overall course than patients with schizophrenia but had poorer functioning than those with bipolar mania, and much poorer than those with unipolar depression. Mood-incongruent psychotic features predict a particularly worse outcome. These findings were reaffirmed at a 10-year follow-up.25 Mood symptoms portend a better outcome than do symptoms of schizophrenia.
The lifetime suicide risk for patients with SAD is estimated at 5%, with a higher risk associated with the presence of depressive symptoms.26 One study found that women with SAD had a 17.5-year reduced life expectancy (64.1 years) compared with a reduction of 8.0 years for men (69.4 years).27
Comorbidity
Patients with SAD are commonly diagnosed with other psychiatric disorders, including anxiety disorders, obsessive-compulsive disorder, posttraumatic stress disorder, and substance use disorders.21,28,29 When compared with the general population, patients with SAD are at higher risk for coronary heart disease, stroke, obesity, and smoking, likely contributing to their decreased life expectancy.27,30 Because second-generation antipsychotics (SGAs) are often used to treat SAD, patients with SAD are at risk for metabolic syndrome and diabetes mellitus.30
Clinical assessment
Because there are no diagnostic, laboratory, or neuroimaging tests for SAD, the most important basis for making the diagnosis is the patient’s history, supplemented by collateral history from family members or friends, and medical records. Determining the percentage of time spent in a mood episode (DSM-5 Criterion C) is especially important.31 This requires the clinician to pay close attention to the temporal relationship of psychotic and mood symptoms.
Continue to: Differential diagnosis
Differential diagnosis
The differential diagnosis for SAD is broad because it includes all of the possibilities usually considered for major mood disorders and for psychotic disorders5:
- schizophrenia
- bipolar disorder with psychotic features
- major depressive disorder with psychotic features
- depressive or bipolar disorders with catatonic features
- personality disorders (especially the schizotypal, paranoid, and borderline types)
- major neurocognitive disorders in which there are mood and psychotic symptoms
- substance/medication-induced psychotic disorder
- disorders induced by medical conditions.
With schizophrenia, the duration of all episodes of a mood syndrome is brief (<50% of the total duration of the illness) relative to the duration of the psychotic symptoms. Although psychotic symptoms may occur in persons with mood disorders, they are generally not present in the absence of depression or mania, helping to set the boundary between SAD and psychotic mania or depression. As for personality disorders, the individual will not have a true psychosis, although some symptoms, such as feelings of unreality, paranoia, or magical thinking, may cause diagnostic confusion.
Medical conditions also can present with psychotic and mood symptoms and need to be ruled out. These include psychotic disorder due to another medical condition, and delirium. A thorough medical workup should be performed to rule out any possible medical causes for the symptoms.
Substance use should also be ruled out as the cause of the symptoms because many substances are associated with mood and psychotic symptoms. It is usually clear from the history, physical examination, or laboratory tests when a medication/illicit substance has initiated and maintained the disorder.
Neurologic conditions. If a neurologic condition is suspected, a neurologic evaluation may be warranted, including laboratory tests, brain imaging to identify specific anatomical abnormalities, lumbar puncture with cerebrospinal fluid analysis, and an electroencephalogram to rule out a convulsive disorder.
Continue to: Clinical symptoms
Clinical symptoms
The signs and symptoms of SAD include those typically seen in schizophrenia and the mood disorders. Thus, the patient may exhibit elated mood and/or grandiosity, or severe depression, combined with mood-incongruent psychotic features such as paranoid delusions. The symptoms may present together or in an alternating fashion, and psychotic symptoms may be mood-congruent or mood-incongruent. Mr. C’s case illustrates some of the symptoms of the disorder.
Brain imaging
Significant changes have been reported to occur in the brain structure and function in persons with SAD. Neuroimaging studies using voxel-based morphometry have shown significant reductions in gray matter volume in several areas of the brain, including the medial prefrontal cortex, insula, Rolandic operculum, parts of the temporal lobe, and the hippocampus.32-35 Amann et al32 found that patients with SAD and schizophrenia had widespread and overlapping areas of significant volume reduction, but patients with bipolar disorder did not. These studies suggest that at least from a neuroimaging standpoint, SAD is more closely related to schizophrenia than bipolar disorder, and could represent a variant of schizophrenia.
Treatment of SAD
The pharmacotherapy of SAD is mostly empirical because of the lack of randomized controlled trials. Clinicians have traditionally prescribed an antipsychotic agent along with either a mood stabilizer (eg,
Since that exhaustive review,
Patients with SAD will require maintenance treatment for ongoing symptom control. Medication that is effective for treatment of an acute episode should be considered for maintenance treatment. Both the extended-release and long-acting injectable (LAI) formulations of paliperidone have been shown to be efficacious in the maintenance treatment of patients with SAD.40 The LAI form of paliperidone significantly delayed psychotic, depressive, and manic relapses, improved clinical rating scale scores, and increased medication adherence.41,42 In an open-label study, olanzapine LAI was effective in long-term maintenance treatment, although approximately 40% of patients experienced significant weight gain.43 One concern with olanzapine is the possible occurrence of a post-injection delirium/sedation syndrome. For that reason, patients receiving olanzapine must be monitored for at least 3 hours post-injection. The paliperidone LAI does not require monitoring after injection.
Continue to: There is a single clinical trial...
There is a single clinical trial showing that patients with SAD can be successfully switched from other antipsychotics to
Other approaches
Electroconvulsive therapy (ECT) should be considered for patients with SAD who are acutely ill and have failed to respond adequately to medication. ECT is especially relevant in the setting of acute mood symptoms (ie, depressive or manic symptoms co-occurring with psychosis or in the absence of psychosis).45
As currently conceptualized, the diagnosis of SAD is made in persons having an admixture of mood and psychotic symptoms, although by definition mood symptoms must take up the majority (≥50%) of the total duration of the illness. Unfortunately, SAD has been inadequately researched due to the unreliability of its definition and concerns about its validity. The long-term course of SAD is midway between mood and psychotic disorders, and the disorder can cause significant disability.
Bottom Line
Schizoaffective disorder (SAD) is characterized by the presence of symptoms of a major mood episode (a depressive or manic episode) concurrent with symptoms of schizophrenia. The most important basis for establishing the diagnosis is the patient’s history. Determining the percentage of time spent in a mood episode is especially important. Treatment usually consists of an antipsychotic plus a mood stabilizer or antidepressant. Electroconvulsive therapy is an option for patients with SAD who do not respond well to medication.
Related Resources
- Wy TJP, Saadabadi A. Schizoaffective disorder. NCBI Bookshelf: StatPearls Publishing. Published January 2020. https://www.ncbi.nlm.nih.gov/books/NBK541012/. Updated April 15, 2020.
- Parker G. How well does the DSM-5 capture schizoaffective disorder? Can J Psychiatry. 2019;64(9):607-610.
Drug Brand Names
Aripiprazole • Abilify
Lithium • Eskalith, Lithobid
Lurasidone • Latuda
Olanzapine • Zyprexa
Olanzapine long-acting injectable • Zyprexa Relprevv
Paliperidone • Invega
Paliperidone palmitate • Invega sustenna
Valproate • Depacon
1. Miller JN, Black DW. Schizoaffective disorder: a review. Ann Clin Psychiatry. 2019;31(1):47-53.
2. Kasanin J. The acute schizoaffective psychoses. Am J Psychiatry. 1933;90:97-126.
3. Diagnostic and statistical manual of mental disorders, 1st ed. Washington, DC: American Psychiatric Association; 1952.
4. Diagnostic and statistical manual of mental disorders, 3rd ed, revision. Washington, DC: American Psychiatric Association; 1987.
5. Diagnostic and statistical manual of mental disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.
6. Malaspina D, Owen M, Heckers S, et al. Schizoaffective disorder in the DSM-5. Schizophr Res. 2013;150:21-25.
7. Cheniaux E, Landeria-Fernandez J, Telles LL, et al. Does schizoaffective disorder really exist? A systematic review of the studies that compared schizoaffective disorder with schizophrenia or mood disorders. J Affect Disord. 2008;106:209-217.
8. Kantrowitz JT, Citrome L. Schizoaffective disorder: a review of current research themes and pharmacologic management. CNS Drugs. 2011;25:317-331.
9. Regier DA, Narrow WE, Clarke DE, et al. DSM-5 field trials in the United States and Canada, Part II: test-retest reliability of selected categorical diagnoses. Am J Psychiatry. 2013;170:59-70.
10. Wilson JE, Nian H, Heckers S. The schizoaffective disorder diagnosis: a conundrum in the clinical setting. Eur Arch Psychiatry Clin Neurosci. 2014;264:29-34.
11. Santelmann H, Franklin J, Bußhoff J, Baethge C. Test-retest reliability of schizoaffective disorder compared with schizophrenia, bipolar disorder, and unipolar depression--a systematic review and meta-analysis. Bipolar Disord. 2015;17:753-768.
12. Perälä J, Suvisaari J, Saarni SI, et al. Lifetime Prevalence of psychotic and bipolar I disorders in a general population. JAMA Psychiatry. 2007;64:19-28.
13. Scully PJ, Owens JM, Kinsella A, et al. Schizophrenia, schizoaffective and bipolar disorder within an epidemiologically complete, homogeneous population in rural Ireland: small area variation in rate. Schizophr Res. 2004;67:143-155.
14. Keck PE Jr, McElroy SE, Strakowski SM, et al. Pharmacologic treatment of schizoaffective disorder. Psychopharmacol. 1994;114:529-538.
15. Levinson DF, Umapathy C, Musthaq M. Treatment of schizoaffective disorder and schizophrenia with mood symptoms. Am J Psychiatry. 1999;156:1138-1148.
16. Angst J, Felder W, Lohmeyer B. Course of schizoaffective psychoses: results of a follow-up study. Schizophr Bull. 1980;6:579-585.
17. Lenz G, Simhandl C, Thau K, et al. Temporal stability of diagnostic criteria for functional psychoses. Psychopathol. 1991;24:328-335.
18. Malhi GS, Green M, Fagiolini A, et al. Schizoaffective disorder: diagnostic issues and future recommendations. Bipolar Disord. 2008;10:215-230.
19. Marneros A, Deister A, Rohde A. Psychopathological and social status of patients with affective, schizophrenic and schizoaffective disorders after long‐term course. Acta Psychiatr Scand. 1990;82:352-358.
20. Werry JS, McClellan JM, Chard L. Childhood and adolescent schizophrenic, bipolar, and schizoaffective disorders: a clinical and outcome study. J Am Acad Child Adolesc Psychiatry. 1991;30:457-465.
21. Abrams DJ, Rojas DC, Arciniegas DB. Is schizoaffective disorder a distinct categorical diagnosis? A critical review of the literature. Neuropsychiatr Dis Treat. 2008;4:1089-1109.
22. Bromet EJ, Kotov R, Fochtmann LJ, et al. Diagnostic shifts during the decade following first admission for psychosis. Am J Psychiatry. 2011;168:1186-1194.
23. Salvatore P, Baldessarini RJ, Tohen M, et al. The McLean-Harvard First Episode Project: two-year stability of DSM-IV diagnoses in 500 first-episode psychotic disorder patients. J Clin Psychiatry. 2009;70:458-466.
24. Grossman LS, Harrow M, Goldberg JF, et al. Outcome of schizoaffective disorder at two long term follow-ups: comparisons with outcome of schizophrenia and affective disorders. Am J Psychiatry. 1991;148:1359-1365.
25. Harrow M, Grossman L, Herbener E, et al. Ten-year outcome: patients with schizoaffective disorders, schizophrenia, affective disorders and mood-incongruent psychotic symptoms. Br J Psychiatry. 2000;177:421-426.
26. Hor K, Taylor M. Review: suicide and schizophrenia: a systematic review of rates and risk factors. J Psychopharmacol. 2010;24:81-90.
27. Chang CK, Hayes RD, Perera G, et al. Life expectancy at birth for people with serious mental illness and other major disorders from a secondary mental health care case register in London. PLoS ONE. 2011;6:e19590.
28. Byerly M, Goodman W, Acholonu W, et al. Obsessive compulsive symptoms in schizophrenia: frequency and clinical features. Schizophr Res. 2005;76:309-316.
29. Strauss JL, Calhoun PS, Marx CE, et al. Comorbid posttraumatic stress disorder is associated with suicidality in male veterans with schizophrenia or schizoaffective disorder. Schizophr Res. 2006;84:165-169.
30. Fagiolini A, Goracci A. The effects of undertreated chronic medical illnesses in patients with severe mental disorders. J Clin Psychiatry. 2009;70:22-29.
31. Black DW, Grant JE. DSM-5 guidebook: the essential companion to the diagnostic and statistical manual of mental disorders, 5th edition. Washington, DC: American Psychiatric Publishing; 2014.
32. Amann BL, Canales-Rodríguez EJ, Madre M, et al. Brain structural changes in schizoaffective disorder compared to schizophrenia and bipolar disorder. Acta Psychiatr Scand. 2016;133:23-33.
33. Ivleva EI, Bidesi AS, Keshavan MS, et al. Gray matter volume as an intermediate phenotype for psychosis: Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP). Am J Psychiatry. 2013;170:1285-1296.
34. Ivleva EI, Bidesi AS, Thomas BP, et al. Brain gray matter phenotypes across the psychosis dimension. Psychiatry Res. 2012;204:13-24.
35. Radonic
36. Jäger M, Becker T, Weinmann S, et al. Treatment of schizoaffective disorder - a challenge for evidence-based psychiatry. Acta Psychiatr Scand. 2010;121:22-32.
37. Glick ID, Mankosli R, Eudicone JM, et al. The efficacy, safety, and tolerability of aripiprazole for the treatment of schizoaffective disorder: results from a pooled analysis of a sub-population of subjects from two randomized, double-blind, placebo controlled, pivotal trials. J Affect Disord. 2009;115:18-26.
38. Canuso CM, Lindenmayer JP, Kosik-Gonzalez C, et al. A randomized, double-blind, placebo controlled study of 2 dose ranges of paliperidone extended-release in the treatment of subjects with schizoaffective disorder. J Clin Psychiatry. 2010;71:587-598.
39. Canuso CM, Schooler NR, Carothers J, et al. Paliperidone extended-release in schizoaffective disorder: a randomized controlled trial comparing a flexible-dose with placebo in patients treated with and without antidepressants and/or mood stabilizers. J Clin Psychopharmacol. 2010;30:487-495.
40. Lindenmayer JP, Kaur A. Antipsychotic management of schizoaffective disorder: a review. Drugs. 2016;76:589-604.
41. Alphs L, Fu DJ, Turkoz I. Paliperidone for the treatment of schizoaffective disorder. Expert Opin Pharmacother. 2016;176:871-883.
42. Bossie CA, Turkoz I, Alphs L, et al. Paliperidone palmitate once-monthly treatment in recent onset and chronic illness patients with schizoaffective disorder. J Nerv Ment Dis. 2017;205:324-328.
43. McDonnell DP, Landry J, Detke HC. Long-term safety and efficacy of olanzapine long-acting injection in patients with schizophrenia or schizoaffective disorder: a 6-year, multinational, single-arm, open-label study. Int Clin Psychopharmacol. 2014;29:322-331.
44. McEvoy JP, Citrome L, Hernandez D, et al. Effectiveness of lurasidone in patients with schizophrenia or schizoaffective disorder switched from other antipsychotics: a randomized, 6-week, open-label study. J Clin Psychiatry. 2013;74:170-179.
45. Mankad MV, Beyer JL, Wiener RD, et al. Manual of electroconvulsive therapy. Washington, DC: American Psychiatric Publishing; 2010.
1. Miller JN, Black DW. Schizoaffective disorder: a review. Ann Clin Psychiatry. 2019;31(1):47-53.
2. Kasanin J. The acute schizoaffective psychoses. Am J Psychiatry. 1933;90:97-126.
3. Diagnostic and statistical manual of mental disorders, 1st ed. Washington, DC: American Psychiatric Association; 1952.
4. Diagnostic and statistical manual of mental disorders, 3rd ed, revision. Washington, DC: American Psychiatric Association; 1987.
5. Diagnostic and statistical manual of mental disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.
6. Malaspina D, Owen M, Heckers S, et al. Schizoaffective disorder in the DSM-5. Schizophr Res. 2013;150:21-25.
7. Cheniaux E, Landeria-Fernandez J, Telles LL, et al. Does schizoaffective disorder really exist? A systematic review of the studies that compared schizoaffective disorder with schizophrenia or mood disorders. J Affect Disord. 2008;106:209-217.
8. Kantrowitz JT, Citrome L. Schizoaffective disorder: a review of current research themes and pharmacologic management. CNS Drugs. 2011;25:317-331.
9. Regier DA, Narrow WE, Clarke DE, et al. DSM-5 field trials in the United States and Canada, Part II: test-retest reliability of selected categorical diagnoses. Am J Psychiatry. 2013;170:59-70.
10. Wilson JE, Nian H, Heckers S. The schizoaffective disorder diagnosis: a conundrum in the clinical setting. Eur Arch Psychiatry Clin Neurosci. 2014;264:29-34.
11. Santelmann H, Franklin J, Bußhoff J, Baethge C. Test-retest reliability of schizoaffective disorder compared with schizophrenia, bipolar disorder, and unipolar depression--a systematic review and meta-analysis. Bipolar Disord. 2015;17:753-768.
12. Perälä J, Suvisaari J, Saarni SI, et al. Lifetime Prevalence of psychotic and bipolar I disorders in a general population. JAMA Psychiatry. 2007;64:19-28.
13. Scully PJ, Owens JM, Kinsella A, et al. Schizophrenia, schizoaffective and bipolar disorder within an epidemiologically complete, homogeneous population in rural Ireland: small area variation in rate. Schizophr Res. 2004;67:143-155.
14. Keck PE Jr, McElroy SE, Strakowski SM, et al. Pharmacologic treatment of schizoaffective disorder. Psychopharmacol. 1994;114:529-538.
15. Levinson DF, Umapathy C, Musthaq M. Treatment of schizoaffective disorder and schizophrenia with mood symptoms. Am J Psychiatry. 1999;156:1138-1148.
16. Angst J, Felder W, Lohmeyer B. Course of schizoaffective psychoses: results of a follow-up study. Schizophr Bull. 1980;6:579-585.
17. Lenz G, Simhandl C, Thau K, et al. Temporal stability of diagnostic criteria for functional psychoses. Psychopathol. 1991;24:328-335.
18. Malhi GS, Green M, Fagiolini A, et al. Schizoaffective disorder: diagnostic issues and future recommendations. Bipolar Disord. 2008;10:215-230.
19. Marneros A, Deister A, Rohde A. Psychopathological and social status of patients with affective, schizophrenic and schizoaffective disorders after long‐term course. Acta Psychiatr Scand. 1990;82:352-358.
20. Werry JS, McClellan JM, Chard L. Childhood and adolescent schizophrenic, bipolar, and schizoaffective disorders: a clinical and outcome study. J Am Acad Child Adolesc Psychiatry. 1991;30:457-465.
21. Abrams DJ, Rojas DC, Arciniegas DB. Is schizoaffective disorder a distinct categorical diagnosis? A critical review of the literature. Neuropsychiatr Dis Treat. 2008;4:1089-1109.
22. Bromet EJ, Kotov R, Fochtmann LJ, et al. Diagnostic shifts during the decade following first admission for psychosis. Am J Psychiatry. 2011;168:1186-1194.
23. Salvatore P, Baldessarini RJ, Tohen M, et al. The McLean-Harvard First Episode Project: two-year stability of DSM-IV diagnoses in 500 first-episode psychotic disorder patients. J Clin Psychiatry. 2009;70:458-466.
24. Grossman LS, Harrow M, Goldberg JF, et al. Outcome of schizoaffective disorder at two long term follow-ups: comparisons with outcome of schizophrenia and affective disorders. Am J Psychiatry. 1991;148:1359-1365.
25. Harrow M, Grossman L, Herbener E, et al. Ten-year outcome: patients with schizoaffective disorders, schizophrenia, affective disorders and mood-incongruent psychotic symptoms. Br J Psychiatry. 2000;177:421-426.
26. Hor K, Taylor M. Review: suicide and schizophrenia: a systematic review of rates and risk factors. J Psychopharmacol. 2010;24:81-90.
27. Chang CK, Hayes RD, Perera G, et al. Life expectancy at birth for people with serious mental illness and other major disorders from a secondary mental health care case register in London. PLoS ONE. 2011;6:e19590.
28. Byerly M, Goodman W, Acholonu W, et al. Obsessive compulsive symptoms in schizophrenia: frequency and clinical features. Schizophr Res. 2005;76:309-316.
29. Strauss JL, Calhoun PS, Marx CE, et al. Comorbid posttraumatic stress disorder is associated with suicidality in male veterans with schizophrenia or schizoaffective disorder. Schizophr Res. 2006;84:165-169.
30. Fagiolini A, Goracci A. The effects of undertreated chronic medical illnesses in patients with severe mental disorders. J Clin Psychiatry. 2009;70:22-29.
31. Black DW, Grant JE. DSM-5 guidebook: the essential companion to the diagnostic and statistical manual of mental disorders, 5th edition. Washington, DC: American Psychiatric Publishing; 2014.
32. Amann BL, Canales-Rodríguez EJ, Madre M, et al. Brain structural changes in schizoaffective disorder compared to schizophrenia and bipolar disorder. Acta Psychiatr Scand. 2016;133:23-33.
33. Ivleva EI, Bidesi AS, Keshavan MS, et al. Gray matter volume as an intermediate phenotype for psychosis: Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP). Am J Psychiatry. 2013;170:1285-1296.
34. Ivleva EI, Bidesi AS, Thomas BP, et al. Brain gray matter phenotypes across the psychosis dimension. Psychiatry Res. 2012;204:13-24.
35. Radonic
36. Jäger M, Becker T, Weinmann S, et al. Treatment of schizoaffective disorder - a challenge for evidence-based psychiatry. Acta Psychiatr Scand. 2010;121:22-32.
37. Glick ID, Mankosli R, Eudicone JM, et al. The efficacy, safety, and tolerability of aripiprazole for the treatment of schizoaffective disorder: results from a pooled analysis of a sub-population of subjects from two randomized, double-blind, placebo controlled, pivotal trials. J Affect Disord. 2009;115:18-26.
38. Canuso CM, Lindenmayer JP, Kosik-Gonzalez C, et al. A randomized, double-blind, placebo controlled study of 2 dose ranges of paliperidone extended-release in the treatment of subjects with schizoaffective disorder. J Clin Psychiatry. 2010;71:587-598.
39. Canuso CM, Schooler NR, Carothers J, et al. Paliperidone extended-release in schizoaffective disorder: a randomized controlled trial comparing a flexible-dose with placebo in patients treated with and without antidepressants and/or mood stabilizers. J Clin Psychopharmacol. 2010;30:487-495.
40. Lindenmayer JP, Kaur A. Antipsychotic management of schizoaffective disorder: a review. Drugs. 2016;76:589-604.
41. Alphs L, Fu DJ, Turkoz I. Paliperidone for the treatment of schizoaffective disorder. Expert Opin Pharmacother. 2016;176:871-883.
42. Bossie CA, Turkoz I, Alphs L, et al. Paliperidone palmitate once-monthly treatment in recent onset and chronic illness patients with schizoaffective disorder. J Nerv Ment Dis. 2017;205:324-328.
43. McDonnell DP, Landry J, Detke HC. Long-term safety and efficacy of olanzapine long-acting injection in patients with schizophrenia or schizoaffective disorder: a 6-year, multinational, single-arm, open-label study. Int Clin Psychopharmacol. 2014;29:322-331.
44. McEvoy JP, Citrome L, Hernandez D, et al. Effectiveness of lurasidone in patients with schizophrenia or schizoaffective disorder switched from other antipsychotics: a randomized, 6-week, open-label study. J Clin Psychiatry. 2013;74:170-179.
45. Mankad MV, Beyer JL, Wiener RD, et al. Manual of electroconvulsive therapy. Washington, DC: American Psychiatric Publishing; 2010.
Assessing decision-making capacity
Medical and surgical inpatient teams often consult psychiatrists to help assess a patient’s decision-making capacity (DMC). Completing a DMC assessment can be a source of stress and frustration for psychiatry residents; however, the process can be significantly improved by following a consistent and focused psychiatric interview. In our institution, the most frequently used tool for assessing DMC is the Aid to Capacity Evaluation (ACE).1 The American Academy of Family Physicians offers a printer-friendly adaptation2 of the ACE assessment.
Reasons for a DMC consultation
When accepting a DMC consultation, make sure to specify for which medical decision the primary team would like the patient to be evaluated so that the consultation can be most helpful and specific to primary team’s concerns.3 The 4 most common reasons for a DMC consultation are:
Acute changes in mental status. These changes may be due to hypoxia, infection, medication, metabolic disturbances, or other medical conditions. Often, the diagnosis is delirium due to a medical condition, and assessing for DMC is deferred until the delirium resolves.
Refusal of a recommended treatment. One of the most frequent reasons for a DMC consultation is when a patient declines the primary team’s treatment recommendations. These recommendations may include medications, interventions (procedural or surgical), or discharge planning (such as transfer to a rehabilitation facility or skilled nursing care facility).
Consenting to a risky or invasive treatment too hastily. This occurs less often than the other 3 scenarios, most likely because capacity is rarely questioned when a patient’s decision aligns with the physicians’ recommendations.
Having risk factors for impaired decision-making. One of the most common reasons for involving psychiatry in a DMC consultation is when the patient has a risk factor that may impair his/her decision-making.
These risk factors include:
- a chronic psychiatric or neurologic condition
- a significant cultural or language barrier
- a low or unknown education level
- anxiety or discomfort with institutional health care settings
- age <18 or >85.
Continue to: When should you put off a DMC consultation?
When should you put off a DMC consultation?
There are situations in which a DMC consultation should be declined or postponed. A DMC consultation is not appropriate for patients who have a court-appointed legal guardian because these patients are considered legally incapacitated. Although such patients may still choose to participate in shared decision-making with the treatment team and communicate those decisions to their legal guardian, all treatment decisions are made by their legal guardian.
Consider delaying DMC consultations for patients with acute changes in mental status, including delirium, or those who are sedated or intubated. On the other hand, patients not excluded from a DMC assessment include those with mild or major neurocognitive disorders (such as Alzheimer’s disease or other types of dementia), intellectual disabilities, a durable power of attorney (DPOA), or legal charges. It is important to note that a diagnosis of a neurocognitive disorder does not preclude capacity, and capacity may therefore vary based on the complexity of medical decision.
Prepare for the interview
Prior to meeting the patient, familiarize yourself with his/her reason for admission, diagnosis, medical workup, treatment provided thus far, and proposed future treatment. If possible, attempt to gather the patient’s medical and psychiatric history from chart review, which may be obtained from outside medical records or inferred from the patient’s current medication list. Review the chart for any signs that the patient is in a delirious state, including the use of psychotropic medications for agitation, restraints, or a sitter at bedside. Finally, speak with the patient’s nurse before entering the patient’s room. This may provide valuable information regarding the patient’s willingness to participate (including any hostility or aggression toward clinicians), any barriers to the interview (such as hearing or language difficulties), and if any family or friends are present at the bedside.
During the interview
The structure of a decision-making capacity evaluation has been well documented elsewhere1,2 and, if completed, is sufficient for determining DMC. Asking the patient about additional psychiatric histories, including hospitalizations, suicide attempts, or a family history of psychiatric illness, may be counterproductive and frustrating for the patient, especially if the interview has already been lengthy and emotionally exhausting. Therefore, it is often appropriate to shorten the psychiatric interview to assess for symptoms of anxiety and depression, perform a brief suicide risk assessment, and assess for the presence of auditory or visual hallucinations, or delusions. This allows for a complete mental status exam while still focusing the interview on determining DMC. If time allows and the patient is willing to participate, it can be helpful to perform a Montreal Cognitive Assessment (MoCA) or Mini-Mental State Exam, although a score that indicates some level of cognitive impairment (<26 on MoCA4) does not necessarily preclude patient from having capacity for certain medical decisions. Additionally, if the patient does not understand a question, explain it and return to it later to check for comprehension.
Making a recommendation
Patients are presumed to be capable; therefore, if the determination is not clear, err on the side of capacity. Additional information may be helpful from the patient’s family, friends, DPOA, or guardian, especially as it pertains to the patient’s past wishes and medical decisions made in similar situations. If available and pertinent, review the patient’s advance health care directive.
Communicate your recommendations to the primary team clearly and concisely, including if the evaluation is incomplete, and if the patient will be seen again by the consult team, because this may determine disposition planning. Finally, if the patient is deemed to not have DMC, the primary team must then establish a surrogate decision maker on the patient’s behalf. Because the protocol and hierarchy of next-of-kin varies by state law and institution policy, it is essential to involve social work and case management
1. Joint Centre for Bioethics. Aid to capacity evaluation (ACE). http://www.jcb.utoronto.ca/tools/documents/ace.pdf. Published 1996. Accessed July 20, 2020.
2. American Academy of Family Physicians. Aid to capacity evaluation. https://www.aafp.org/afp/2001/0715/afp20010715p299-f2.pdf. Published 2000. Accessed July 20, 2020.
3. Tunzi M. Can the patient decide? Evaluating patient capacity in practice. Am Fam Physician. 2001;64(2):299-306.
4. Montreal Cognitive Assessment. FAQ. https://www.mocatest.org/faq/. Accessed July 20, 2020.
Medical and surgical inpatient teams often consult psychiatrists to help assess a patient’s decision-making capacity (DMC). Completing a DMC assessment can be a source of stress and frustration for psychiatry residents; however, the process can be significantly improved by following a consistent and focused psychiatric interview. In our institution, the most frequently used tool for assessing DMC is the Aid to Capacity Evaluation (ACE).1 The American Academy of Family Physicians offers a printer-friendly adaptation2 of the ACE assessment.
Reasons for a DMC consultation
When accepting a DMC consultation, make sure to specify for which medical decision the primary team would like the patient to be evaluated so that the consultation can be most helpful and specific to primary team’s concerns.3 The 4 most common reasons for a DMC consultation are:
Acute changes in mental status. These changes may be due to hypoxia, infection, medication, metabolic disturbances, or other medical conditions. Often, the diagnosis is delirium due to a medical condition, and assessing for DMC is deferred until the delirium resolves.
Refusal of a recommended treatment. One of the most frequent reasons for a DMC consultation is when a patient declines the primary team’s treatment recommendations. These recommendations may include medications, interventions (procedural or surgical), or discharge planning (such as transfer to a rehabilitation facility or skilled nursing care facility).
Consenting to a risky or invasive treatment too hastily. This occurs less often than the other 3 scenarios, most likely because capacity is rarely questioned when a patient’s decision aligns with the physicians’ recommendations.
Having risk factors for impaired decision-making. One of the most common reasons for involving psychiatry in a DMC consultation is when the patient has a risk factor that may impair his/her decision-making.
These risk factors include:
- a chronic psychiatric or neurologic condition
- a significant cultural or language barrier
- a low or unknown education level
- anxiety or discomfort with institutional health care settings
- age <18 or >85.
Continue to: When should you put off a DMC consultation?
When should you put off a DMC consultation?
There are situations in which a DMC consultation should be declined or postponed. A DMC consultation is not appropriate for patients who have a court-appointed legal guardian because these patients are considered legally incapacitated. Although such patients may still choose to participate in shared decision-making with the treatment team and communicate those decisions to their legal guardian, all treatment decisions are made by their legal guardian.
Consider delaying DMC consultations for patients with acute changes in mental status, including delirium, or those who are sedated or intubated. On the other hand, patients not excluded from a DMC assessment include those with mild or major neurocognitive disorders (such as Alzheimer’s disease or other types of dementia), intellectual disabilities, a durable power of attorney (DPOA), or legal charges. It is important to note that a diagnosis of a neurocognitive disorder does not preclude capacity, and capacity may therefore vary based on the complexity of medical decision.
Prepare for the interview
Prior to meeting the patient, familiarize yourself with his/her reason for admission, diagnosis, medical workup, treatment provided thus far, and proposed future treatment. If possible, attempt to gather the patient’s medical and psychiatric history from chart review, which may be obtained from outside medical records or inferred from the patient’s current medication list. Review the chart for any signs that the patient is in a delirious state, including the use of psychotropic medications for agitation, restraints, or a sitter at bedside. Finally, speak with the patient’s nurse before entering the patient’s room. This may provide valuable information regarding the patient’s willingness to participate (including any hostility or aggression toward clinicians), any barriers to the interview (such as hearing or language difficulties), and if any family or friends are present at the bedside.
During the interview
The structure of a decision-making capacity evaluation has been well documented elsewhere1,2 and, if completed, is sufficient for determining DMC. Asking the patient about additional psychiatric histories, including hospitalizations, suicide attempts, or a family history of psychiatric illness, may be counterproductive and frustrating for the patient, especially if the interview has already been lengthy and emotionally exhausting. Therefore, it is often appropriate to shorten the psychiatric interview to assess for symptoms of anxiety and depression, perform a brief suicide risk assessment, and assess for the presence of auditory or visual hallucinations, or delusions. This allows for a complete mental status exam while still focusing the interview on determining DMC. If time allows and the patient is willing to participate, it can be helpful to perform a Montreal Cognitive Assessment (MoCA) or Mini-Mental State Exam, although a score that indicates some level of cognitive impairment (<26 on MoCA4) does not necessarily preclude patient from having capacity for certain medical decisions. Additionally, if the patient does not understand a question, explain it and return to it later to check for comprehension.
Making a recommendation
Patients are presumed to be capable; therefore, if the determination is not clear, err on the side of capacity. Additional information may be helpful from the patient’s family, friends, DPOA, or guardian, especially as it pertains to the patient’s past wishes and medical decisions made in similar situations. If available and pertinent, review the patient’s advance health care directive.
Communicate your recommendations to the primary team clearly and concisely, including if the evaluation is incomplete, and if the patient will be seen again by the consult team, because this may determine disposition planning. Finally, if the patient is deemed to not have DMC, the primary team must then establish a surrogate decision maker on the patient’s behalf. Because the protocol and hierarchy of next-of-kin varies by state law and institution policy, it is essential to involve social work and case management
Medical and surgical inpatient teams often consult psychiatrists to help assess a patient’s decision-making capacity (DMC). Completing a DMC assessment can be a source of stress and frustration for psychiatry residents; however, the process can be significantly improved by following a consistent and focused psychiatric interview. In our institution, the most frequently used tool for assessing DMC is the Aid to Capacity Evaluation (ACE).1 The American Academy of Family Physicians offers a printer-friendly adaptation2 of the ACE assessment.
Reasons for a DMC consultation
When accepting a DMC consultation, make sure to specify for which medical decision the primary team would like the patient to be evaluated so that the consultation can be most helpful and specific to primary team’s concerns.3 The 4 most common reasons for a DMC consultation are:
Acute changes in mental status. These changes may be due to hypoxia, infection, medication, metabolic disturbances, or other medical conditions. Often, the diagnosis is delirium due to a medical condition, and assessing for DMC is deferred until the delirium resolves.
Refusal of a recommended treatment. One of the most frequent reasons for a DMC consultation is when a patient declines the primary team’s treatment recommendations. These recommendations may include medications, interventions (procedural or surgical), or discharge planning (such as transfer to a rehabilitation facility or skilled nursing care facility).
Consenting to a risky or invasive treatment too hastily. This occurs less often than the other 3 scenarios, most likely because capacity is rarely questioned when a patient’s decision aligns with the physicians’ recommendations.
Having risk factors for impaired decision-making. One of the most common reasons for involving psychiatry in a DMC consultation is when the patient has a risk factor that may impair his/her decision-making.
These risk factors include:
- a chronic psychiatric or neurologic condition
- a significant cultural or language barrier
- a low or unknown education level
- anxiety or discomfort with institutional health care settings
- age <18 or >85.
Continue to: When should you put off a DMC consultation?
When should you put off a DMC consultation?
There are situations in which a DMC consultation should be declined or postponed. A DMC consultation is not appropriate for patients who have a court-appointed legal guardian because these patients are considered legally incapacitated. Although such patients may still choose to participate in shared decision-making with the treatment team and communicate those decisions to their legal guardian, all treatment decisions are made by their legal guardian.
Consider delaying DMC consultations for patients with acute changes in mental status, including delirium, or those who are sedated or intubated. On the other hand, patients not excluded from a DMC assessment include those with mild or major neurocognitive disorders (such as Alzheimer’s disease or other types of dementia), intellectual disabilities, a durable power of attorney (DPOA), or legal charges. It is important to note that a diagnosis of a neurocognitive disorder does not preclude capacity, and capacity may therefore vary based on the complexity of medical decision.
Prepare for the interview
Prior to meeting the patient, familiarize yourself with his/her reason for admission, diagnosis, medical workup, treatment provided thus far, and proposed future treatment. If possible, attempt to gather the patient’s medical and psychiatric history from chart review, which may be obtained from outside medical records or inferred from the patient’s current medication list. Review the chart for any signs that the patient is in a delirious state, including the use of psychotropic medications for agitation, restraints, or a sitter at bedside. Finally, speak with the patient’s nurse before entering the patient’s room. This may provide valuable information regarding the patient’s willingness to participate (including any hostility or aggression toward clinicians), any barriers to the interview (such as hearing or language difficulties), and if any family or friends are present at the bedside.
During the interview
The structure of a decision-making capacity evaluation has been well documented elsewhere1,2 and, if completed, is sufficient for determining DMC. Asking the patient about additional psychiatric histories, including hospitalizations, suicide attempts, or a family history of psychiatric illness, may be counterproductive and frustrating for the patient, especially if the interview has already been lengthy and emotionally exhausting. Therefore, it is often appropriate to shorten the psychiatric interview to assess for symptoms of anxiety and depression, perform a brief suicide risk assessment, and assess for the presence of auditory or visual hallucinations, or delusions. This allows for a complete mental status exam while still focusing the interview on determining DMC. If time allows and the patient is willing to participate, it can be helpful to perform a Montreal Cognitive Assessment (MoCA) or Mini-Mental State Exam, although a score that indicates some level of cognitive impairment (<26 on MoCA4) does not necessarily preclude patient from having capacity for certain medical decisions. Additionally, if the patient does not understand a question, explain it and return to it later to check for comprehension.
Making a recommendation
Patients are presumed to be capable; therefore, if the determination is not clear, err on the side of capacity. Additional information may be helpful from the patient’s family, friends, DPOA, or guardian, especially as it pertains to the patient’s past wishes and medical decisions made in similar situations. If available and pertinent, review the patient’s advance health care directive.
Communicate your recommendations to the primary team clearly and concisely, including if the evaluation is incomplete, and if the patient will be seen again by the consult team, because this may determine disposition planning. Finally, if the patient is deemed to not have DMC, the primary team must then establish a surrogate decision maker on the patient’s behalf. Because the protocol and hierarchy of next-of-kin varies by state law and institution policy, it is essential to involve social work and case management
1. Joint Centre for Bioethics. Aid to capacity evaluation (ACE). http://www.jcb.utoronto.ca/tools/documents/ace.pdf. Published 1996. Accessed July 20, 2020.
2. American Academy of Family Physicians. Aid to capacity evaluation. https://www.aafp.org/afp/2001/0715/afp20010715p299-f2.pdf. Published 2000. Accessed July 20, 2020.
3. Tunzi M. Can the patient decide? Evaluating patient capacity in practice. Am Fam Physician. 2001;64(2):299-306.
4. Montreal Cognitive Assessment. FAQ. https://www.mocatest.org/faq/. Accessed July 20, 2020.
1. Joint Centre for Bioethics. Aid to capacity evaluation (ACE). http://www.jcb.utoronto.ca/tools/documents/ace.pdf. Published 1996. Accessed July 20, 2020.
2. American Academy of Family Physicians. Aid to capacity evaluation. https://www.aafp.org/afp/2001/0715/afp20010715p299-f2.pdf. Published 2000. Accessed July 20, 2020.
3. Tunzi M. Can the patient decide? Evaluating patient capacity in practice. Am Fam Physician. 2001;64(2):299-306.
4. Montreal Cognitive Assessment. FAQ. https://www.mocatest.org/faq/. Accessed July 20, 2020.
When the professional becomes personal
I arrived at the inpatient psychiatry unit to begin my last overnight call shift as an intern. When I received sign-out from the day-shift resident, Dr. A (all names have been changed to protect anonymity), I was surprised to learn that the medical student assigned for call that day, G, did not present for his shift. In my residency program, a third-year medical student was assigned to accompany an intern during call shifts. While this assignment was for the medical student’s “learning purposes,” the presence of a medical student was vital for the intern. The high volume of patients who needed to be seen while on call was difficult to manage, and the help of a medical student certainly lessened that burden.
During her shift, Dr. A had texted G regarding his missed shift, but he replied that he was busy with a research project and did not intend to attend his call shift. Dr. A and I agreed that G’s behavior was unusual, especially because we had both worked with him before and had found him to be highly motivated and competent. Dr. A said that she was going to follow up with the clerkship director about G’s missed shift. While I was initially angry about having to work the call shift alone, I was quickly overcome with patient care. I labored through the night, and then spent the next day sleeping and recovering.
The following morning, I was back on the inpatient unit to start the work week. I was performing my usual morning pre-rounding when I received shocking news: a medical student had completed suicide on the school’s campus. After processing this news, I asked for the name of the student. It was G.
I sat in disbelief. How could a medical student who was supposed to work with me just 2 days ago have completed suicide? How could such a bright and well-presenting student decide to end his life? I voiced these thoughts to my colleague, who responded, “He must have been preparing to do it instead of coming to your call shift.” This statement hit me like a ton of bricks. Should I have done more to reach out to him? If I had spoken with him, could I have intervened and arrested his planning?
Later, I found out that G had been diagnosed with bipolar disorder. He had shared his diagnosis with some of his classmates and his psychiatry attending. G had wanted to share his success story as someone with mental illness who could have a career in medicine. However, because mental illness carries stigma, the attending had warned G about possible negative consequences in professional settings if he chose to share his diagnosis openly. G expressed disappointment with this advice. Subsequently, he had appeared more withdrawn during his clerkship engagements.
As psychiatrists, we expect to have conversations with our patients about thoughts of suicide, but such discussions with our physician colleagues are far from the norm. We know that the rate of suicide in physicians is higher than in the general population1—particularly in women2—but stigma often prevents those who work in medicine from seeking treatment.3 Unfortunately, professional requirements and attitudes perpetuate barriers to accessing mental health care.4 As long as licensure concerns or other negative professional consequences persist, physicians will avoid seeking potentially life-saving treatment.
I felt guilty for having been angry at G for missing my call shift. I knew that the sequence of events could not be changed, but that did not stop me from wondering, “What if?” What if I had reached out? What if Dr. A had corresponded differently? If we want to prevent tragic outcomes like G’s, then we need to fix our flawed system. We need to allow physicians to seek treatment and share their experience without punitive professional consequences, because suicide is permanent, and there is no undoing.
1. Schernhammer ES, Colditz GA. Suicide rates among physicians: a quantitative and gender assessment (meta-analysis). Am J Psychiatry. 2004;161(12):2295-2302.
2. Duarte D, El-Hagrassy MM, Couto TCE, et al. Male and female physician suicidality: a systematic review and meta-analysis [published online March 4, 2020]. JAMA Psychiatry. 2020;77(6):1-11.
3. Worley LLM. Our fallen peers: a mandate for change. Acad Psychiatry. 2008;32(1):8-12.
4. Center C, Davis M, Detre T, et al. Confronting depression and suicide in physicians: a consensus statement. JAMA. 2003;289(23):3161-3166.
I arrived at the inpatient psychiatry unit to begin my last overnight call shift as an intern. When I received sign-out from the day-shift resident, Dr. A (all names have been changed to protect anonymity), I was surprised to learn that the medical student assigned for call that day, G, did not present for his shift. In my residency program, a third-year medical student was assigned to accompany an intern during call shifts. While this assignment was for the medical student’s “learning purposes,” the presence of a medical student was vital for the intern. The high volume of patients who needed to be seen while on call was difficult to manage, and the help of a medical student certainly lessened that burden.
During her shift, Dr. A had texted G regarding his missed shift, but he replied that he was busy with a research project and did not intend to attend his call shift. Dr. A and I agreed that G’s behavior was unusual, especially because we had both worked with him before and had found him to be highly motivated and competent. Dr. A said that she was going to follow up with the clerkship director about G’s missed shift. While I was initially angry about having to work the call shift alone, I was quickly overcome with patient care. I labored through the night, and then spent the next day sleeping and recovering.
The following morning, I was back on the inpatient unit to start the work week. I was performing my usual morning pre-rounding when I received shocking news: a medical student had completed suicide on the school’s campus. After processing this news, I asked for the name of the student. It was G.
I sat in disbelief. How could a medical student who was supposed to work with me just 2 days ago have completed suicide? How could such a bright and well-presenting student decide to end his life? I voiced these thoughts to my colleague, who responded, “He must have been preparing to do it instead of coming to your call shift.” This statement hit me like a ton of bricks. Should I have done more to reach out to him? If I had spoken with him, could I have intervened and arrested his planning?
Later, I found out that G had been diagnosed with bipolar disorder. He had shared his diagnosis with some of his classmates and his psychiatry attending. G had wanted to share his success story as someone with mental illness who could have a career in medicine. However, because mental illness carries stigma, the attending had warned G about possible negative consequences in professional settings if he chose to share his diagnosis openly. G expressed disappointment with this advice. Subsequently, he had appeared more withdrawn during his clerkship engagements.
As psychiatrists, we expect to have conversations with our patients about thoughts of suicide, but such discussions with our physician colleagues are far from the norm. We know that the rate of suicide in physicians is higher than in the general population1—particularly in women2—but stigma often prevents those who work in medicine from seeking treatment.3 Unfortunately, professional requirements and attitudes perpetuate barriers to accessing mental health care.4 As long as licensure concerns or other negative professional consequences persist, physicians will avoid seeking potentially life-saving treatment.
I felt guilty for having been angry at G for missing my call shift. I knew that the sequence of events could not be changed, but that did not stop me from wondering, “What if?” What if I had reached out? What if Dr. A had corresponded differently? If we want to prevent tragic outcomes like G’s, then we need to fix our flawed system. We need to allow physicians to seek treatment and share their experience without punitive professional consequences, because suicide is permanent, and there is no undoing.
I arrived at the inpatient psychiatry unit to begin my last overnight call shift as an intern. When I received sign-out from the day-shift resident, Dr. A (all names have been changed to protect anonymity), I was surprised to learn that the medical student assigned for call that day, G, did not present for his shift. In my residency program, a third-year medical student was assigned to accompany an intern during call shifts. While this assignment was for the medical student’s “learning purposes,” the presence of a medical student was vital for the intern. The high volume of patients who needed to be seen while on call was difficult to manage, and the help of a medical student certainly lessened that burden.
During her shift, Dr. A had texted G regarding his missed shift, but he replied that he was busy with a research project and did not intend to attend his call shift. Dr. A and I agreed that G’s behavior was unusual, especially because we had both worked with him before and had found him to be highly motivated and competent. Dr. A said that she was going to follow up with the clerkship director about G’s missed shift. While I was initially angry about having to work the call shift alone, I was quickly overcome with patient care. I labored through the night, and then spent the next day sleeping and recovering.
The following morning, I was back on the inpatient unit to start the work week. I was performing my usual morning pre-rounding when I received shocking news: a medical student had completed suicide on the school’s campus. After processing this news, I asked for the name of the student. It was G.
I sat in disbelief. How could a medical student who was supposed to work with me just 2 days ago have completed suicide? How could such a bright and well-presenting student decide to end his life? I voiced these thoughts to my colleague, who responded, “He must have been preparing to do it instead of coming to your call shift.” This statement hit me like a ton of bricks. Should I have done more to reach out to him? If I had spoken with him, could I have intervened and arrested his planning?
Later, I found out that G had been diagnosed with bipolar disorder. He had shared his diagnosis with some of his classmates and his psychiatry attending. G had wanted to share his success story as someone with mental illness who could have a career in medicine. However, because mental illness carries stigma, the attending had warned G about possible negative consequences in professional settings if he chose to share his diagnosis openly. G expressed disappointment with this advice. Subsequently, he had appeared more withdrawn during his clerkship engagements.
As psychiatrists, we expect to have conversations with our patients about thoughts of suicide, but such discussions with our physician colleagues are far from the norm. We know that the rate of suicide in physicians is higher than in the general population1—particularly in women2—but stigma often prevents those who work in medicine from seeking treatment.3 Unfortunately, professional requirements and attitudes perpetuate barriers to accessing mental health care.4 As long as licensure concerns or other negative professional consequences persist, physicians will avoid seeking potentially life-saving treatment.
I felt guilty for having been angry at G for missing my call shift. I knew that the sequence of events could not be changed, but that did not stop me from wondering, “What if?” What if I had reached out? What if Dr. A had corresponded differently? If we want to prevent tragic outcomes like G’s, then we need to fix our flawed system. We need to allow physicians to seek treatment and share their experience without punitive professional consequences, because suicide is permanent, and there is no undoing.
1. Schernhammer ES, Colditz GA. Suicide rates among physicians: a quantitative and gender assessment (meta-analysis). Am J Psychiatry. 2004;161(12):2295-2302.
2. Duarte D, El-Hagrassy MM, Couto TCE, et al. Male and female physician suicidality: a systematic review and meta-analysis [published online March 4, 2020]. JAMA Psychiatry. 2020;77(6):1-11.
3. Worley LLM. Our fallen peers: a mandate for change. Acad Psychiatry. 2008;32(1):8-12.
4. Center C, Davis M, Detre T, et al. Confronting depression and suicide in physicians: a consensus statement. JAMA. 2003;289(23):3161-3166.
1. Schernhammer ES, Colditz GA. Suicide rates among physicians: a quantitative and gender assessment (meta-analysis). Am J Psychiatry. 2004;161(12):2295-2302.
2. Duarte D, El-Hagrassy MM, Couto TCE, et al. Male and female physician suicidality: a systematic review and meta-analysis [published online March 4, 2020]. JAMA Psychiatry. 2020;77(6):1-11.
3. Worley LLM. Our fallen peers: a mandate for change. Acad Psychiatry. 2008;32(1):8-12.
4. Center C, Davis M, Detre T, et al. Confronting depression and suicide in physicians: a consensus statement. JAMA. 2003;289(23):3161-3166.
Enduring the ordeal of a quadruple threat is especially arduous for psychiatric patients
These are unusually stressful days for everyone, especially our patients. We are all experiencing a turbulent mix of emotions as we try to cope with a confluence of threats to both our lives and to life as we know it. Peace of mind has become so elusive due to the relentless overlapping waves of fear, sadness, anger, and uncertainty. We are all grieving in a different way, but our psychiatric patients are suffering the most.
Fear. It only takes 1 traumatic event to trigger posttraumatic stress disorder (PTSD). Yet over the past few months, we have been afflicted by 4 jarring traumatic events, individually and as a society. Just a few months ago, it would have been impossible to imagine the conflux of 4 concurrent seismic threats to our well-being. A toxic political zeitgeist was the backdrop, which we bemoaned and tried to compartmentalize, despite the corrosive political environment shrouding the country. Then the deadly coronavirus disease 2019 (COVID-19) pandemic suddenly arrived, imposing draconian health-preserving measures that impacted every individual’s daily life in countless detrimental ways. Fear prevailed as we all sheltered at home, stopped commuting to work, canceled all trips, distanced ourselves from our friends and relatives, and watched depressing and anxiety-provoking television and read online news throughout our waking hours. Hoarding food and household supplies became endemic due to fear about survival.
Sadness. The agonizing prospect of a national financial necrosis followed the threat of serious illness or death. The economy came to a screeching halt, hemorrhaging millions of jobs. Unemployed parents stayed home with their morose children whose schools were shuttered, leaving them deprived of socializing with their friends. The government hurried with financial chemotherapy, printing trillions of dollars to prevent economic collapse, to avert potential poverty and hunger for many. The fear of the pandemic became coupled with sadness over the loss of livelihoods and grief for the loss of liberty and the ability to pursue happiness, or even small pleasures.
Anger. Then a tsunami of anger was generated by the brutal and sadistic death of a black man in police custody. This was a spark that ignited a massive amount of previously dormant racial tension dating back to the dark days of slavery. Peaceful protests were marred by destructive riots. The explosive fury was perhaps intensified by the protestors having been being locked up for weeks and having to wear masks, both of which were symbolic of being held down and “unable to breathe,” like the murdered Mr. George Floyd.
An epidemic of destroying statues followed. Heavy statues that appeared invincible for decades were dismantled from their plinth in a matter of minutes, signifying extreme frustration with the social injustice that remains despite the transformational laws of the Civil Rights Acts of 1960 and 1964. Suddenly—like falling dominoes—statues, flags, names of military bases, and previously venerated monuments were removed, changed, vandalized, or threatened with destruction. The founders of the republic were also maligned because they were slave owners 2 centuries ago. The paradigm shift spawned by the rage over racial inequality was disconcerting and dramatic. The anger and rampage spawned a sense that a tipping point in our society has been reached.
Uncertainty. The confluence of political instability, a deadly pandemic, economic collapse, and racial tensions were like the 4 horsemen of mass PTSD. The result was an agonizing uncertainty about the impact of these changes, and whether a sense of normalcy will ever return. It became apparent to all of us that our social structure has changed forever across multiple fundamental domains: public health, social, political, and financial. The wait for a vaccine for COVID-19 seems interminable, and racial healing and harmony seems elusive. Economic recovery may be possible, but political detoxification appears unlikely. The fate of police departments, condemned because of the deplorable and illegal acts of a few, and the safety of citizens, usually guaranteed by law and order, seem uncertain. Like COVID-19, angst has rapidly spread across the population.
The price our patients pay
The ingredients of a large-scale societal PTSD, similar to what probably happens during a world war, are now in place. Even resilient individuals may buckle during quadruple ordeals such as this one. So imagine what is happening to our patients, rendered fragile and vulnerable to threats by their pre-existing psychiatric illness. They all pay a heavy price. Patients with anxiety disorders will decompensate, with more panic attacks. Patients burdened by depression will worsen, with more hopelessness, despair, and suicidal ideation due to anxiety and loneliness. Patients with bipolar disorder will become more labile and irritable, and their comorbid anxiety will intensify. Patients with schizophrenia will become more paranoid, depressed, and anxious. Patients with autism will become more agitated and aggressive because their cherished daily routines are disrupted. Patients with obsessive-compulsive disorder will react to their germaphobia by washing their hands and cleaning everything around them even more frequently, and they (along with everyone else) will become hoarders.
Hope and healing
As psychiatrists, we are determined to transcend our own stress, rise above it all, and attend to the pervasive sadness, grief, anger, and uncertainty all around us, but especially among our patients, for whom the anguish of a psychiatric disorder is further compounded by 4 additional ordeals. This is our moment of truth as healers of our patients’ souls, because they look to us to provide them with hope to help navigate these trying times into full health. And we psychiatrists, along with fellow mental health professionals, are up to this unprecedented challenge.
These are unusually stressful days for everyone, especially our patients. We are all experiencing a turbulent mix of emotions as we try to cope with a confluence of threats to both our lives and to life as we know it. Peace of mind has become so elusive due to the relentless overlapping waves of fear, sadness, anger, and uncertainty. We are all grieving in a different way, but our psychiatric patients are suffering the most.
Fear. It only takes 1 traumatic event to trigger posttraumatic stress disorder (PTSD). Yet over the past few months, we have been afflicted by 4 jarring traumatic events, individually and as a society. Just a few months ago, it would have been impossible to imagine the conflux of 4 concurrent seismic threats to our well-being. A toxic political zeitgeist was the backdrop, which we bemoaned and tried to compartmentalize, despite the corrosive political environment shrouding the country. Then the deadly coronavirus disease 2019 (COVID-19) pandemic suddenly arrived, imposing draconian health-preserving measures that impacted every individual’s daily life in countless detrimental ways. Fear prevailed as we all sheltered at home, stopped commuting to work, canceled all trips, distanced ourselves from our friends and relatives, and watched depressing and anxiety-provoking television and read online news throughout our waking hours. Hoarding food and household supplies became endemic due to fear about survival.
Sadness. The agonizing prospect of a national financial necrosis followed the threat of serious illness or death. The economy came to a screeching halt, hemorrhaging millions of jobs. Unemployed parents stayed home with their morose children whose schools were shuttered, leaving them deprived of socializing with their friends. The government hurried with financial chemotherapy, printing trillions of dollars to prevent economic collapse, to avert potential poverty and hunger for many. The fear of the pandemic became coupled with sadness over the loss of livelihoods and grief for the loss of liberty and the ability to pursue happiness, or even small pleasures.
Anger. Then a tsunami of anger was generated by the brutal and sadistic death of a black man in police custody. This was a spark that ignited a massive amount of previously dormant racial tension dating back to the dark days of slavery. Peaceful protests were marred by destructive riots. The explosive fury was perhaps intensified by the protestors having been being locked up for weeks and having to wear masks, both of which were symbolic of being held down and “unable to breathe,” like the murdered Mr. George Floyd.
An epidemic of destroying statues followed. Heavy statues that appeared invincible for decades were dismantled from their plinth in a matter of minutes, signifying extreme frustration with the social injustice that remains despite the transformational laws of the Civil Rights Acts of 1960 and 1964. Suddenly—like falling dominoes—statues, flags, names of military bases, and previously venerated monuments were removed, changed, vandalized, or threatened with destruction. The founders of the republic were also maligned because they were slave owners 2 centuries ago. The paradigm shift spawned by the rage over racial inequality was disconcerting and dramatic. The anger and rampage spawned a sense that a tipping point in our society has been reached.
Uncertainty. The confluence of political instability, a deadly pandemic, economic collapse, and racial tensions were like the 4 horsemen of mass PTSD. The result was an agonizing uncertainty about the impact of these changes, and whether a sense of normalcy will ever return. It became apparent to all of us that our social structure has changed forever across multiple fundamental domains: public health, social, political, and financial. The wait for a vaccine for COVID-19 seems interminable, and racial healing and harmony seems elusive. Economic recovery may be possible, but political detoxification appears unlikely. The fate of police departments, condemned because of the deplorable and illegal acts of a few, and the safety of citizens, usually guaranteed by law and order, seem uncertain. Like COVID-19, angst has rapidly spread across the population.
The price our patients pay
The ingredients of a large-scale societal PTSD, similar to what probably happens during a world war, are now in place. Even resilient individuals may buckle during quadruple ordeals such as this one. So imagine what is happening to our patients, rendered fragile and vulnerable to threats by their pre-existing psychiatric illness. They all pay a heavy price. Patients with anxiety disorders will decompensate, with more panic attacks. Patients burdened by depression will worsen, with more hopelessness, despair, and suicidal ideation due to anxiety and loneliness. Patients with bipolar disorder will become more labile and irritable, and their comorbid anxiety will intensify. Patients with schizophrenia will become more paranoid, depressed, and anxious. Patients with autism will become more agitated and aggressive because their cherished daily routines are disrupted. Patients with obsessive-compulsive disorder will react to their germaphobia by washing their hands and cleaning everything around them even more frequently, and they (along with everyone else) will become hoarders.
Hope and healing
As psychiatrists, we are determined to transcend our own stress, rise above it all, and attend to the pervasive sadness, grief, anger, and uncertainty all around us, but especially among our patients, for whom the anguish of a psychiatric disorder is further compounded by 4 additional ordeals. This is our moment of truth as healers of our patients’ souls, because they look to us to provide them with hope to help navigate these trying times into full health. And we psychiatrists, along with fellow mental health professionals, are up to this unprecedented challenge.
These are unusually stressful days for everyone, especially our patients. We are all experiencing a turbulent mix of emotions as we try to cope with a confluence of threats to both our lives and to life as we know it. Peace of mind has become so elusive due to the relentless overlapping waves of fear, sadness, anger, and uncertainty. We are all grieving in a different way, but our psychiatric patients are suffering the most.
Fear. It only takes 1 traumatic event to trigger posttraumatic stress disorder (PTSD). Yet over the past few months, we have been afflicted by 4 jarring traumatic events, individually and as a society. Just a few months ago, it would have been impossible to imagine the conflux of 4 concurrent seismic threats to our well-being. A toxic political zeitgeist was the backdrop, which we bemoaned and tried to compartmentalize, despite the corrosive political environment shrouding the country. Then the deadly coronavirus disease 2019 (COVID-19) pandemic suddenly arrived, imposing draconian health-preserving measures that impacted every individual’s daily life in countless detrimental ways. Fear prevailed as we all sheltered at home, stopped commuting to work, canceled all trips, distanced ourselves from our friends and relatives, and watched depressing and anxiety-provoking television and read online news throughout our waking hours. Hoarding food and household supplies became endemic due to fear about survival.
Sadness. The agonizing prospect of a national financial necrosis followed the threat of serious illness or death. The economy came to a screeching halt, hemorrhaging millions of jobs. Unemployed parents stayed home with their morose children whose schools were shuttered, leaving them deprived of socializing with their friends. The government hurried with financial chemotherapy, printing trillions of dollars to prevent economic collapse, to avert potential poverty and hunger for many. The fear of the pandemic became coupled with sadness over the loss of livelihoods and grief for the loss of liberty and the ability to pursue happiness, or even small pleasures.
Anger. Then a tsunami of anger was generated by the brutal and sadistic death of a black man in police custody. This was a spark that ignited a massive amount of previously dormant racial tension dating back to the dark days of slavery. Peaceful protests were marred by destructive riots. The explosive fury was perhaps intensified by the protestors having been being locked up for weeks and having to wear masks, both of which were symbolic of being held down and “unable to breathe,” like the murdered Mr. George Floyd.
An epidemic of destroying statues followed. Heavy statues that appeared invincible for decades were dismantled from their plinth in a matter of minutes, signifying extreme frustration with the social injustice that remains despite the transformational laws of the Civil Rights Acts of 1960 and 1964. Suddenly—like falling dominoes—statues, flags, names of military bases, and previously venerated monuments were removed, changed, vandalized, or threatened with destruction. The founders of the republic were also maligned because they were slave owners 2 centuries ago. The paradigm shift spawned by the rage over racial inequality was disconcerting and dramatic. The anger and rampage spawned a sense that a tipping point in our society has been reached.
Uncertainty. The confluence of political instability, a deadly pandemic, economic collapse, and racial tensions were like the 4 horsemen of mass PTSD. The result was an agonizing uncertainty about the impact of these changes, and whether a sense of normalcy will ever return. It became apparent to all of us that our social structure has changed forever across multiple fundamental domains: public health, social, political, and financial. The wait for a vaccine for COVID-19 seems interminable, and racial healing and harmony seems elusive. Economic recovery may be possible, but political detoxification appears unlikely. The fate of police departments, condemned because of the deplorable and illegal acts of a few, and the safety of citizens, usually guaranteed by law and order, seem uncertain. Like COVID-19, angst has rapidly spread across the population.
The price our patients pay
The ingredients of a large-scale societal PTSD, similar to what probably happens during a world war, are now in place. Even resilient individuals may buckle during quadruple ordeals such as this one. So imagine what is happening to our patients, rendered fragile and vulnerable to threats by their pre-existing psychiatric illness. They all pay a heavy price. Patients with anxiety disorders will decompensate, with more panic attacks. Patients burdened by depression will worsen, with more hopelessness, despair, and suicidal ideation due to anxiety and loneliness. Patients with bipolar disorder will become more labile and irritable, and their comorbid anxiety will intensify. Patients with schizophrenia will become more paranoid, depressed, and anxious. Patients with autism will become more agitated and aggressive because their cherished daily routines are disrupted. Patients with obsessive-compulsive disorder will react to their germaphobia by washing their hands and cleaning everything around them even more frequently, and they (along with everyone else) will become hoarders.
Hope and healing
As psychiatrists, we are determined to transcend our own stress, rise above it all, and attend to the pervasive sadness, grief, anger, and uncertainty all around us, but especially among our patients, for whom the anguish of a psychiatric disorder is further compounded by 4 additional ordeals. This is our moment of truth as healers of our patients’ souls, because they look to us to provide them with hope to help navigate these trying times into full health. And we psychiatrists, along with fellow mental health professionals, are up to this unprecedented challenge.
Differing views of ‘behavioral health’
In the wake of Dr. Nasrallah’s recent editorial “Stop calling it ‘behavioral health:’ Psychiatry is much more” (From the Editor,
Naming a field, institute, department, or group of collaborators is crucially important, and must be undertaken with care. We all are familiar with Departments of Psychiatry, Departments of Psychiatry and Psychology, and Institutes for everything from Behavioral Health to Living. Even within the discipline of psychiatry, there have been adjustments over time in subspecialties (as seen with consultation-liaison psychiatry becoming psychosomatic medicine and then back again).
In our hospital system, we have recently adopted the term “Behavioral Health Institute” to denote the work and worth of significant numbers of caregivers (psychiatrists, psychologists, chemical dependency counselors, social workers, child life workers, advanced practice nurses, and others) who strive to improve the health and well-being of patients with both substance abuse and mental illness. We endeavor to remain mindful that a diversity of providers are involved in caring for and about our patients, and that “psychiatry” cannot—and should not—be the extent of how we conceptualize our services.
We submit that the modern view of behavioral health is ahead of other fields of medicine in recognizing that concepts, such as teamwork and diversity, are key to achieving positive patient outcomes. By identifying our providers as part of a Behavioral Health Institute, we acknowledge that not all mental distress is psychiatric illness but may still benefit from intervention and, importantly, that psychiatrists are not the center of the mental health (behavioral health) world. Treatments ranging from medication management to psychiatric procedures to psychotherapeutic modalities show the depth and breadth of our field, and the multiplicity of providers and modalities should be considered laudable. Recognizing the complexities inherent in behavioral health and its varied treatment options does not diminish but, in fact, elevates the field of psychiatry—and psychiatrists themselves.
Further, we note that behavioral health is not the only term that casts a larger net than the physician in a respective field. Does the term “primary care” insult internal medicine, family medicine, and pediatric physicians? Physicians and health care teams join in partnership with patients and families, either to cure or learn how to manage disease. We believe that constructing a health care system centered on physicians and their identities, rather than on patients and treatment outcomes, has been foolish. To that end, the tenor of Dr. Nasrallah’s editorial runs counter to the overall efforts of our field to improve collaboration, and, at its extreme, such articles promote the antiquated notion of physician elitism.
The editorial’s historical context is of course important, and the caution not to water down what “we” do (as psychiatrists) is appropriate. However, instead of comporting ourselves in a psychiatry-centric way, the use of the term behavioral health allows all of us to acknowledge (with appreciation and humility) the many contributors who work in our field. The use of a broad-minded, inclusive term neither minimizes nor trivializes psychiatry as a medical specialty. Rather, accepting this term and this mindset can place psychiatrists in the unique role of being innovators for the rest of medicine, because we embrace multidisciplinary teams and the value that interdisciplinary care can bring to patients and colleagues alike.
Jeanne Lackamp, MD, DFAPA, FACLP
Director, Pain Management Institute
University Hospitals Health System
Case Western Reserve University School of Medicine
Cleveland, Ohio
Patrick Runnels, MD, MBA
Chief Medical Officer, Population Health – Behavioral Health
University Hospitals Health System
Case Western Reserve University School of Medicine
Cleveland, Ohio
Lori Locke, RN, MSN
Director, Psychiatry Service Line and Nursing Practice
University Hospitals Health System
Case Western Reserve University School of Medicine
Cleveland, Ohio
Erum Ahmad, MD
Director, Child and Adolescent Psychiatry Unit
University Hospitals Health System
Case Western Reserve University School of Medicine
Cleveland, Ohio
Robert Ronis, MD, MPH
Douglas Danford Bond Professor and Chairman
Psychiatrist-in-Chief
University Hospitals Health System
Case Western Reserve University School of Medicine
Cleveland, Ohio
Continue to: Dr. Nasrallah responds
Dr. Nasrallah responds
I thank my Cleveland colleagues for their letter, and I welcome their disagreement with the tenets of my editorial. I still insist that the term “behavioral health” has a very narrow meaning that is not equivalent to psychiatry or psychology or social work or psychiatric nursing practice. This term should not be conflated with the widely used “mental health,” which is used as an overarching term for all professionals involved in the care of psychiatric brain disorders that manifest as various mental illnesses and substance use disorders.
While I am an advocate for multidisciplinary collaborations that benefit our patients, I will always uphold psychiatry as a medical specialty whose unique identity should not be sacrificed on the altar of politically correct egalitarianism of the mental health disciplines. Call it elitist if you like, but the fact is that the extensive medical school, residency, and fellowship training of psychiatrists stand out among all the other mental health disciplines. Psychiatrists are the best trained in all components of the biopsychosocial model (which I acquired many years ago from the father of the concept, George Engel, one of my teachers at the University of Rochester Residency Program).
You bring up primary care as an analogy for behavioral health. I assure you, none of the medical specialists included under that umbrella term refer to themselves as primary care physicians (PCPs) (or, God forbid, providers!). They identify themselves as family physicians, internists, pediatricians, and gynecologists. It is for the convenience of the health care systems and insurance companies that clinicians are called PCPs, which homogenizes them into a fuzzy amalgam and disguises their true medical identities as specialists.
So we agree to disagree. Diversity of opinions is a sacred principle. But I still think that a more accurate name for your Behavioral Health Institute would be “Institute of Psychiatric Medicine and Brain Health.” Behavioral health, which actually refers to educating people about implementing principles of evidence-based healthy habits and behaviors that prevent or reduce the risk of mental illness and/or substance use, is a small sliver of your overall mission. As you’ll notice from the other letters we’ve received, the vast majority of our readers agree that psychiatric medicine is far more than behavioral health.
Henry A. Nasrallah, MD
Professor of Psychiatry, Neurology, and Neuroscience
Medical Director: Neuropsychiatry
Director, Schizophrenia and Neuropsychiatry Programs
University of Cincinnati College of Medicine
Cincinnati, Ohio
Professor Emeritus, Saint Louis University
St. Louis, Missouri
Continue to: I thoroughly enjoyed...
I thoroughly enjoyed Dr. Nasrallah’s editorial and agree completely. Veterans Affairs, my employer for the last 12 years, has fully bought into the use of “behavioral health” and its implications for its many psychiatrists. I have grown very tired of the constant minimization of psychiatric practice, and it is so good to hear from an affirming voice.
Barbara Day, MD
US Department of Veterans Affairs
Ann Arbor, Michigan
Dr. Nasrallah’s editorial made my heart sing! I have been practicing psychiatry since 1979, and have always bristled when called a “provider” or any of the other terms Dr. Nasrallah described. As a graduate of Johns Hopkins Medical School, I had professors who themselves had been taught by Harry Stack Sullivan and Frida Fromm Reichman, and during my residency at the University of Chicago, I sat in discussions with both Bruno Bettelheim and Heinz Kohut. I felt part of an honorable tradition, and even though biological psychiatry was on the ascendency, these analytical luminaries were part of my learning the “art” of psychiatry. It is not so easy to feel good about a specialty that has had such a history as ours, but my own experiences could never be reduced to being called a behavioral health provider. Dr. Nasrallah’s thoughts are very encouraging, and I thank him!
John Engers, MD
Private psychiatric practice (retired)
Fremont, California
Dr. Nasrallah’s editorial resonated with one of my pet peeves. I’ve been telling my medical students for years that we psychiatrists treat disorders of thinking, emotions, and behavior associated with mental illness, and that the term “behavioral health,” though possibly well intentioned, is a euphemism to reduce stigma.
Irl Extein, MD
Private psychiatric practice
Delray Beach, Florida
Clinical Affiliate Associate Professor, Florida
Atlantic University College of Medicine
Boca Raton, Florida
Continue to: I enjoyed...
I enjoyed Dr. Nasrallah’s editorial regarding “behavioral health.” In New England, we have very clear delineation among psychiatry, mental health, and behavioral health. Only physicians can practice psychiatry because it is a medical specialty. Nurse practitioners and psychologists, on the other hand, are specialists in the field of mental health, as are psychiatrists, so mental health is a more encompassing term. Behavioral health encompasses all of the above plus counselors. Because insurers generally pay counselors, nurse practitioners, and psychiatrists, they use the term behavioral health because it wouldn’t be right for them to pay a counselor for a psychiatric intervention. So as a psychiatrist, I respond when being referred to as a psychiatrist, mental health specialist, or behavioral health specialist. And thankfully, per American Medical Association policy, psychiatrists are not providers.
Stu Gitlow, MD, MPH
Executive Director
Annenberg Physician Training Program in Addictive Disease
Woonsocket, Rhode Island
I was grateful for Dr. Nasrallah’s editorial regarding the misnomer of referring to psychiatry as “behavioral health.” Until this editorial, I had wondered if I was the only one bothered by the term. Many people are under the assumption that behavioral health is a politically correct term that helps to lessen stigmatism. I completely disagree. Without question, it adds to the stigmatism. The term behavioral health is belittling to our patients. For example, calling a psychiatric inpatient unit a “behavioral health unit” implies that if patients would just change their behaviors, they wouldn’t have serious biological psychiatric illness. It insinuates that the patients cause and perpetuate their illnesses, such as schizophrenia or bipolar disorder, by behaving poorly. Granted, we teach behavior modification to help manage psychiatric illness, but so, too, do our colleagues in other medical fields teach behavior modification to manage other organ-related illnesses. Some nearly ubiquitous examples include doctors advising patients to lower stress, modify diet, exercise, and take medications as prescribed. Yet, for example, in the case of a patient with diabetes, we don’t refer to diabetic ketoacidosis treatment as behavioral health treatment, though the patient’s behavior no doubt contributes to this condition. And we certainly would never call the ICU or stepdown unit the “behavioral health unit,” even though adequate holistic treatment in these settings includes counseling the patient with diabetes on changing his/her behaviors that led to the ketoacidosis. Just as in diabetes, the underlying basis of psychiatric illness is biologic processes gone awry. First and foremost, a psychiatric medical illness requires complicated and often precarious medications to treat. As in other medical specialties, modifying behavior does not treat the illness, but merely serves to help transmute the course.
In sum, I wholly agree with Dr. Nasrallah’s eloquent assessment regarding the problems with the title behavioral health in lieu of psychiatry. I also might have taken the discussion a step a further: Because psychiatric illness affects every aspect of a person’s life—such as work, social, and personal—it requires a terminology commensurate with the medical gravity it warrants. So in addition to not referring to the specialty as behavioral health, I have wondered if the name psychiatry could be replaced with a more medical-sounding term such as “cerebrology” or something of the sort. But one step at time.
Stacie Lauro, MD, ABPN
Attending in Psychiatry, Emergency Room, and Consultation Liaison
Mindcare Solutions
Tampa, Florida
The evolution within our field of the use of “behavioral health” has disturbed me to the same extent it has for Dr. Nasrallah. I founded and direct a psychiatric treatment facility in Florida. We are a teaching facility affiliated with 3 psychiatric residencies, 8 medical schools, and 60 physician assistant (PA) schools. In all of the literature (eg, evaluations) from the PA schools, they refer to their rotation with my program as “behavioral health.” I have been attempting to correct them for years! I teach all residents and students to correctly use the terms “psychiatry” and “psychiatric.” I understand there may be stigma associated with the latter terms, but the field reinforces that stigma by avoiding the use of these terms.
Robert A. Moran, MD, FAPA, FASAM
CEO and Medical Director, Family Center for Recovery
Lantana, Florida
Continue to: Pre-authorization and 'hold harmless' clauses
Pre-authorization and ‘hold harmless’ clauses
Regarding Dr. Nasrallah’s editorial “Pre-authorization is illegal, unethical, and adversely disrupts patient care” (From the Editor,
Recently to my surprise, while navigating a pre-authorization request for a young patient with bipolar disorder who had accepted the inclusion of lurasidone in his treatment regimen while hospitalized, I found that the CoverMyMeds Business Associate Agreement is required for a user to accomplish pre-authorization online. Having a little extra time for due diligence that day, I read this lengthy agreement carefully. The CoverMyMeds user agreement purports not to offer “medical advice, does not determine medical necessity, insurance coverage or copays and does not otherwise engage in the practice of medicine” (see www.covermymeds.com/main/about/privacy/tos/). Interestingly, the agreement goes on to purport that the whole process is for informational purposes only, not a substitute for clinicians, professional medical judgment, or for individual patient assessments and examinations. Of course, another factor is that the information provided by the process is “solely at the user’s and health care provider’s own risk.” Finally, the agreement requires the user to agree to “indemnify, defend, and hold harmless CoverMyMeds and its affiliates … from any demands, claims, damages, liabilities, expenses, or harms (including attorneys’ fees) arising out of or related to your use of our Services or breach of these Terms of Service.”
Throughout my 25 years of solo private practice, I have refused to sign hold harmless clauses and I refused to sign the CoverMyMeds user agreement. I have made it my practice never to obtain pre-authorization unless the patient is with me in the room during an appointment because the process of navigating pre-authorization does become part of the treatment, however unfortunately. As an alternative, for my patient with bipolar disorder, I was able to use a phone number to talk to a representative of the pharmacy benefit plan that was contracted with CoverMyMeds. Without signing on to be a Business Associate, we accomplished the goal of continuing with the medication as recommended and implemented for 2 preceding months (often pre-authorization actually means continuing authorization, doesn’t it?). I believe if all psychiatrists were to adopt this kind of stance, we could make a change. I know there are anti-trust considerations involved in fee negotiations, but when it comes to the egregious practices of managed care, pre-authorization, and hold harmless clauses, it seems to me that we can mount a counteroffensive to great effect.
Further, I want to stand in strong support of Dr. Nasrallah’s editorial “Stop calling it ‘behavioral health’: Psychiatry is much more.” When I began my first job post-fellowship, I was alarmed to find that our outpatient offices had been named a “counseling center.” Due to such misleading, stigmatizing characterizations, as Dr. Nasrallah pointed out, we have only slid further down the slope into the realm of “providers of behavioral health services.” As an old hand working psychiatric locum tenens told me, we psychiatrists had long since missed the chance to “band together like musk oxen” to defend our profession.
However, I believe it is not too late. With the strength of Dr. Nasrallah’s leadership and a more overt, collective stubbornness coupled with an undying commitment to excellence, we can and must push hard against the insurance and hospital entities, which continue to profiteer from the practice of medicine without a license—using the tools of hold harmless clauses, anti-trust laws in their favor, and misinformation about the scope and efficacy of practicing psychiatry per se. The challenge is to figure out exactly how to proceed.
Although some manage to thrive in independent practice, collectively our struggle seems considerable, but not insurmountable.
David B. Robinson, MD, MPH
Diplomate, American Board of Psychiatry and Neurology in Child, Adolescent and Adult Psychiatry
Fellow, American Psychiatric Association
Private psychiatric practice
Alaska Psychiatric Concepts
Juneau, Alaska
In the wake of Dr. Nasrallah’s recent editorial “Stop calling it ‘behavioral health:’ Psychiatry is much more” (From the Editor,
Naming a field, institute, department, or group of collaborators is crucially important, and must be undertaken with care. We all are familiar with Departments of Psychiatry, Departments of Psychiatry and Psychology, and Institutes for everything from Behavioral Health to Living. Even within the discipline of psychiatry, there have been adjustments over time in subspecialties (as seen with consultation-liaison psychiatry becoming psychosomatic medicine and then back again).
In our hospital system, we have recently adopted the term “Behavioral Health Institute” to denote the work and worth of significant numbers of caregivers (psychiatrists, psychologists, chemical dependency counselors, social workers, child life workers, advanced practice nurses, and others) who strive to improve the health and well-being of patients with both substance abuse and mental illness. We endeavor to remain mindful that a diversity of providers are involved in caring for and about our patients, and that “psychiatry” cannot—and should not—be the extent of how we conceptualize our services.
We submit that the modern view of behavioral health is ahead of other fields of medicine in recognizing that concepts, such as teamwork and diversity, are key to achieving positive patient outcomes. By identifying our providers as part of a Behavioral Health Institute, we acknowledge that not all mental distress is psychiatric illness but may still benefit from intervention and, importantly, that psychiatrists are not the center of the mental health (behavioral health) world. Treatments ranging from medication management to psychiatric procedures to psychotherapeutic modalities show the depth and breadth of our field, and the multiplicity of providers and modalities should be considered laudable. Recognizing the complexities inherent in behavioral health and its varied treatment options does not diminish but, in fact, elevates the field of psychiatry—and psychiatrists themselves.
Further, we note that behavioral health is not the only term that casts a larger net than the physician in a respective field. Does the term “primary care” insult internal medicine, family medicine, and pediatric physicians? Physicians and health care teams join in partnership with patients and families, either to cure or learn how to manage disease. We believe that constructing a health care system centered on physicians and their identities, rather than on patients and treatment outcomes, has been foolish. To that end, the tenor of Dr. Nasrallah’s editorial runs counter to the overall efforts of our field to improve collaboration, and, at its extreme, such articles promote the antiquated notion of physician elitism.
The editorial’s historical context is of course important, and the caution not to water down what “we” do (as psychiatrists) is appropriate. However, instead of comporting ourselves in a psychiatry-centric way, the use of the term behavioral health allows all of us to acknowledge (with appreciation and humility) the many contributors who work in our field. The use of a broad-minded, inclusive term neither minimizes nor trivializes psychiatry as a medical specialty. Rather, accepting this term and this mindset can place psychiatrists in the unique role of being innovators for the rest of medicine, because we embrace multidisciplinary teams and the value that interdisciplinary care can bring to patients and colleagues alike.
Jeanne Lackamp, MD, DFAPA, FACLP
Director, Pain Management Institute
University Hospitals Health System
Case Western Reserve University School of Medicine
Cleveland, Ohio
Patrick Runnels, MD, MBA
Chief Medical Officer, Population Health – Behavioral Health
University Hospitals Health System
Case Western Reserve University School of Medicine
Cleveland, Ohio
Lori Locke, RN, MSN
Director, Psychiatry Service Line and Nursing Practice
University Hospitals Health System
Case Western Reserve University School of Medicine
Cleveland, Ohio
Erum Ahmad, MD
Director, Child and Adolescent Psychiatry Unit
University Hospitals Health System
Case Western Reserve University School of Medicine
Cleveland, Ohio
Robert Ronis, MD, MPH
Douglas Danford Bond Professor and Chairman
Psychiatrist-in-Chief
University Hospitals Health System
Case Western Reserve University School of Medicine
Cleveland, Ohio
Continue to: Dr. Nasrallah responds
Dr. Nasrallah responds
I thank my Cleveland colleagues for their letter, and I welcome their disagreement with the tenets of my editorial. I still insist that the term “behavioral health” has a very narrow meaning that is not equivalent to psychiatry or psychology or social work or psychiatric nursing practice. This term should not be conflated with the widely used “mental health,” which is used as an overarching term for all professionals involved in the care of psychiatric brain disorders that manifest as various mental illnesses and substance use disorders.
While I am an advocate for multidisciplinary collaborations that benefit our patients, I will always uphold psychiatry as a medical specialty whose unique identity should not be sacrificed on the altar of politically correct egalitarianism of the mental health disciplines. Call it elitist if you like, but the fact is that the extensive medical school, residency, and fellowship training of psychiatrists stand out among all the other mental health disciplines. Psychiatrists are the best trained in all components of the biopsychosocial model (which I acquired many years ago from the father of the concept, George Engel, one of my teachers at the University of Rochester Residency Program).
You bring up primary care as an analogy for behavioral health. I assure you, none of the medical specialists included under that umbrella term refer to themselves as primary care physicians (PCPs) (or, God forbid, providers!). They identify themselves as family physicians, internists, pediatricians, and gynecologists. It is for the convenience of the health care systems and insurance companies that clinicians are called PCPs, which homogenizes them into a fuzzy amalgam and disguises their true medical identities as specialists.
So we agree to disagree. Diversity of opinions is a sacred principle. But I still think that a more accurate name for your Behavioral Health Institute would be “Institute of Psychiatric Medicine and Brain Health.” Behavioral health, which actually refers to educating people about implementing principles of evidence-based healthy habits and behaviors that prevent or reduce the risk of mental illness and/or substance use, is a small sliver of your overall mission. As you’ll notice from the other letters we’ve received, the vast majority of our readers agree that psychiatric medicine is far more than behavioral health.
Henry A. Nasrallah, MD
Professor of Psychiatry, Neurology, and Neuroscience
Medical Director: Neuropsychiatry
Director, Schizophrenia and Neuropsychiatry Programs
University of Cincinnati College of Medicine
Cincinnati, Ohio
Professor Emeritus, Saint Louis University
St. Louis, Missouri
Continue to: I thoroughly enjoyed...
I thoroughly enjoyed Dr. Nasrallah’s editorial and agree completely. Veterans Affairs, my employer for the last 12 years, has fully bought into the use of “behavioral health” and its implications for its many psychiatrists. I have grown very tired of the constant minimization of psychiatric practice, and it is so good to hear from an affirming voice.
Barbara Day, MD
US Department of Veterans Affairs
Ann Arbor, Michigan
Dr. Nasrallah’s editorial made my heart sing! I have been practicing psychiatry since 1979, and have always bristled when called a “provider” or any of the other terms Dr. Nasrallah described. As a graduate of Johns Hopkins Medical School, I had professors who themselves had been taught by Harry Stack Sullivan and Frida Fromm Reichman, and during my residency at the University of Chicago, I sat in discussions with both Bruno Bettelheim and Heinz Kohut. I felt part of an honorable tradition, and even though biological psychiatry was on the ascendency, these analytical luminaries were part of my learning the “art” of psychiatry. It is not so easy to feel good about a specialty that has had such a history as ours, but my own experiences could never be reduced to being called a behavioral health provider. Dr. Nasrallah’s thoughts are very encouraging, and I thank him!
John Engers, MD
Private psychiatric practice (retired)
Fremont, California
Dr. Nasrallah’s editorial resonated with one of my pet peeves. I’ve been telling my medical students for years that we psychiatrists treat disorders of thinking, emotions, and behavior associated with mental illness, and that the term “behavioral health,” though possibly well intentioned, is a euphemism to reduce stigma.
Irl Extein, MD
Private psychiatric practice
Delray Beach, Florida
Clinical Affiliate Associate Professor, Florida
Atlantic University College of Medicine
Boca Raton, Florida
Continue to: I enjoyed...
I enjoyed Dr. Nasrallah’s editorial regarding “behavioral health.” In New England, we have very clear delineation among psychiatry, mental health, and behavioral health. Only physicians can practice psychiatry because it is a medical specialty. Nurse practitioners and psychologists, on the other hand, are specialists in the field of mental health, as are psychiatrists, so mental health is a more encompassing term. Behavioral health encompasses all of the above plus counselors. Because insurers generally pay counselors, nurse practitioners, and psychiatrists, they use the term behavioral health because it wouldn’t be right for them to pay a counselor for a psychiatric intervention. So as a psychiatrist, I respond when being referred to as a psychiatrist, mental health specialist, or behavioral health specialist. And thankfully, per American Medical Association policy, psychiatrists are not providers.
Stu Gitlow, MD, MPH
Executive Director
Annenberg Physician Training Program in Addictive Disease
Woonsocket, Rhode Island
I was grateful for Dr. Nasrallah’s editorial regarding the misnomer of referring to psychiatry as “behavioral health.” Until this editorial, I had wondered if I was the only one bothered by the term. Many people are under the assumption that behavioral health is a politically correct term that helps to lessen stigmatism. I completely disagree. Without question, it adds to the stigmatism. The term behavioral health is belittling to our patients. For example, calling a psychiatric inpatient unit a “behavioral health unit” implies that if patients would just change their behaviors, they wouldn’t have serious biological psychiatric illness. It insinuates that the patients cause and perpetuate their illnesses, such as schizophrenia or bipolar disorder, by behaving poorly. Granted, we teach behavior modification to help manage psychiatric illness, but so, too, do our colleagues in other medical fields teach behavior modification to manage other organ-related illnesses. Some nearly ubiquitous examples include doctors advising patients to lower stress, modify diet, exercise, and take medications as prescribed. Yet, for example, in the case of a patient with diabetes, we don’t refer to diabetic ketoacidosis treatment as behavioral health treatment, though the patient’s behavior no doubt contributes to this condition. And we certainly would never call the ICU or stepdown unit the “behavioral health unit,” even though adequate holistic treatment in these settings includes counseling the patient with diabetes on changing his/her behaviors that led to the ketoacidosis. Just as in diabetes, the underlying basis of psychiatric illness is biologic processes gone awry. First and foremost, a psychiatric medical illness requires complicated and often precarious medications to treat. As in other medical specialties, modifying behavior does not treat the illness, but merely serves to help transmute the course.
In sum, I wholly agree with Dr. Nasrallah’s eloquent assessment regarding the problems with the title behavioral health in lieu of psychiatry. I also might have taken the discussion a step a further: Because psychiatric illness affects every aspect of a person’s life—such as work, social, and personal—it requires a terminology commensurate with the medical gravity it warrants. So in addition to not referring to the specialty as behavioral health, I have wondered if the name psychiatry could be replaced with a more medical-sounding term such as “cerebrology” or something of the sort. But one step at time.
Stacie Lauro, MD, ABPN
Attending in Psychiatry, Emergency Room, and Consultation Liaison
Mindcare Solutions
Tampa, Florida
The evolution within our field of the use of “behavioral health” has disturbed me to the same extent it has for Dr. Nasrallah. I founded and direct a psychiatric treatment facility in Florida. We are a teaching facility affiliated with 3 psychiatric residencies, 8 medical schools, and 60 physician assistant (PA) schools. In all of the literature (eg, evaluations) from the PA schools, they refer to their rotation with my program as “behavioral health.” I have been attempting to correct them for years! I teach all residents and students to correctly use the terms “psychiatry” and “psychiatric.” I understand there may be stigma associated with the latter terms, but the field reinforces that stigma by avoiding the use of these terms.
Robert A. Moran, MD, FAPA, FASAM
CEO and Medical Director, Family Center for Recovery
Lantana, Florida
Continue to: Pre-authorization and 'hold harmless' clauses
Pre-authorization and ‘hold harmless’ clauses
Regarding Dr. Nasrallah’s editorial “Pre-authorization is illegal, unethical, and adversely disrupts patient care” (From the Editor,
Recently to my surprise, while navigating a pre-authorization request for a young patient with bipolar disorder who had accepted the inclusion of lurasidone in his treatment regimen while hospitalized, I found that the CoverMyMeds Business Associate Agreement is required for a user to accomplish pre-authorization online. Having a little extra time for due diligence that day, I read this lengthy agreement carefully. The CoverMyMeds user agreement purports not to offer “medical advice, does not determine medical necessity, insurance coverage or copays and does not otherwise engage in the practice of medicine” (see www.covermymeds.com/main/about/privacy/tos/). Interestingly, the agreement goes on to purport that the whole process is for informational purposes only, not a substitute for clinicians, professional medical judgment, or for individual patient assessments and examinations. Of course, another factor is that the information provided by the process is “solely at the user’s and health care provider’s own risk.” Finally, the agreement requires the user to agree to “indemnify, defend, and hold harmless CoverMyMeds and its affiliates … from any demands, claims, damages, liabilities, expenses, or harms (including attorneys’ fees) arising out of or related to your use of our Services or breach of these Terms of Service.”
Throughout my 25 years of solo private practice, I have refused to sign hold harmless clauses and I refused to sign the CoverMyMeds user agreement. I have made it my practice never to obtain pre-authorization unless the patient is with me in the room during an appointment because the process of navigating pre-authorization does become part of the treatment, however unfortunately. As an alternative, for my patient with bipolar disorder, I was able to use a phone number to talk to a representative of the pharmacy benefit plan that was contracted with CoverMyMeds. Without signing on to be a Business Associate, we accomplished the goal of continuing with the medication as recommended and implemented for 2 preceding months (often pre-authorization actually means continuing authorization, doesn’t it?). I believe if all psychiatrists were to adopt this kind of stance, we could make a change. I know there are anti-trust considerations involved in fee negotiations, but when it comes to the egregious practices of managed care, pre-authorization, and hold harmless clauses, it seems to me that we can mount a counteroffensive to great effect.
Further, I want to stand in strong support of Dr. Nasrallah’s editorial “Stop calling it ‘behavioral health’: Psychiatry is much more.” When I began my first job post-fellowship, I was alarmed to find that our outpatient offices had been named a “counseling center.” Due to such misleading, stigmatizing characterizations, as Dr. Nasrallah pointed out, we have only slid further down the slope into the realm of “providers of behavioral health services.” As an old hand working psychiatric locum tenens told me, we psychiatrists had long since missed the chance to “band together like musk oxen” to defend our profession.
However, I believe it is not too late. With the strength of Dr. Nasrallah’s leadership and a more overt, collective stubbornness coupled with an undying commitment to excellence, we can and must push hard against the insurance and hospital entities, which continue to profiteer from the practice of medicine without a license—using the tools of hold harmless clauses, anti-trust laws in their favor, and misinformation about the scope and efficacy of practicing psychiatry per se. The challenge is to figure out exactly how to proceed.
Although some manage to thrive in independent practice, collectively our struggle seems considerable, but not insurmountable.
David B. Robinson, MD, MPH
Diplomate, American Board of Psychiatry and Neurology in Child, Adolescent and Adult Psychiatry
Fellow, American Psychiatric Association
Private psychiatric practice
Alaska Psychiatric Concepts
Juneau, Alaska
In the wake of Dr. Nasrallah’s recent editorial “Stop calling it ‘behavioral health:’ Psychiatry is much more” (From the Editor,
Naming a field, institute, department, or group of collaborators is crucially important, and must be undertaken with care. We all are familiar with Departments of Psychiatry, Departments of Psychiatry and Psychology, and Institutes for everything from Behavioral Health to Living. Even within the discipline of psychiatry, there have been adjustments over time in subspecialties (as seen with consultation-liaison psychiatry becoming psychosomatic medicine and then back again).
In our hospital system, we have recently adopted the term “Behavioral Health Institute” to denote the work and worth of significant numbers of caregivers (psychiatrists, psychologists, chemical dependency counselors, social workers, child life workers, advanced practice nurses, and others) who strive to improve the health and well-being of patients with both substance abuse and mental illness. We endeavor to remain mindful that a diversity of providers are involved in caring for and about our patients, and that “psychiatry” cannot—and should not—be the extent of how we conceptualize our services.
We submit that the modern view of behavioral health is ahead of other fields of medicine in recognizing that concepts, such as teamwork and diversity, are key to achieving positive patient outcomes. By identifying our providers as part of a Behavioral Health Institute, we acknowledge that not all mental distress is psychiatric illness but may still benefit from intervention and, importantly, that psychiatrists are not the center of the mental health (behavioral health) world. Treatments ranging from medication management to psychiatric procedures to psychotherapeutic modalities show the depth and breadth of our field, and the multiplicity of providers and modalities should be considered laudable. Recognizing the complexities inherent in behavioral health and its varied treatment options does not diminish but, in fact, elevates the field of psychiatry—and psychiatrists themselves.
Further, we note that behavioral health is not the only term that casts a larger net than the physician in a respective field. Does the term “primary care” insult internal medicine, family medicine, and pediatric physicians? Physicians and health care teams join in partnership with patients and families, either to cure or learn how to manage disease. We believe that constructing a health care system centered on physicians and their identities, rather than on patients and treatment outcomes, has been foolish. To that end, the tenor of Dr. Nasrallah’s editorial runs counter to the overall efforts of our field to improve collaboration, and, at its extreme, such articles promote the antiquated notion of physician elitism.
The editorial’s historical context is of course important, and the caution not to water down what “we” do (as psychiatrists) is appropriate. However, instead of comporting ourselves in a psychiatry-centric way, the use of the term behavioral health allows all of us to acknowledge (with appreciation and humility) the many contributors who work in our field. The use of a broad-minded, inclusive term neither minimizes nor trivializes psychiatry as a medical specialty. Rather, accepting this term and this mindset can place psychiatrists in the unique role of being innovators for the rest of medicine, because we embrace multidisciplinary teams and the value that interdisciplinary care can bring to patients and colleagues alike.
Jeanne Lackamp, MD, DFAPA, FACLP
Director, Pain Management Institute
University Hospitals Health System
Case Western Reserve University School of Medicine
Cleveland, Ohio
Patrick Runnels, MD, MBA
Chief Medical Officer, Population Health – Behavioral Health
University Hospitals Health System
Case Western Reserve University School of Medicine
Cleveland, Ohio
Lori Locke, RN, MSN
Director, Psychiatry Service Line and Nursing Practice
University Hospitals Health System
Case Western Reserve University School of Medicine
Cleveland, Ohio
Erum Ahmad, MD
Director, Child and Adolescent Psychiatry Unit
University Hospitals Health System
Case Western Reserve University School of Medicine
Cleveland, Ohio
Robert Ronis, MD, MPH
Douglas Danford Bond Professor and Chairman
Psychiatrist-in-Chief
University Hospitals Health System
Case Western Reserve University School of Medicine
Cleveland, Ohio
Continue to: Dr. Nasrallah responds
Dr. Nasrallah responds
I thank my Cleveland colleagues for their letter, and I welcome their disagreement with the tenets of my editorial. I still insist that the term “behavioral health” has a very narrow meaning that is not equivalent to psychiatry or psychology or social work or psychiatric nursing practice. This term should not be conflated with the widely used “mental health,” which is used as an overarching term for all professionals involved in the care of psychiatric brain disorders that manifest as various mental illnesses and substance use disorders.
While I am an advocate for multidisciplinary collaborations that benefit our patients, I will always uphold psychiatry as a medical specialty whose unique identity should not be sacrificed on the altar of politically correct egalitarianism of the mental health disciplines. Call it elitist if you like, but the fact is that the extensive medical school, residency, and fellowship training of psychiatrists stand out among all the other mental health disciplines. Psychiatrists are the best trained in all components of the biopsychosocial model (which I acquired many years ago from the father of the concept, George Engel, one of my teachers at the University of Rochester Residency Program).
You bring up primary care as an analogy for behavioral health. I assure you, none of the medical specialists included under that umbrella term refer to themselves as primary care physicians (PCPs) (or, God forbid, providers!). They identify themselves as family physicians, internists, pediatricians, and gynecologists. It is for the convenience of the health care systems and insurance companies that clinicians are called PCPs, which homogenizes them into a fuzzy amalgam and disguises their true medical identities as specialists.
So we agree to disagree. Diversity of opinions is a sacred principle. But I still think that a more accurate name for your Behavioral Health Institute would be “Institute of Psychiatric Medicine and Brain Health.” Behavioral health, which actually refers to educating people about implementing principles of evidence-based healthy habits and behaviors that prevent or reduce the risk of mental illness and/or substance use, is a small sliver of your overall mission. As you’ll notice from the other letters we’ve received, the vast majority of our readers agree that psychiatric medicine is far more than behavioral health.
Henry A. Nasrallah, MD
Professor of Psychiatry, Neurology, and Neuroscience
Medical Director: Neuropsychiatry
Director, Schizophrenia and Neuropsychiatry Programs
University of Cincinnati College of Medicine
Cincinnati, Ohio
Professor Emeritus, Saint Louis University
St. Louis, Missouri
Continue to: I thoroughly enjoyed...
I thoroughly enjoyed Dr. Nasrallah’s editorial and agree completely. Veterans Affairs, my employer for the last 12 years, has fully bought into the use of “behavioral health” and its implications for its many psychiatrists. I have grown very tired of the constant minimization of psychiatric practice, and it is so good to hear from an affirming voice.
Barbara Day, MD
US Department of Veterans Affairs
Ann Arbor, Michigan
Dr. Nasrallah’s editorial made my heart sing! I have been practicing psychiatry since 1979, and have always bristled when called a “provider” or any of the other terms Dr. Nasrallah described. As a graduate of Johns Hopkins Medical School, I had professors who themselves had been taught by Harry Stack Sullivan and Frida Fromm Reichman, and during my residency at the University of Chicago, I sat in discussions with both Bruno Bettelheim and Heinz Kohut. I felt part of an honorable tradition, and even though biological psychiatry was on the ascendency, these analytical luminaries were part of my learning the “art” of psychiatry. It is not so easy to feel good about a specialty that has had such a history as ours, but my own experiences could never be reduced to being called a behavioral health provider. Dr. Nasrallah’s thoughts are very encouraging, and I thank him!
John Engers, MD
Private psychiatric practice (retired)
Fremont, California
Dr. Nasrallah’s editorial resonated with one of my pet peeves. I’ve been telling my medical students for years that we psychiatrists treat disorders of thinking, emotions, and behavior associated with mental illness, and that the term “behavioral health,” though possibly well intentioned, is a euphemism to reduce stigma.
Irl Extein, MD
Private psychiatric practice
Delray Beach, Florida
Clinical Affiliate Associate Professor, Florida
Atlantic University College of Medicine
Boca Raton, Florida
Continue to: I enjoyed...
I enjoyed Dr. Nasrallah’s editorial regarding “behavioral health.” In New England, we have very clear delineation among psychiatry, mental health, and behavioral health. Only physicians can practice psychiatry because it is a medical specialty. Nurse practitioners and psychologists, on the other hand, are specialists in the field of mental health, as are psychiatrists, so mental health is a more encompassing term. Behavioral health encompasses all of the above plus counselors. Because insurers generally pay counselors, nurse practitioners, and psychiatrists, they use the term behavioral health because it wouldn’t be right for them to pay a counselor for a psychiatric intervention. So as a psychiatrist, I respond when being referred to as a psychiatrist, mental health specialist, or behavioral health specialist. And thankfully, per American Medical Association policy, psychiatrists are not providers.
Stu Gitlow, MD, MPH
Executive Director
Annenberg Physician Training Program in Addictive Disease
Woonsocket, Rhode Island
I was grateful for Dr. Nasrallah’s editorial regarding the misnomer of referring to psychiatry as “behavioral health.” Until this editorial, I had wondered if I was the only one bothered by the term. Many people are under the assumption that behavioral health is a politically correct term that helps to lessen stigmatism. I completely disagree. Without question, it adds to the stigmatism. The term behavioral health is belittling to our patients. For example, calling a psychiatric inpatient unit a “behavioral health unit” implies that if patients would just change their behaviors, they wouldn’t have serious biological psychiatric illness. It insinuates that the patients cause and perpetuate their illnesses, such as schizophrenia or bipolar disorder, by behaving poorly. Granted, we teach behavior modification to help manage psychiatric illness, but so, too, do our colleagues in other medical fields teach behavior modification to manage other organ-related illnesses. Some nearly ubiquitous examples include doctors advising patients to lower stress, modify diet, exercise, and take medications as prescribed. Yet, for example, in the case of a patient with diabetes, we don’t refer to diabetic ketoacidosis treatment as behavioral health treatment, though the patient’s behavior no doubt contributes to this condition. And we certainly would never call the ICU or stepdown unit the “behavioral health unit,” even though adequate holistic treatment in these settings includes counseling the patient with diabetes on changing his/her behaviors that led to the ketoacidosis. Just as in diabetes, the underlying basis of psychiatric illness is biologic processes gone awry. First and foremost, a psychiatric medical illness requires complicated and often precarious medications to treat. As in other medical specialties, modifying behavior does not treat the illness, but merely serves to help transmute the course.
In sum, I wholly agree with Dr. Nasrallah’s eloquent assessment regarding the problems with the title behavioral health in lieu of psychiatry. I also might have taken the discussion a step a further: Because psychiatric illness affects every aspect of a person’s life—such as work, social, and personal—it requires a terminology commensurate with the medical gravity it warrants. So in addition to not referring to the specialty as behavioral health, I have wondered if the name psychiatry could be replaced with a more medical-sounding term such as “cerebrology” or something of the sort. But one step at time.
Stacie Lauro, MD, ABPN
Attending in Psychiatry, Emergency Room, and Consultation Liaison
Mindcare Solutions
Tampa, Florida
The evolution within our field of the use of “behavioral health” has disturbed me to the same extent it has for Dr. Nasrallah. I founded and direct a psychiatric treatment facility in Florida. We are a teaching facility affiliated with 3 psychiatric residencies, 8 medical schools, and 60 physician assistant (PA) schools. In all of the literature (eg, evaluations) from the PA schools, they refer to their rotation with my program as “behavioral health.” I have been attempting to correct them for years! I teach all residents and students to correctly use the terms “psychiatry” and “psychiatric.” I understand there may be stigma associated with the latter terms, but the field reinforces that stigma by avoiding the use of these terms.
Robert A. Moran, MD, FAPA, FASAM
CEO and Medical Director, Family Center for Recovery
Lantana, Florida
Continue to: Pre-authorization and 'hold harmless' clauses
Pre-authorization and ‘hold harmless’ clauses
Regarding Dr. Nasrallah’s editorial “Pre-authorization is illegal, unethical, and adversely disrupts patient care” (From the Editor,
Recently to my surprise, while navigating a pre-authorization request for a young patient with bipolar disorder who had accepted the inclusion of lurasidone in his treatment regimen while hospitalized, I found that the CoverMyMeds Business Associate Agreement is required for a user to accomplish pre-authorization online. Having a little extra time for due diligence that day, I read this lengthy agreement carefully. The CoverMyMeds user agreement purports not to offer “medical advice, does not determine medical necessity, insurance coverage or copays and does not otherwise engage in the practice of medicine” (see www.covermymeds.com/main/about/privacy/tos/). Interestingly, the agreement goes on to purport that the whole process is for informational purposes only, not a substitute for clinicians, professional medical judgment, or for individual patient assessments and examinations. Of course, another factor is that the information provided by the process is “solely at the user’s and health care provider’s own risk.” Finally, the agreement requires the user to agree to “indemnify, defend, and hold harmless CoverMyMeds and its affiliates … from any demands, claims, damages, liabilities, expenses, or harms (including attorneys’ fees) arising out of or related to your use of our Services or breach of these Terms of Service.”
Throughout my 25 years of solo private practice, I have refused to sign hold harmless clauses and I refused to sign the CoverMyMeds user agreement. I have made it my practice never to obtain pre-authorization unless the patient is with me in the room during an appointment because the process of navigating pre-authorization does become part of the treatment, however unfortunately. As an alternative, for my patient with bipolar disorder, I was able to use a phone number to talk to a representative of the pharmacy benefit plan that was contracted with CoverMyMeds. Without signing on to be a Business Associate, we accomplished the goal of continuing with the medication as recommended and implemented for 2 preceding months (often pre-authorization actually means continuing authorization, doesn’t it?). I believe if all psychiatrists were to adopt this kind of stance, we could make a change. I know there are anti-trust considerations involved in fee negotiations, but when it comes to the egregious practices of managed care, pre-authorization, and hold harmless clauses, it seems to me that we can mount a counteroffensive to great effect.
Further, I want to stand in strong support of Dr. Nasrallah’s editorial “Stop calling it ‘behavioral health’: Psychiatry is much more.” When I began my first job post-fellowship, I was alarmed to find that our outpatient offices had been named a “counseling center.” Due to such misleading, stigmatizing characterizations, as Dr. Nasrallah pointed out, we have only slid further down the slope into the realm of “providers of behavioral health services.” As an old hand working psychiatric locum tenens told me, we psychiatrists had long since missed the chance to “band together like musk oxen” to defend our profession.
However, I believe it is not too late. With the strength of Dr. Nasrallah’s leadership and a more overt, collective stubbornness coupled with an undying commitment to excellence, we can and must push hard against the insurance and hospital entities, which continue to profiteer from the practice of medicine without a license—using the tools of hold harmless clauses, anti-trust laws in their favor, and misinformation about the scope and efficacy of practicing psychiatry per se. The challenge is to figure out exactly how to proceed.
Although some manage to thrive in independent practice, collectively our struggle seems considerable, but not insurmountable.
David B. Robinson, MD, MPH
Diplomate, American Board of Psychiatry and Neurology in Child, Adolescent and Adult Psychiatry
Fellow, American Psychiatric Association
Private psychiatric practice
Alaska Psychiatric Concepts
Juneau, Alaska
CYP450 interactions between illicit substances and prescription medications
Ms. L, age 37, presents to psychiatric emergency services with command auditory hallucinations, ideas of reference, and suicidal ideation.
Ms. L has a 22-year history of schizophrenia. Additionally, she has a history of cocaine use disorder (in remission for 12 years), cannabis use disorder (in remission for 6 months), type 2 diabetes mellitus, and hypertension. Her psychotic symptoms are well controlled on a regimen of
On interview, Ms. L reports smoking cannabis each day for the past month and using $400 worth of cocaine over 2 days. She is experiencing intense guilt over these relapses and is admitted to the inpatient adult psychiatry unit. On admission, Ms. L’s clozapine and norclozapine trough levels (drawn approximately 12 hours after last administration documented by the ACT member) are 300 and 275 ng/mL, respectively. Generally, clozapine levels >350 to 420 ng/mL are considered therapeutic, and a clozapine-to-norclozapine ratio of 2:1 is desirable for maximum efficacy and tolerability. Because Ms. L’s clozapine level is <350 and her ratio is approximately 1:1, her clozapine treatment is subtherapeutic.
Because Ms. L has a history of documented adherence to and benefit from her current medication regimen, no changes are made during her 3-week hospital stay. She notices a gradual reduction in auditory hallucinations, no longer wants to harm herself, and is motivated to regain sobriety.
At the time of discharge, Ms. L’s clozapine and norclozapine trough levels are 550 and 250 ng/mL, respectively, which indicates a more favorable clozapine-to-norclozapine ratio of approximately 2:1 and a clozapine level greater than the recommended minimum threshold of 350 ng/mL. While cocaine ingestion presumably played a role in her acute decompensation, the treatment team determined that Ms. L’s relapse to cannabis use likely contributed to low clozapine levels by induction of cytochrome P450 (CYP) 1A2, and subsequently led to the delayed recovery of symptom control.1
The use of illicit substances is a widespread, growing problem. According to the 2017 National Survey on Drug Use and Health, 11.5% of Americans age ≥12 had used an illicit substance (ie, use of marijuana, cocaine, heroin, hallucinogens, inhalants, or methamphetamine, or misuse of prescription psychotherapeutics) in the past month.2 While illicit substance use is of particular public health interest due to a known increase in mortality and health care spending, there has been little discussion of the impact of illicit drug use on concurrent pharmacologic therapy. Just as prescription medications have pharmacokinetic drug–drug interactions with each other, so do illicit substances, though far less is known about their impact on the treatment of medical conditions.
Pharmacokinetic interactions
Key pharmacokinetic interactions have been reported with cocaine, marijuana, amphetamines, and opioids. The Table1-8 summarizes the metabolism of illicit substances.
Continue to: Cocaine
Cocaine is largely metabolized by serum esterases such as pseudocholinesterase, human carboxylesterase-1 (hCE-1), and human carboxylesterase-2 (hCE-2), to inactive metabolites benzoylecgonine (35% to 45%) and ecgonine (32% to 49%).2 However, a smaller portion (2.6% to 6.2%) undergoes hepatic N-demethylation by CYP3A4 to norcocaine.3 Norcocaine is an active metabolite responsible for some of the toxic effects of cocaine (eg, hepatotoxicity).4,5 Several commonly prescribed medications are known inducers of CYP3A4 (eg, phenytoin, carbamazepine) and may lead to increased levels of the toxic metabolite when used concurrently with cocaine. Additionally, the use of cocaine with acetylcholinesterase inhibitors, such as donepezil, may lead to reduction of serum esterases and shunt cocaine metabolism toward the hepatic pathway, thus increasing norcocaine formation.3
Cannabis. The metabolism and drug–drug interactions of cannabis can be separated by its 2 main components: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). A review conducted in 2014 concluded that THC is primarily metabolized by CYP2C9 and 3A4, while CBD is metabolized by CYP2C19 and 3A4.6 Oral administration of ketoconazole, a CYP3A4 inhibitor, along with cannabis extract has been shown to increase the maximum concentration (Cmax) and area under the curve (AUC) of THC by 1.2- and 1.8-fold, respectively, while increasing both Cmaxand AUC of CBD by 2-fold.6 In addition, CYP2C9 poor metabolizers have been shown to experience significant increases in THC exposure and reductions in metabolite formation, further supporting the role of CYP enzymes in cannabis metabolism.6
There is also evidence of enzyme induction by cannabis. Individuals who reported smoking marijuana experienced greater clearance of theophylline, a substrate of CYP1A2, than did those who reported not smoking marijuana.1,6 As with cigarette smoking, this effect appears to be a direct result of the hydrocarbons found in marijuana smoke rather than the cannabis itself, as there is a lack of evidence for enzyme induction when the drug is orally ingested.6
Amphetamine and methamphetamine appear to be both substrates and competitive inhibitors of CYP2D6.7 Rats administered quinidine (a strong 2D6 inhibitor) had 2-fold elevations in AUC and decreased clearance of amphetamine and its metabolites.8 Amphetamine-related recreational drugs, such as 3,4-methylenedioxy-methamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA), are substrates of CYP2D6 and CYP3A4, while MDMA also undergoes substantial metabolism by CYP1A2.3,7,9
Opioids. Heroin is metabolized to 6‑monoacetylmorphine (6-MAM) and morphine by hCE-1, hCE-2, and pseudocholinesterase, and has minimal impact on CYP enzymes. However, while morphine is primarily metabolized to inactive metabolites by UGT2B7, it does undergo minor metabolism through CYP3A4 and 2C8 pathways, creating potential for drug interactions with medications that inhibit or induce CYP3A4.10
Continue to: An underappreciated risk of illicit substance use
An underappreciated risk of illicit substance use
There is a paucity of evidence regarding the metabolism and pharmacokinetic interactions with illicit substances, and further research is needed. Despite the absence of comprehensive data on the subject, the available information indicates the use of illicit substances may have a significant impact on medications used to treat comorbid conditions. Alternatively, those medications may affect the kinetics of recreationally used substances. The risk of adverse consequences of drug–drug interactions is yet another reason patients should be encouraged to avoid use of substances and seek treatment for substance use disorders. When determining the most appropriate therapy for comorbid conditions for patients who are using illicit substances and are likely to continue to do so, clinicians should take into consideration potential interactions among prescription medications and the specific illicit substances the patient uses.
Related Resources
- Lindsey W, Stewart D, Childress D. Drug interactions between common illicit drugs and prescription therapies. Am J Drug Alcohol Abuse. 2012;38(4):334-343.
- Maurer H, Sauer C, Theobald D. Toxicokinetics of drugs of abuse: current knowledge of the isoenzymes involved in the human metabolism of tetrahydrocannabinol, cocaine, heroin, morphine, and codeine. Ther Drug Monit. 2006;28(3):447-453.
- Dean A. Illicit drugs and drug interactions. Pharmacist. 2006;25(9):684-689.
Drug Brand Names
Carbamazepine • Carbatrol, Tegretol
Clozapine • Clozaril
Donepezil • Aricept
Ketoconazole • Nizoral
Paliperidone palmitate • Invega sustenna
Phenytoin • Dilantin, Phenytek
Quinidine • Cardioquin, Duraquin
Theophylline • Elixophylline, Theochron
1. Jusko WJ, Schentag JJ, Clark JH, et al. Enhanced biotransformation of theophylline in marihuana and tobacco smokers. Clin Pharmacol Ther. 1978;24(4):405-410.
2. Substance Abuse and Mental Health Services Administration. Results from the 2017 National Survey on Drug Use and Health: Detailed Tables. https://www.samhsa.gov/data/sites/default/files/cbhsq-reports/NSDUHDetailedTabs2017/NSDUHDetailedTabs2017.htm#tab1-1A. Published 2019. Accessed February 7, 2020.
3. Quinn D, Wodak A, Day R. Pharmacokinetic and pharmacodynamic principles of illicit drug use and treatment of illicit drug users. Clin Pharmacokinet. 1997;33(5):344-400.
4. Ndikum-Moffor FM, Schoeb TR, Roberts SM. Liver toxicity from norcocaine nitroxide, an N-oxidative metabolite of cocaine. J Pharmacol Exp Ther. 1998;284(1):413-419.
5. Pellinen P, Honkakoski P, Stenbäck F, et al. Cocaine N-demethylation and the metabolism-related hepatotoxicity can be prevented by cytochrome P450 3A inhibitors. Eur J Pharmacol. 1994;270(1):35-43.
6. Stout S, Cimino N. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev. 2013;46(1):86-95.
7. Kraemer T, Maurer H. Toxicokinetics of amphetamines: metabolism and toxicokinetic data of designer drugs, amphetamine, methamphetamine, and their N-alkyl derivatives. Ther Drug Monit. 2002;24(2):277-289.
8. Markowitz J, Patrick K. Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder. Clin Pharmacokinet. 2001;40(10):753-772.
9. Kreth K, Kovar K, Schwab M, et al. Identification of the human cytochromes P450 involved in the oxidative metabolism of “ecstasy”-related designer drugs. Biochem Pharmacol. 2000;59(12):1563-1571.
10. Meyer M, Maurer H. Absorption, distribution, metabolism and excretion pharmacogenomics of drugs of abuse. Pharmacogenomics. 2011;12(2):215-233.
Ms. L, age 37, presents to psychiatric emergency services with command auditory hallucinations, ideas of reference, and suicidal ideation.
Ms. L has a 22-year history of schizophrenia. Additionally, she has a history of cocaine use disorder (in remission for 12 years), cannabis use disorder (in remission for 6 months), type 2 diabetes mellitus, and hypertension. Her psychotic symptoms are well controlled on a regimen of
On interview, Ms. L reports smoking cannabis each day for the past month and using $400 worth of cocaine over 2 days. She is experiencing intense guilt over these relapses and is admitted to the inpatient adult psychiatry unit. On admission, Ms. L’s clozapine and norclozapine trough levels (drawn approximately 12 hours after last administration documented by the ACT member) are 300 and 275 ng/mL, respectively. Generally, clozapine levels >350 to 420 ng/mL are considered therapeutic, and a clozapine-to-norclozapine ratio of 2:1 is desirable for maximum efficacy and tolerability. Because Ms. L’s clozapine level is <350 and her ratio is approximately 1:1, her clozapine treatment is subtherapeutic.
Because Ms. L has a history of documented adherence to and benefit from her current medication regimen, no changes are made during her 3-week hospital stay. She notices a gradual reduction in auditory hallucinations, no longer wants to harm herself, and is motivated to regain sobriety.
At the time of discharge, Ms. L’s clozapine and norclozapine trough levels are 550 and 250 ng/mL, respectively, which indicates a more favorable clozapine-to-norclozapine ratio of approximately 2:1 and a clozapine level greater than the recommended minimum threshold of 350 ng/mL. While cocaine ingestion presumably played a role in her acute decompensation, the treatment team determined that Ms. L’s relapse to cannabis use likely contributed to low clozapine levels by induction of cytochrome P450 (CYP) 1A2, and subsequently led to the delayed recovery of symptom control.1
The use of illicit substances is a widespread, growing problem. According to the 2017 National Survey on Drug Use and Health, 11.5% of Americans age ≥12 had used an illicit substance (ie, use of marijuana, cocaine, heroin, hallucinogens, inhalants, or methamphetamine, or misuse of prescription psychotherapeutics) in the past month.2 While illicit substance use is of particular public health interest due to a known increase in mortality and health care spending, there has been little discussion of the impact of illicit drug use on concurrent pharmacologic therapy. Just as prescription medications have pharmacokinetic drug–drug interactions with each other, so do illicit substances, though far less is known about their impact on the treatment of medical conditions.
Pharmacokinetic interactions
Key pharmacokinetic interactions have been reported with cocaine, marijuana, amphetamines, and opioids. The Table1-8 summarizes the metabolism of illicit substances.
Continue to: Cocaine
Cocaine is largely metabolized by serum esterases such as pseudocholinesterase, human carboxylesterase-1 (hCE-1), and human carboxylesterase-2 (hCE-2), to inactive metabolites benzoylecgonine (35% to 45%) and ecgonine (32% to 49%).2 However, a smaller portion (2.6% to 6.2%) undergoes hepatic N-demethylation by CYP3A4 to norcocaine.3 Norcocaine is an active metabolite responsible for some of the toxic effects of cocaine (eg, hepatotoxicity).4,5 Several commonly prescribed medications are known inducers of CYP3A4 (eg, phenytoin, carbamazepine) and may lead to increased levels of the toxic metabolite when used concurrently with cocaine. Additionally, the use of cocaine with acetylcholinesterase inhibitors, such as donepezil, may lead to reduction of serum esterases and shunt cocaine metabolism toward the hepatic pathway, thus increasing norcocaine formation.3
Cannabis. The metabolism and drug–drug interactions of cannabis can be separated by its 2 main components: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). A review conducted in 2014 concluded that THC is primarily metabolized by CYP2C9 and 3A4, while CBD is metabolized by CYP2C19 and 3A4.6 Oral administration of ketoconazole, a CYP3A4 inhibitor, along with cannabis extract has been shown to increase the maximum concentration (Cmax) and area under the curve (AUC) of THC by 1.2- and 1.8-fold, respectively, while increasing both Cmaxand AUC of CBD by 2-fold.6 In addition, CYP2C9 poor metabolizers have been shown to experience significant increases in THC exposure and reductions in metabolite formation, further supporting the role of CYP enzymes in cannabis metabolism.6
There is also evidence of enzyme induction by cannabis. Individuals who reported smoking marijuana experienced greater clearance of theophylline, a substrate of CYP1A2, than did those who reported not smoking marijuana.1,6 As with cigarette smoking, this effect appears to be a direct result of the hydrocarbons found in marijuana smoke rather than the cannabis itself, as there is a lack of evidence for enzyme induction when the drug is orally ingested.6
Amphetamine and methamphetamine appear to be both substrates and competitive inhibitors of CYP2D6.7 Rats administered quinidine (a strong 2D6 inhibitor) had 2-fold elevations in AUC and decreased clearance of amphetamine and its metabolites.8 Amphetamine-related recreational drugs, such as 3,4-methylenedioxy-methamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA), are substrates of CYP2D6 and CYP3A4, while MDMA also undergoes substantial metabolism by CYP1A2.3,7,9
Opioids. Heroin is metabolized to 6‑monoacetylmorphine (6-MAM) and morphine by hCE-1, hCE-2, and pseudocholinesterase, and has minimal impact on CYP enzymes. However, while morphine is primarily metabolized to inactive metabolites by UGT2B7, it does undergo minor metabolism through CYP3A4 and 2C8 pathways, creating potential for drug interactions with medications that inhibit or induce CYP3A4.10
Continue to: An underappreciated risk of illicit substance use
An underappreciated risk of illicit substance use
There is a paucity of evidence regarding the metabolism and pharmacokinetic interactions with illicit substances, and further research is needed. Despite the absence of comprehensive data on the subject, the available information indicates the use of illicit substances may have a significant impact on medications used to treat comorbid conditions. Alternatively, those medications may affect the kinetics of recreationally used substances. The risk of adverse consequences of drug–drug interactions is yet another reason patients should be encouraged to avoid use of substances and seek treatment for substance use disorders. When determining the most appropriate therapy for comorbid conditions for patients who are using illicit substances and are likely to continue to do so, clinicians should take into consideration potential interactions among prescription medications and the specific illicit substances the patient uses.
Related Resources
- Lindsey W, Stewart D, Childress D. Drug interactions between common illicit drugs and prescription therapies. Am J Drug Alcohol Abuse. 2012;38(4):334-343.
- Maurer H, Sauer C, Theobald D. Toxicokinetics of drugs of abuse: current knowledge of the isoenzymes involved in the human metabolism of tetrahydrocannabinol, cocaine, heroin, morphine, and codeine. Ther Drug Monit. 2006;28(3):447-453.
- Dean A. Illicit drugs and drug interactions. Pharmacist. 2006;25(9):684-689.
Drug Brand Names
Carbamazepine • Carbatrol, Tegretol
Clozapine • Clozaril
Donepezil • Aricept
Ketoconazole • Nizoral
Paliperidone palmitate • Invega sustenna
Phenytoin • Dilantin, Phenytek
Quinidine • Cardioquin, Duraquin
Theophylline • Elixophylline, Theochron
Ms. L, age 37, presents to psychiatric emergency services with command auditory hallucinations, ideas of reference, and suicidal ideation.
Ms. L has a 22-year history of schizophrenia. Additionally, she has a history of cocaine use disorder (in remission for 12 years), cannabis use disorder (in remission for 6 months), type 2 diabetes mellitus, and hypertension. Her psychotic symptoms are well controlled on a regimen of
On interview, Ms. L reports smoking cannabis each day for the past month and using $400 worth of cocaine over 2 days. She is experiencing intense guilt over these relapses and is admitted to the inpatient adult psychiatry unit. On admission, Ms. L’s clozapine and norclozapine trough levels (drawn approximately 12 hours after last administration documented by the ACT member) are 300 and 275 ng/mL, respectively. Generally, clozapine levels >350 to 420 ng/mL are considered therapeutic, and a clozapine-to-norclozapine ratio of 2:1 is desirable for maximum efficacy and tolerability. Because Ms. L’s clozapine level is <350 and her ratio is approximately 1:1, her clozapine treatment is subtherapeutic.
Because Ms. L has a history of documented adherence to and benefit from her current medication regimen, no changes are made during her 3-week hospital stay. She notices a gradual reduction in auditory hallucinations, no longer wants to harm herself, and is motivated to regain sobriety.
At the time of discharge, Ms. L’s clozapine and norclozapine trough levels are 550 and 250 ng/mL, respectively, which indicates a more favorable clozapine-to-norclozapine ratio of approximately 2:1 and a clozapine level greater than the recommended minimum threshold of 350 ng/mL. While cocaine ingestion presumably played a role in her acute decompensation, the treatment team determined that Ms. L’s relapse to cannabis use likely contributed to low clozapine levels by induction of cytochrome P450 (CYP) 1A2, and subsequently led to the delayed recovery of symptom control.1
The use of illicit substances is a widespread, growing problem. According to the 2017 National Survey on Drug Use and Health, 11.5% of Americans age ≥12 had used an illicit substance (ie, use of marijuana, cocaine, heroin, hallucinogens, inhalants, or methamphetamine, or misuse of prescription psychotherapeutics) in the past month.2 While illicit substance use is of particular public health interest due to a known increase in mortality and health care spending, there has been little discussion of the impact of illicit drug use on concurrent pharmacologic therapy. Just as prescription medications have pharmacokinetic drug–drug interactions with each other, so do illicit substances, though far less is known about their impact on the treatment of medical conditions.
Pharmacokinetic interactions
Key pharmacokinetic interactions have been reported with cocaine, marijuana, amphetamines, and opioids. The Table1-8 summarizes the metabolism of illicit substances.
Continue to: Cocaine
Cocaine is largely metabolized by serum esterases such as pseudocholinesterase, human carboxylesterase-1 (hCE-1), and human carboxylesterase-2 (hCE-2), to inactive metabolites benzoylecgonine (35% to 45%) and ecgonine (32% to 49%).2 However, a smaller portion (2.6% to 6.2%) undergoes hepatic N-demethylation by CYP3A4 to norcocaine.3 Norcocaine is an active metabolite responsible for some of the toxic effects of cocaine (eg, hepatotoxicity).4,5 Several commonly prescribed medications are known inducers of CYP3A4 (eg, phenytoin, carbamazepine) and may lead to increased levels of the toxic metabolite when used concurrently with cocaine. Additionally, the use of cocaine with acetylcholinesterase inhibitors, such as donepezil, may lead to reduction of serum esterases and shunt cocaine metabolism toward the hepatic pathway, thus increasing norcocaine formation.3
Cannabis. The metabolism and drug–drug interactions of cannabis can be separated by its 2 main components: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). A review conducted in 2014 concluded that THC is primarily metabolized by CYP2C9 and 3A4, while CBD is metabolized by CYP2C19 and 3A4.6 Oral administration of ketoconazole, a CYP3A4 inhibitor, along with cannabis extract has been shown to increase the maximum concentration (Cmax) and area under the curve (AUC) of THC by 1.2- and 1.8-fold, respectively, while increasing both Cmaxand AUC of CBD by 2-fold.6 In addition, CYP2C9 poor metabolizers have been shown to experience significant increases in THC exposure and reductions in metabolite formation, further supporting the role of CYP enzymes in cannabis metabolism.6
There is also evidence of enzyme induction by cannabis. Individuals who reported smoking marijuana experienced greater clearance of theophylline, a substrate of CYP1A2, than did those who reported not smoking marijuana.1,6 As with cigarette smoking, this effect appears to be a direct result of the hydrocarbons found in marijuana smoke rather than the cannabis itself, as there is a lack of evidence for enzyme induction when the drug is orally ingested.6
Amphetamine and methamphetamine appear to be both substrates and competitive inhibitors of CYP2D6.7 Rats administered quinidine (a strong 2D6 inhibitor) had 2-fold elevations in AUC and decreased clearance of amphetamine and its metabolites.8 Amphetamine-related recreational drugs, such as 3,4-methylenedioxy-methamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA), are substrates of CYP2D6 and CYP3A4, while MDMA also undergoes substantial metabolism by CYP1A2.3,7,9
Opioids. Heroin is metabolized to 6‑monoacetylmorphine (6-MAM) and morphine by hCE-1, hCE-2, and pseudocholinesterase, and has minimal impact on CYP enzymes. However, while morphine is primarily metabolized to inactive metabolites by UGT2B7, it does undergo minor metabolism through CYP3A4 and 2C8 pathways, creating potential for drug interactions with medications that inhibit or induce CYP3A4.10
Continue to: An underappreciated risk of illicit substance use
An underappreciated risk of illicit substance use
There is a paucity of evidence regarding the metabolism and pharmacokinetic interactions with illicit substances, and further research is needed. Despite the absence of comprehensive data on the subject, the available information indicates the use of illicit substances may have a significant impact on medications used to treat comorbid conditions. Alternatively, those medications may affect the kinetics of recreationally used substances. The risk of adverse consequences of drug–drug interactions is yet another reason patients should be encouraged to avoid use of substances and seek treatment for substance use disorders. When determining the most appropriate therapy for comorbid conditions for patients who are using illicit substances and are likely to continue to do so, clinicians should take into consideration potential interactions among prescription medications and the specific illicit substances the patient uses.
Related Resources
- Lindsey W, Stewart D, Childress D. Drug interactions between common illicit drugs and prescription therapies. Am J Drug Alcohol Abuse. 2012;38(4):334-343.
- Maurer H, Sauer C, Theobald D. Toxicokinetics of drugs of abuse: current knowledge of the isoenzymes involved in the human metabolism of tetrahydrocannabinol, cocaine, heroin, morphine, and codeine. Ther Drug Monit. 2006;28(3):447-453.
- Dean A. Illicit drugs and drug interactions. Pharmacist. 2006;25(9):684-689.
Drug Brand Names
Carbamazepine • Carbatrol, Tegretol
Clozapine • Clozaril
Donepezil • Aricept
Ketoconazole • Nizoral
Paliperidone palmitate • Invega sustenna
Phenytoin • Dilantin, Phenytek
Quinidine • Cardioquin, Duraquin
Theophylline • Elixophylline, Theochron
1. Jusko WJ, Schentag JJ, Clark JH, et al. Enhanced biotransformation of theophylline in marihuana and tobacco smokers. Clin Pharmacol Ther. 1978;24(4):405-410.
2. Substance Abuse and Mental Health Services Administration. Results from the 2017 National Survey on Drug Use and Health: Detailed Tables. https://www.samhsa.gov/data/sites/default/files/cbhsq-reports/NSDUHDetailedTabs2017/NSDUHDetailedTabs2017.htm#tab1-1A. Published 2019. Accessed February 7, 2020.
3. Quinn D, Wodak A, Day R. Pharmacokinetic and pharmacodynamic principles of illicit drug use and treatment of illicit drug users. Clin Pharmacokinet. 1997;33(5):344-400.
4. Ndikum-Moffor FM, Schoeb TR, Roberts SM. Liver toxicity from norcocaine nitroxide, an N-oxidative metabolite of cocaine. J Pharmacol Exp Ther. 1998;284(1):413-419.
5. Pellinen P, Honkakoski P, Stenbäck F, et al. Cocaine N-demethylation and the metabolism-related hepatotoxicity can be prevented by cytochrome P450 3A inhibitors. Eur J Pharmacol. 1994;270(1):35-43.
6. Stout S, Cimino N. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev. 2013;46(1):86-95.
7. Kraemer T, Maurer H. Toxicokinetics of amphetamines: metabolism and toxicokinetic data of designer drugs, amphetamine, methamphetamine, and their N-alkyl derivatives. Ther Drug Monit. 2002;24(2):277-289.
8. Markowitz J, Patrick K. Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder. Clin Pharmacokinet. 2001;40(10):753-772.
9. Kreth K, Kovar K, Schwab M, et al. Identification of the human cytochromes P450 involved in the oxidative metabolism of “ecstasy”-related designer drugs. Biochem Pharmacol. 2000;59(12):1563-1571.
10. Meyer M, Maurer H. Absorption, distribution, metabolism and excretion pharmacogenomics of drugs of abuse. Pharmacogenomics. 2011;12(2):215-233.
1. Jusko WJ, Schentag JJ, Clark JH, et al. Enhanced biotransformation of theophylline in marihuana and tobacco smokers. Clin Pharmacol Ther. 1978;24(4):405-410.
2. Substance Abuse and Mental Health Services Administration. Results from the 2017 National Survey on Drug Use and Health: Detailed Tables. https://www.samhsa.gov/data/sites/default/files/cbhsq-reports/NSDUHDetailedTabs2017/NSDUHDetailedTabs2017.htm#tab1-1A. Published 2019. Accessed February 7, 2020.
3. Quinn D, Wodak A, Day R. Pharmacokinetic and pharmacodynamic principles of illicit drug use and treatment of illicit drug users. Clin Pharmacokinet. 1997;33(5):344-400.
4. Ndikum-Moffor FM, Schoeb TR, Roberts SM. Liver toxicity from norcocaine nitroxide, an N-oxidative metabolite of cocaine. J Pharmacol Exp Ther. 1998;284(1):413-419.
5. Pellinen P, Honkakoski P, Stenbäck F, et al. Cocaine N-demethylation and the metabolism-related hepatotoxicity can be prevented by cytochrome P450 3A inhibitors. Eur J Pharmacol. 1994;270(1):35-43.
6. Stout S, Cimino N. Exogenous cannabinoids as substrates, inhibitors, and inducers of human drug metabolizing enzymes: a systematic review. Drug Metab Rev. 2013;46(1):86-95.
7. Kraemer T, Maurer H. Toxicokinetics of amphetamines: metabolism and toxicokinetic data of designer drugs, amphetamine, methamphetamine, and their N-alkyl derivatives. Ther Drug Monit. 2002;24(2):277-289.
8. Markowitz J, Patrick K. Pharmacokinetic and pharmacodynamic drug interactions in the treatment of attention-deficit hyperactivity disorder. Clin Pharmacokinet. 2001;40(10):753-772.
9. Kreth K, Kovar K, Schwab M, et al. Identification of the human cytochromes P450 involved in the oxidative metabolism of “ecstasy”-related designer drugs. Biochem Pharmacol. 2000;59(12):1563-1571.
10. Meyer M, Maurer H. Absorption, distribution, metabolism and excretion pharmacogenomics of drugs of abuse. Pharmacogenomics. 2011;12(2):215-233.
