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Repetitive hits to the head tied to depression, poor cognition in later life
A history of repetitive hits to the head (RHI), even without noticeable symptoms, is linked to a significantly increased risk of depression and poorer cognition later in life, new research shows.
“We found that a history of exposure to [repetitive hits to the head] from contact sports, military service, or physical abuse, as well as a history of TBI (traumatic brain injury), corresponded to more symptoms of later life depression and worse cognitive function,” lead author Michael Alosco, PhD, associate professor of neurology and codirector of the Boston University Alzheimer’s Disease Center Clinical Core, told Medscape Medical News.
He added that the findings underscore the importance of assessing repetitive head impacts (RHI).
The study was published online June 26 in Neurology.
Largest study to date
It is well known that sustaining a TBI is associated with worse later life cognition or mood problems, said Alosco. However, in the current research the investigators hypothesized that RHI may be a key driver of some of these outcomes, Alosco said.
Previous studies have been small or have only examined male former football players.
“What’s unique about our study is that we focused on a history of RHIs, and it is the largest study of its kind, incorporating over 30,000 males and females with different types of exposure to these RHIs.”
The researchers used data from the Brain Health Registry, an internet-based registry that longitudinally monitors cognition and functioning of participants (age 40 years and older).
Participants completed the Ohio State University TBI Identification Method (OSU TBI-ID) and answered a yes/no question: “Have you ever had a period of time in which you experienced multiple, repeated impacts to your head (eg, history of abuse, contact sports, military duty)?”
Participants also completed the Geriatric Depression Scale (GDS-15), the CogState Battery (CBB), and the Lumos Labs NeuroCognitive Performance Tests (NCPT). Demographic information included age, sex, race/ethnicity, and level of education.
Negative synergistic effect
Of the total sample (N = 13,323, mean age 62 years, 72.5% female, 88.6% White) 725 participants (5%) reported exposure to RHI, with contact sports as the most common cause, followed by physical abuse and then military duty; about 55% (7277 participants) reported TBI.
The researchers noted that 44.4% of those exposed to RHI and 70.3% of those who reported TBI were female. However, those with a history of contact sports were predominantly male and those reporting a history of abuse were predominantly women.
Among study participants who completed the GDS-15, 16.4% reported symptoms of depression, similar to rates reported among community-dwelling older adults.
Compared to the unexposed group, participants who reported TBI with loss of consciousness (LOC) and participants who reported TBI without LOC both had higher scores on the GDS-15 (beta = 0.75 [95% CI, 0.59-0.91] and beta = 0.43 [95% CI, 0.31-0.54], respectively).
A history of RHI was associated with an even higher depression score (beta = 1.24 [95% CI, 0.36-2.12).
Depression increased in tandem with increased exposure, with the lowest GDS-15 scores found in the unexposed group and subsequent increases in scores as exposure to RHI was introduced and TBI severity increased. The GDS scores were highest in those who had RHI plus TBI with LOC.
Participants with a history of RHI and/or TBI also had worse scores on tests of memory, learning, processing speed, and reaction time, compared with unexposed participants.
In particular, TBI with LOC had the most neuropsychological associations.
TBI without LOC had a negative effect on CogState tests measuring Identification and processing speed (beta = 0.004 [95% CI, 0-0.01] and beta = 0.004 [95% CI, 0.0002-0.01], respectively), whereas RHI predicted a worse processing speed score (beta = .02 [95% CI, 0.01-0.05]).
The presence of both RHI and TBI (with or without LOC) had a “synergistic negative effect” on neuropsychological performance, with a “consistent statistically significant finding” for worse neuropsychological test performance for those who had RHI and TBI with LOC, compared with those who had not sustained RHI.
Alosco said the findings highlight the need for clinicians to educate and inform parents/guardians of kids playing (or considering playing) contact sports about the research and potential risks associated with these activities.
If we want to prevent long-term problems, one way is not to expose [people] to these hits. Everyone takes risks in life with everything, but the more we can understand and mitigate the risks, the better,” Alosco said.
“A significant contribution”
Commenting on the findings for Medscape Medical News, Temitayo Oyegbile-Chidi, MD, PhD, a pediatric neurologist with Health Peak Inc, McLean, Virginia, and a member of the American Academy of Neurology, said the study “makes a significant contribution to the literature, as neurologists who specialized in TBI have long yearned to understand the long-term effects of repeated head impact on the brain and cognition.”
Clinicians should “inquire about a history of prior head impacts on all our patients, regardless of age, especially if they are experiencing or showing signs of unexpected cognitive dysfunction or mental health concerns,” said Oyegbile-Chidi, who was not involved with the study.
For those who have sustained single or repeated head impacts with or without associated LOC in the past, “it is important … to keep in mind that depression and cognitive dysfunction may persist or present even many years after the impact was sustained,” she added.
The study was supported by a grant from the National Institutes of Health. Alosco has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Oyegbile-Chidi has disclosed no relevant financial relationships.
A history of repetitive hits to the head (RHI), even without noticeable symptoms, is linked to a significantly increased risk of depression and poorer cognition later in life, new research shows.
“We found that a history of exposure to [repetitive hits to the head] from contact sports, military service, or physical abuse, as well as a history of TBI (traumatic brain injury), corresponded to more symptoms of later life depression and worse cognitive function,” lead author Michael Alosco, PhD, associate professor of neurology and codirector of the Boston University Alzheimer’s Disease Center Clinical Core, told Medscape Medical News.
He added that the findings underscore the importance of assessing repetitive head impacts (RHI).
The study was published online June 26 in Neurology.
Largest study to date
It is well known that sustaining a TBI is associated with worse later life cognition or mood problems, said Alosco. However, in the current research the investigators hypothesized that RHI may be a key driver of some of these outcomes, Alosco said.
Previous studies have been small or have only examined male former football players.
“What’s unique about our study is that we focused on a history of RHIs, and it is the largest study of its kind, incorporating over 30,000 males and females with different types of exposure to these RHIs.”
The researchers used data from the Brain Health Registry, an internet-based registry that longitudinally monitors cognition and functioning of participants (age 40 years and older).
Participants completed the Ohio State University TBI Identification Method (OSU TBI-ID) and answered a yes/no question: “Have you ever had a period of time in which you experienced multiple, repeated impacts to your head (eg, history of abuse, contact sports, military duty)?”
Participants also completed the Geriatric Depression Scale (GDS-15), the CogState Battery (CBB), and the Lumos Labs NeuroCognitive Performance Tests (NCPT). Demographic information included age, sex, race/ethnicity, and level of education.
Negative synergistic effect
Of the total sample (N = 13,323, mean age 62 years, 72.5% female, 88.6% White) 725 participants (5%) reported exposure to RHI, with contact sports as the most common cause, followed by physical abuse and then military duty; about 55% (7277 participants) reported TBI.
The researchers noted that 44.4% of those exposed to RHI and 70.3% of those who reported TBI were female. However, those with a history of contact sports were predominantly male and those reporting a history of abuse were predominantly women.
Among study participants who completed the GDS-15, 16.4% reported symptoms of depression, similar to rates reported among community-dwelling older adults.
Compared to the unexposed group, participants who reported TBI with loss of consciousness (LOC) and participants who reported TBI without LOC both had higher scores on the GDS-15 (beta = 0.75 [95% CI, 0.59-0.91] and beta = 0.43 [95% CI, 0.31-0.54], respectively).
A history of RHI was associated with an even higher depression score (beta = 1.24 [95% CI, 0.36-2.12).
Depression increased in tandem with increased exposure, with the lowest GDS-15 scores found in the unexposed group and subsequent increases in scores as exposure to RHI was introduced and TBI severity increased. The GDS scores were highest in those who had RHI plus TBI with LOC.
Participants with a history of RHI and/or TBI also had worse scores on tests of memory, learning, processing speed, and reaction time, compared with unexposed participants.
In particular, TBI with LOC had the most neuropsychological associations.
TBI without LOC had a negative effect on CogState tests measuring Identification and processing speed (beta = 0.004 [95% CI, 0-0.01] and beta = 0.004 [95% CI, 0.0002-0.01], respectively), whereas RHI predicted a worse processing speed score (beta = .02 [95% CI, 0.01-0.05]).
The presence of both RHI and TBI (with or without LOC) had a “synergistic negative effect” on neuropsychological performance, with a “consistent statistically significant finding” for worse neuropsychological test performance for those who had RHI and TBI with LOC, compared with those who had not sustained RHI.
Alosco said the findings highlight the need for clinicians to educate and inform parents/guardians of kids playing (or considering playing) contact sports about the research and potential risks associated with these activities.
If we want to prevent long-term problems, one way is not to expose [people] to these hits. Everyone takes risks in life with everything, but the more we can understand and mitigate the risks, the better,” Alosco said.
“A significant contribution”
Commenting on the findings for Medscape Medical News, Temitayo Oyegbile-Chidi, MD, PhD, a pediatric neurologist with Health Peak Inc, McLean, Virginia, and a member of the American Academy of Neurology, said the study “makes a significant contribution to the literature, as neurologists who specialized in TBI have long yearned to understand the long-term effects of repeated head impact on the brain and cognition.”
Clinicians should “inquire about a history of prior head impacts on all our patients, regardless of age, especially if they are experiencing or showing signs of unexpected cognitive dysfunction or mental health concerns,” said Oyegbile-Chidi, who was not involved with the study.
For those who have sustained single or repeated head impacts with or without associated LOC in the past, “it is important … to keep in mind that depression and cognitive dysfunction may persist or present even many years after the impact was sustained,” she added.
The study was supported by a grant from the National Institutes of Health. Alosco has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Oyegbile-Chidi has disclosed no relevant financial relationships.
A history of repetitive hits to the head (RHI), even without noticeable symptoms, is linked to a significantly increased risk of depression and poorer cognition later in life, new research shows.
“We found that a history of exposure to [repetitive hits to the head] from contact sports, military service, or physical abuse, as well as a history of TBI (traumatic brain injury), corresponded to more symptoms of later life depression and worse cognitive function,” lead author Michael Alosco, PhD, associate professor of neurology and codirector of the Boston University Alzheimer’s Disease Center Clinical Core, told Medscape Medical News.
He added that the findings underscore the importance of assessing repetitive head impacts (RHI).
The study was published online June 26 in Neurology.
Largest study to date
It is well known that sustaining a TBI is associated with worse later life cognition or mood problems, said Alosco. However, in the current research the investigators hypothesized that RHI may be a key driver of some of these outcomes, Alosco said.
Previous studies have been small or have only examined male former football players.
“What’s unique about our study is that we focused on a history of RHIs, and it is the largest study of its kind, incorporating over 30,000 males and females with different types of exposure to these RHIs.”
The researchers used data from the Brain Health Registry, an internet-based registry that longitudinally monitors cognition and functioning of participants (age 40 years and older).
Participants completed the Ohio State University TBI Identification Method (OSU TBI-ID) and answered a yes/no question: “Have you ever had a period of time in which you experienced multiple, repeated impacts to your head (eg, history of abuse, contact sports, military duty)?”
Participants also completed the Geriatric Depression Scale (GDS-15), the CogState Battery (CBB), and the Lumos Labs NeuroCognitive Performance Tests (NCPT). Demographic information included age, sex, race/ethnicity, and level of education.
Negative synergistic effect
Of the total sample (N = 13,323, mean age 62 years, 72.5% female, 88.6% White) 725 participants (5%) reported exposure to RHI, with contact sports as the most common cause, followed by physical abuse and then military duty; about 55% (7277 participants) reported TBI.
The researchers noted that 44.4% of those exposed to RHI and 70.3% of those who reported TBI were female. However, those with a history of contact sports were predominantly male and those reporting a history of abuse were predominantly women.
Among study participants who completed the GDS-15, 16.4% reported symptoms of depression, similar to rates reported among community-dwelling older adults.
Compared to the unexposed group, participants who reported TBI with loss of consciousness (LOC) and participants who reported TBI without LOC both had higher scores on the GDS-15 (beta = 0.75 [95% CI, 0.59-0.91] and beta = 0.43 [95% CI, 0.31-0.54], respectively).
A history of RHI was associated with an even higher depression score (beta = 1.24 [95% CI, 0.36-2.12).
Depression increased in tandem with increased exposure, with the lowest GDS-15 scores found in the unexposed group and subsequent increases in scores as exposure to RHI was introduced and TBI severity increased. The GDS scores were highest in those who had RHI plus TBI with LOC.
Participants with a history of RHI and/or TBI also had worse scores on tests of memory, learning, processing speed, and reaction time, compared with unexposed participants.
In particular, TBI with LOC had the most neuropsychological associations.
TBI without LOC had a negative effect on CogState tests measuring Identification and processing speed (beta = 0.004 [95% CI, 0-0.01] and beta = 0.004 [95% CI, 0.0002-0.01], respectively), whereas RHI predicted a worse processing speed score (beta = .02 [95% CI, 0.01-0.05]).
The presence of both RHI and TBI (with or without LOC) had a “synergistic negative effect” on neuropsychological performance, with a “consistent statistically significant finding” for worse neuropsychological test performance for those who had RHI and TBI with LOC, compared with those who had not sustained RHI.
Alosco said the findings highlight the need for clinicians to educate and inform parents/guardians of kids playing (or considering playing) contact sports about the research and potential risks associated with these activities.
If we want to prevent long-term problems, one way is not to expose [people] to these hits. Everyone takes risks in life with everything, but the more we can understand and mitigate the risks, the better,” Alosco said.
“A significant contribution”
Commenting on the findings for Medscape Medical News, Temitayo Oyegbile-Chidi, MD, PhD, a pediatric neurologist with Health Peak Inc, McLean, Virginia, and a member of the American Academy of Neurology, said the study “makes a significant contribution to the literature, as neurologists who specialized in TBI have long yearned to understand the long-term effects of repeated head impact on the brain and cognition.”
Clinicians should “inquire about a history of prior head impacts on all our patients, regardless of age, especially if they are experiencing or showing signs of unexpected cognitive dysfunction or mental health concerns,” said Oyegbile-Chidi, who was not involved with the study.
For those who have sustained single or repeated head impacts with or without associated LOC in the past, “it is important … to keep in mind that depression and cognitive dysfunction may persist or present even many years after the impact was sustained,” she added.
The study was supported by a grant from the National Institutes of Health. Alosco has disclosed no relevant financial relationships. The other authors’ disclosures are listed on the original paper. Oyegbile-Chidi has disclosed no relevant financial relationships.
Post-PCI mortality higher in Blacks vs. Whites, regardless of comorbidities
A combined analysis of 10 prospective trials, intended to shed light on racial disparities in percutaneous coronary intervention (PCI) outcomes, saw sharply higher risks of death and myocardial infarction (MI) for Blacks compared with Whites.
The burden of comorbidities, including diabetes, was greater for Hispanics and Blacks, compared with Whites, but only in Blacks were PCI outcomes significantly worse even after controlling for such conditions and other baseline risk factors.
The analysis based on more than 22,000 patients was published July 6 in JACC: Cardiovascular Interventions,with lead author Mordechai Golomb, MD, Cardiovascular Research Foundation, New York.
In the study based on patient-level data from the different trials, the adjusted risk of MI after PCI was increased 45% at 1 year and 55% after 5 years for Blacks, compared with Whites. Their risk of death at 1 year was doubled, and their risk of major adverse cardiac events (MACE) was up by 28% at 5 years.
“Improving health care and outcomes for minorities is essential, and we are hopeful that our work may help direct these efforts, senior author Gregg W. Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said in an interview.
“But this won’t happen without active, concerted efforts to promote change and opportunity, a task for government, regulators, payers, hospital administrators, physicians, and all health care providers,” he said. “Understanding patient outcomes according to race and ethnicity is essential to optimize health for all patients,” but “most prior studies in this regard have looked at population-based data.”
In contrast, the current study used hospital source records – which are considered more accurate than administrative databases – and event coding reports, Dr. Stone said, plus angiographic core laboratory analyses for all patients, which allows “an independent assessment of the extent and type of coronary artery disease and procedural outcomes.”
The analysis “demonstrated that even when upfront treatments are presumably similar [across racial groups] in a clinical trial setting, longitudinal outcomes still differ by race,” Michael Nanna, MD, said in an interview.
The “troubling” results “highlight the persistence of racial disparities in health care and the need to renew our focus on closing these gaps [and] is yet another call to action for clinicians, researchers, and the health care system at large,” said Dr. Nanna, of Duke University Medical Center, Durham, N.C., and lead author on an editorial accompanying the published analysis.
Of the 10 randomized controlled trials included in the study, which encompassed 22,638 patients, 9 were stent comparisons and 1 compared antithrombotic regimens in patients with acute coronary syndromes (ACS), the authors noted. The median follow-up was about 1,100 days.
White patients made up 90.9% of the combined cohort, Black patients comprised 4.1%, Hispanics 2.1%, and Asians 1.8% – figures that “confirm the well-known fact that minority groups are underrepresented in clinical trials,” Dr. Stone said.
There were notable demographic and clinical differences at baseline between the four groups.
For example, Black patients tended to be younger than White, Hispanic, and Asian patients. Black and Hispanic patients were also less likely to be male, compared with White patients.
Both Black and Hispanic patients had more comorbidities than Whites did at baseline, the authors observe. For example, Black and Hispanic patients had a greater body mass index, compared with Whites, whereas it was lower for Asians; and they had more diabetes and more hypertension than Whites (P < .0001 for all differences). Hispanics were more likely to have ACS at baseline, compared with Whites, and less likely to have stable coronary artery disease (CAD) (P < .0001 for all differences). Similar proportions of Blacks and of Whites had stable CAD (about 32% of each) and ACS (about 68% in both cases). Rates of hyperlipidemia and stable CAD were greater and rates of ACS was lower in Asians than the other three race groups (P < .0001 for each difference). In adjusted analysis, the risk of MACE at 5 years was significantly increased for Blacks, compared with Whites (hazard ratio, 1.28; 95% CI, 1.05-1.57; P = .01). The same applied to MI (HR, 1.55; 95% CI, 1.15-2.09; P = .004). At 1 year, Blacks showed higher risks for death (HR, 2.06; 95% CI, 1.26-3.36; P = .004) and for MI (HR, 1.45; 95% CI, 1.01-2.10; P = .045), compared with Whites.
No significant increases in risk for outcomes at 1 and 5 years were seen for Hispanics or Asians, compared with Whites.
Covariates in the analyses included age, sex, body mass index, diabetes, current smoking, hypertension, hyperlipidemia, history of MI or coronary revascularization, clinical CAD presentation, category of stent, and race stratified by study.
Even with underlying genotypic differences between Blacks and Whites, much of the difference in risk for outcomes “should have been accounted for when the researchers adjusted for these clinical phenotypes,” the editorial notes.
Some of the difference in risk must have derived from uncontrolled-for variables, and “[b]eyond genetics, it is clear that race is also a surrogate for other socioeconomic factors that influence both medical care and patient outcomes,” the editorialists wrote.
The adjusted analysis, noted Golomb et al, suggests “that for Hispanic patients, the excess risk for adverse clinical outcomes may have been attributable to a higher prevalence of risk factors. In contrast, the excess risk for adverse clinical outcomes for Black patients persisted even after adjustment for baseline risk factors.”
As such, they agreed: “The observed increased risk may be explained by differences that are not fully captured in traditional cardiovascular risk factor assessment, including socioeconomic differences and education, treatment compliance rates, and yet-to-be-elucidated genetic differences and/or other factors.”
Dr. Stone said that such socioeconomic considerations may include reduced access to care and insurance coverage; lack of preventive care, disease awareness, and education; delayed presentation; and varying levels of provided care.
“Possible genetic or environmental-related differences in the development and progression of atherosclerosis and other disease processes” may also be involved.
“Achieving representative proportions of minorities in clinical trials is essential but has proved challenging,” Dr. Stone said. “We must ensure that adequate numbers of hospitals and providers that are serving these patients participate in multicenter trials, and trust has to be developed so that minority populations have confidence to enroll in studies.”
Dr. Stone reported holding equity options in Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestro Biomed, Aria, Cardiac Success, the MedFocus family of funds, and Valfix and receiving consulting fees from Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore Ablative Solutions, Miracor, Neovasc, W-Wave, Abiomed, and others. Disclosures for the other authors are in the report. Nanna reports no relevant financial relationships; other coauthor disclosures are provided with the editorial.
A version of this article originally appeared on Medscape.com.
A combined analysis of 10 prospective trials, intended to shed light on racial disparities in percutaneous coronary intervention (PCI) outcomes, saw sharply higher risks of death and myocardial infarction (MI) for Blacks compared with Whites.
The burden of comorbidities, including diabetes, was greater for Hispanics and Blacks, compared with Whites, but only in Blacks were PCI outcomes significantly worse even after controlling for such conditions and other baseline risk factors.
The analysis based on more than 22,000 patients was published July 6 in JACC: Cardiovascular Interventions,with lead author Mordechai Golomb, MD, Cardiovascular Research Foundation, New York.
In the study based on patient-level data from the different trials, the adjusted risk of MI after PCI was increased 45% at 1 year and 55% after 5 years for Blacks, compared with Whites. Their risk of death at 1 year was doubled, and their risk of major adverse cardiac events (MACE) was up by 28% at 5 years.
“Improving health care and outcomes for minorities is essential, and we are hopeful that our work may help direct these efforts, senior author Gregg W. Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said in an interview.
“But this won’t happen without active, concerted efforts to promote change and opportunity, a task for government, regulators, payers, hospital administrators, physicians, and all health care providers,” he said. “Understanding patient outcomes according to race and ethnicity is essential to optimize health for all patients,” but “most prior studies in this regard have looked at population-based data.”
In contrast, the current study used hospital source records – which are considered more accurate than administrative databases – and event coding reports, Dr. Stone said, plus angiographic core laboratory analyses for all patients, which allows “an independent assessment of the extent and type of coronary artery disease and procedural outcomes.”
The analysis “demonstrated that even when upfront treatments are presumably similar [across racial groups] in a clinical trial setting, longitudinal outcomes still differ by race,” Michael Nanna, MD, said in an interview.
The “troubling” results “highlight the persistence of racial disparities in health care and the need to renew our focus on closing these gaps [and] is yet another call to action for clinicians, researchers, and the health care system at large,” said Dr. Nanna, of Duke University Medical Center, Durham, N.C., and lead author on an editorial accompanying the published analysis.
Of the 10 randomized controlled trials included in the study, which encompassed 22,638 patients, 9 were stent comparisons and 1 compared antithrombotic regimens in patients with acute coronary syndromes (ACS), the authors noted. The median follow-up was about 1,100 days.
White patients made up 90.9% of the combined cohort, Black patients comprised 4.1%, Hispanics 2.1%, and Asians 1.8% – figures that “confirm the well-known fact that minority groups are underrepresented in clinical trials,” Dr. Stone said.
There were notable demographic and clinical differences at baseline between the four groups.
For example, Black patients tended to be younger than White, Hispanic, and Asian patients. Black and Hispanic patients were also less likely to be male, compared with White patients.
Both Black and Hispanic patients had more comorbidities than Whites did at baseline, the authors observe. For example, Black and Hispanic patients had a greater body mass index, compared with Whites, whereas it was lower for Asians; and they had more diabetes and more hypertension than Whites (P < .0001 for all differences). Hispanics were more likely to have ACS at baseline, compared with Whites, and less likely to have stable coronary artery disease (CAD) (P < .0001 for all differences). Similar proportions of Blacks and of Whites had stable CAD (about 32% of each) and ACS (about 68% in both cases). Rates of hyperlipidemia and stable CAD were greater and rates of ACS was lower in Asians than the other three race groups (P < .0001 for each difference). In adjusted analysis, the risk of MACE at 5 years was significantly increased for Blacks, compared with Whites (hazard ratio, 1.28; 95% CI, 1.05-1.57; P = .01). The same applied to MI (HR, 1.55; 95% CI, 1.15-2.09; P = .004). At 1 year, Blacks showed higher risks for death (HR, 2.06; 95% CI, 1.26-3.36; P = .004) and for MI (HR, 1.45; 95% CI, 1.01-2.10; P = .045), compared with Whites.
No significant increases in risk for outcomes at 1 and 5 years were seen for Hispanics or Asians, compared with Whites.
Covariates in the analyses included age, sex, body mass index, diabetes, current smoking, hypertension, hyperlipidemia, history of MI or coronary revascularization, clinical CAD presentation, category of stent, and race stratified by study.
Even with underlying genotypic differences between Blacks and Whites, much of the difference in risk for outcomes “should have been accounted for when the researchers adjusted for these clinical phenotypes,” the editorial notes.
Some of the difference in risk must have derived from uncontrolled-for variables, and “[b]eyond genetics, it is clear that race is also a surrogate for other socioeconomic factors that influence both medical care and patient outcomes,” the editorialists wrote.
The adjusted analysis, noted Golomb et al, suggests “that for Hispanic patients, the excess risk for adverse clinical outcomes may have been attributable to a higher prevalence of risk factors. In contrast, the excess risk for adverse clinical outcomes for Black patients persisted even after adjustment for baseline risk factors.”
As such, they agreed: “The observed increased risk may be explained by differences that are not fully captured in traditional cardiovascular risk factor assessment, including socioeconomic differences and education, treatment compliance rates, and yet-to-be-elucidated genetic differences and/or other factors.”
Dr. Stone said that such socioeconomic considerations may include reduced access to care and insurance coverage; lack of preventive care, disease awareness, and education; delayed presentation; and varying levels of provided care.
“Possible genetic or environmental-related differences in the development and progression of atherosclerosis and other disease processes” may also be involved.
“Achieving representative proportions of minorities in clinical trials is essential but has proved challenging,” Dr. Stone said. “We must ensure that adequate numbers of hospitals and providers that are serving these patients participate in multicenter trials, and trust has to be developed so that minority populations have confidence to enroll in studies.”
Dr. Stone reported holding equity options in Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestro Biomed, Aria, Cardiac Success, the MedFocus family of funds, and Valfix and receiving consulting fees from Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore Ablative Solutions, Miracor, Neovasc, W-Wave, Abiomed, and others. Disclosures for the other authors are in the report. Nanna reports no relevant financial relationships; other coauthor disclosures are provided with the editorial.
A version of this article originally appeared on Medscape.com.
A combined analysis of 10 prospective trials, intended to shed light on racial disparities in percutaneous coronary intervention (PCI) outcomes, saw sharply higher risks of death and myocardial infarction (MI) for Blacks compared with Whites.
The burden of comorbidities, including diabetes, was greater for Hispanics and Blacks, compared with Whites, but only in Blacks were PCI outcomes significantly worse even after controlling for such conditions and other baseline risk factors.
The analysis based on more than 22,000 patients was published July 6 in JACC: Cardiovascular Interventions,with lead author Mordechai Golomb, MD, Cardiovascular Research Foundation, New York.
In the study based on patient-level data from the different trials, the adjusted risk of MI after PCI was increased 45% at 1 year and 55% after 5 years for Blacks, compared with Whites. Their risk of death at 1 year was doubled, and their risk of major adverse cardiac events (MACE) was up by 28% at 5 years.
“Improving health care and outcomes for minorities is essential, and we are hopeful that our work may help direct these efforts, senior author Gregg W. Stone, MD, Icahn School of Medicine at Mount Sinai, New York, said in an interview.
“But this won’t happen without active, concerted efforts to promote change and opportunity, a task for government, regulators, payers, hospital administrators, physicians, and all health care providers,” he said. “Understanding patient outcomes according to race and ethnicity is essential to optimize health for all patients,” but “most prior studies in this regard have looked at population-based data.”
In contrast, the current study used hospital source records – which are considered more accurate than administrative databases – and event coding reports, Dr. Stone said, plus angiographic core laboratory analyses for all patients, which allows “an independent assessment of the extent and type of coronary artery disease and procedural outcomes.”
The analysis “demonstrated that even when upfront treatments are presumably similar [across racial groups] in a clinical trial setting, longitudinal outcomes still differ by race,” Michael Nanna, MD, said in an interview.
The “troubling” results “highlight the persistence of racial disparities in health care and the need to renew our focus on closing these gaps [and] is yet another call to action for clinicians, researchers, and the health care system at large,” said Dr. Nanna, of Duke University Medical Center, Durham, N.C., and lead author on an editorial accompanying the published analysis.
Of the 10 randomized controlled trials included in the study, which encompassed 22,638 patients, 9 were stent comparisons and 1 compared antithrombotic regimens in patients with acute coronary syndromes (ACS), the authors noted. The median follow-up was about 1,100 days.
White patients made up 90.9% of the combined cohort, Black patients comprised 4.1%, Hispanics 2.1%, and Asians 1.8% – figures that “confirm the well-known fact that minority groups are underrepresented in clinical trials,” Dr. Stone said.
There were notable demographic and clinical differences at baseline between the four groups.
For example, Black patients tended to be younger than White, Hispanic, and Asian patients. Black and Hispanic patients were also less likely to be male, compared with White patients.
Both Black and Hispanic patients had more comorbidities than Whites did at baseline, the authors observe. For example, Black and Hispanic patients had a greater body mass index, compared with Whites, whereas it was lower for Asians; and they had more diabetes and more hypertension than Whites (P < .0001 for all differences). Hispanics were more likely to have ACS at baseline, compared with Whites, and less likely to have stable coronary artery disease (CAD) (P < .0001 for all differences). Similar proportions of Blacks and of Whites had stable CAD (about 32% of each) and ACS (about 68% in both cases). Rates of hyperlipidemia and stable CAD were greater and rates of ACS was lower in Asians than the other three race groups (P < .0001 for each difference). In adjusted analysis, the risk of MACE at 5 years was significantly increased for Blacks, compared with Whites (hazard ratio, 1.28; 95% CI, 1.05-1.57; P = .01). The same applied to MI (HR, 1.55; 95% CI, 1.15-2.09; P = .004). At 1 year, Blacks showed higher risks for death (HR, 2.06; 95% CI, 1.26-3.36; P = .004) and for MI (HR, 1.45; 95% CI, 1.01-2.10; P = .045), compared with Whites.
No significant increases in risk for outcomes at 1 and 5 years were seen for Hispanics or Asians, compared with Whites.
Covariates in the analyses included age, sex, body mass index, diabetes, current smoking, hypertension, hyperlipidemia, history of MI or coronary revascularization, clinical CAD presentation, category of stent, and race stratified by study.
Even with underlying genotypic differences between Blacks and Whites, much of the difference in risk for outcomes “should have been accounted for when the researchers adjusted for these clinical phenotypes,” the editorial notes.
Some of the difference in risk must have derived from uncontrolled-for variables, and “[b]eyond genetics, it is clear that race is also a surrogate for other socioeconomic factors that influence both medical care and patient outcomes,” the editorialists wrote.
The adjusted analysis, noted Golomb et al, suggests “that for Hispanic patients, the excess risk for adverse clinical outcomes may have been attributable to a higher prevalence of risk factors. In contrast, the excess risk for adverse clinical outcomes for Black patients persisted even after adjustment for baseline risk factors.”
As such, they agreed: “The observed increased risk may be explained by differences that are not fully captured in traditional cardiovascular risk factor assessment, including socioeconomic differences and education, treatment compliance rates, and yet-to-be-elucidated genetic differences and/or other factors.”
Dr. Stone said that such socioeconomic considerations may include reduced access to care and insurance coverage; lack of preventive care, disease awareness, and education; delayed presentation; and varying levels of provided care.
“Possible genetic or environmental-related differences in the development and progression of atherosclerosis and other disease processes” may also be involved.
“Achieving representative proportions of minorities in clinical trials is essential but has proved challenging,” Dr. Stone said. “We must ensure that adequate numbers of hospitals and providers that are serving these patients participate in multicenter trials, and trust has to be developed so that minority populations have confidence to enroll in studies.”
Dr. Stone reported holding equity options in Ancora, Qool Therapeutics, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestro Biomed, Aria, Cardiac Success, the MedFocus family of funds, and Valfix and receiving consulting fees from Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore Ablative Solutions, Miracor, Neovasc, W-Wave, Abiomed, and others. Disclosures for the other authors are in the report. Nanna reports no relevant financial relationships; other coauthor disclosures are provided with the editorial.
A version of this article originally appeared on Medscape.com.
Three stages to COVID-19 brain damage, new review suggests
In stage 1, viral damage is limited to epithelial cells of the nose and mouth, and in stage 2 blood clots that form in the lungs may travel to the brain, leading to stroke. In stage 3, the virus crosses the blood-brain barrier and invades the brain.
“Our major take-home points are that patients with COVID-19 symptoms, such as shortness of breath, headache, or dizziness, may have neurological symptoms that, at the time of hospitalization, might not be noticed or prioritized, or whose neurological symptoms may become apparent only after they leave the hospital,” lead author Majid Fotuhi, MD, PhD, medical director of NeuroGrow Brain Fitness Center in McLean, Va., said.
“Hospitalized patients with COVID-19 should have a neurological evaluation and ideally a brain MRI before leaving the hospital; and, if there are abnormalities, they should follow up with a neurologist in 3-4 months,” said Dr. Fotuhi, who is also affiliate staff at Johns Hopkins Medicine, Baltimore.
The review was published online June 8 in the Journal of Alzheimer’s Disease.
Wreaks CNS havoc
It has become “increasingly evident” that SARS-CoV-2 can cause neurologic manifestations, including anosmia, seizures, stroke, confusion, encephalopathy, and total paralysis, the authors wrote.
They noted that SARS-CoV-2 binds to ACE2, which facilitates the conversion of angiotensin II to angiotensin. After ACE2 has bound to respiratory epithelial cells and then to epithelial cells in blood vessels, SARS-CoV-2 triggers the formation of a “cytokine storm.”
These cytokines, in turn, increase vascular permeability, edema, and widespread inflammation, as well as triggering “hypercoagulation cascades,” which cause small and large blood clots that affect multiple organs.
If SARS-CoV-2 crosses the blood-brain barrier, directly entering the brain, it can contribute to demyelination or neurodegeneration.
“We very thoroughly reviewed the literature published between Jan. 1 and May 1, 2020, about neurological issues [in COVID-19] and what I found interesting is that so many neurological things can happen due to a virus which is so small,” said Dr. Fotuhi.
“This virus’ DNA has such limited information, and yet it can wreak havoc on our nervous system because it kicks off such a potent defense system in our body that damages our nervous system,” he said.
Three-stage classification
- Stage 1: The extent of SARS-CoV-2 binding to the ACE2 receptors is limited to the nasal and gustatory epithelial cells, with the cytokine storm remaining “low and controlled.” During this stage, patients may experience smell or taste impairments, but often recover without any interventions.
- Stage 2: A “robust immune response” is activated by the virus, leading to inflammation in the blood vessels, increased hypercoagulability factors, and the formation of blood clots in cerebral arteries and veins. The patient may therefore experience either large or small strokes. Additional stage 2 symptoms include fatigue, hemiplegia, sensory loss, , tetraplegia, , or ataxia.
- Stage 3: The cytokine storm in the blood vessels is so severe that it causes an “explosive inflammatory response” and penetrates the blood-brain barrier, leading to the entry of cytokines, blood components, and viral particles into the brain parenchyma and causing neuronal cell death and encephalitis. This stage can be characterized by seizures, confusion, , coma, loss of consciousness, or death.
“Patients in stage 3 are more likely to have long-term consequences, because there is evidence that the virus particles have actually penetrated the brain, and we know that SARS-CoV-2 can remain dormant in neurons for many years,” said Dr. Fotuhi.
“Studies of coronaviruses have shown a link between the viruses and the risk of multiple sclerosis or Parkinson’s disease even decades later,” he added.
“Based on several reports in recent months, between 36% to 55% of patients with COVID-19 that are hospitalized have some neurological symptoms, but if you don’t look for them, you won’t see them,” Dr. Fotuhi noted.
As a result, patients should be monitored over time after discharge, as they may develop cognitive dysfunction down the road.
Additionally, “it is imperative for patients [hospitalized with COVID-19] to get a baseline MRI before leaving the hospital so that we have a starting point for future evaluation and treatment,” said Dr. Fotuhi.
“The good news is that neurological manifestations of COVID-19 are treatable,” and “can improve with intensive training,” including lifestyle changes – such as a heart-healthy diet, regular physical activity, stress reduction, improved sleep, biofeedback, and brain rehabilitation, Dr. Fotuhi added.
Routine MRI not necessary
Kenneth Tyler, MD, chair of the department of neurology at the University of Colorado at Denver, Aurora, disagreed that all hospitalized patients with COVID-19 should routinely receive an MRI.
“Whenever you are using a piece of equipment on patients who are COVID-19 infected, you risk introducing the infection to uninfected patients,” he said. Instead, “the indication is in patients who develop unexplained neurological manifestations – altered mental status or focal seizures, for example – because in those cases, you do need to understand whether there are underlying structural abnormalities,” said Dr. Tyler, who was not involved in the review.
Also commenting on the review, Vanja Douglas, MD, associate professor of clinical neurology, University of California, San Francisco, described the review as “thorough” and suggested it may “help us understand how to design observational studies to test whether the associations are due to severe respiratory illness or are specific to SARS-CoV-2 infection.”
Dr. Douglas, who was not involved in the review, added that it is “helpful in giving us a sense of which neurologic syndromes have been observed in COVID-19 patients, and therefore which patients neurologists may want to screen more carefully during the pandemic.”
The study had no specific funding. Dr. Fotuhi disclosed no relevant financial relationships. One coauthor reported receiving consulting fees as a member of the scientific advisory board for Brainreader and reports royalties for expert witness consultation in conjunction with Neurevolution. Dr. Tyler and Dr. Douglas disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In stage 1, viral damage is limited to epithelial cells of the nose and mouth, and in stage 2 blood clots that form in the lungs may travel to the brain, leading to stroke. In stage 3, the virus crosses the blood-brain barrier and invades the brain.
“Our major take-home points are that patients with COVID-19 symptoms, such as shortness of breath, headache, or dizziness, may have neurological symptoms that, at the time of hospitalization, might not be noticed or prioritized, or whose neurological symptoms may become apparent only after they leave the hospital,” lead author Majid Fotuhi, MD, PhD, medical director of NeuroGrow Brain Fitness Center in McLean, Va., said.
“Hospitalized patients with COVID-19 should have a neurological evaluation and ideally a brain MRI before leaving the hospital; and, if there are abnormalities, they should follow up with a neurologist in 3-4 months,” said Dr. Fotuhi, who is also affiliate staff at Johns Hopkins Medicine, Baltimore.
The review was published online June 8 in the Journal of Alzheimer’s Disease.
Wreaks CNS havoc
It has become “increasingly evident” that SARS-CoV-2 can cause neurologic manifestations, including anosmia, seizures, stroke, confusion, encephalopathy, and total paralysis, the authors wrote.
They noted that SARS-CoV-2 binds to ACE2, which facilitates the conversion of angiotensin II to angiotensin. After ACE2 has bound to respiratory epithelial cells and then to epithelial cells in blood vessels, SARS-CoV-2 triggers the formation of a “cytokine storm.”
These cytokines, in turn, increase vascular permeability, edema, and widespread inflammation, as well as triggering “hypercoagulation cascades,” which cause small and large blood clots that affect multiple organs.
If SARS-CoV-2 crosses the blood-brain barrier, directly entering the brain, it can contribute to demyelination or neurodegeneration.
“We very thoroughly reviewed the literature published between Jan. 1 and May 1, 2020, about neurological issues [in COVID-19] and what I found interesting is that so many neurological things can happen due to a virus which is so small,” said Dr. Fotuhi.
“This virus’ DNA has such limited information, and yet it can wreak havoc on our nervous system because it kicks off such a potent defense system in our body that damages our nervous system,” he said.
Three-stage classification
- Stage 1: The extent of SARS-CoV-2 binding to the ACE2 receptors is limited to the nasal and gustatory epithelial cells, with the cytokine storm remaining “low and controlled.” During this stage, patients may experience smell or taste impairments, but often recover without any interventions.
- Stage 2: A “robust immune response” is activated by the virus, leading to inflammation in the blood vessels, increased hypercoagulability factors, and the formation of blood clots in cerebral arteries and veins. The patient may therefore experience either large or small strokes. Additional stage 2 symptoms include fatigue, hemiplegia, sensory loss, , tetraplegia, , or ataxia.
- Stage 3: The cytokine storm in the blood vessels is so severe that it causes an “explosive inflammatory response” and penetrates the blood-brain barrier, leading to the entry of cytokines, blood components, and viral particles into the brain parenchyma and causing neuronal cell death and encephalitis. This stage can be characterized by seizures, confusion, , coma, loss of consciousness, or death.
“Patients in stage 3 are more likely to have long-term consequences, because there is evidence that the virus particles have actually penetrated the brain, and we know that SARS-CoV-2 can remain dormant in neurons for many years,” said Dr. Fotuhi.
“Studies of coronaviruses have shown a link between the viruses and the risk of multiple sclerosis or Parkinson’s disease even decades later,” he added.
“Based on several reports in recent months, between 36% to 55% of patients with COVID-19 that are hospitalized have some neurological symptoms, but if you don’t look for them, you won’t see them,” Dr. Fotuhi noted.
As a result, patients should be monitored over time after discharge, as they may develop cognitive dysfunction down the road.
Additionally, “it is imperative for patients [hospitalized with COVID-19] to get a baseline MRI before leaving the hospital so that we have a starting point for future evaluation and treatment,” said Dr. Fotuhi.
“The good news is that neurological manifestations of COVID-19 are treatable,” and “can improve with intensive training,” including lifestyle changes – such as a heart-healthy diet, regular physical activity, stress reduction, improved sleep, biofeedback, and brain rehabilitation, Dr. Fotuhi added.
Routine MRI not necessary
Kenneth Tyler, MD, chair of the department of neurology at the University of Colorado at Denver, Aurora, disagreed that all hospitalized patients with COVID-19 should routinely receive an MRI.
“Whenever you are using a piece of equipment on patients who are COVID-19 infected, you risk introducing the infection to uninfected patients,” he said. Instead, “the indication is in patients who develop unexplained neurological manifestations – altered mental status or focal seizures, for example – because in those cases, you do need to understand whether there are underlying structural abnormalities,” said Dr. Tyler, who was not involved in the review.
Also commenting on the review, Vanja Douglas, MD, associate professor of clinical neurology, University of California, San Francisco, described the review as “thorough” and suggested it may “help us understand how to design observational studies to test whether the associations are due to severe respiratory illness or are specific to SARS-CoV-2 infection.”
Dr. Douglas, who was not involved in the review, added that it is “helpful in giving us a sense of which neurologic syndromes have been observed in COVID-19 patients, and therefore which patients neurologists may want to screen more carefully during the pandemic.”
The study had no specific funding. Dr. Fotuhi disclosed no relevant financial relationships. One coauthor reported receiving consulting fees as a member of the scientific advisory board for Brainreader and reports royalties for expert witness consultation in conjunction with Neurevolution. Dr. Tyler and Dr. Douglas disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
In stage 1, viral damage is limited to epithelial cells of the nose and mouth, and in stage 2 blood clots that form in the lungs may travel to the brain, leading to stroke. In stage 3, the virus crosses the blood-brain barrier and invades the brain.
“Our major take-home points are that patients with COVID-19 symptoms, such as shortness of breath, headache, or dizziness, may have neurological symptoms that, at the time of hospitalization, might not be noticed or prioritized, or whose neurological symptoms may become apparent only after they leave the hospital,” lead author Majid Fotuhi, MD, PhD, medical director of NeuroGrow Brain Fitness Center in McLean, Va., said.
“Hospitalized patients with COVID-19 should have a neurological evaluation and ideally a brain MRI before leaving the hospital; and, if there are abnormalities, they should follow up with a neurologist in 3-4 months,” said Dr. Fotuhi, who is also affiliate staff at Johns Hopkins Medicine, Baltimore.
The review was published online June 8 in the Journal of Alzheimer’s Disease.
Wreaks CNS havoc
It has become “increasingly evident” that SARS-CoV-2 can cause neurologic manifestations, including anosmia, seizures, stroke, confusion, encephalopathy, and total paralysis, the authors wrote.
They noted that SARS-CoV-2 binds to ACE2, which facilitates the conversion of angiotensin II to angiotensin. After ACE2 has bound to respiratory epithelial cells and then to epithelial cells in blood vessels, SARS-CoV-2 triggers the formation of a “cytokine storm.”
These cytokines, in turn, increase vascular permeability, edema, and widespread inflammation, as well as triggering “hypercoagulation cascades,” which cause small and large blood clots that affect multiple organs.
If SARS-CoV-2 crosses the blood-brain barrier, directly entering the brain, it can contribute to demyelination or neurodegeneration.
“We very thoroughly reviewed the literature published between Jan. 1 and May 1, 2020, about neurological issues [in COVID-19] and what I found interesting is that so many neurological things can happen due to a virus which is so small,” said Dr. Fotuhi.
“This virus’ DNA has such limited information, and yet it can wreak havoc on our nervous system because it kicks off such a potent defense system in our body that damages our nervous system,” he said.
Three-stage classification
- Stage 1: The extent of SARS-CoV-2 binding to the ACE2 receptors is limited to the nasal and gustatory epithelial cells, with the cytokine storm remaining “low and controlled.” During this stage, patients may experience smell or taste impairments, but often recover without any interventions.
- Stage 2: A “robust immune response” is activated by the virus, leading to inflammation in the blood vessels, increased hypercoagulability factors, and the formation of blood clots in cerebral arteries and veins. The patient may therefore experience either large or small strokes. Additional stage 2 symptoms include fatigue, hemiplegia, sensory loss, , tetraplegia, , or ataxia.
- Stage 3: The cytokine storm in the blood vessels is so severe that it causes an “explosive inflammatory response” and penetrates the blood-brain barrier, leading to the entry of cytokines, blood components, and viral particles into the brain parenchyma and causing neuronal cell death and encephalitis. This stage can be characterized by seizures, confusion, , coma, loss of consciousness, or death.
“Patients in stage 3 are more likely to have long-term consequences, because there is evidence that the virus particles have actually penetrated the brain, and we know that SARS-CoV-2 can remain dormant in neurons for many years,” said Dr. Fotuhi.
“Studies of coronaviruses have shown a link between the viruses and the risk of multiple sclerosis or Parkinson’s disease even decades later,” he added.
“Based on several reports in recent months, between 36% to 55% of patients with COVID-19 that are hospitalized have some neurological symptoms, but if you don’t look for them, you won’t see them,” Dr. Fotuhi noted.
As a result, patients should be monitored over time after discharge, as they may develop cognitive dysfunction down the road.
Additionally, “it is imperative for patients [hospitalized with COVID-19] to get a baseline MRI before leaving the hospital so that we have a starting point for future evaluation and treatment,” said Dr. Fotuhi.
“The good news is that neurological manifestations of COVID-19 are treatable,” and “can improve with intensive training,” including lifestyle changes – such as a heart-healthy diet, regular physical activity, stress reduction, improved sleep, biofeedback, and brain rehabilitation, Dr. Fotuhi added.
Routine MRI not necessary
Kenneth Tyler, MD, chair of the department of neurology at the University of Colorado at Denver, Aurora, disagreed that all hospitalized patients with COVID-19 should routinely receive an MRI.
“Whenever you are using a piece of equipment on patients who are COVID-19 infected, you risk introducing the infection to uninfected patients,” he said. Instead, “the indication is in patients who develop unexplained neurological manifestations – altered mental status or focal seizures, for example – because in those cases, you do need to understand whether there are underlying structural abnormalities,” said Dr. Tyler, who was not involved in the review.
Also commenting on the review, Vanja Douglas, MD, associate professor of clinical neurology, University of California, San Francisco, described the review as “thorough” and suggested it may “help us understand how to design observational studies to test whether the associations are due to severe respiratory illness or are specific to SARS-CoV-2 infection.”
Dr. Douglas, who was not involved in the review, added that it is “helpful in giving us a sense of which neurologic syndromes have been observed in COVID-19 patients, and therefore which patients neurologists may want to screen more carefully during the pandemic.”
The study had no specific funding. Dr. Fotuhi disclosed no relevant financial relationships. One coauthor reported receiving consulting fees as a member of the scientific advisory board for Brainreader and reports royalties for expert witness consultation in conjunction with Neurevolution. Dr. Tyler and Dr. Douglas disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Do SSRIs raise the risk of violent crime?
Selective serotonin reuptake inhibitors (SSRIs) are associated with an increased risk of committing a violent crime, an effect that may linger up to 12 weeks after treatment discontinuation, new research suggests. However,
A large population-based study of more than 800,000 individuals showed those taking these antidepressants had an overall 2.7% increased risk of committing a violent crime while on the medications compared with when they were not taking them.
The increased risk persisted up to 12 weeks after discontinuing SSRIs and then returned to pretreatment levels. The risk was highest in younger individuals and those with a history of a prior violent crime.
“Our findings should be interpreted with caution [because] we do not know how far the association between SSRI medication and violent crime reflect causation,” lead author Tyra Lagerberg, MSc, a PhD candidate at Karolinska Institute, Sweden, said in an interview.
“Our findings should not be used as grounds for individuals to go off their [SSRI] medication or for clinicians to withhold medication from those who might benefit from it,” Ms. Lagerberg said.
The study was published online May 29 in European Neuropsychopharmacology.
Previous concerns
There has been “apprehension” about a possible association between SSRIs and elevated risk of aggression and violence, especially in young people, but it “remains unclear” if there is a similar risk in middle-aged and older adults, the authors noted. Moreover, it is unclear whether the risk of violence varies with time after initiating and discontinuing SSRI treatment.
To assess how the risk of violent crime might vary by age and time after SSRI treatment initiation and discontinuation, the researchers calculated absolute rates of violent crime per 1000 person-years during on- and off-treatment periods and also conducted within-group analyses.
The cohort, which was derived from several Swedish national registers, included all individuals in Sweden prescribed an SSRI between Jan. 1, 2006, and Dec. 31, 2013 (n = 785,337, 64.2% female) over an average follow-up of 7.3 years.
Some of the covariates used in the analyses included age, recent or previous violent crime, use of non-SSRI medications, sex, family income, education, county of residence, birth country, and lifetime diagnoses.
“Rare” effect
Almost the entire study cohort (99%) changed their SSRI treatment over the follow-up period. During this time, of the full study cohort, 2.7% committed violent crimes (21,203 crimes in 5,707,293 person-years).
More men than women were convicted of a violent crime (5.7% vs 1.0%, respectively).
Absolute rates of violent crime were lower in treated versus nontreated periods across all age categories (other than those between 15 and 24 years) when covariates were not taken into account.
However, when hazards during the on- and off-treatment periods were compared and adjusted for covariables, SSRI treatment was associated with a “modest increased” risk of violent crime (HR, 1.10) – particularly in those ages 15-25 years and ages 25–34 years (HR, 1.19 and 1.16, respectively).
Moreover, further analysis stratifying the cohort according to previous violent crime revealed that the elevated risk for violent crime convictions “seemed to be confined to the individuals with previous criminality,” compared to those with no criminal history (HR, 1.13 vs. 1.07).
The within-individual analysis included 2.6% of the overall cohort who experienced SSRI treatment switching as well as ≥1 violent event.
These individuals differed from the overall cohort in that they tended to be younger (close to half were aged 15-24 years compared with one quarter in the overall cohort) and predominantly male (77% vs. 36%, respectively).
When the hazard of violent crime was compared between individuals’ periods on and off medication, there was a significantly increased hazard during treatment in the whole cohort (HR, 1.26), but in particular, in those aged 25-34 years and 35-44 years (HR, 1.35 and 1.15, respectively).
The within-individual HRs remained elevated for up to 12 weeks post discontinuation of the SSRI (HR, 1.37 during the first 28 days; HR, 1.20 during days 29-84). Although women had a significantly elevated on-treatment hazard in the youngest age category, they had a lower incidence of crime across ages.
Treatment with benzodiazepines was associated with a significantly higher hazard of violent crime and treatment with non-SSRI antidepressants was associated with a “modest but nonsignificantly elevated” hazard.
By contrast, treatment with other psychotropic drugs was not associated with elevated risk.
Warn patients
Commenting on the study, Eduard Vieta, MD, PhD, professor of psychiatry, Institute of Neuroscience, University of Barcelona, Spain, and author of an accompanying editorial, said it’s still not known if the mediating factor in the increased risk of violent crime was the SSRI or the underlying mental condition that prompted the prescription.
Dr. Vieta, who was not involved with the study, added that the results “raise a note of caution in terms of making a very accurate diagnosis and treatment in patients with a history of conviction, violence, or criminality, and opting ideally for psychosocial therapies whenever possible in this population.”
Also commenting on the study, Michael Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings are “not easy to brush away or explain away.”
Dr. Thase, who was not involved with the study, continued, “although it is a small finding, it is also a serious problem.”
He suggested the risk should be treated in a similar way to the risk for suicidal thoughts or behaviors.
“Just as you might caution patients [initiating treatment with SSRIs] regarding that risk, you might broaden your counsel to include other types of violent behavior because the same process that provokes the risk of self-harm for a given person may be externalized and provoke harm or violence toward others.”
Ms. Lagerberg added that further research is needed to confirm their findings and “inform whether – and if so, how – clinical practice should change.”
The study was supported by the Swedish Research Council, Horizon 2020 ACTION project, Stockholm County Council, and Thurings Foundation. Ms. Lagerberg has reported no relevant financial relationships. Other author disclosures are listed in the article. Dr. Vieta and coauthors have reported no relevant financial relationships. Dr. Thase has reported consulting with and receiving research funding from many of the companies that manufacture/sell antidepressants.
This article first appeared on Medscape.com.
Selective serotonin reuptake inhibitors (SSRIs) are associated with an increased risk of committing a violent crime, an effect that may linger up to 12 weeks after treatment discontinuation, new research suggests. However,
A large population-based study of more than 800,000 individuals showed those taking these antidepressants had an overall 2.7% increased risk of committing a violent crime while on the medications compared with when they were not taking them.
The increased risk persisted up to 12 weeks after discontinuing SSRIs and then returned to pretreatment levels. The risk was highest in younger individuals and those with a history of a prior violent crime.
“Our findings should be interpreted with caution [because] we do not know how far the association between SSRI medication and violent crime reflect causation,” lead author Tyra Lagerberg, MSc, a PhD candidate at Karolinska Institute, Sweden, said in an interview.
“Our findings should not be used as grounds for individuals to go off their [SSRI] medication or for clinicians to withhold medication from those who might benefit from it,” Ms. Lagerberg said.
The study was published online May 29 in European Neuropsychopharmacology.
Previous concerns
There has been “apprehension” about a possible association between SSRIs and elevated risk of aggression and violence, especially in young people, but it “remains unclear” if there is a similar risk in middle-aged and older adults, the authors noted. Moreover, it is unclear whether the risk of violence varies with time after initiating and discontinuing SSRI treatment.
To assess how the risk of violent crime might vary by age and time after SSRI treatment initiation and discontinuation, the researchers calculated absolute rates of violent crime per 1000 person-years during on- and off-treatment periods and also conducted within-group analyses.
The cohort, which was derived from several Swedish national registers, included all individuals in Sweden prescribed an SSRI between Jan. 1, 2006, and Dec. 31, 2013 (n = 785,337, 64.2% female) over an average follow-up of 7.3 years.
Some of the covariates used in the analyses included age, recent or previous violent crime, use of non-SSRI medications, sex, family income, education, county of residence, birth country, and lifetime diagnoses.
“Rare” effect
Almost the entire study cohort (99%) changed their SSRI treatment over the follow-up period. During this time, of the full study cohort, 2.7% committed violent crimes (21,203 crimes in 5,707,293 person-years).
More men than women were convicted of a violent crime (5.7% vs 1.0%, respectively).
Absolute rates of violent crime were lower in treated versus nontreated periods across all age categories (other than those between 15 and 24 years) when covariates were not taken into account.
However, when hazards during the on- and off-treatment periods were compared and adjusted for covariables, SSRI treatment was associated with a “modest increased” risk of violent crime (HR, 1.10) – particularly in those ages 15-25 years and ages 25–34 years (HR, 1.19 and 1.16, respectively).
Moreover, further analysis stratifying the cohort according to previous violent crime revealed that the elevated risk for violent crime convictions “seemed to be confined to the individuals with previous criminality,” compared to those with no criminal history (HR, 1.13 vs. 1.07).
The within-individual analysis included 2.6% of the overall cohort who experienced SSRI treatment switching as well as ≥1 violent event.
These individuals differed from the overall cohort in that they tended to be younger (close to half were aged 15-24 years compared with one quarter in the overall cohort) and predominantly male (77% vs. 36%, respectively).
When the hazard of violent crime was compared between individuals’ periods on and off medication, there was a significantly increased hazard during treatment in the whole cohort (HR, 1.26), but in particular, in those aged 25-34 years and 35-44 years (HR, 1.35 and 1.15, respectively).
The within-individual HRs remained elevated for up to 12 weeks post discontinuation of the SSRI (HR, 1.37 during the first 28 days; HR, 1.20 during days 29-84). Although women had a significantly elevated on-treatment hazard in the youngest age category, they had a lower incidence of crime across ages.
Treatment with benzodiazepines was associated with a significantly higher hazard of violent crime and treatment with non-SSRI antidepressants was associated with a “modest but nonsignificantly elevated” hazard.
By contrast, treatment with other psychotropic drugs was not associated with elevated risk.
Warn patients
Commenting on the study, Eduard Vieta, MD, PhD, professor of psychiatry, Institute of Neuroscience, University of Barcelona, Spain, and author of an accompanying editorial, said it’s still not known if the mediating factor in the increased risk of violent crime was the SSRI or the underlying mental condition that prompted the prescription.
Dr. Vieta, who was not involved with the study, added that the results “raise a note of caution in terms of making a very accurate diagnosis and treatment in patients with a history of conviction, violence, or criminality, and opting ideally for psychosocial therapies whenever possible in this population.”
Also commenting on the study, Michael Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings are “not easy to brush away or explain away.”
Dr. Thase, who was not involved with the study, continued, “although it is a small finding, it is also a serious problem.”
He suggested the risk should be treated in a similar way to the risk for suicidal thoughts or behaviors.
“Just as you might caution patients [initiating treatment with SSRIs] regarding that risk, you might broaden your counsel to include other types of violent behavior because the same process that provokes the risk of self-harm for a given person may be externalized and provoke harm or violence toward others.”
Ms. Lagerberg added that further research is needed to confirm their findings and “inform whether – and if so, how – clinical practice should change.”
The study was supported by the Swedish Research Council, Horizon 2020 ACTION project, Stockholm County Council, and Thurings Foundation. Ms. Lagerberg has reported no relevant financial relationships. Other author disclosures are listed in the article. Dr. Vieta and coauthors have reported no relevant financial relationships. Dr. Thase has reported consulting with and receiving research funding from many of the companies that manufacture/sell antidepressants.
This article first appeared on Medscape.com.
Selective serotonin reuptake inhibitors (SSRIs) are associated with an increased risk of committing a violent crime, an effect that may linger up to 12 weeks after treatment discontinuation, new research suggests. However,
A large population-based study of more than 800,000 individuals showed those taking these antidepressants had an overall 2.7% increased risk of committing a violent crime while on the medications compared with when they were not taking them.
The increased risk persisted up to 12 weeks after discontinuing SSRIs and then returned to pretreatment levels. The risk was highest in younger individuals and those with a history of a prior violent crime.
“Our findings should be interpreted with caution [because] we do not know how far the association between SSRI medication and violent crime reflect causation,” lead author Tyra Lagerberg, MSc, a PhD candidate at Karolinska Institute, Sweden, said in an interview.
“Our findings should not be used as grounds for individuals to go off their [SSRI] medication or for clinicians to withhold medication from those who might benefit from it,” Ms. Lagerberg said.
The study was published online May 29 in European Neuropsychopharmacology.
Previous concerns
There has been “apprehension” about a possible association between SSRIs and elevated risk of aggression and violence, especially in young people, but it “remains unclear” if there is a similar risk in middle-aged and older adults, the authors noted. Moreover, it is unclear whether the risk of violence varies with time after initiating and discontinuing SSRI treatment.
To assess how the risk of violent crime might vary by age and time after SSRI treatment initiation and discontinuation, the researchers calculated absolute rates of violent crime per 1000 person-years during on- and off-treatment periods and also conducted within-group analyses.
The cohort, which was derived from several Swedish national registers, included all individuals in Sweden prescribed an SSRI between Jan. 1, 2006, and Dec. 31, 2013 (n = 785,337, 64.2% female) over an average follow-up of 7.3 years.
Some of the covariates used in the analyses included age, recent or previous violent crime, use of non-SSRI medications, sex, family income, education, county of residence, birth country, and lifetime diagnoses.
“Rare” effect
Almost the entire study cohort (99%) changed their SSRI treatment over the follow-up period. During this time, of the full study cohort, 2.7% committed violent crimes (21,203 crimes in 5,707,293 person-years).
More men than women were convicted of a violent crime (5.7% vs 1.0%, respectively).
Absolute rates of violent crime were lower in treated versus nontreated periods across all age categories (other than those between 15 and 24 years) when covariates were not taken into account.
However, when hazards during the on- and off-treatment periods were compared and adjusted for covariables, SSRI treatment was associated with a “modest increased” risk of violent crime (HR, 1.10) – particularly in those ages 15-25 years and ages 25–34 years (HR, 1.19 and 1.16, respectively).
Moreover, further analysis stratifying the cohort according to previous violent crime revealed that the elevated risk for violent crime convictions “seemed to be confined to the individuals with previous criminality,” compared to those with no criminal history (HR, 1.13 vs. 1.07).
The within-individual analysis included 2.6% of the overall cohort who experienced SSRI treatment switching as well as ≥1 violent event.
These individuals differed from the overall cohort in that they tended to be younger (close to half were aged 15-24 years compared with one quarter in the overall cohort) and predominantly male (77% vs. 36%, respectively).
When the hazard of violent crime was compared between individuals’ periods on and off medication, there was a significantly increased hazard during treatment in the whole cohort (HR, 1.26), but in particular, in those aged 25-34 years and 35-44 years (HR, 1.35 and 1.15, respectively).
The within-individual HRs remained elevated for up to 12 weeks post discontinuation of the SSRI (HR, 1.37 during the first 28 days; HR, 1.20 during days 29-84). Although women had a significantly elevated on-treatment hazard in the youngest age category, they had a lower incidence of crime across ages.
Treatment with benzodiazepines was associated with a significantly higher hazard of violent crime and treatment with non-SSRI antidepressants was associated with a “modest but nonsignificantly elevated” hazard.
By contrast, treatment with other psychotropic drugs was not associated with elevated risk.
Warn patients
Commenting on the study, Eduard Vieta, MD, PhD, professor of psychiatry, Institute of Neuroscience, University of Barcelona, Spain, and author of an accompanying editorial, said it’s still not known if the mediating factor in the increased risk of violent crime was the SSRI or the underlying mental condition that prompted the prescription.
Dr. Vieta, who was not involved with the study, added that the results “raise a note of caution in terms of making a very accurate diagnosis and treatment in patients with a history of conviction, violence, or criminality, and opting ideally for psychosocial therapies whenever possible in this population.”
Also commenting on the study, Michael Thase, MD, professor of psychiatry, University of Pennsylvania, Philadelphia, said the findings are “not easy to brush away or explain away.”
Dr. Thase, who was not involved with the study, continued, “although it is a small finding, it is also a serious problem.”
He suggested the risk should be treated in a similar way to the risk for suicidal thoughts or behaviors.
“Just as you might caution patients [initiating treatment with SSRIs] regarding that risk, you might broaden your counsel to include other types of violent behavior because the same process that provokes the risk of self-harm for a given person may be externalized and provoke harm or violence toward others.”
Ms. Lagerberg added that further research is needed to confirm their findings and “inform whether – and if so, how – clinical practice should change.”
The study was supported by the Swedish Research Council, Horizon 2020 ACTION project, Stockholm County Council, and Thurings Foundation. Ms. Lagerberg has reported no relevant financial relationships. Other author disclosures are listed in the article. Dr. Vieta and coauthors have reported no relevant financial relationships. Dr. Thase has reported consulting with and receiving research funding from many of the companies that manufacture/sell antidepressants.
This article first appeared on Medscape.com.
New guidance to help manage OCD during COVID-19
Two international specialty societies have jointly released new guidance on management of obsessive-compulsive disorder (OCD) during the COVID-19 pandemic.
“Individuals with OCD, particularly those with contamination concerns or hypochondriacal kinds of worries associated with OCD, people who have perfectionistic type of rituals, or who worry about transmitting COVID-19 [to others] might be particularly vulnerable to this pandemic,” statement coauthor Michael Van Ameringen, MD, professor, of the department of psychiatry and behavioral neurosciences, McMaster University, Hamilton, Ont., said in an interview.
The guidance, issued by the International College of Obsessive Compulsive Spectrum Disorders (ICOCS) and the Obsessive-Compulsive and Related Disorders Research Network (OCRN) of the European College of Neuropsychopharmacology, emphasizes the importance of using pharmacotherapy as a first-line approach, suspending or reducing exposure and response prevention (ERP), and offering psychoeducation.
The statement was published in the July issue of Comprehensive Psychiatry.
Confirm OCD diagnosis
A diagnosis of OCD should be confirmed, and it is important to clarify whether the current symptoms are a “rational or exaggerated response to recent highly stressful events” or a worsening of obsessive-compulsive symptomatology, the statement notes.
Some patients may experience an exacerbation of comorbid conditions such as anxiety disorder, depression, bipolar disorder, or posttraumatic stress disorder (PTSD), which may need to be managed separately.
The authors recommend consulting the World Health Organization (WHO) guidelines regarding mental health and psychosocial considerations during the COVID-19 outbreak.
“Several suicidal patients with OCD have come to the clinic during the pandemic,” reported Dr. Van Ameringen, director of the MacAnxiety Research Centre in Hamilton. “They felt overwhelmed and that they were contaminating themselves with everything they did, including breathing.”
The authors encourage clinicians to assess suicide risk using validated instruments, such as the Columbia Suicide Severity Rating Scale, and hospitalize patients if necessary.
Pharmacotherapy is “the most efficacious first-line treatment modality” for adults and children with OCD and contamination, washing, or cleaning symptoms during the pandemic, the authors note.
They recommend a stepwise pharmacotherapeutic approach:
Type of medication
- Selective serotonin reuptake inhibitor (SSRI) as first choice.
- Another SSRI if no response to first SSRI.
- Clomipramine as third choice.
Dosage
- Gradually increase suboptimal dose, paying attention to contraindications, adverse effects.
SSRI resistance
- Low-dose adjunctive antipsychotic (for example, aripiprazole, risperidone, quetiapine, olanzapine), for incomplete response, especially if tic is present.
Adherence
- Ensure patient can obtain an adequate supply of medication and is taking it regularly.
- Involve family/caregivers if adherence is problematic.
- Pill organizers and reminder apps may be helpful.
A role for CBT?
Under ordinary circumstances, CBT is considered a first-line intervention for OCD. However, there are risks associated specifically with ERP during the pandemic.
“In ERP, people are being exposed to things that trigger their OCD, so those with contamination fears may be asked to touch things in public places, then resist washing their hands, which would counter public health recommendations,” Dr. Van Ameringen said.
In vivo exposure should be paused, but some ERP interventions can be adapted or modified “on a case-by-case basis,” the authors state. For patients whose exposure is unrelated to contamination, other ERP treatment plans can be continued.
The authors recommend using therapy time to “prevent patients from deteriorating” by encouraging them to engage in activity scheduling and structuring the day to include physical activity, enjoyable activities, practices that enhance sleep, and mindfulness.
Limit news exposure
A central component of managing OCD during the pandemic is providing “balanced information” about the known risks and impact of COVID-19, the authors stated.
Dr. Van Ameringen recounted that he has seen patients who have washed their hands for hours and bleached or even boiled their hands.
“Some [patients with OCD] wonder if it’s safe to touch a newspaper or if they can catch the virus if they go outside, even if no one is around,” he reported. “Some wonder if they should ‘quarantine’ a package or wear gloves to bed.”
It has been helpful, for example, to show them the public health guidance of the WHO or CDC advising that 20 seconds of hand washing is adequate, he said.
“We have also seen that some of the sources of information about COVID-19 haven’t been factually correct and that people were watching the news all day and being bombarded with information from every source, which was making their symptoms a thousand times worse,” Dr. Van Ameringen reported.
Therefore, The authors also advise clinicians to “take a compassionate, calming,” and culturally sensitive approach to inform all interventions.
Unique anchor
Commenting on the statement in an interview, Debanjan Banerjee, MD, geriatric psychiatry senior resident, National Institute of Mental Health and Neurosciences, Bangalore, India, said that this “comprehensive guideline, based on expert experience, will serve as a guiding framework for physicians and psychiatrists globally.”
In the “absence of systemic data so far, this guideline can provide a unique anchor of a global consensus on how to take care of those with preexisting OCD or newly emergent cases” said Dr. Banerjee, who was not involved in authoring the statement.
Also commenting on the statement, Jonathan Abramowitz, PhD, professor of psychology and neuroscience, University of North Carolina at Chapel Hill, said that he “generally agrees” with these guidelines but disagrees with the “apparent recommendations to scale back” ERP.
“The fact is that effective and safe ERP is possible, even during this time, even following the scientific guidance,” stated Dr. Abramowitz, editor-in-chief of the Journal of Obsessive-Compulsive and Related Disorders. He was not involved in the statement.
He noted that the International OCD Foundation offers educational programs for clinicians regarding the safe use of ERP during this time.
The authors acknowledge that their guideline is “largely based on empirical evidence” and should be regarded as “preliminary.” The guidance “will be updated as new information arises.”
No specific source of funding for the statement is listed. Dr. Van Ameringen reports being on the advisory boards of Allergan, Almatica, Brainsway, Janssen, Lundbeck, Myriad Neuroscience, Otsuka, and Purdue Pharma (Canada); is on the speakers bureau for Allergan, Lundbeck, Otsuka, Pfizer, Purdue Pharma (Canada) and Takeda; and has received research support from Janssen, Purdue Pharma (Canada), the Canada Foundation for Innovation, and Hamilton Academic Health Sciences Organization. The other authors’ disclosures are listed on the original paper. Dr. Banerjee and Dr. Abramowitz have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Two international specialty societies have jointly released new guidance on management of obsessive-compulsive disorder (OCD) during the COVID-19 pandemic.
“Individuals with OCD, particularly those with contamination concerns or hypochondriacal kinds of worries associated with OCD, people who have perfectionistic type of rituals, or who worry about transmitting COVID-19 [to others] might be particularly vulnerable to this pandemic,” statement coauthor Michael Van Ameringen, MD, professor, of the department of psychiatry and behavioral neurosciences, McMaster University, Hamilton, Ont., said in an interview.
The guidance, issued by the International College of Obsessive Compulsive Spectrum Disorders (ICOCS) and the Obsessive-Compulsive and Related Disorders Research Network (OCRN) of the European College of Neuropsychopharmacology, emphasizes the importance of using pharmacotherapy as a first-line approach, suspending or reducing exposure and response prevention (ERP), and offering psychoeducation.
The statement was published in the July issue of Comprehensive Psychiatry.
Confirm OCD diagnosis
A diagnosis of OCD should be confirmed, and it is important to clarify whether the current symptoms are a “rational or exaggerated response to recent highly stressful events” or a worsening of obsessive-compulsive symptomatology, the statement notes.
Some patients may experience an exacerbation of comorbid conditions such as anxiety disorder, depression, bipolar disorder, or posttraumatic stress disorder (PTSD), which may need to be managed separately.
The authors recommend consulting the World Health Organization (WHO) guidelines regarding mental health and psychosocial considerations during the COVID-19 outbreak.
“Several suicidal patients with OCD have come to the clinic during the pandemic,” reported Dr. Van Ameringen, director of the MacAnxiety Research Centre in Hamilton. “They felt overwhelmed and that they were contaminating themselves with everything they did, including breathing.”
The authors encourage clinicians to assess suicide risk using validated instruments, such as the Columbia Suicide Severity Rating Scale, and hospitalize patients if necessary.
Pharmacotherapy is “the most efficacious first-line treatment modality” for adults and children with OCD and contamination, washing, or cleaning symptoms during the pandemic, the authors note.
They recommend a stepwise pharmacotherapeutic approach:
Type of medication
- Selective serotonin reuptake inhibitor (SSRI) as first choice.
- Another SSRI if no response to first SSRI.
- Clomipramine as third choice.
Dosage
- Gradually increase suboptimal dose, paying attention to contraindications, adverse effects.
SSRI resistance
- Low-dose adjunctive antipsychotic (for example, aripiprazole, risperidone, quetiapine, olanzapine), for incomplete response, especially if tic is present.
Adherence
- Ensure patient can obtain an adequate supply of medication and is taking it regularly.
- Involve family/caregivers if adherence is problematic.
- Pill organizers and reminder apps may be helpful.
A role for CBT?
Under ordinary circumstances, CBT is considered a first-line intervention for OCD. However, there are risks associated specifically with ERP during the pandemic.
“In ERP, people are being exposed to things that trigger their OCD, so those with contamination fears may be asked to touch things in public places, then resist washing their hands, which would counter public health recommendations,” Dr. Van Ameringen said.
In vivo exposure should be paused, but some ERP interventions can be adapted or modified “on a case-by-case basis,” the authors state. For patients whose exposure is unrelated to contamination, other ERP treatment plans can be continued.
The authors recommend using therapy time to “prevent patients from deteriorating” by encouraging them to engage in activity scheduling and structuring the day to include physical activity, enjoyable activities, practices that enhance sleep, and mindfulness.
Limit news exposure
A central component of managing OCD during the pandemic is providing “balanced information” about the known risks and impact of COVID-19, the authors stated.
Dr. Van Ameringen recounted that he has seen patients who have washed their hands for hours and bleached or even boiled their hands.
“Some [patients with OCD] wonder if it’s safe to touch a newspaper or if they can catch the virus if they go outside, even if no one is around,” he reported. “Some wonder if they should ‘quarantine’ a package or wear gloves to bed.”
It has been helpful, for example, to show them the public health guidance of the WHO or CDC advising that 20 seconds of hand washing is adequate, he said.
“We have also seen that some of the sources of information about COVID-19 haven’t been factually correct and that people were watching the news all day and being bombarded with information from every source, which was making their symptoms a thousand times worse,” Dr. Van Ameringen reported.
Therefore, The authors also advise clinicians to “take a compassionate, calming,” and culturally sensitive approach to inform all interventions.
Unique anchor
Commenting on the statement in an interview, Debanjan Banerjee, MD, geriatric psychiatry senior resident, National Institute of Mental Health and Neurosciences, Bangalore, India, said that this “comprehensive guideline, based on expert experience, will serve as a guiding framework for physicians and psychiatrists globally.”
In the “absence of systemic data so far, this guideline can provide a unique anchor of a global consensus on how to take care of those with preexisting OCD or newly emergent cases” said Dr. Banerjee, who was not involved in authoring the statement.
Also commenting on the statement, Jonathan Abramowitz, PhD, professor of psychology and neuroscience, University of North Carolina at Chapel Hill, said that he “generally agrees” with these guidelines but disagrees with the “apparent recommendations to scale back” ERP.
“The fact is that effective and safe ERP is possible, even during this time, even following the scientific guidance,” stated Dr. Abramowitz, editor-in-chief of the Journal of Obsessive-Compulsive and Related Disorders. He was not involved in the statement.
He noted that the International OCD Foundation offers educational programs for clinicians regarding the safe use of ERP during this time.
The authors acknowledge that their guideline is “largely based on empirical evidence” and should be regarded as “preliminary.” The guidance “will be updated as new information arises.”
No specific source of funding for the statement is listed. Dr. Van Ameringen reports being on the advisory boards of Allergan, Almatica, Brainsway, Janssen, Lundbeck, Myriad Neuroscience, Otsuka, and Purdue Pharma (Canada); is on the speakers bureau for Allergan, Lundbeck, Otsuka, Pfizer, Purdue Pharma (Canada) and Takeda; and has received research support from Janssen, Purdue Pharma (Canada), the Canada Foundation for Innovation, and Hamilton Academic Health Sciences Organization. The other authors’ disclosures are listed on the original paper. Dr. Banerjee and Dr. Abramowitz have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Two international specialty societies have jointly released new guidance on management of obsessive-compulsive disorder (OCD) during the COVID-19 pandemic.
“Individuals with OCD, particularly those with contamination concerns or hypochondriacal kinds of worries associated with OCD, people who have perfectionistic type of rituals, or who worry about transmitting COVID-19 [to others] might be particularly vulnerable to this pandemic,” statement coauthor Michael Van Ameringen, MD, professor, of the department of psychiatry and behavioral neurosciences, McMaster University, Hamilton, Ont., said in an interview.
The guidance, issued by the International College of Obsessive Compulsive Spectrum Disorders (ICOCS) and the Obsessive-Compulsive and Related Disorders Research Network (OCRN) of the European College of Neuropsychopharmacology, emphasizes the importance of using pharmacotherapy as a first-line approach, suspending or reducing exposure and response prevention (ERP), and offering psychoeducation.
The statement was published in the July issue of Comprehensive Psychiatry.
Confirm OCD diagnosis
A diagnosis of OCD should be confirmed, and it is important to clarify whether the current symptoms are a “rational or exaggerated response to recent highly stressful events” or a worsening of obsessive-compulsive symptomatology, the statement notes.
Some patients may experience an exacerbation of comorbid conditions such as anxiety disorder, depression, bipolar disorder, or posttraumatic stress disorder (PTSD), which may need to be managed separately.
The authors recommend consulting the World Health Organization (WHO) guidelines regarding mental health and psychosocial considerations during the COVID-19 outbreak.
“Several suicidal patients with OCD have come to the clinic during the pandemic,” reported Dr. Van Ameringen, director of the MacAnxiety Research Centre in Hamilton. “They felt overwhelmed and that they were contaminating themselves with everything they did, including breathing.”
The authors encourage clinicians to assess suicide risk using validated instruments, such as the Columbia Suicide Severity Rating Scale, and hospitalize patients if necessary.
Pharmacotherapy is “the most efficacious first-line treatment modality” for adults and children with OCD and contamination, washing, or cleaning symptoms during the pandemic, the authors note.
They recommend a stepwise pharmacotherapeutic approach:
Type of medication
- Selective serotonin reuptake inhibitor (SSRI) as first choice.
- Another SSRI if no response to first SSRI.
- Clomipramine as third choice.
Dosage
- Gradually increase suboptimal dose, paying attention to contraindications, adverse effects.
SSRI resistance
- Low-dose adjunctive antipsychotic (for example, aripiprazole, risperidone, quetiapine, olanzapine), for incomplete response, especially if tic is present.
Adherence
- Ensure patient can obtain an adequate supply of medication and is taking it regularly.
- Involve family/caregivers if adherence is problematic.
- Pill organizers and reminder apps may be helpful.
A role for CBT?
Under ordinary circumstances, CBT is considered a first-line intervention for OCD. However, there are risks associated specifically with ERP during the pandemic.
“In ERP, people are being exposed to things that trigger their OCD, so those with contamination fears may be asked to touch things in public places, then resist washing their hands, which would counter public health recommendations,” Dr. Van Ameringen said.
In vivo exposure should be paused, but some ERP interventions can be adapted or modified “on a case-by-case basis,” the authors state. For patients whose exposure is unrelated to contamination, other ERP treatment plans can be continued.
The authors recommend using therapy time to “prevent patients from deteriorating” by encouraging them to engage in activity scheduling and structuring the day to include physical activity, enjoyable activities, practices that enhance sleep, and mindfulness.
Limit news exposure
A central component of managing OCD during the pandemic is providing “balanced information” about the known risks and impact of COVID-19, the authors stated.
Dr. Van Ameringen recounted that he has seen patients who have washed their hands for hours and bleached or even boiled their hands.
“Some [patients with OCD] wonder if it’s safe to touch a newspaper or if they can catch the virus if they go outside, even if no one is around,” he reported. “Some wonder if they should ‘quarantine’ a package or wear gloves to bed.”
It has been helpful, for example, to show them the public health guidance of the WHO or CDC advising that 20 seconds of hand washing is adequate, he said.
“We have also seen that some of the sources of information about COVID-19 haven’t been factually correct and that people were watching the news all day and being bombarded with information from every source, which was making their symptoms a thousand times worse,” Dr. Van Ameringen reported.
Therefore, The authors also advise clinicians to “take a compassionate, calming,” and culturally sensitive approach to inform all interventions.
Unique anchor
Commenting on the statement in an interview, Debanjan Banerjee, MD, geriatric psychiatry senior resident, National Institute of Mental Health and Neurosciences, Bangalore, India, said that this “comprehensive guideline, based on expert experience, will serve as a guiding framework for physicians and psychiatrists globally.”
In the “absence of systemic data so far, this guideline can provide a unique anchor of a global consensus on how to take care of those with preexisting OCD or newly emergent cases” said Dr. Banerjee, who was not involved in authoring the statement.
Also commenting on the statement, Jonathan Abramowitz, PhD, professor of psychology and neuroscience, University of North Carolina at Chapel Hill, said that he “generally agrees” with these guidelines but disagrees with the “apparent recommendations to scale back” ERP.
“The fact is that effective and safe ERP is possible, even during this time, even following the scientific guidance,” stated Dr. Abramowitz, editor-in-chief of the Journal of Obsessive-Compulsive and Related Disorders. He was not involved in the statement.
He noted that the International OCD Foundation offers educational programs for clinicians regarding the safe use of ERP during this time.
The authors acknowledge that their guideline is “largely based on empirical evidence” and should be regarded as “preliminary.” The guidance “will be updated as new information arises.”
No specific source of funding for the statement is listed. Dr. Van Ameringen reports being on the advisory boards of Allergan, Almatica, Brainsway, Janssen, Lundbeck, Myriad Neuroscience, Otsuka, and Purdue Pharma (Canada); is on the speakers bureau for Allergan, Lundbeck, Otsuka, Pfizer, Purdue Pharma (Canada) and Takeda; and has received research support from Janssen, Purdue Pharma (Canada), the Canada Foundation for Innovation, and Hamilton Academic Health Sciences Organization. The other authors’ disclosures are listed on the original paper. Dr. Banerjee and Dr. Abramowitz have disclosed no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
More evidence hydroxychloroquine is ineffective, harmful in COVID-19
Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.
In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.
Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.
Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.
“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
‘Inconclusive’ evidence
The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.
Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.
“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.
The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.
They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.
Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).
The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.
Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).
Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
Comorbidities and underlying conditions
The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.
“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.
No significant differences were found in distribution of demographics and comorbidities between the groups.
As good as it gets
“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.
Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.
After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.
Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).
“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.
“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.
“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.
“Let the science speak for itself”
Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”
Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”
Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.
He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”
Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”
Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”
The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.
In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.
Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.
Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.
“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
‘Inconclusive’ evidence
The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.
Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.
“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.
The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.
They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.
Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).
The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.
Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).
Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
Comorbidities and underlying conditions
The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.
“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.
No significant differences were found in distribution of demographics and comorbidities between the groups.
As good as it gets
“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.
Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.
After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.
Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).
“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.
“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.
“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.
“Let the science speak for itself”
Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”
Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”
Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.
He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”
Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”
Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”
The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Hydroxychloroquine and chloroquine, with or without azithromycin or clarithromycin, offer no benefit in treating patients with COVID-19 and, instead, are associated with ventricular arrhythmias and higher rates of mortality, according to a major new international study.
In the largest observational study of its kind, including close to 100,000 people in 671 hospitals on six continents, investigators compared outcomes in 15,000 patients with COVID-19 treated with hydroxychloroquine and chloroquine alone or in combination with a macrolide with 80,000 control patients with COVID-19 not receiving these agents.
Treatment with any of these medications, either alone or in combination, was associated with increased death during hospitalization; compared with about 10% in control group patients, mortality rates ranged from more than 16% to almost 24% in the treated groups.
Patients treated with hydroxychloroquine plus a macrolide showed the highest rates of serious cardiac arrhythmias, and, even after accounting for demographic factors and comorbidities, this combination was found to be associated with a more than 5-fold increase in the risk of developing a serious arrhythmia while in the hospital.
“In this real-world study, the biggest yet, we looked at 100,000 patients [with COVID-19] across six continents and found not the slightest hint of benefits and only risks, and the data is pretty straightforward,” study coauthor Frank Ruschitzka, MD, director of the Heart Center at University Hospital, Zürich, said in an interview. The study was published online May 22 in The Lancet.
‘Inconclusive’ evidence
The absence of an effective treatment for COVID-19 has led to the “repurposing” of the antimalarial drug chloroquine and its analogue hydroxychloroquine, which is used for treating autoimmune disease, but this approach is based on anecdotal evidence or open-label randomized trials that have been “largely inconclusive,” the authors wrote.
Additional agents used to treat COVID-19 are second-generation macrolides (azithromycin or clarithromycin), in combination with chloroquine or hydroxychloroquine, “despite limited evidence” and the risk for ventricular arrhythmias, the authors noted.
“Our primary question was whether there was any associated benefits of the use of hydroxychloroquine, chloroquine, or a combined regimen with macrolides in treating COVID-19, and — if there was no benefit — would there be harm?” lead author Mandeep R. Mehra, MD, MSc, William Harvey Distinguished Chair in Advanced Cardiovascular Medicine, Brigham and Women’s Hospital, Boston, said in an interview.
The investigators used data from a multinational registry comprising 671 hospitals that included patients (n = 96,032; mean age 53.8 years; 46.3% female) who had been hospitalized between Dec. 20, 2019, and April 14, 2020, with confirmed COVID-19 infection.
They also collected data about demographics, underlying comorbidities, and medical history, and medications that patients were taking at baseline.
Patients receiving treatment (n = 14,888) were divided into four groups: those receiving chloroquine alone (n = 1,868), those receiving chloroquine with a macrolide (n = 3,783), those receiving hydroxychloroquine alone (n = 3,016) and those receiving hydroxychloroquine with a macrolide (n = 6,221).
The remaining patients not treated with these regimens (n = 81,144) were regarded as the control group.
Most patients (65.9%) came from North America, followed by Europe (17.39%), Asia (7.9%), Africa (4.6%), South America (3.7%), and Australia (0.6%). Most (66.9%) were white, followed by patients of Asian origin (14.1%), black patients (9.4%), and Hispanic patients (6.2%).
Comorbidities and underlying conditions included obesity, hyperlipidemia, and hypertension in about 30%.
Comorbidities and underlying conditions
The investigators conducted multiple analyses to control for confounding variables, including Cox proportional hazards regression and propensity score matching analyses.
“In an observational study, there is always a chance of residual confounding, which is why we did propensity score based matched analyses,” Dr. Ruschitzka explained.
No significant differences were found in distribution of demographics and comorbidities between the groups.
As good as it gets
“We found no benefit in any of the four treatment regimens for hospitalized patients with COVID-19, but we did notice higher rates of death and serious ventricular arrhythmias in these patients, compared to the controls,” Dr. Mehra reported.
Of the patients in the control group, roughly 9.3% died during their hospitalization, compared with 16.4% of patients treated with chloroquine alone, 18.0% of those treated with hydroxychloroquine alone, 22.2% of those treated with chloroquine and a macrolide, and 23.8% of those treated with hydroxychloroquine and a macrolide.
After accounting for confounding variables, the researchers estimated that the excess mortality risk attributable to use of the drug regimen ranged from 34% to 45%.
Patients treated with any of the four regimens sustained more serious arrhythmias, compared with those in the control group (0.35), with the biggest increase seen in the group treated with the combination of hydroxychloroquine plus a macrolide (8.1%), followed by chloroquine with a macrolide (6.5%), hydroxychloroquine alone (6.1%), and chloroquine alone (4.3%).
“We were fairly reassured that, although the study was observational, the signals were robust and consistent across all regions of the world in diverse populations, and we did not see any muting of that signal, depending on region,” Dr. Mehra said.
“Two months ago, we were all scratching our heads about how to treat patients with COVID-19, and then came a drug [hydroxychloroquine] with some anecdotal evidence, but now we have 2 months more experience, and we looked to science to provide some answer,” Dr. Ruschitzka said.
“Although this was not a randomized, controlled trial, so we do not have a definite answer, the data provided in this [large, multinational] real-world study is as good as it gets and the best data we have,” he concluded.
“Let the science speak for itself”
Commenting on the study in an interview, Christian Funck-Brentano, MD, from the Hospital Pitié-Salpêtrière and Sorbonne University, both in Paris, said that, although the study is observational and therefore not as reliable as a randomized controlled trial, it is “nevertheless well-documented, studied a huge amount of people, and utilized several sensitivity methods, all of which showed the same results.”
Dr. Funck-Brentano, who is the coauthor of an accompanying editorial in The Lancet and was not involved with the study, said that “we now have no evidence that hydroxychloroquine and chloroquine alone or in combination with a macrolide do any good and we have potential evidence that they do harm and kill people.”
Also commenting on the study in an interview, David Holtgrave, PhD, dean of the School of Public Health at the State University of New York at Albany, said that, “while no one observational study alone would lead to a firm clinical recommendation, I think it is helpful for physicians and public health officials to be aware of the findings of the peer-reviewed observational studies to date and the National Institutes of Health COVID-19 treatment guidelines and the Food and Drug Administration’s statement of drug safety concern about hydroxychloroquine to inform their decision-making as we await the results of randomized clinical trials of these drugs for the treatment of COVID-19,” said Dr. Holtgrave, who was not involved with the study.
He added that, to his knowledge, there are “still no published studies of prophylactic use of these drugs to prevent COVID-19.”
Dr. Mehra emphasized that a cardinal principle of practicing medicine is “first do no harm” and “even in situations where you believe a desperate disease calls for desperate measures, responsible physicians should take a step back and ask if we are doing harm, and until we can say we aren’t, I don’t think it’s wise to push something like this in the absence of good efficacy data.”
Dr. Ruschitzka added that those who are encouraging the use of these agents “should review their decision based on today’s data and let the science speak for itself.”
The study was supported by the William Harvey Distinguished Chair in Advanced Cardiovascular Medicine at Brigham and Women’s Hospital, Boston. Dr. Mehra reported personal fees from Abbott, Medtronic, Janssen, Mesoblast, Portola, Bayer, Baim Institute for Clinical Research, NuPulseCV, FineHeart, Leviticus, Roivant, and Triple Gene. Dr. Ruschitzka was paid for time spent as a committee member for clinical trials, advisory boards, other forms of consulting, and lectures or presentations; these payments were made directly to the University of Zürich and no personal payments were received in relation to these trials or other activities. Dr. Funck-Brentano, his coauthor, and Dr. Holtgrave declared no relevant financial relationships.
A version of this article originally appeared on Medscape.com.