Doug Brunk

LAS VEGAS – Is the relationship between major depressive disorder and the development of cancer, cardiovascular disease, and other medical conditions a coincidence, or is there more at play?

According to Charles B. Nemeroff, MD, PhD, a host of circumstances potentially underlies this association, including treatment of the medical disorder itself.

Courtesy University of Texas, Austin

“The best example of that is probably the use of interferon-alpha for the treatment of malignant melanoma,” Dr. Nemeroff, professor and chair of the department of psychiatry and behavioral sciences at the University of Texas at Austin, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “Many patients treated with interferon-alpha ended up with very severe depression, including several documented suicides. Another possibility of the relationship between depression and medical disorders is that treating a patient for depression could result in a medical disorder. The best example of this is the use of 20 mg of olanzapine to augment the effects of an antidepressant, resulting in a 50-pound weight gain and the development of type 2 diabetes and metabolic syndrome. Both of those scenarios are well understood.”

Then there’s the behavioral aspects of the relationship, he continued, in which patients adopt the mindset that “I’m depressed. I don’t want to exercise. I’m a couch potato. I have been gaining a lot of weight. It’s bad for my heart.”

Converging biology is another possibility. “Is it possible that the biology of depression is linked to the biology of other disorders?” asked Dr. Nemeroff, who directs the university’s Institute for Early Life Adversity Research. “We can talk about this in relation to thyroid disease, a well known cause of depression, but we can also talk about the relationship to other disorders. There’s amazing epidemiologic evidence that patients with PTSD are much more likely to develop Alzheimer’s disease than patients without PTSD.”

Psychosocial issues also play a role. He recalled seeing patient in a clinic for the underserved who had underlying severe ulcerative colitis and anemia and couldn’t afford medical treatment. “The patient had a low hemoglobin, so it was impossible to distinguish between that and whether they had a primary depressive disorder or not,” he said.

In a study that explored the relationship between major depression and cancer, Dr. Nemeroff and colleagues found that the prevalence was highest in those with pancreatic cancer (50%), followed by oropharyngeal (40%), colon (13-25%), breast (18-25%), and gynecologic (23%), and Hodgkin’s lymphoma (17%) (Arch Gen Psychiatry 1995;52[2]:89-99). “Not all cancers have the same rate of depression,” he said. “One of the central questions is, not so much is the cancer patient depressed, but is depression a risk factor for developing cancer? The answer is a resounding yes. But what we don’t know is if you treat the depression aggressively, can you reduce that risk of either developing cancer or the progression of cancer?”

Dr. Nemeroff spotlighted several studies largely from the oncology literature, including a prospective survival analysis of 578 women with early-stage breast cancer (Lancet 1999;354:1331-6). After 5 years, 395 were alive and without relapse, 50 were alive with relapse, and 133 had died. The researchers found a significantly increased risk of death from all causes by 5 years in women with a high depression score (HR 3.59). There was a significantly increased risk of relapse or death at 5 years in women with high scores on helplessness and hopelessness measures.

In an analysis of the association between breast cancer and traumatic events, women who had severe stress or a traumatic event had lower rates of disease-free intervals (J Psychosomatic Res 2007;63:233-9). Another study by the same investigators found that a decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer (J Clin Oncol 2010;29:413-20). The median survival was 53.6 months for women with decreasing depression scores over 1 year and 25.1 months for women with increasing depression scores.

A more recent study of cervical cancer patients found that those exposed to psychological stress had an increased risk of cancer-specific mortality (HR 1.33) (Cancer Res 2019;79:3965-72). The association was mainly driven by distress experienced within 1 year before or after diagnosis (HR 1.30) but not afterward (HR 1.12). In addition, data from the large longitudinal Nurses’ Health Study II found that women with high PTSD symptoms had a twofold greater risk of ovarian cancer compared with women who had no trauma exposure (Cancer Res 2019;79:5113-20).

Authors of a separate study analyzed data from the Women’s Health Initiative to examine if depression precedes the development of a cancer diagnosis. They found that depression 3 years before a diagnosis of breast cancer was associated with all-cause mortality (HR 1.35) (Cancer 2017;123[16]:3107-15). Meanwhile, among women with late-stage breast cancer, newly developed depression at year 3 was significantly associated with all-cause mortality (HR 2.0) and breast cancer-specific mortality (HR 2.42). “That’s a pretty amazing finding,” Dr. Nemeroff said. “We have to think about depression as a systemic illness. What is depression doing that’s creating a fertile environment for cancer or worsening of cancer?”

He then discussed the risk of suicide in patients who are newly diagnosed with cancer. “No one ever talks about this, and I can’t get anybody to support research in this area,” he said. In one of the first studies on the topic, researchers conducted a case-control study of Medicare patients and determined risk of suicide among those with cancer was 2.3-fold higher compared with controls, even after adjustment for psychiatric illness and the risk of dying within a year (J Clin Oncol 2008;26[29]:4720-4). More recently, authors of a large population-based study in England found that the overall standardized mortality ratio for suicide was 1.20 (JAMA Psychiatry 2019;76[1]51-60). The risk was highest among patients with mesothelioma, with a 4.51-fold risk, followed by pancreatic (3.89-fold), esophageal (2.65-fold), lung (2.57-fold), and stomach cancer (2.20-fold). “They reported that the first 6 months after the diagnosis is associated with an increased risk of suicide – unrelated to prognosis,” Dr. Nemeroff said.

A separate analysis of SEER data from 1973-2014 and comprising more than 8.6 million cancer patients found that newly diagnosed cancer patients are 4.4 times more likely to die from suicide than patients in the same age group without cancer (Nat Commun 2019;10[1]:207). The highest risk was in lung cancer, followed by head and neck, testes, bladder, and Hodgkin’s lymphoma.

According to Dr. Nemeroff, the association between depression and the risk of certain forms of cancer or with a poor cancer prognosis “may have to do with immune function. Depression is associated with a change in inflammatory markers that very likely control the microenvironment of the tumor.” For example, he said, if the depressed environment is associated with a marked increase in tumor necrosis factor, interleukin 6, and other inflammatory markers, “that probably contributes to the body’s ability to fight disease. Ironically, depression is associated with an increase in inflammation but a decreased in T cell function. Remember, there are two fundamental types of immunity: the antibody response and the cellular response. What’s odd about depression is that there’s an increase in inflammatory markers but a decrease in the ability of T cells to function in terms of cellular immunity.”

Dr. Nemeroff disclosed that he has served as a consultant and/or scientific adviser for numerous pharmaceutical companies. He has received research and grant support from the National Institutes of Health.

LAS VEGAS – Is the relationship between major depressive disorder and the development of cancer, cardiovascular disease, and other medical conditions a coincidence, or is there more at play?

According to Charles B. Nemeroff, MD, PhD, a host of circumstances potentially underlies this association, including treatment of the medical disorder itself.

Courtesy University of Texas, Austin

“The best example of that is probably the use of interferon-alpha for the treatment of malignant melanoma,” Dr. Nemeroff, professor and chair of the department of psychiatry and behavioral sciences at the University of Texas at Austin, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “Many patients treated with interferon-alpha ended up with very severe depression, including several documented suicides. Another possibility of the relationship between depression and medical disorders is that treating a patient for depression could result in a medical disorder. The best example of this is the use of 20 mg of olanzapine to augment the effects of an antidepressant, resulting in a 50-pound weight gain and the development of type 2 diabetes and metabolic syndrome. Both of those scenarios are well understood.”

Then there’s the behavioral aspects of the relationship, he continued, in which patients adopt the mindset that “I’m depressed. I don’t want to exercise. I’m a couch potato. I have been gaining a lot of weight. It’s bad for my heart.”

Converging biology is another possibility. “Is it possible that the biology of depression is linked to the biology of other disorders?” asked Dr. Nemeroff, who directs the university’s Institute for Early Life Adversity Research. “We can talk about this in relation to thyroid disease, a well known cause of depression, but we can also talk about the relationship to other disorders. There’s amazing epidemiologic evidence that patients with PTSD are much more likely to develop Alzheimer’s disease than patients without PTSD.”

Psychosocial issues also play a role. He recalled seeing patient in a clinic for the underserved who had underlying severe ulcerative colitis and anemia and couldn’t afford medical treatment. “The patient had a low hemoglobin, so it was impossible to distinguish between that and whether they had a primary depressive disorder or not,” he said.

In a study that explored the relationship between major depression and cancer, Dr. Nemeroff and colleagues found that the prevalence was highest in those with pancreatic cancer (50%), followed by oropharyngeal (40%), colon (13-25%), breast (18-25%), and gynecologic (23%), and Hodgkin’s lymphoma (17%) (Arch Gen Psychiatry 1995;52[2]:89-99). “Not all cancers have the same rate of depression,” he said. “One of the central questions is, not so much is the cancer patient depressed, but is depression a risk factor for developing cancer? The answer is a resounding yes. But what we don’t know is if you treat the depression aggressively, can you reduce that risk of either developing cancer or the progression of cancer?”

Dr. Nemeroff spotlighted several studies largely from the oncology literature, including a prospective survival analysis of 578 women with early-stage breast cancer (Lancet 1999;354:1331-6). After 5 years, 395 were alive and without relapse, 50 were alive with relapse, and 133 had died. The researchers found a significantly increased risk of death from all causes by 5 years in women with a high depression score (HR 3.59). There was a significantly increased risk of relapse or death at 5 years in women with high scores on helplessness and hopelessness measures.

In an analysis of the association between breast cancer and traumatic events, women who had severe stress or a traumatic event had lower rates of disease-free intervals (J Psychosomatic Res 2007;63:233-9). Another study by the same investigators found that a decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer (J Clin Oncol 2010;29:413-20). The median survival was 53.6 months for women with decreasing depression scores over 1 year and 25.1 months for women with increasing depression scores.

A more recent study of cervical cancer patients found that those exposed to psychological stress had an increased risk of cancer-specific mortality (HR 1.33) (Cancer Res 2019;79:3965-72). The association was mainly driven by distress experienced within 1 year before or after diagnosis (HR 1.30) but not afterward (HR 1.12). In addition, data from the large longitudinal Nurses’ Health Study II found that women with high PTSD symptoms had a twofold greater risk of ovarian cancer compared with women who had no trauma exposure (Cancer Res 2019;79:5113-20).

Authors of a separate study analyzed data from the Women’s Health Initiative to examine if depression precedes the development of a cancer diagnosis. They found that depression 3 years before a diagnosis of breast cancer was associated with all-cause mortality (HR 1.35) (Cancer 2017;123[16]:3107-15). Meanwhile, among women with late-stage breast cancer, newly developed depression at year 3 was significantly associated with all-cause mortality (HR 2.0) and breast cancer-specific mortality (HR 2.42). “That’s a pretty amazing finding,” Dr. Nemeroff said. “We have to think about depression as a systemic illness. What is depression doing that’s creating a fertile environment for cancer or worsening of cancer?”

He then discussed the risk of suicide in patients who are newly diagnosed with cancer. “No one ever talks about this, and I can’t get anybody to support research in this area,” he said. In one of the first studies on the topic, researchers conducted a case-control study of Medicare patients and determined risk of suicide among those with cancer was 2.3-fold higher compared with controls, even after adjustment for psychiatric illness and the risk of dying within a year (J Clin Oncol 2008;26[29]:4720-4). More recently, authors of a large population-based study in England found that the overall standardized mortality ratio for suicide was 1.20 (JAMA Psychiatry 2019;76[1]51-60). The risk was highest among patients with mesothelioma, with a 4.51-fold risk, followed by pancreatic (3.89-fold), esophageal (2.65-fold), lung (2.57-fold), and stomach cancer (2.20-fold). “They reported that the first 6 months after the diagnosis is associated with an increased risk of suicide – unrelated to prognosis,” Dr. Nemeroff said.

A separate analysis of SEER data from 1973-2014 and comprising more than 8.6 million cancer patients found that newly diagnosed cancer patients are 4.4 times more likely to die from suicide than patients in the same age group without cancer (Nat Commun 2019;10[1]:207). The highest risk was in lung cancer, followed by head and neck, testes, bladder, and Hodgkin’s lymphoma.

According to Dr. Nemeroff, the association between depression and the risk of certain forms of cancer or with a poor cancer prognosis “may have to do with immune function. Depression is associated with a change in inflammatory markers that very likely control the microenvironment of the tumor.” For example, he said, if the depressed environment is associated with a marked increase in tumor necrosis factor, interleukin 6, and other inflammatory markers, “that probably contributes to the body’s ability to fight disease. Ironically, depression is associated with an increase in inflammation but a decreased in T cell function. Remember, there are two fundamental types of immunity: the antibody response and the cellular response. What’s odd about depression is that there’s an increase in inflammatory markers but a decrease in the ability of T cells to function in terms of cellular immunity.”

Dr. Nemeroff disclosed that he has served as a consultant and/or scientific adviser for numerous pharmaceutical companies. He has received research and grant support from the National Institutes of Health.

LAS VEGAS – Is the relationship between major depressive disorder and the development of cancer, cardiovascular disease, and other medical conditions a coincidence, or is there more at play?

According to Charles B. Nemeroff, MD, PhD, a host of circumstances potentially underlies this association, including treatment of the medical disorder itself.

Courtesy University of Texas, Austin

“The best example of that is probably the use of interferon-alpha for the treatment of malignant melanoma,” Dr. Nemeroff, professor and chair of the department of psychiatry and behavioral sciences at the University of Texas at Austin, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “Many patients treated with interferon-alpha ended up with very severe depression, including several documented suicides. Another possibility of the relationship between depression and medical disorders is that treating a patient for depression could result in a medical disorder. The best example of this is the use of 20 mg of olanzapine to augment the effects of an antidepressant, resulting in a 50-pound weight gain and the development of type 2 diabetes and metabolic syndrome. Both of those scenarios are well understood.”

Then there’s the behavioral aspects of the relationship, he continued, in which patients adopt the mindset that “I’m depressed. I don’t want to exercise. I’m a couch potato. I have been gaining a lot of weight. It’s bad for my heart.”

Converging biology is another possibility. “Is it possible that the biology of depression is linked to the biology of other disorders?” asked Dr. Nemeroff, who directs the university’s Institute for Early Life Adversity Research. “We can talk about this in relation to thyroid disease, a well known cause of depression, but we can also talk about the relationship to other disorders. There’s amazing epidemiologic evidence that patients with PTSD are much more likely to develop Alzheimer’s disease than patients without PTSD.”

Psychosocial issues also play a role. He recalled seeing patient in a clinic for the underserved who had underlying severe ulcerative colitis and anemia and couldn’t afford medical treatment. “The patient had a low hemoglobin, so it was impossible to distinguish between that and whether they had a primary depressive disorder or not,” he said.

In a study that explored the relationship between major depression and cancer, Dr. Nemeroff and colleagues found that the prevalence was highest in those with pancreatic cancer (50%), followed by oropharyngeal (40%), colon (13-25%), breast (18-25%), and gynecologic (23%), and Hodgkin’s lymphoma (17%) (Arch Gen Psychiatry 1995;52[2]:89-99). “Not all cancers have the same rate of depression,” he said. “One of the central questions is, not so much is the cancer patient depressed, but is depression a risk factor for developing cancer? The answer is a resounding yes. But what we don’t know is if you treat the depression aggressively, can you reduce that risk of either developing cancer or the progression of cancer?”

Dr. Nemeroff spotlighted several studies largely from the oncology literature, including a prospective survival analysis of 578 women with early-stage breast cancer (Lancet 1999;354:1331-6). After 5 years, 395 were alive and without relapse, 50 were alive with relapse, and 133 had died. The researchers found a significantly increased risk of death from all causes by 5 years in women with a high depression score (HR 3.59). There was a significantly increased risk of relapse or death at 5 years in women with high scores on helplessness and hopelessness measures.

In an analysis of the association between breast cancer and traumatic events, women who had severe stress or a traumatic event had lower rates of disease-free intervals (J Psychosomatic Res 2007;63:233-9). Another study by the same investigators found that a decrease in depression symptoms is associated with longer survival in patients with metastatic breast cancer (J Clin Oncol 2010;29:413-20). The median survival was 53.6 months for women with decreasing depression scores over 1 year and 25.1 months for women with increasing depression scores.

A more recent study of cervical cancer patients found that those exposed to psychological stress had an increased risk of cancer-specific mortality (HR 1.33) (Cancer Res 2019;79:3965-72). The association was mainly driven by distress experienced within 1 year before or after diagnosis (HR 1.30) but not afterward (HR 1.12). In addition, data from the large longitudinal Nurses’ Health Study II found that women with high PTSD symptoms had a twofold greater risk of ovarian cancer compared with women who had no trauma exposure (Cancer Res 2019;79:5113-20).

Authors of a separate study analyzed data from the Women’s Health Initiative to examine if depression precedes the development of a cancer diagnosis. They found that depression 3 years before a diagnosis of breast cancer was associated with all-cause mortality (HR 1.35) (Cancer 2017;123[16]:3107-15). Meanwhile, among women with late-stage breast cancer, newly developed depression at year 3 was significantly associated with all-cause mortality (HR 2.0) and breast cancer-specific mortality (HR 2.42). “That’s a pretty amazing finding,” Dr. Nemeroff said. “We have to think about depression as a systemic illness. What is depression doing that’s creating a fertile environment for cancer or worsening of cancer?”

He then discussed the risk of suicide in patients who are newly diagnosed with cancer. “No one ever talks about this, and I can’t get anybody to support research in this area,” he said. In one of the first studies on the topic, researchers conducted a case-control study of Medicare patients and determined risk of suicide among those with cancer was 2.3-fold higher compared with controls, even after adjustment for psychiatric illness and the risk of dying within a year (J Clin Oncol 2008;26[29]:4720-4). More recently, authors of a large population-based study in England found that the overall standardized mortality ratio for suicide was 1.20 (JAMA Psychiatry 2019;76[1]51-60). The risk was highest among patients with mesothelioma, with a 4.51-fold risk, followed by pancreatic (3.89-fold), esophageal (2.65-fold), lung (2.57-fold), and stomach cancer (2.20-fold). “They reported that the first 6 months after the diagnosis is associated with an increased risk of suicide – unrelated to prognosis,” Dr. Nemeroff said.

A separate analysis of SEER data from 1973-2014 and comprising more than 8.6 million cancer patients found that newly diagnosed cancer patients are 4.4 times more likely to die from suicide than patients in the same age group without cancer (Nat Commun 2019;10[1]:207). The highest risk was in lung cancer, followed by head and neck, testes, bladder, and Hodgkin’s lymphoma.

According to Dr. Nemeroff, the association between depression and the risk of certain forms of cancer or with a poor cancer prognosis “may have to do with immune function. Depression is associated with a change in inflammatory markers that very likely control the microenvironment of the tumor.” For example, he said, if the depressed environment is associated with a marked increase in tumor necrosis factor, interleukin 6, and other inflammatory markers, “that probably contributes to the body’s ability to fight disease. Ironically, depression is associated with an increase in inflammation but a decreased in T cell function. Remember, there are two fundamental types of immunity: the antibody response and the cellular response. What’s odd about depression is that there’s an increase in inflammatory markers but a decrease in the ability of T cells to function in terms of cellular immunity.”

Dr. Nemeroff disclosed that he has served as a consultant and/or scientific adviser for numerous pharmaceutical companies. He has received research and grant support from the National Institutes of Health.

LAS VEGAS – Someday, pharmacogenomics will advance precision psychiatry, but in the opinion of Erika L. Nurmi, MD, PhD, routine use of genetic testing to guide clinical treatment decisions is not indicated.

“It’s misleading to rely on results of genetic tests to drive clinical treatment,” Dr. Nurmi, a child and adolescent psychiatrist in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “There’s a lot of hope and promise there. But currently, we only know the tip of the iceberg about how drugs work and the genetics influencing these effects. Current testing is probably a very poor reflection of the complexity of drug effects.”

According to Dr. Nurmi, there are at least 165 Food and Drug Administration–approved drugs with pharmacogenetic information on 64 different biomarkers – 37% with CYP p450 notations. Of these, 32 psychiatric drugs have pharmacogenetic information, and most of them are dosing recommendations based on whether a patient has the variant. However, there is wide public acceptance of genetic testing in preventing the wrong drug from being used, in selecting the best drug dose, and avoiding side effects (Pharmacogenomics 2012;12[3]:197-204). “Most people have a lot of hope [for genetic testing in psychiatry],” Dr. Nurmi said. “But is the science really there? It doesn’t matter, because these companies are doing it, and you are being shown these reports from patients. Whether or not the science supports it, we’re going to have to interpret these reports and explain them to our patients – even if we don’t order them.”

Currently, she continued, clinicians practice trial and error prescribing where they might try one treatment in a class that they think that will work based on previous literature. If nothing works, they try another one. If that’s intolerable, they try a third treatment, and so on. “When we finally find the right treatment, it can take some time to get the dosing right,” Dr. Nurmi said. “So, it can take many months to get a child on the right medication. Precision treatment, on the other hand, would start off by taking a saliva or blood sample to get a printout that lets physicians know which drugs might be used with caution because they might lack efficacy at standard doses, which ones would likely have adverse effects at standard doses, and which are the best choices and what are the dosing recommendations for those choices. If we could get all the information to guide us, that would be a useful product, but right now, we don’t know enough to be able to make these determinations.”

Current evidence-based genetic testing supports a limited role for CYP2D6 and CYP2C19 genotyping because most psychiatric drugs are metabolized by those two enzymes. Poor metabolizers have two dysfunctional copies of the enzyme-encoding gene. This results in increased drug plasma levels with a potentially increased rate of adverse effects.

“Intermediate and extensive metabolizers usually have a normal phenotype, but you can also have ultrarapid metabolizers who have duplications or other enhancing mutations of the CYP gene,” Dr. Nurmi said. “This can result in lower bioavailability and possibly efficacy. Psychiatrists treat poor metabolizers and ultrarapid metabolizers all the time, because the variants are very common.” An estimated 10% of White people are poor metabolizers at the CYP2D6 gene while about 7% are ultrarapid metabolizers. At the same time, an estimated 20% of Asians, Africans, and Whites are poor metabolizers at the CYP2C19 gene. “So, you’re seeing a lot of this in your practice, and you’re probably changing dosing based on genetic differences in metabolism,” she said.

The only FDA pharmacodynamic treatment guideline is for the risk of Stevens-Johnson syndrome (SJS) with the use of carbamazepine. In a study of 44 patients with SJS, all were positive for the HLA-B*1502 variant, compared with 3% of carbamazepine-tolerant patients (Nature 2004;428[6982]:486). The frequency of carrying this variant is an estimated 1:10,000 among Whites and 1:1,000 among Asians. In 2007, the FDA recommended that patients of Asian ancestry should be screened for HLA-B*1502 prior to starting carbamazepine.

Genetic variation also predicts clinical outcome with atomoxetine use. “Most child psychiatrists I know think atomoxetine doesn’t work as a second-line nonstimulant medication for ADHD,” Dr. Nurmi said. “I’d like to convince you that why you think it doesn’t work is because of the genetics.” In a study published in 2019, Dr. Nurmi and colleagues reviewed medical literature and provided therapeutic recommendations for atomoxetine therapy based on CYP2D6 genotype (Clin Pharmacol Ther 2019 Jul;106[1]:94-102). They observed 10- to 30-fold plasma differences in drug exposure between normal metabolizers and poor metabolizers.

“Poor metabolizers therefore get more benefit, but they are also going to get more side effects,” she said. “FDA recommended doses are inadequate for normal metabolizers, so they had to make guidelines based on poor metabolizers because there would be too much risk for them at higher doses. One-third of individuals require doses above the FDA limit to achieve a therapeutic drug level.”

Dr. Nurmi warned that the existing evidence base for using these genetic tests in children “is really poor. There is no data in adults with any diagnosis other than depression, and even those studies are plagued by concerns. When you’re implementing decision support tools in your practice, the key factors are patient presentation, history and symptoms, your clinical skills, the evidence base, FDA recommendations, and patient autonomy. Appropriate incorporation of genetic data should include avoiding a medication with high toxicity (like SJS), titration planning (dose and titration speed adjustments), and choosing between medications in the same class with an indication or evidence base for the target disorder.” She added that while the benefit of current genetic testing is limited, it may help some patients feel more comfortable tolerating a medication. “For example, being able to tell someone with anxiety that their genetics suggests that they will not have side effects could be very powerful,” she said.

In a 2018 safety communication, the FDA warned the public about its concerns with companies making claims about how to use genetic test results to manage medication treatments that are not supported by recommendations in the FDA-approved drug labeling or other scientific evidence. The American Academy of Child and Adolescent Psychiatry also published a guide for patients and families.

Dr. Nurmi disclosed that she is an unpaid advisory board member for Myriad Genetics and the Tourette Association of America, a paid adviser for Teva Pharmaceuticals, and a recipient of research support from Emalex Pharmaceuticals. She has received research funding from the National Institutes Health, the International OCD Foundation, the Tourette Association of America, and the Brain & Behavior Research Foundation.

LAS VEGAS – Someday, pharmacogenomics will advance precision psychiatry, but in the opinion of Erika L. Nurmi, MD, PhD, routine use of genetic testing to guide clinical treatment decisions is not indicated.

“It’s misleading to rely on results of genetic tests to drive clinical treatment,” Dr. Nurmi, a child and adolescent psychiatrist in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “There’s a lot of hope and promise there. But currently, we only know the tip of the iceberg about how drugs work and the genetics influencing these effects. Current testing is probably a very poor reflection of the complexity of drug effects.”

According to Dr. Nurmi, there are at least 165 Food and Drug Administration–approved drugs with pharmacogenetic information on 64 different biomarkers – 37% with CYP p450 notations. Of these, 32 psychiatric drugs have pharmacogenetic information, and most of them are dosing recommendations based on whether a patient has the variant. However, there is wide public acceptance of genetic testing in preventing the wrong drug from being used, in selecting the best drug dose, and avoiding side effects (Pharmacogenomics 2012;12[3]:197-204). “Most people have a lot of hope [for genetic testing in psychiatry],” Dr. Nurmi said. “But is the science really there? It doesn’t matter, because these companies are doing it, and you are being shown these reports from patients. Whether or not the science supports it, we’re going to have to interpret these reports and explain them to our patients – even if we don’t order them.”

Currently, she continued, clinicians practice trial and error prescribing where they might try one treatment in a class that they think that will work based on previous literature. If nothing works, they try another one. If that’s intolerable, they try a third treatment, and so on. “When we finally find the right treatment, it can take some time to get the dosing right,” Dr. Nurmi said. “So, it can take many months to get a child on the right medication. Precision treatment, on the other hand, would start off by taking a saliva or blood sample to get a printout that lets physicians know which drugs might be used with caution because they might lack efficacy at standard doses, which ones would likely have adverse effects at standard doses, and which are the best choices and what are the dosing recommendations for those choices. If we could get all the information to guide us, that would be a useful product, but right now, we don’t know enough to be able to make these determinations.”

Current evidence-based genetic testing supports a limited role for CYP2D6 and CYP2C19 genotyping because most psychiatric drugs are metabolized by those two enzymes. Poor metabolizers have two dysfunctional copies of the enzyme-encoding gene. This results in increased drug plasma levels with a potentially increased rate of adverse effects.

“Intermediate and extensive metabolizers usually have a normal phenotype, but you can also have ultrarapid metabolizers who have duplications or other enhancing mutations of the CYP gene,” Dr. Nurmi said. “This can result in lower bioavailability and possibly efficacy. Psychiatrists treat poor metabolizers and ultrarapid metabolizers all the time, because the variants are very common.” An estimated 10% of White people are poor metabolizers at the CYP2D6 gene while about 7% are ultrarapid metabolizers. At the same time, an estimated 20% of Asians, Africans, and Whites are poor metabolizers at the CYP2C19 gene. “So, you’re seeing a lot of this in your practice, and you’re probably changing dosing based on genetic differences in metabolism,” she said.

The only FDA pharmacodynamic treatment guideline is for the risk of Stevens-Johnson syndrome (SJS) with the use of carbamazepine. In a study of 44 patients with SJS, all were positive for the HLA-B*1502 variant, compared with 3% of carbamazepine-tolerant patients (Nature 2004;428[6982]:486). The frequency of carrying this variant is an estimated 1:10,000 among Whites and 1:1,000 among Asians. In 2007, the FDA recommended that patients of Asian ancestry should be screened for HLA-B*1502 prior to starting carbamazepine.

Genetic variation also predicts clinical outcome with atomoxetine use. “Most child psychiatrists I know think atomoxetine doesn’t work as a second-line nonstimulant medication for ADHD,” Dr. Nurmi said. “I’d like to convince you that why you think it doesn’t work is because of the genetics.” In a study published in 2019, Dr. Nurmi and colleagues reviewed medical literature and provided therapeutic recommendations for atomoxetine therapy based on CYP2D6 genotype (Clin Pharmacol Ther 2019 Jul;106[1]:94-102). They observed 10- to 30-fold plasma differences in drug exposure between normal metabolizers and poor metabolizers.

“Poor metabolizers therefore get more benefit, but they are also going to get more side effects,” she said. “FDA recommended doses are inadequate for normal metabolizers, so they had to make guidelines based on poor metabolizers because there would be too much risk for them at higher doses. One-third of individuals require doses above the FDA limit to achieve a therapeutic drug level.”

Dr. Nurmi warned that the existing evidence base for using these genetic tests in children “is really poor. There is no data in adults with any diagnosis other than depression, and even those studies are plagued by concerns. When you’re implementing decision support tools in your practice, the key factors are patient presentation, history and symptoms, your clinical skills, the evidence base, FDA recommendations, and patient autonomy. Appropriate incorporation of genetic data should include avoiding a medication with high toxicity (like SJS), titration planning (dose and titration speed adjustments), and choosing between medications in the same class with an indication or evidence base for the target disorder.” She added that while the benefit of current genetic testing is limited, it may help some patients feel more comfortable tolerating a medication. “For example, being able to tell someone with anxiety that their genetics suggests that they will not have side effects could be very powerful,” she said.

In a 2018 safety communication, the FDA warned the public about its concerns with companies making claims about how to use genetic test results to manage medication treatments that are not supported by recommendations in the FDA-approved drug labeling or other scientific evidence. The American Academy of Child and Adolescent Psychiatry also published a guide for patients and families.

Dr. Nurmi disclosed that she is an unpaid advisory board member for Myriad Genetics and the Tourette Association of America, a paid adviser for Teva Pharmaceuticals, and a recipient of research support from Emalex Pharmaceuticals. She has received research funding from the National Institutes Health, the International OCD Foundation, the Tourette Association of America, and the Brain & Behavior Research Foundation.

LAS VEGAS – Someday, pharmacogenomics will advance precision psychiatry, but in the opinion of Erika L. Nurmi, MD, PhD, routine use of genetic testing to guide clinical treatment decisions is not indicated.

“It’s misleading to rely on results of genetic tests to drive clinical treatment,” Dr. Nurmi, a child and adolescent psychiatrist in the department of psychiatry and biobehavioral sciences at the University of California, Los Angeles, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “There’s a lot of hope and promise there. But currently, we only know the tip of the iceberg about how drugs work and the genetics influencing these effects. Current testing is probably a very poor reflection of the complexity of drug effects.”

According to Dr. Nurmi, there are at least 165 Food and Drug Administration–approved drugs with pharmacogenetic information on 64 different biomarkers – 37% with CYP p450 notations. Of these, 32 psychiatric drugs have pharmacogenetic information, and most of them are dosing recommendations based on whether a patient has the variant. However, there is wide public acceptance of genetic testing in preventing the wrong drug from being used, in selecting the best drug dose, and avoiding side effects (Pharmacogenomics 2012;12[3]:197-204). “Most people have a lot of hope [for genetic testing in psychiatry],” Dr. Nurmi said. “But is the science really there? It doesn’t matter, because these companies are doing it, and you are being shown these reports from patients. Whether or not the science supports it, we’re going to have to interpret these reports and explain them to our patients – even if we don’t order them.”

Currently, she continued, clinicians practice trial and error prescribing where they might try one treatment in a class that they think that will work based on previous literature. If nothing works, they try another one. If that’s intolerable, they try a third treatment, and so on. “When we finally find the right treatment, it can take some time to get the dosing right,” Dr. Nurmi said. “So, it can take many months to get a child on the right medication. Precision treatment, on the other hand, would start off by taking a saliva or blood sample to get a printout that lets physicians know which drugs might be used with caution because they might lack efficacy at standard doses, which ones would likely have adverse effects at standard doses, and which are the best choices and what are the dosing recommendations for those choices. If we could get all the information to guide us, that would be a useful product, but right now, we don’t know enough to be able to make these determinations.”

Current evidence-based genetic testing supports a limited role for CYP2D6 and CYP2C19 genotyping because most psychiatric drugs are metabolized by those two enzymes. Poor metabolizers have two dysfunctional copies of the enzyme-encoding gene. This results in increased drug plasma levels with a potentially increased rate of adverse effects.

“Intermediate and extensive metabolizers usually have a normal phenotype, but you can also have ultrarapid metabolizers who have duplications or other enhancing mutations of the CYP gene,” Dr. Nurmi said. “This can result in lower bioavailability and possibly efficacy. Psychiatrists treat poor metabolizers and ultrarapid metabolizers all the time, because the variants are very common.” An estimated 10% of White people are poor metabolizers at the CYP2D6 gene while about 7% are ultrarapid metabolizers. At the same time, an estimated 20% of Asians, Africans, and Whites are poor metabolizers at the CYP2C19 gene. “So, you’re seeing a lot of this in your practice, and you’re probably changing dosing based on genetic differences in metabolism,” she said.

The only FDA pharmacodynamic treatment guideline is for the risk of Stevens-Johnson syndrome (SJS) with the use of carbamazepine. In a study of 44 patients with SJS, all were positive for the HLA-B*1502 variant, compared with 3% of carbamazepine-tolerant patients (Nature 2004;428[6982]:486). The frequency of carrying this variant is an estimated 1:10,000 among Whites and 1:1,000 among Asians. In 2007, the FDA recommended that patients of Asian ancestry should be screened for HLA-B*1502 prior to starting carbamazepine.

Genetic variation also predicts clinical outcome with atomoxetine use. “Most child psychiatrists I know think atomoxetine doesn’t work as a second-line nonstimulant medication for ADHD,” Dr. Nurmi said. “I’d like to convince you that why you think it doesn’t work is because of the genetics.” In a study published in 2019, Dr. Nurmi and colleagues reviewed medical literature and provided therapeutic recommendations for atomoxetine therapy based on CYP2D6 genotype (Clin Pharmacol Ther 2019 Jul;106[1]:94-102). They observed 10- to 30-fold plasma differences in drug exposure between normal metabolizers and poor metabolizers.

“Poor metabolizers therefore get more benefit, but they are also going to get more side effects,” she said. “FDA recommended doses are inadequate for normal metabolizers, so they had to make guidelines based on poor metabolizers because there would be too much risk for them at higher doses. One-third of individuals require doses above the FDA limit to achieve a therapeutic drug level.”

Dr. Nurmi warned that the existing evidence base for using these genetic tests in children “is really poor. There is no data in adults with any diagnosis other than depression, and even those studies are plagued by concerns. When you’re implementing decision support tools in your practice, the key factors are patient presentation, history and symptoms, your clinical skills, the evidence base, FDA recommendations, and patient autonomy. Appropriate incorporation of genetic data should include avoiding a medication with high toxicity (like SJS), titration planning (dose and titration speed adjustments), and choosing between medications in the same class with an indication or evidence base for the target disorder.” She added that while the benefit of current genetic testing is limited, it may help some patients feel more comfortable tolerating a medication. “For example, being able to tell someone with anxiety that their genetics suggests that they will not have side effects could be very powerful,” she said.

In a 2018 safety communication, the FDA warned the public about its concerns with companies making claims about how to use genetic test results to manage medication treatments that are not supported by recommendations in the FDA-approved drug labeling or other scientific evidence. The American Academy of Child and Adolescent Psychiatry also published a guide for patients and families.

Dr. Nurmi disclosed that she is an unpaid advisory board member for Myriad Genetics and the Tourette Association of America, a paid adviser for Teva Pharmaceuticals, and a recipient of research support from Emalex Pharmaceuticals. She has received research funding from the National Institutes Health, the International OCD Foundation, the Tourette Association of America, and the Brain & Behavior Research Foundation.

LAS VEGAS – While frontline health care workers may have been disproportionately impacted by the COVID-19 pandemic, the entire workforce has experienced some level of anxiety, stress, loss, grief, and trauma, according to Jon A. Levenson, MD.

“There are those who will need mental health treatment, so creating an easy way to reach out for help and facilitate linkage with care is critically important,” Dr. Levenson, associate professor of psychiatry at Columbia University Irving Medical Center, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “The vast majority of our workforce will thrive with proper support. But what can each of us do to take care of ourselves?”

Step one is to recognize common stress reactions as well as signs of distress. He offered the oxygen mask metaphor, the idea that before we can take care of and support anyone else, we must first take care of ourselves. “When people are stressed, they don’t always think about the oxygen mask metaphor,” Dr. Levenson said. Step two is to practice and model self-care by adopting principles often discussed in acceptance and commitment therapy: to focus on what you can control, not on what you can’t control.

“We can’t control the amount of toilet paper at the grocery store, how long the pandemic will last, or how others have reacted,” Dr. Levenson said. “We also can’t control other people’s motives, predict what will happen, or the actions of others, including whether they will follow social distancing guidelines or not.”

How about what we can control? One is a positive attitude, “which can sustain people during times of intense stress,” he said. “Other things that we can do include turn off the news and find fun and enriching activities to do at home, whether it be playing a game with family or reaching out to friends through an iPad or a smartphone. You can also follow [Centers for Disease Control and Prevention] recommendations, control your own social distancing, and limit social media activity, which can be stressful. We can also control our kindness and grace.” He added that resilience does not mean “snapping back” to how you were before the pandemic, but rather “learning to integrate the adverse experiences into who you are and growing with them, which is sometimes known as posttraumatic growth.”

Dr. Levenson encouraged health care workers to use their coping resources, connect to others, and cultivate their values and purpose in life as they navigate these challenging times. “You also want to promote realistic optimism; find a way to stay positive,” he said. “We emphasize to our staff that while you won’t forget this time, focus on what you can control – your positive relationships – and remind yourself of your values and sources of gratitude. Figure out, and reflect on, what you care about, and then care about it. Remind yourself in a deliberate, purposeful way what anchors you to your job, which in the health care setting tends to be a desire to care for others, to assist those in need, and to work in teams. We also encourage staff to refrain from judgment. Guilt is a normal and near-universal response to this stressor, but there are many ways to contribute without a judgmental or guilty tone.”

Other tips for self-support are to remind yourself that it is not selfish to take breaks. “The needs of your patients are not more important than your own needs,” Dr. Levenson said. “Working nonstop can put you at higher risk for stress, exhaustion, and illness. You may need to give yourself more time to step back and recover from workplace challenges or extended coverage for peers; this is important. We remind our staff that your work may feel more emotionally draining than usual because everything is more intense overall during the COVID-19 pandemic. This reminder helps staff normalize what they already may be experiencing, and in turn, to further support each other.”

Soothing activities to relieve stress include meditation, prayer, deep and slow breathing, relaxation exercises, yoga, mindfulness, stretching, staying hydrated, eating healthfully, exercise, and getting sufficient sleep. Other stress management tips include avoiding excessive alcohol intake, reaching out to others, asking for assistance, and delegating when possible. “We want to promote psychological flexibility: the ability to stay in contact with the present moment,” he said. “We encourage our peers to be aware of unpleasant thoughts and feelings, and to try to redirect negative thought patterns to a proactive problem-solving approach; this includes choosing one’s behaviors based on the situation and personal values.”

Dr. Levenson reported having no disclosures related to his presentation.

LAS VEGAS – While frontline health care workers may have been disproportionately impacted by the COVID-19 pandemic, the entire workforce has experienced some level of anxiety, stress, loss, grief, and trauma, according to Jon A. Levenson, MD.

“There are those who will need mental health treatment, so creating an easy way to reach out for help and facilitate linkage with care is critically important,” Dr. Levenson, associate professor of psychiatry at Columbia University Irving Medical Center, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “The vast majority of our workforce will thrive with proper support. But what can each of us do to take care of ourselves?”

Step one is to recognize common stress reactions as well as signs of distress. He offered the oxygen mask metaphor, the idea that before we can take care of and support anyone else, we must first take care of ourselves. “When people are stressed, they don’t always think about the oxygen mask metaphor,” Dr. Levenson said. Step two is to practice and model self-care by adopting principles often discussed in acceptance and commitment therapy: to focus on what you can control, not on what you can’t control.

“We can’t control the amount of toilet paper at the grocery store, how long the pandemic will last, or how others have reacted,” Dr. Levenson said. “We also can’t control other people’s motives, predict what will happen, or the actions of others, including whether they will follow social distancing guidelines or not.”

How about what we can control? One is a positive attitude, “which can sustain people during times of intense stress,” he said. “Other things that we can do include turn off the news and find fun and enriching activities to do at home, whether it be playing a game with family or reaching out to friends through an iPad or a smartphone. You can also follow [Centers for Disease Control and Prevention] recommendations, control your own social distancing, and limit social media activity, which can be stressful. We can also control our kindness and grace.” He added that resilience does not mean “snapping back” to how you were before the pandemic, but rather “learning to integrate the adverse experiences into who you are and growing with them, which is sometimes known as posttraumatic growth.”

Dr. Levenson encouraged health care workers to use their coping resources, connect to others, and cultivate their values and purpose in life as they navigate these challenging times. “You also want to promote realistic optimism; find a way to stay positive,” he said. “We emphasize to our staff that while you won’t forget this time, focus on what you can control – your positive relationships – and remind yourself of your values and sources of gratitude. Figure out, and reflect on, what you care about, and then care about it. Remind yourself in a deliberate, purposeful way what anchors you to your job, which in the health care setting tends to be a desire to care for others, to assist those in need, and to work in teams. We also encourage staff to refrain from judgment. Guilt is a normal and near-universal response to this stressor, but there are many ways to contribute without a judgmental or guilty tone.”

Other tips for self-support are to remind yourself that it is not selfish to take breaks. “The needs of your patients are not more important than your own needs,” Dr. Levenson said. “Working nonstop can put you at higher risk for stress, exhaustion, and illness. You may need to give yourself more time to step back and recover from workplace challenges or extended coverage for peers; this is important. We remind our staff that your work may feel more emotionally draining than usual because everything is more intense overall during the COVID-19 pandemic. This reminder helps staff normalize what they already may be experiencing, and in turn, to further support each other.”

Soothing activities to relieve stress include meditation, prayer, deep and slow breathing, relaxation exercises, yoga, mindfulness, stretching, staying hydrated, eating healthfully, exercise, and getting sufficient sleep. Other stress management tips include avoiding excessive alcohol intake, reaching out to others, asking for assistance, and delegating when possible. “We want to promote psychological flexibility: the ability to stay in contact with the present moment,” he said. “We encourage our peers to be aware of unpleasant thoughts and feelings, and to try to redirect negative thought patterns to a proactive problem-solving approach; this includes choosing one’s behaviors based on the situation and personal values.”

Dr. Levenson reported having no disclosures related to his presentation.

LAS VEGAS – While frontline health care workers may have been disproportionately impacted by the COVID-19 pandemic, the entire workforce has experienced some level of anxiety, stress, loss, grief, and trauma, according to Jon A. Levenson, MD.

“There are those who will need mental health treatment, so creating an easy way to reach out for help and facilitate linkage with care is critically important,” Dr. Levenson, associate professor of psychiatry at Columbia University Irving Medical Center, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “The vast majority of our workforce will thrive with proper support. But what can each of us do to take care of ourselves?”

Step one is to recognize common stress reactions as well as signs of distress. He offered the oxygen mask metaphor, the idea that before we can take care of and support anyone else, we must first take care of ourselves. “When people are stressed, they don’t always think about the oxygen mask metaphor,” Dr. Levenson said. Step two is to practice and model self-care by adopting principles often discussed in acceptance and commitment therapy: to focus on what you can control, not on what you can’t control.

“We can’t control the amount of toilet paper at the grocery store, how long the pandemic will last, or how others have reacted,” Dr. Levenson said. “We also can’t control other people’s motives, predict what will happen, or the actions of others, including whether they will follow social distancing guidelines or not.”

How about what we can control? One is a positive attitude, “which can sustain people during times of intense stress,” he said. “Other things that we can do include turn off the news and find fun and enriching activities to do at home, whether it be playing a game with family or reaching out to friends through an iPad or a smartphone. You can also follow [Centers for Disease Control and Prevention] recommendations, control your own social distancing, and limit social media activity, which can be stressful. We can also control our kindness and grace.” He added that resilience does not mean “snapping back” to how you were before the pandemic, but rather “learning to integrate the adverse experiences into who you are and growing with them, which is sometimes known as posttraumatic growth.”

Dr. Levenson encouraged health care workers to use their coping resources, connect to others, and cultivate their values and purpose in life as they navigate these challenging times. “You also want to promote realistic optimism; find a way to stay positive,” he said. “We emphasize to our staff that while you won’t forget this time, focus on what you can control – your positive relationships – and remind yourself of your values and sources of gratitude. Figure out, and reflect on, what you care about, and then care about it. Remind yourself in a deliberate, purposeful way what anchors you to your job, which in the health care setting tends to be a desire to care for others, to assist those in need, and to work in teams. We also encourage staff to refrain from judgment. Guilt is a normal and near-universal response to this stressor, but there are many ways to contribute without a judgmental or guilty tone.”

Other tips for self-support are to remind yourself that it is not selfish to take breaks. “The needs of your patients are not more important than your own needs,” Dr. Levenson said. “Working nonstop can put you at higher risk for stress, exhaustion, and illness. You may need to give yourself more time to step back and recover from workplace challenges or extended coverage for peers; this is important. We remind our staff that your work may feel more emotionally draining than usual because everything is more intense overall during the COVID-19 pandemic. This reminder helps staff normalize what they already may be experiencing, and in turn, to further support each other.”

Soothing activities to relieve stress include meditation, prayer, deep and slow breathing, relaxation exercises, yoga, mindfulness, stretching, staying hydrated, eating healthfully, exercise, and getting sufficient sleep. Other stress management tips include avoiding excessive alcohol intake, reaching out to others, asking for assistance, and delegating when possible. “We want to promote psychological flexibility: the ability to stay in contact with the present moment,” he said. “We encourage our peers to be aware of unpleasant thoughts and feelings, and to try to redirect negative thought patterns to a proactive problem-solving approach; this includes choosing one’s behaviors based on the situation and personal values.”

Dr. Levenson reported having no disclosures related to his presentation.

LAS VEGAS – Long after the acute phase of the COVID-19 pandemic subsides, the psychological sequelae and behavioral effects of persistent distress will likely persist for health care workers, according to Jon A. Levenson, MD.

“We can learn from previous pandemics and epidemics, which will be important for us going forward from COVID-19,” Dr. Levenson, associate professor of psychiatry at Columbia University Irving Medical Center, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association.

During the severe acute respiratory syndrome (SARS) epidemic in 2005, 68% of health care workers reported significant job-related stress, including increased workload, changing work duties, redeployment, shortage of medical supplies, concerns about insufficient personal protective equipment (PPE), lack of safety at work, absence of effective treatment protocols, inconsistent organizational support and information and misinformation from hospital management, and witnessing intense pain, isolation, and loss on a daily basis with few opportunities to take breaks (Psychiatr Serv. 2020 Oct 6. doi: 10.1176/appi.ps.202000274).

Personal concerns associated with psychopathological symptoms included spreading infection to family members; feeling responsibility for family members’ social isolation; self-isolating to avoid infecting family, which can lead to increased loneliness and sadness. “For those who were working remotely, this level of work is hard and challenging,” Dr. Levenson said. “For those who are parents, the 24-hour childcare responsibilities exist on top of work. They often found they can’t unwind with friends.”

Across SARS, MERS, Ebola, and swine flu, a wide range of prevalence in symptoms of distress, stress, anxiety, depressive symptoms, and substance use emerged, he continued. During COVID-19, at least three studies reported significant percentages of distress, depression, anxiety, insomnia, and PTSD among health care workers (JAMA Netw Open. 2020;3[3]:e203976, Front Psychol. 2020 Dec 8;11:608986., and Gen Hosp Psychiatry. Sep-Oct 2020;66:1-8).

“Who is at most-increased risk?” Dr. Levenson asked. “Women; those who are younger and have fewer years of work experience; those working on the front lines such as nurses and advanced practice professionals; and people with preexisting vulnerabilities to psychiatric disorders including anxiety, depression, obsessional symptoms, substance use, suicidal behavior, and impulse control disorders are likely to be especially vulnerable to stress-related symptoms.”

At CUIMC, there were certain “tipping points,” to the vulnerability of health care worker well-being in the early stage of the COVID-19 pandemic, he said, including the loss of an emergency medicine physician colleague from death by suicide. “On the national level there were so many other issues going on such as health care disparities of the COVID-19 infection itself, the murder of George Floyd in Minneapolis, other issues of racial injustice, a tense political climate with an upcoming election at the time, and other factors related to the natural climate concerns,” he said. This prompted several faculty members in the CUIMC department of psychiatry including Claude Ann Mellins, PhD, Laurel S. Mayer, MD, and Lourival Baptista-Neto, MD, to partner with ColumbiaDoctors and New York-Presbyterian Hospital and develop a model of care for health care workers known as CopeColumbia, a virtual program intended to address staff burnout and fatigue, with an emphasis on prevention and promotion of resilience.* It launched in March of 2020 and consists of 1:1 peer support, a peer support group program, town halls/webinars, and an active web site.

The 1:1 peer support sessions typically last 20-30 minutes and provide easy access for all distressed hospital and medical center staff. “We have a phone line staffed by Columbia psychiatrists and psychologists so that a distressed staff member can reach support directly,” he said. The format of these sessions includes a brief discussion of challenges and brainstorming around potential coping strategies. “This is not a psychotherapy session,” Dr. Levenson said. “Each session can be individualized to further assess the type of distress or to implement rating scales such as the Generalized Anxiety Disorder-7 scale to assess for signs and symptoms consistent with GAD. There are options to schedule a second or third peer support session, or a prompt referral within Columbia psychiatry when indicated.”

A typical peer support group meeting lasts about 30 minutes and comprises individual divisions or departments. Some goals of the peer groups are to discuss unique challenges of the work environment and to encourage the members of the group to come up with solutions; to promote team support and coping; to teach resilience-enhancing strategies from empirically based treatments such as CBT, “and to end each meeting with expressions of gratitude and of thanks within the group,” he said.

According to Dr. Levenson, sample questions CopeColumbia faculty use to facilitate coping, include “which coping skills are working for you?”; “Are you able to be present?”; “Have you honored loss with any specific ways or traditions?”; “Do you have any work buddies who support you and vice versa?”; “Can your work community build off each other’s individual strengths to help both the individual and the work group cope optimally?”; and “How can your work team help facilitate each other to best support each other?”

Other aspects of the CopeColumbia program include town halls/grand rounds that range from 30 to 60 minutes in length. “It may be a virtual presentation from a mental health professional on specific aspects of coping such as relaxation techniques,” he said. “The focus is how to manage stress, anxiety, trauma, loss, and grief. It also includes an active Q&A to engage staff participants. The advantage of this format is that you can reach many staff in an entire department.” The program also has an active web site for staff with both internal and external support links including mindfulness, meditation, exercise, parenting suggestions/caregiving, and other resources to promote well-being and resilience for staff and family.

To date, certain themes emerged from the 1:1 and peer support group sessions, including expressions of difficulty adapting to “such a new reality,” compared with the pre-COVID era. “Staff would often express anticipatory anxiety and uncertainty, such as is there going to be another surge of COVID-19 cases, and will there be a change in policies?” Dr. Levenson said. “There was a lot of expression of stress and frustration related to politicizing the virus and public containment strategies, both on a local and national level.”

Staff also mentioned the loss of usual coping strategies because of prolonged social isolation, especially for those doing remote work, and the loss of usual support resources that have helped them in the past. “They also reported delayed trauma and grief reactions, including symptoms of depression, anxiety, and posttraumatic stress,” he said. “Health care workers with children mentioned high levels of stress related to childcare, increased workload, and what seems like an impossible work-life balance.” Many reported exhaustion and irritability, “which could affect and cause tension within the work group and challenges to effective team cohesion,” he said. “There were also stressors related to the impact of racial injustices and the [presidential] election that could exacerbate the impact of COVID-19.”

Dr. Levenson hopes that CopeColumbia serves as a model for other health care systems looking for ways to support the mental well-being of their employees. “We want to promote the message that emotional health should have the same priority level as physical health,” he said. “The term that I like to use is total health. Addressing the well-being of health care workers is critical for a healthy workforce and for delivering high-quality patient care.”

He reported having no relevant financial disclosures related to his presentation.

Correction, 2/28/22: An earlier version of this article misstated Dr. Lourival Baptista-Neto's name.

LAS VEGAS – Long after the acute phase of the COVID-19 pandemic subsides, the psychological sequelae and behavioral effects of persistent distress will likely persist for health care workers, according to Jon A. Levenson, MD.

“We can learn from previous pandemics and epidemics, which will be important for us going forward from COVID-19,” Dr. Levenson, associate professor of psychiatry at Columbia University Irving Medical Center, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association.

During the severe acute respiratory syndrome (SARS) epidemic in 2005, 68% of health care workers reported significant job-related stress, including increased workload, changing work duties, redeployment, shortage of medical supplies, concerns about insufficient personal protective equipment (PPE), lack of safety at work, absence of effective treatment protocols, inconsistent organizational support and information and misinformation from hospital management, and witnessing intense pain, isolation, and loss on a daily basis with few opportunities to take breaks (Psychiatr Serv. 2020 Oct 6. doi: 10.1176/appi.ps.202000274).

Personal concerns associated with psychopathological symptoms included spreading infection to family members; feeling responsibility for family members’ social isolation; self-isolating to avoid infecting family, which can lead to increased loneliness and sadness. “For those who were working remotely, this level of work is hard and challenging,” Dr. Levenson said. “For those who are parents, the 24-hour childcare responsibilities exist on top of work. They often found they can’t unwind with friends.”

Across SARS, MERS, Ebola, and swine flu, a wide range of prevalence in symptoms of distress, stress, anxiety, depressive symptoms, and substance use emerged, he continued. During COVID-19, at least three studies reported significant percentages of distress, depression, anxiety, insomnia, and PTSD among health care workers (JAMA Netw Open. 2020;3[3]:e203976, Front Psychol. 2020 Dec 8;11:608986., and Gen Hosp Psychiatry. Sep-Oct 2020;66:1-8).

“Who is at most-increased risk?” Dr. Levenson asked. “Women; those who are younger and have fewer years of work experience; those working on the front lines such as nurses and advanced practice professionals; and people with preexisting vulnerabilities to psychiatric disorders including anxiety, depression, obsessional symptoms, substance use, suicidal behavior, and impulse control disorders are likely to be especially vulnerable to stress-related symptoms.”

At CUIMC, there were certain “tipping points,” to the vulnerability of health care worker well-being in the early stage of the COVID-19 pandemic, he said, including the loss of an emergency medicine physician colleague from death by suicide. “On the national level there were so many other issues going on such as health care disparities of the COVID-19 infection itself, the murder of George Floyd in Minneapolis, other issues of racial injustice, a tense political climate with an upcoming election at the time, and other factors related to the natural climate concerns,” he said. This prompted several faculty members in the CUIMC department of psychiatry including Claude Ann Mellins, PhD, Laurel S. Mayer, MD, and Lourival Baptista-Neto, MD, to partner with ColumbiaDoctors and New York-Presbyterian Hospital and develop a model of care for health care workers known as CopeColumbia, a virtual program intended to address staff burnout and fatigue, with an emphasis on prevention and promotion of resilience.* It launched in March of 2020 and consists of 1:1 peer support, a peer support group program, town halls/webinars, and an active web site.

The 1:1 peer support sessions typically last 20-30 minutes and provide easy access for all distressed hospital and medical center staff. “We have a phone line staffed by Columbia psychiatrists and psychologists so that a distressed staff member can reach support directly,” he said. The format of these sessions includes a brief discussion of challenges and brainstorming around potential coping strategies. “This is not a psychotherapy session,” Dr. Levenson said. “Each session can be individualized to further assess the type of distress or to implement rating scales such as the Generalized Anxiety Disorder-7 scale to assess for signs and symptoms consistent with GAD. There are options to schedule a second or third peer support session, or a prompt referral within Columbia psychiatry when indicated.”

A typical peer support group meeting lasts about 30 minutes and comprises individual divisions or departments. Some goals of the peer groups are to discuss unique challenges of the work environment and to encourage the members of the group to come up with solutions; to promote team support and coping; to teach resilience-enhancing strategies from empirically based treatments such as CBT, “and to end each meeting with expressions of gratitude and of thanks within the group,” he said.

According to Dr. Levenson, sample questions CopeColumbia faculty use to facilitate coping, include “which coping skills are working for you?”; “Are you able to be present?”; “Have you honored loss with any specific ways or traditions?”; “Do you have any work buddies who support you and vice versa?”; “Can your work community build off each other’s individual strengths to help both the individual and the work group cope optimally?”; and “How can your work team help facilitate each other to best support each other?”

Other aspects of the CopeColumbia program include town halls/grand rounds that range from 30 to 60 minutes in length. “It may be a virtual presentation from a mental health professional on specific aspects of coping such as relaxation techniques,” he said. “The focus is how to manage stress, anxiety, trauma, loss, and grief. It also includes an active Q&A to engage staff participants. The advantage of this format is that you can reach many staff in an entire department.” The program also has an active web site for staff with both internal and external support links including mindfulness, meditation, exercise, parenting suggestions/caregiving, and other resources to promote well-being and resilience for staff and family.

To date, certain themes emerged from the 1:1 and peer support group sessions, including expressions of difficulty adapting to “such a new reality,” compared with the pre-COVID era. “Staff would often express anticipatory anxiety and uncertainty, such as is there going to be another surge of COVID-19 cases, and will there be a change in policies?” Dr. Levenson said. “There was a lot of expression of stress and frustration related to politicizing the virus and public containment strategies, both on a local and national level.”

Staff also mentioned the loss of usual coping strategies because of prolonged social isolation, especially for those doing remote work, and the loss of usual support resources that have helped them in the past. “They also reported delayed trauma and grief reactions, including symptoms of depression, anxiety, and posttraumatic stress,” he said. “Health care workers with children mentioned high levels of stress related to childcare, increased workload, and what seems like an impossible work-life balance.” Many reported exhaustion and irritability, “which could affect and cause tension within the work group and challenges to effective team cohesion,” he said. “There were also stressors related to the impact of racial injustices and the [presidential] election that could exacerbate the impact of COVID-19.”

Dr. Levenson hopes that CopeColumbia serves as a model for other health care systems looking for ways to support the mental well-being of their employees. “We want to promote the message that emotional health should have the same priority level as physical health,” he said. “The term that I like to use is total health. Addressing the well-being of health care workers is critical for a healthy workforce and for delivering high-quality patient care.”

He reported having no relevant financial disclosures related to his presentation.

Correction, 2/28/22: An earlier version of this article misstated Dr. Lourival Baptista-Neto's name.

LAS VEGAS – Long after the acute phase of the COVID-19 pandemic subsides, the psychological sequelae and behavioral effects of persistent distress will likely persist for health care workers, according to Jon A. Levenson, MD.

“We can learn from previous pandemics and epidemics, which will be important for us going forward from COVID-19,” Dr. Levenson, associate professor of psychiatry at Columbia University Irving Medical Center, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association.

During the severe acute respiratory syndrome (SARS) epidemic in 2005, 68% of health care workers reported significant job-related stress, including increased workload, changing work duties, redeployment, shortage of medical supplies, concerns about insufficient personal protective equipment (PPE), lack of safety at work, absence of effective treatment protocols, inconsistent organizational support and information and misinformation from hospital management, and witnessing intense pain, isolation, and loss on a daily basis with few opportunities to take breaks (Psychiatr Serv. 2020 Oct 6. doi: 10.1176/appi.ps.202000274).

Personal concerns associated with psychopathological symptoms included spreading infection to family members; feeling responsibility for family members’ social isolation; self-isolating to avoid infecting family, which can lead to increased loneliness and sadness. “For those who were working remotely, this level of work is hard and challenging,” Dr. Levenson said. “For those who are parents, the 24-hour childcare responsibilities exist on top of work. They often found they can’t unwind with friends.”

Across SARS, MERS, Ebola, and swine flu, a wide range of prevalence in symptoms of distress, stress, anxiety, depressive symptoms, and substance use emerged, he continued. During COVID-19, at least three studies reported significant percentages of distress, depression, anxiety, insomnia, and PTSD among health care workers (JAMA Netw Open. 2020;3[3]:e203976, Front Psychol. 2020 Dec 8;11:608986., and Gen Hosp Psychiatry. Sep-Oct 2020;66:1-8).

“Who is at most-increased risk?” Dr. Levenson asked. “Women; those who are younger and have fewer years of work experience; those working on the front lines such as nurses and advanced practice professionals; and people with preexisting vulnerabilities to psychiatric disorders including anxiety, depression, obsessional symptoms, substance use, suicidal behavior, and impulse control disorders are likely to be especially vulnerable to stress-related symptoms.”

At CUIMC, there were certain “tipping points,” to the vulnerability of health care worker well-being in the early stage of the COVID-19 pandemic, he said, including the loss of an emergency medicine physician colleague from death by suicide. “On the national level there were so many other issues going on such as health care disparities of the COVID-19 infection itself, the murder of George Floyd in Minneapolis, other issues of racial injustice, a tense political climate with an upcoming election at the time, and other factors related to the natural climate concerns,” he said. This prompted several faculty members in the CUIMC department of psychiatry including Claude Ann Mellins, PhD, Laurel S. Mayer, MD, and Lourival Baptista-Neto, MD, to partner with ColumbiaDoctors and New York-Presbyterian Hospital and develop a model of care for health care workers known as CopeColumbia, a virtual program intended to address staff burnout and fatigue, with an emphasis on prevention and promotion of resilience.* It launched in March of 2020 and consists of 1:1 peer support, a peer support group program, town halls/webinars, and an active web site.

The 1:1 peer support sessions typically last 20-30 minutes and provide easy access for all distressed hospital and medical center staff. “We have a phone line staffed by Columbia psychiatrists and psychologists so that a distressed staff member can reach support directly,” he said. The format of these sessions includes a brief discussion of challenges and brainstorming around potential coping strategies. “This is not a psychotherapy session,” Dr. Levenson said. “Each session can be individualized to further assess the type of distress or to implement rating scales such as the Generalized Anxiety Disorder-7 scale to assess for signs and symptoms consistent with GAD. There are options to schedule a second or third peer support session, or a prompt referral within Columbia psychiatry when indicated.”

A typical peer support group meeting lasts about 30 minutes and comprises individual divisions or departments. Some goals of the peer groups are to discuss unique challenges of the work environment and to encourage the members of the group to come up with solutions; to promote team support and coping; to teach resilience-enhancing strategies from empirically based treatments such as CBT, “and to end each meeting with expressions of gratitude and of thanks within the group,” he said.

According to Dr. Levenson, sample questions CopeColumbia faculty use to facilitate coping, include “which coping skills are working for you?”; “Are you able to be present?”; “Have you honored loss with any specific ways or traditions?”; “Do you have any work buddies who support you and vice versa?”; “Can your work community build off each other’s individual strengths to help both the individual and the work group cope optimally?”; and “How can your work team help facilitate each other to best support each other?”

Other aspects of the CopeColumbia program include town halls/grand rounds that range from 30 to 60 minutes in length. “It may be a virtual presentation from a mental health professional on specific aspects of coping such as relaxation techniques,” he said. “The focus is how to manage stress, anxiety, trauma, loss, and grief. It also includes an active Q&A to engage staff participants. The advantage of this format is that you can reach many staff in an entire department.” The program also has an active web site for staff with both internal and external support links including mindfulness, meditation, exercise, parenting suggestions/caregiving, and other resources to promote well-being and resilience for staff and family.

To date, certain themes emerged from the 1:1 and peer support group sessions, including expressions of difficulty adapting to “such a new reality,” compared with the pre-COVID era. “Staff would often express anticipatory anxiety and uncertainty, such as is there going to be another surge of COVID-19 cases, and will there be a change in policies?” Dr. Levenson said. “There was a lot of expression of stress and frustration related to politicizing the virus and public containment strategies, both on a local and national level.”

Staff also mentioned the loss of usual coping strategies because of prolonged social isolation, especially for those doing remote work, and the loss of usual support resources that have helped them in the past. “They also reported delayed trauma and grief reactions, including symptoms of depression, anxiety, and posttraumatic stress,” he said. “Health care workers with children mentioned high levels of stress related to childcare, increased workload, and what seems like an impossible work-life balance.” Many reported exhaustion and irritability, “which could affect and cause tension within the work group and challenges to effective team cohesion,” he said. “There were also stressors related to the impact of racial injustices and the [presidential] election that could exacerbate the impact of COVID-19.”

Dr. Levenson hopes that CopeColumbia serves as a model for other health care systems looking for ways to support the mental well-being of their employees. “We want to promote the message that emotional health should have the same priority level as physical health,” he said. “The term that I like to use is total health. Addressing the well-being of health care workers is critical for a healthy workforce and for delivering high-quality patient care.”

He reported having no relevant financial disclosures related to his presentation.

Correction, 2/28/22: An earlier version of this article misstated Dr. Lourival Baptista-Neto's name.

LAS VEGAS – How do you know when a patient is a candidate for electroconvulsive therapy (ECT)?

In the opinion of Mark S. George, MD, it depends on the level of treatment resistance, other treatments the person may be receiving for severe depression or bipolar disorder, and the level of acuity.

“Acute ECT is also useful for catatonia that does not resolve with benzodiazepines, and it also works well for acute suicidality,” Dr. George, distinguished professor of psychiatry, radiology, and neurology at the Medical University of South Carolina, Charleston, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “The other reason you would go straight to ECT would be if someone has had good prior ECT response.”

ECT is the oldest biological psychiatry therapy, a treatment that he characterized as “our most effective treatment for depression. It is lifesaving. Some studies suggests that ECT is effective in Parkinson’s disease and schizophrenia. Antidepressant effects generally take 2-3 weeks, but quicker responses are sometimes seen, especially in patients with bipolar depression.”

In the past 20 years of research studies involving ECT, investigators have discovered that a generalized seizure of adequate duration is necessary for adequate antidepressant effects; reduced therapeutic effects are seen with parietal placement, meaning that proper scalp placement matters; a dose titration over the 12 treatments improves efficacy, and smaller pulse widths are more effective and may result in fewer toxic side effects. “ECT is still relatively spatially crude compared with the other brain stimulation treatments,” said Dr. George, editor-in-chief of Brain Stimulation. “It’s also invasive, requiring repeated anesthesia, and sometimes has possible side effects including impacts on short-term memory.”

An emerging adjunct to ECT is cervical invasive vagus nerve stimulation (VNS) therapy, in which mild electrical pulses applied to the left vagus nerve in the neck send signals to the brain. “Surgeons wrap a wire around the vagus nerve and connect the wire to a generator which is embedded in the chest wall,” Dr. George explained. “The generator sends out a signal through the vagus nerve intermittently. You can program how it does that.”

A device from LivaNova known as the VNS Pulse Model 102 Generator was granted clearance for depression based on a comparative study, but in the absence of class I evidence. The generator is about the size of a quarter, is embedded under the skin, and its battery lasts for 8-10 years. “Patients are given a static magnet to use to turn the device off if they’re having side effects, as a safety precaution,” said Dr. George, a staff physician at the Ralph H. Johnson VA Medical Center in Charleston. “The side effects are mainly stimulation-based and typically decrease over time. There is a low rate of treatment discontinuation and no signal for treatment-related emergence of suicidal ideation/behavior. Sometimes you can get emergent mania or hypermania, but it’s rare. It’s pretty safe, but the insurance companies have been very slow to pay. You only get about 30% remission, this takes several months to years to achieve, and there’s no way to tell who’s going to respond before you place the device.”

However, results from a 5-year observational study of patients with treatment-resistant depression who were treated at 61 sites with VNS or treatment as usual found that the antidepressant effects built over time compared with treatment as usual (Am J Psychiatry 2017;174[7]:640-8). “There is remarkable durability but it’s not very fast,” he said. “It’s three months before you start seeing any differences.”

According to Dr. George, data from an informal registry of Medicare patients who received VNS treatment “did so much better” than untreated patients. “They didn’t need as much ECT and didn’t require as many hospitalizations,” he said. “They weren’t changing medications nearly as much. They found that VNS was saving money and saving people’s lives.” As a result, in September of 2019 LivaNova launched a prospective, multicenter, randomized, controlled, blinded trial of subjects implanted with VNS therapy, called RECOVER. Active treatment and no stimulation control are randomized at least 2 weeks after implantation and observed for 12 months. The study is ongoing with results expected in 2022 or 2023.

Dr. George disclosed that he is a paid consultant for Neurolief, Microtransponder, and Sooma and that he has been a paid consultant for GSK, Cyberonics, NeuroPace, and Jazz. He is an unpaid consultant to Brainsway, Neuronetics, Neostim, Neosync, and Magnus Medical.

LAS VEGAS – How do you know when a patient is a candidate for electroconvulsive therapy (ECT)?

In the opinion of Mark S. George, MD, it depends on the level of treatment resistance, other treatments the person may be receiving for severe depression or bipolar disorder, and the level of acuity.

“Acute ECT is also useful for catatonia that does not resolve with benzodiazepines, and it also works well for acute suicidality,” Dr. George, distinguished professor of psychiatry, radiology, and neurology at the Medical University of South Carolina, Charleston, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “The other reason you would go straight to ECT would be if someone has had good prior ECT response.”

ECT is the oldest biological psychiatry therapy, a treatment that he characterized as “our most effective treatment for depression. It is lifesaving. Some studies suggests that ECT is effective in Parkinson’s disease and schizophrenia. Antidepressant effects generally take 2-3 weeks, but quicker responses are sometimes seen, especially in patients with bipolar depression.”

In the past 20 years of research studies involving ECT, investigators have discovered that a generalized seizure of adequate duration is necessary for adequate antidepressant effects; reduced therapeutic effects are seen with parietal placement, meaning that proper scalp placement matters; a dose titration over the 12 treatments improves efficacy, and smaller pulse widths are more effective and may result in fewer toxic side effects. “ECT is still relatively spatially crude compared with the other brain stimulation treatments,” said Dr. George, editor-in-chief of Brain Stimulation. “It’s also invasive, requiring repeated anesthesia, and sometimes has possible side effects including impacts on short-term memory.”

An emerging adjunct to ECT is cervical invasive vagus nerve stimulation (VNS) therapy, in which mild electrical pulses applied to the left vagus nerve in the neck send signals to the brain. “Surgeons wrap a wire around the vagus nerve and connect the wire to a generator which is embedded in the chest wall,” Dr. George explained. “The generator sends out a signal through the vagus nerve intermittently. You can program how it does that.”

A device from LivaNova known as the VNS Pulse Model 102 Generator was granted clearance for depression based on a comparative study, but in the absence of class I evidence. The generator is about the size of a quarter, is embedded under the skin, and its battery lasts for 8-10 years. “Patients are given a static magnet to use to turn the device off if they’re having side effects, as a safety precaution,” said Dr. George, a staff physician at the Ralph H. Johnson VA Medical Center in Charleston. “The side effects are mainly stimulation-based and typically decrease over time. There is a low rate of treatment discontinuation and no signal for treatment-related emergence of suicidal ideation/behavior. Sometimes you can get emergent mania or hypermania, but it’s rare. It’s pretty safe, but the insurance companies have been very slow to pay. You only get about 30% remission, this takes several months to years to achieve, and there’s no way to tell who’s going to respond before you place the device.”

However, results from a 5-year observational study of patients with treatment-resistant depression who were treated at 61 sites with VNS or treatment as usual found that the antidepressant effects built over time compared with treatment as usual (Am J Psychiatry 2017;174[7]:640-8). “There is remarkable durability but it’s not very fast,” he said. “It’s three months before you start seeing any differences.”

According to Dr. George, data from an informal registry of Medicare patients who received VNS treatment “did so much better” than untreated patients. “They didn’t need as much ECT and didn’t require as many hospitalizations,” he said. “They weren’t changing medications nearly as much. They found that VNS was saving money and saving people’s lives.” As a result, in September of 2019 LivaNova launched a prospective, multicenter, randomized, controlled, blinded trial of subjects implanted with VNS therapy, called RECOVER. Active treatment and no stimulation control are randomized at least 2 weeks after implantation and observed for 12 months. The study is ongoing with results expected in 2022 or 2023.

Dr. George disclosed that he is a paid consultant for Neurolief, Microtransponder, and Sooma and that he has been a paid consultant for GSK, Cyberonics, NeuroPace, and Jazz. He is an unpaid consultant to Brainsway, Neuronetics, Neostim, Neosync, and Magnus Medical.

LAS VEGAS – How do you know when a patient is a candidate for electroconvulsive therapy (ECT)?

In the opinion of Mark S. George, MD, it depends on the level of treatment resistance, other treatments the person may be receiving for severe depression or bipolar disorder, and the level of acuity.

“Acute ECT is also useful for catatonia that does not resolve with benzodiazepines, and it also works well for acute suicidality,” Dr. George, distinguished professor of psychiatry, radiology, and neurology at the Medical University of South Carolina, Charleston, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “The other reason you would go straight to ECT would be if someone has had good prior ECT response.”

ECT is the oldest biological psychiatry therapy, a treatment that he characterized as “our most effective treatment for depression. It is lifesaving. Some studies suggests that ECT is effective in Parkinson’s disease and schizophrenia. Antidepressant effects generally take 2-3 weeks, but quicker responses are sometimes seen, especially in patients with bipolar depression.”

In the past 20 years of research studies involving ECT, investigators have discovered that a generalized seizure of adequate duration is necessary for adequate antidepressant effects; reduced therapeutic effects are seen with parietal placement, meaning that proper scalp placement matters; a dose titration over the 12 treatments improves efficacy, and smaller pulse widths are more effective and may result in fewer toxic side effects. “ECT is still relatively spatially crude compared with the other brain stimulation treatments,” said Dr. George, editor-in-chief of Brain Stimulation. “It’s also invasive, requiring repeated anesthesia, and sometimes has possible side effects including impacts on short-term memory.”

An emerging adjunct to ECT is cervical invasive vagus nerve stimulation (VNS) therapy, in which mild electrical pulses applied to the left vagus nerve in the neck send signals to the brain. “Surgeons wrap a wire around the vagus nerve and connect the wire to a generator which is embedded in the chest wall,” Dr. George explained. “The generator sends out a signal through the vagus nerve intermittently. You can program how it does that.”

A device from LivaNova known as the VNS Pulse Model 102 Generator was granted clearance for depression based on a comparative study, but in the absence of class I evidence. The generator is about the size of a quarter, is embedded under the skin, and its battery lasts for 8-10 years. “Patients are given a static magnet to use to turn the device off if they’re having side effects, as a safety precaution,” said Dr. George, a staff physician at the Ralph H. Johnson VA Medical Center in Charleston. “The side effects are mainly stimulation-based and typically decrease over time. There is a low rate of treatment discontinuation and no signal for treatment-related emergence of suicidal ideation/behavior. Sometimes you can get emergent mania or hypermania, but it’s rare. It’s pretty safe, but the insurance companies have been very slow to pay. You only get about 30% remission, this takes several months to years to achieve, and there’s no way to tell who’s going to respond before you place the device.”

However, results from a 5-year observational study of patients with treatment-resistant depression who were treated at 61 sites with VNS or treatment as usual found that the antidepressant effects built over time compared with treatment as usual (Am J Psychiatry 2017;174[7]:640-8). “There is remarkable durability but it’s not very fast,” he said. “It’s three months before you start seeing any differences.”

According to Dr. George, data from an informal registry of Medicare patients who received VNS treatment “did so much better” than untreated patients. “They didn’t need as much ECT and didn’t require as many hospitalizations,” he said. “They weren’t changing medications nearly as much. They found that VNS was saving money and saving people’s lives.” As a result, in September of 2019 LivaNova launched a prospective, multicenter, randomized, controlled, blinded trial of subjects implanted with VNS therapy, called RECOVER. Active treatment and no stimulation control are randomized at least 2 weeks after implantation and observed for 12 months. The study is ongoing with results expected in 2022 or 2023.

Dr. George disclosed that he is a paid consultant for Neurolief, Microtransponder, and Sooma and that he has been a paid consultant for GSK, Cyberonics, NeuroPace, and Jazz. He is an unpaid consultant to Brainsway, Neuronetics, Neostim, Neosync, and Magnus Medical.

When counseling patients with warts, Adam Friedman, MD, admits that he feels like a character from “Game of Thrones” since many treatment options are “medieval and painful,” from duct tape occlusion to the stings of liquid nitrogen and salicylic acid.

“We can combine destructive, immunologic, and cytotoxic approaches,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said at the ODAC Dermatology, Aesthetic & Surgical Conference. “It’s not one or the other, we want to be aggressive. Combining therapies in the office and at home will accelerate clearance of warts; monotherapy just doesn’t cut it.”

At the initial clinic visit, he advises asking patients how long the warts have been present, because sometimes they will go away within a year or two without treatment. “If someone says, ‘I’ve had these for years,’ you know you’re in for the long haul and you have to be aggressive with their therapy,” Dr. Friedman said. “Sometimes you’ll pick up plantar warts on a full-body skin exam and the patient may say, ‘I really don’t care. Please don’t touch them,’ so it’s important to understand how they are impacting quality of life.”

Patients should also be asked what treatments they have used previously, and it is important to set some realistic expectations and dispel some myths, Dr. Friedman said. “One of the most important things is that you must get these patients back. This is not often a one and done approach; you need to keep hitting them [with therapy], because if you let one infected keratinocyte survive, it’s going to come back and it’s still going to be contagious – more likely for that patient than for anyone else.”

The application of liquid nitrogen is a popular, inexpensive destructive treatment option, with spray canisters that cost about $600. “You have to consider the temperature of the liquid nitrogen spray because melanocytes die at negative 5 degrees Celsius, so you have to be mindful in patients with darker skin tones that you may leave with permanent dyschromia, meaning hypopigmentation or depigmentation when you do this,” he said. Because it is painful, “we’re limited when it comes to treating children with warts who are younger than 9 or 10. I don’t think the Q-tip method or dipping a hemostat in cryogen and touching the tip really works. You’ve got to create a nice ice ball that thaws and kills the infected keratinocytes.”

Dr. Friedman favors a 10-second freeze of the wart, usually for two to three cycles depending on its anatomic location, and he may give patients imiquimod or 5-FU to use at home for 5 nights of the week. A recently published study found that the use of ultrasound gel increases the efficacy of cryotherapy in the treatment of warts.

Another destructive treatment approach is cantharidin 0.7% applied topically in the office. It is believed to activate neutral serine proteases that cause degeneration of the desmosomal plaque, leading to detachment of tonofilaments from desmosomes. Repeat in-office applications within 14-21 days may be necessary for this treatment, which is not approved by the Food and Drug Administration. “It is painless on application unless there’s a break in the skin,” Dr. Friedman said.

For warts on thicker areas such as palms and soles, he often employs combination therapy with cantharidin 1%, salicylic acid 30%, and podophyllotoxin 5%. “This can hurt a little bit, but some patients require only one treatment for cure,” he said. “Efficacy depends on the size of the wart.”

VP-102, a proprietary, drug-device combination product containing cantharidin, 0.7% “is coming down the pike,” Dr. Friedman said. “From the data we have, it seems that pairing with a curette or a #15 blade first gets better penetration, which makes sense. Patients come back every 3-4 weeks for treatment. It is a big investment, but it is worth it. I tell patients it’s not worth starting if you’re not going to see it through. I tell them, ‘we’re going to see a lot of each other until this is clear.’ ”

As for immunomodulatory approaches, imiquimod 5% cream is approved for treating genital and perianal warts. In Dr. Friedman’s clinical experience, it has limited efficacy on keratinized skin unless the surface has been disrupted, “so don’t even waste your time unless you are using some approach to enhance skin penetration,” he advised. “Insurance coverage can be a challenge,” he added.

He recommends application with salicylic acid alternating with imiquimod 5% cream every night at bedtime – under occlusion for thicker skinned areas.

For patients who favor use of natural products, off-label ingenol mebutate is an option. A case series of its use in 17 patients with anogenital warts found that 16 experienced clearance of all warts treated with either 0.05% or 0.015% ingenol mebutate gel. Local irritation occurred within 24-48 hours and lasted 2-5 days.

A natural alternative treatment is Candida albicans skin test antigen (Candin), especially for cases of multiple lesions on the hands and feet, because a field effect can be achieved, Dr. Friedman said. “The idea here is simple. At most, you’re talking about injecting a sentinel wart with 0.3 mL Candin 2-10 times every 3 weeks. The wart may be in a field of warts. That will induce an immune reaction that brings in the cavalry. I find that it works very well but it is painful, so when you’re injecting the feet, get the foot positioned well, because that patient may inadvertently kick you in the face [upon injection].”

Authors of a recent systematic review and meta-analysis highlighted the efficacy for systemic retinoids in the treatment of warts, particularly recalcitrant or recurrent types (Dermatol Ther 2021 34[2]:e14793). “Tazarotene is going to be your best bet if you can get it,” Dr. Friedman said. “If you have to go lower like OTC adapalene or tretinoin, be my guest, but tazarotene works best by slowing down that rapid turnover that the virus is imparting on the basal keratinocyte layer. It can enhance penetration of drug but also thin the warts out.”

Dr. Friedman characterized human papilloma virus (HPV) vaccines, such as Gardasil 9, as “one of the greatest innovations” in the treatment of warts. While indicated as a preventive strategy, “it also works as treatment. I’ve had patients with recalcitrant genital warts who will clear after taking the vaccine. It is something to think about as an adjuvant to everything we do, because it can function as a treatment.”

Another immunologic treatment option is the oral H2-receptor antagonist cimetidine taken 30 mg/kg per day for 3-5 months. “There is mixed evidence of efficacy with this,” Dr. Friedman said. “I tend to use it in cases of innumerable flat warts.”

As for cytotoxic options for treating warts, bleomycin works at 250-1,000 U/mL injected per lesion, with lidocaine. “This is painful to patients both on application and post treatment,” he said. “But it works really well when used properly.”

In one study of 46 patients who received intralesional bleomycin, 74% patients had complete resolution of all warts with an average of 1.7 treatments. About 70% of patients experienced pain that lasted less than 2 days after treatment. In a separate study of patients treated with bleomycin for warts, researchers in India diluted bleomycin with lidocaine to help mitigate some of that pain.

An additional cytotoxic option, 5-FU in formulations of 5% cream/solution or 1% cream, can effectively treat warts. Dr. Friedman typically suggests application to the affected area twice daily for 3-5 weeks. “The cost can be high especially for off-label use,” he said. He noted that Skin Medicinals makes a compounded wart solution composed of 5% 5-FU and salicylic acid 30% solution. A 50 mL container sells for about $50.

Dr. Friedman had no relevant disclosures related to his presentation.

When counseling patients with warts, Adam Friedman, MD, admits that he feels like a character from “Game of Thrones” since many treatment options are “medieval and painful,” from duct tape occlusion to the stings of liquid nitrogen and salicylic acid.

“We can combine destructive, immunologic, and cytotoxic approaches,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said at the ODAC Dermatology, Aesthetic & Surgical Conference. “It’s not one or the other, we want to be aggressive. Combining therapies in the office and at home will accelerate clearance of warts; monotherapy just doesn’t cut it.”

At the initial clinic visit, he advises asking patients how long the warts have been present, because sometimes they will go away within a year or two without treatment. “If someone says, ‘I’ve had these for years,’ you know you’re in for the long haul and you have to be aggressive with their therapy,” Dr. Friedman said. “Sometimes you’ll pick up plantar warts on a full-body skin exam and the patient may say, ‘I really don’t care. Please don’t touch them,’ so it’s important to understand how they are impacting quality of life.”

Patients should also be asked what treatments they have used previously, and it is important to set some realistic expectations and dispel some myths, Dr. Friedman said. “One of the most important things is that you must get these patients back. This is not often a one and done approach; you need to keep hitting them [with therapy], because if you let one infected keratinocyte survive, it’s going to come back and it’s still going to be contagious – more likely for that patient than for anyone else.”

The application of liquid nitrogen is a popular, inexpensive destructive treatment option, with spray canisters that cost about $600. “You have to consider the temperature of the liquid nitrogen spray because melanocytes die at negative 5 degrees Celsius, so you have to be mindful in patients with darker skin tones that you may leave with permanent dyschromia, meaning hypopigmentation or depigmentation when you do this,” he said. Because it is painful, “we’re limited when it comes to treating children with warts who are younger than 9 or 10. I don’t think the Q-tip method or dipping a hemostat in cryogen and touching the tip really works. You’ve got to create a nice ice ball that thaws and kills the infected keratinocytes.”

Dr. Friedman favors a 10-second freeze of the wart, usually for two to three cycles depending on its anatomic location, and he may give patients imiquimod or 5-FU to use at home for 5 nights of the week. A recently published study found that the use of ultrasound gel increases the efficacy of cryotherapy in the treatment of warts.

Another destructive treatment approach is cantharidin 0.7% applied topically in the office. It is believed to activate neutral serine proteases that cause degeneration of the desmosomal plaque, leading to detachment of tonofilaments from desmosomes. Repeat in-office applications within 14-21 days may be necessary for this treatment, which is not approved by the Food and Drug Administration. “It is painless on application unless there’s a break in the skin,” Dr. Friedman said.

For warts on thicker areas such as palms and soles, he often employs combination therapy with cantharidin 1%, salicylic acid 30%, and podophyllotoxin 5%. “This can hurt a little bit, but some patients require only one treatment for cure,” he said. “Efficacy depends on the size of the wart.”

VP-102, a proprietary, drug-device combination product containing cantharidin, 0.7% “is coming down the pike,” Dr. Friedman said. “From the data we have, it seems that pairing with a curette or a #15 blade first gets better penetration, which makes sense. Patients come back every 3-4 weeks for treatment. It is a big investment, but it is worth it. I tell patients it’s not worth starting if you’re not going to see it through. I tell them, ‘we’re going to see a lot of each other until this is clear.’ ”

As for immunomodulatory approaches, imiquimod 5% cream is approved for treating genital and perianal warts. In Dr. Friedman’s clinical experience, it has limited efficacy on keratinized skin unless the surface has been disrupted, “so don’t even waste your time unless you are using some approach to enhance skin penetration,” he advised. “Insurance coverage can be a challenge,” he added.

He recommends application with salicylic acid alternating with imiquimod 5% cream every night at bedtime – under occlusion for thicker skinned areas.

For patients who favor use of natural products, off-label ingenol mebutate is an option. A case series of its use in 17 patients with anogenital warts found that 16 experienced clearance of all warts treated with either 0.05% or 0.015% ingenol mebutate gel. Local irritation occurred within 24-48 hours and lasted 2-5 days.

A natural alternative treatment is Candida albicans skin test antigen (Candin), especially for cases of multiple lesions on the hands and feet, because a field effect can be achieved, Dr. Friedman said. “The idea here is simple. At most, you’re talking about injecting a sentinel wart with 0.3 mL Candin 2-10 times every 3 weeks. The wart may be in a field of warts. That will induce an immune reaction that brings in the cavalry. I find that it works very well but it is painful, so when you’re injecting the feet, get the foot positioned well, because that patient may inadvertently kick you in the face [upon injection].”

Authors of a recent systematic review and meta-analysis highlighted the efficacy for systemic retinoids in the treatment of warts, particularly recalcitrant or recurrent types (Dermatol Ther 2021 34[2]:e14793). “Tazarotene is going to be your best bet if you can get it,” Dr. Friedman said. “If you have to go lower like OTC adapalene or tretinoin, be my guest, but tazarotene works best by slowing down that rapid turnover that the virus is imparting on the basal keratinocyte layer. It can enhance penetration of drug but also thin the warts out.”

Dr. Friedman characterized human papilloma virus (HPV) vaccines, such as Gardasil 9, as “one of the greatest innovations” in the treatment of warts. While indicated as a preventive strategy, “it also works as treatment. I’ve had patients with recalcitrant genital warts who will clear after taking the vaccine. It is something to think about as an adjuvant to everything we do, because it can function as a treatment.”

Another immunologic treatment option is the oral H2-receptor antagonist cimetidine taken 30 mg/kg per day for 3-5 months. “There is mixed evidence of efficacy with this,” Dr. Friedman said. “I tend to use it in cases of innumerable flat warts.”

As for cytotoxic options for treating warts, bleomycin works at 250-1,000 U/mL injected per lesion, with lidocaine. “This is painful to patients both on application and post treatment,” he said. “But it works really well when used properly.”

In one study of 46 patients who received intralesional bleomycin, 74% patients had complete resolution of all warts with an average of 1.7 treatments. About 70% of patients experienced pain that lasted less than 2 days after treatment. In a separate study of patients treated with bleomycin for warts, researchers in India diluted bleomycin with lidocaine to help mitigate some of that pain.

An additional cytotoxic option, 5-FU in formulations of 5% cream/solution or 1% cream, can effectively treat warts. Dr. Friedman typically suggests application to the affected area twice daily for 3-5 weeks. “The cost can be high especially for off-label use,” he said. He noted that Skin Medicinals makes a compounded wart solution composed of 5% 5-FU and salicylic acid 30% solution. A 50 mL container sells for about $50.

Dr. Friedman had no relevant disclosures related to his presentation.

When counseling patients with warts, Adam Friedman, MD, admits that he feels like a character from “Game of Thrones” since many treatment options are “medieval and painful,” from duct tape occlusion to the stings of liquid nitrogen and salicylic acid.

“We can combine destructive, immunologic, and cytotoxic approaches,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said at the ODAC Dermatology, Aesthetic & Surgical Conference. “It’s not one or the other, we want to be aggressive. Combining therapies in the office and at home will accelerate clearance of warts; monotherapy just doesn’t cut it.”

At the initial clinic visit, he advises asking patients how long the warts have been present, because sometimes they will go away within a year or two without treatment. “If someone says, ‘I’ve had these for years,’ you know you’re in for the long haul and you have to be aggressive with their therapy,” Dr. Friedman said. “Sometimes you’ll pick up plantar warts on a full-body skin exam and the patient may say, ‘I really don’t care. Please don’t touch them,’ so it’s important to understand how they are impacting quality of life.”

Patients should also be asked what treatments they have used previously, and it is important to set some realistic expectations and dispel some myths, Dr. Friedman said. “One of the most important things is that you must get these patients back. This is not often a one and done approach; you need to keep hitting them [with therapy], because if you let one infected keratinocyte survive, it’s going to come back and it’s still going to be contagious – more likely for that patient than for anyone else.”

The application of liquid nitrogen is a popular, inexpensive destructive treatment option, with spray canisters that cost about $600. “You have to consider the temperature of the liquid nitrogen spray because melanocytes die at negative 5 degrees Celsius, so you have to be mindful in patients with darker skin tones that you may leave with permanent dyschromia, meaning hypopigmentation or depigmentation when you do this,” he said. Because it is painful, “we’re limited when it comes to treating children with warts who are younger than 9 or 10. I don’t think the Q-tip method or dipping a hemostat in cryogen and touching the tip really works. You’ve got to create a nice ice ball that thaws and kills the infected keratinocytes.”

Dr. Friedman favors a 10-second freeze of the wart, usually for two to three cycles depending on its anatomic location, and he may give patients imiquimod or 5-FU to use at home for 5 nights of the week. A recently published study found that the use of ultrasound gel increases the efficacy of cryotherapy in the treatment of warts.

Another destructive treatment approach is cantharidin 0.7% applied topically in the office. It is believed to activate neutral serine proteases that cause degeneration of the desmosomal plaque, leading to detachment of tonofilaments from desmosomes. Repeat in-office applications within 14-21 days may be necessary for this treatment, which is not approved by the Food and Drug Administration. “It is painless on application unless there’s a break in the skin,” Dr. Friedman said.

For warts on thicker areas such as palms and soles, he often employs combination therapy with cantharidin 1%, salicylic acid 30%, and podophyllotoxin 5%. “This can hurt a little bit, but some patients require only one treatment for cure,” he said. “Efficacy depends on the size of the wart.”

VP-102, a proprietary, drug-device combination product containing cantharidin, 0.7% “is coming down the pike,” Dr. Friedman said. “From the data we have, it seems that pairing with a curette or a #15 blade first gets better penetration, which makes sense. Patients come back every 3-4 weeks for treatment. It is a big investment, but it is worth it. I tell patients it’s not worth starting if you’re not going to see it through. I tell them, ‘we’re going to see a lot of each other until this is clear.’ ”

As for immunomodulatory approaches, imiquimod 5% cream is approved for treating genital and perianal warts. In Dr. Friedman’s clinical experience, it has limited efficacy on keratinized skin unless the surface has been disrupted, “so don’t even waste your time unless you are using some approach to enhance skin penetration,” he advised. “Insurance coverage can be a challenge,” he added.

He recommends application with salicylic acid alternating with imiquimod 5% cream every night at bedtime – under occlusion for thicker skinned areas.

For patients who favor use of natural products, off-label ingenol mebutate is an option. A case series of its use in 17 patients with anogenital warts found that 16 experienced clearance of all warts treated with either 0.05% or 0.015% ingenol mebutate gel. Local irritation occurred within 24-48 hours and lasted 2-5 days.

A natural alternative treatment is Candida albicans skin test antigen (Candin), especially for cases of multiple lesions on the hands and feet, because a field effect can be achieved, Dr. Friedman said. “The idea here is simple. At most, you’re talking about injecting a sentinel wart with 0.3 mL Candin 2-10 times every 3 weeks. The wart may be in a field of warts. That will induce an immune reaction that brings in the cavalry. I find that it works very well but it is painful, so when you’re injecting the feet, get the foot positioned well, because that patient may inadvertently kick you in the face [upon injection].”

Authors of a recent systematic review and meta-analysis highlighted the efficacy for systemic retinoids in the treatment of warts, particularly recalcitrant or recurrent types (Dermatol Ther 2021 34[2]:e14793). “Tazarotene is going to be your best bet if you can get it,” Dr. Friedman said. “If you have to go lower like OTC adapalene or tretinoin, be my guest, but tazarotene works best by slowing down that rapid turnover that the virus is imparting on the basal keratinocyte layer. It can enhance penetration of drug but also thin the warts out.”

Dr. Friedman characterized human papilloma virus (HPV) vaccines, such as Gardasil 9, as “one of the greatest innovations” in the treatment of warts. While indicated as a preventive strategy, “it also works as treatment. I’ve had patients with recalcitrant genital warts who will clear after taking the vaccine. It is something to think about as an adjuvant to everything we do, because it can function as a treatment.”

Another immunologic treatment option is the oral H2-receptor antagonist cimetidine taken 30 mg/kg per day for 3-5 months. “There is mixed evidence of efficacy with this,” Dr. Friedman said. “I tend to use it in cases of innumerable flat warts.”

As for cytotoxic options for treating warts, bleomycin works at 250-1,000 U/mL injected per lesion, with lidocaine. “This is painful to patients both on application and post treatment,” he said. “But it works really well when used properly.”

In one study of 46 patients who received intralesional bleomycin, 74% patients had complete resolution of all warts with an average of 1.7 treatments. About 70% of patients experienced pain that lasted less than 2 days after treatment. In a separate study of patients treated with bleomycin for warts, researchers in India diluted bleomycin with lidocaine to help mitigate some of that pain.

An additional cytotoxic option, 5-FU in formulations of 5% cream/solution or 1% cream, can effectively treat warts. Dr. Friedman typically suggests application to the affected area twice daily for 3-5 weeks. “The cost can be high especially for off-label use,” he said. He noted that Skin Medicinals makes a compounded wart solution composed of 5% 5-FU and salicylic acid 30% solution. A 50 mL container sells for about $50.

Dr. Friedman had no relevant disclosures related to his presentation.

LAS VEGAS – When evaluating adolescents for suspected substance use disorders, don’t forget to assess for medical conditions such as sexually transmitted diseases and hepatitis C, Timothy E. Wilens, MD, advised during an annual psychopharmacology update held by the Nevada Psychiatric Association.

“We see high rates of STDs, and we have about 10% of our kids who use opioids who already have hepatitis C,” said Dr. Wilens, who is chief of the division of child & adolescent psychiatry at Massachusetts General Hospital, Boston. “These are kids who may be 16, 17, or 18.”

While the CRAFTT Screening Test has been widely used to screen for substance-related risks and problems in adolescents, another more recent option is the Screening to Brief Intervention (S2BI). Both tools collect information about both alcohol and drug use, are supported by strong research, are available for free, and are easy to use, Dr. Wilens said.

After you generate a differential diagnosis for psychiatric/medical symptoms, clinicians should order urine, saliva, or hair toxicology screens. “We don’t recommend that toxicology screens be done by parents; we do the toxicology screens,” he said. “Be careful about certain things like limitations of detection in the case of high-potency benzodiazepines and duration of detection in the case of marijuana use. The other thing is some of our screens can be used qualitatively or quantitatively. Why is that helpful? If you’re following someone who’s on marijuana and they’re cutting back, you can see if use [really] goes down over time.”

In Dr. Wilen’s clinical experience, efforts to stabilize adolescents with substance use disorders are most effective when patients join support groups comprised of other people from similar sociodemographic backgrounds. “There are different self-help philosophies, but when you’re referring, I always tell people: ‘Have the kid look in a mirror.’ So, if you have an LGBTQ patient from the inner city, that person should not be going to an Alcoholics Anonymous meeting of middle-aged persons in the suburbs. That’s not going to work for them. You want them to be with very similar sociodemographic groups if possible.”

Support groups for parents are also helpful. “There are two levels here: Peer groups of parents that help each other with support and find referrals, and there are parent coaching groups, where you have patients work with professionals,” said Dr. Wilens, who is also codirector of the MGH Center for Addiction Medicine. He advises parents to avoid “tough love” as the first step in efforts to help their child. “Tough love is, you throw the kid out of the house because they won’t stop using,” he said. “Where do you think the kid lives if they’re not at home? Where do you think they’re going to go? Maybe to the home of a friend or a family member for 1 or 2 nights but otherwise they’re living on the streets. How do you think they’re going to make a living if they’re living on the streets? They either sell drugs, or they get involved in prostitution. I have worked with more kids who are furious at their parents because they threw them out of the house. I understand where the patients are coming from, but maybe have a graduated exit instead, where the kid has to sleep outside in a camper for 2 nights, or in an isolated room in the house, or to grandma’s house, which smells like mothballs. Have a graduated approach.”

Psychotherapy is the mainstay of treatment and begins with motivational interviewing. To foster a collaborative connection, Dr. Wilens advises clinicians to discuss issues that are problematic instead of focusing on the substance use right off the bat. “Rather than go right to saying, ‘let’s talk about you smoking too much marijuana,’ instead say, ‘what is it you think may be causing the fights with your parents?’ Or, maybe their peer group isn’t accepting them like they used to.”

In his experience, adolescents respond well to goal setting. For example, for patients who say they’re smoking marijuana every day, Dr. Wilens may ask if they can cut back use to three days per week. “I’ll say: ‘I’m going to write this down in the chart,’ ” he said. “They start to work on it. If they come back and they didn’t reach that goal I say: ‘If you can’t cut back it’s okay; I just need to know it.’ ” He also recommends “sobriety sampling” which asks the patient to make a minimal commitment to stop using, for say, 30 days. “Don’t forget to monitor substance use during follow-up meetings.”

According to Dr. Wilens, child psychiatrists can help prevent substance abuse by encouraging discussion within families by the time kids are in fifth grade and encouraging parents to monitor children’s activities, friends, and personal space. “Privacy is a relative term,” he said. “It’s good you’re in their space. Make their beds; go into their bedroom.” He also advises parents to not smoke marijuana behind their kids’ backs. “I love it when parents tell me: ‘They don’t know I smoke marijuana.’ My counter to that is ‘not only do they know, they’re smoking your marijuana.’ ”

He concluded his remarks by encouraging child psychiatrists to advocate for sensible public laws related to marijuana and other substances. “Zero tolerance laws don’t work, because 85% of kids experiment [with drugs],” said Dr. Wilens, who is also professor of psychiatry at Harvard Medical School, Boston. “It works great until it’s your kid or a neighbor’s kid who’s a good kid but gets thrown out of school.”

Dr. Wilens reported that he has received grant support from the National Institutes of Health and the Food and Drug Administration. He has also served as a consultant to Vallon and has a licensing/collaborative agreement with Ironshore and 3D Therapy.

LAS VEGAS – When evaluating adolescents for suspected substance use disorders, don’t forget to assess for medical conditions such as sexually transmitted diseases and hepatitis C, Timothy E. Wilens, MD, advised during an annual psychopharmacology update held by the Nevada Psychiatric Association.

“We see high rates of STDs, and we have about 10% of our kids who use opioids who already have hepatitis C,” said Dr. Wilens, who is chief of the division of child & adolescent psychiatry at Massachusetts General Hospital, Boston. “These are kids who may be 16, 17, or 18.”

While the CRAFTT Screening Test has been widely used to screen for substance-related risks and problems in adolescents, another more recent option is the Screening to Brief Intervention (S2BI). Both tools collect information about both alcohol and drug use, are supported by strong research, are available for free, and are easy to use, Dr. Wilens said.

After you generate a differential diagnosis for psychiatric/medical symptoms, clinicians should order urine, saliva, or hair toxicology screens. “We don’t recommend that toxicology screens be done by parents; we do the toxicology screens,” he said. “Be careful about certain things like limitations of detection in the case of high-potency benzodiazepines and duration of detection in the case of marijuana use. The other thing is some of our screens can be used qualitatively or quantitatively. Why is that helpful? If you’re following someone who’s on marijuana and they’re cutting back, you can see if use [really] goes down over time.”

In Dr. Wilen’s clinical experience, efforts to stabilize adolescents with substance use disorders are most effective when patients join support groups comprised of other people from similar sociodemographic backgrounds. “There are different self-help philosophies, but when you’re referring, I always tell people: ‘Have the kid look in a mirror.’ So, if you have an LGBTQ patient from the inner city, that person should not be going to an Alcoholics Anonymous meeting of middle-aged persons in the suburbs. That’s not going to work for them. You want them to be with very similar sociodemographic groups if possible.”

Support groups for parents are also helpful. “There are two levels here: Peer groups of parents that help each other with support and find referrals, and there are parent coaching groups, where you have patients work with professionals,” said Dr. Wilens, who is also codirector of the MGH Center for Addiction Medicine. He advises parents to avoid “tough love” as the first step in efforts to help their child. “Tough love is, you throw the kid out of the house because they won’t stop using,” he said. “Where do you think the kid lives if they’re not at home? Where do you think they’re going to go? Maybe to the home of a friend or a family member for 1 or 2 nights but otherwise they’re living on the streets. How do you think they’re going to make a living if they’re living on the streets? They either sell drugs, or they get involved in prostitution. I have worked with more kids who are furious at their parents because they threw them out of the house. I understand where the patients are coming from, but maybe have a graduated exit instead, where the kid has to sleep outside in a camper for 2 nights, or in an isolated room in the house, or to grandma’s house, which smells like mothballs. Have a graduated approach.”

Psychotherapy is the mainstay of treatment and begins with motivational interviewing. To foster a collaborative connection, Dr. Wilens advises clinicians to discuss issues that are problematic instead of focusing on the substance use right off the bat. “Rather than go right to saying, ‘let’s talk about you smoking too much marijuana,’ instead say, ‘what is it you think may be causing the fights with your parents?’ Or, maybe their peer group isn’t accepting them like they used to.”

In his experience, adolescents respond well to goal setting. For example, for patients who say they’re smoking marijuana every day, Dr. Wilens may ask if they can cut back use to three days per week. “I’ll say: ‘I’m going to write this down in the chart,’ ” he said. “They start to work on it. If they come back and they didn’t reach that goal I say: ‘If you can’t cut back it’s okay; I just need to know it.’ ” He also recommends “sobriety sampling” which asks the patient to make a minimal commitment to stop using, for say, 30 days. “Don’t forget to monitor substance use during follow-up meetings.”

According to Dr. Wilens, child psychiatrists can help prevent substance abuse by encouraging discussion within families by the time kids are in fifth grade and encouraging parents to monitor children’s activities, friends, and personal space. “Privacy is a relative term,” he said. “It’s good you’re in their space. Make their beds; go into their bedroom.” He also advises parents to not smoke marijuana behind their kids’ backs. “I love it when parents tell me: ‘They don’t know I smoke marijuana.’ My counter to that is ‘not only do they know, they’re smoking your marijuana.’ ”

He concluded his remarks by encouraging child psychiatrists to advocate for sensible public laws related to marijuana and other substances. “Zero tolerance laws don’t work, because 85% of kids experiment [with drugs],” said Dr. Wilens, who is also professor of psychiatry at Harvard Medical School, Boston. “It works great until it’s your kid or a neighbor’s kid who’s a good kid but gets thrown out of school.”

Dr. Wilens reported that he has received grant support from the National Institutes of Health and the Food and Drug Administration. He has also served as a consultant to Vallon and has a licensing/collaborative agreement with Ironshore and 3D Therapy.

LAS VEGAS – When evaluating adolescents for suspected substance use disorders, don’t forget to assess for medical conditions such as sexually transmitted diseases and hepatitis C, Timothy E. Wilens, MD, advised during an annual psychopharmacology update held by the Nevada Psychiatric Association.

“We see high rates of STDs, and we have about 10% of our kids who use opioids who already have hepatitis C,” said Dr. Wilens, who is chief of the division of child & adolescent psychiatry at Massachusetts General Hospital, Boston. “These are kids who may be 16, 17, or 18.”

While the CRAFTT Screening Test has been widely used to screen for substance-related risks and problems in adolescents, another more recent option is the Screening to Brief Intervention (S2BI). Both tools collect information about both alcohol and drug use, are supported by strong research, are available for free, and are easy to use, Dr. Wilens said.

After you generate a differential diagnosis for psychiatric/medical symptoms, clinicians should order urine, saliva, or hair toxicology screens. “We don’t recommend that toxicology screens be done by parents; we do the toxicology screens,” he said. “Be careful about certain things like limitations of detection in the case of high-potency benzodiazepines and duration of detection in the case of marijuana use. The other thing is some of our screens can be used qualitatively or quantitatively. Why is that helpful? If you’re following someone who’s on marijuana and they’re cutting back, you can see if use [really] goes down over time.”

In Dr. Wilen’s clinical experience, efforts to stabilize adolescents with substance use disorders are most effective when patients join support groups comprised of other people from similar sociodemographic backgrounds. “There are different self-help philosophies, but when you’re referring, I always tell people: ‘Have the kid look in a mirror.’ So, if you have an LGBTQ patient from the inner city, that person should not be going to an Alcoholics Anonymous meeting of middle-aged persons in the suburbs. That’s not going to work for them. You want them to be with very similar sociodemographic groups if possible.”

Support groups for parents are also helpful. “There are two levels here: Peer groups of parents that help each other with support and find referrals, and there are parent coaching groups, where you have patients work with professionals,” said Dr. Wilens, who is also codirector of the MGH Center for Addiction Medicine. He advises parents to avoid “tough love” as the first step in efforts to help their child. “Tough love is, you throw the kid out of the house because they won’t stop using,” he said. “Where do you think the kid lives if they’re not at home? Where do you think they’re going to go? Maybe to the home of a friend or a family member for 1 or 2 nights but otherwise they’re living on the streets. How do you think they’re going to make a living if they’re living on the streets? They either sell drugs, or they get involved in prostitution. I have worked with more kids who are furious at their parents because they threw them out of the house. I understand where the patients are coming from, but maybe have a graduated exit instead, where the kid has to sleep outside in a camper for 2 nights, or in an isolated room in the house, or to grandma’s house, which smells like mothballs. Have a graduated approach.”

Psychotherapy is the mainstay of treatment and begins with motivational interviewing. To foster a collaborative connection, Dr. Wilens advises clinicians to discuss issues that are problematic instead of focusing on the substance use right off the bat. “Rather than go right to saying, ‘let’s talk about you smoking too much marijuana,’ instead say, ‘what is it you think may be causing the fights with your parents?’ Or, maybe their peer group isn’t accepting them like they used to.”

In his experience, adolescents respond well to goal setting. For example, for patients who say they’re smoking marijuana every day, Dr. Wilens may ask if they can cut back use to three days per week. “I’ll say: ‘I’m going to write this down in the chart,’ ” he said. “They start to work on it. If they come back and they didn’t reach that goal I say: ‘If you can’t cut back it’s okay; I just need to know it.’ ” He also recommends “sobriety sampling” which asks the patient to make a minimal commitment to stop using, for say, 30 days. “Don’t forget to monitor substance use during follow-up meetings.”

According to Dr. Wilens, child psychiatrists can help prevent substance abuse by encouraging discussion within families by the time kids are in fifth grade and encouraging parents to monitor children’s activities, friends, and personal space. “Privacy is a relative term,” he said. “It’s good you’re in their space. Make their beds; go into their bedroom.” He also advises parents to not smoke marijuana behind their kids’ backs. “I love it when parents tell me: ‘They don’t know I smoke marijuana.’ My counter to that is ‘not only do they know, they’re smoking your marijuana.’ ”

He concluded his remarks by encouraging child psychiatrists to advocate for sensible public laws related to marijuana and other substances. “Zero tolerance laws don’t work, because 85% of kids experiment [with drugs],” said Dr. Wilens, who is also professor of psychiatry at Harvard Medical School, Boston. “It works great until it’s your kid or a neighbor’s kid who’s a good kid but gets thrown out of school.”

Dr. Wilens reported that he has received grant support from the National Institutes of Health and the Food and Drug Administration. He has also served as a consultant to Vallon and has a licensing/collaborative agreement with Ironshore and 3D Therapy.

If you worry that artificial intelligence (AI) will one day replace your own clinical acumen as a dermatologist, Vishal A. Patel, MD, advises you to think differently.

“AI is meant to be an enhancement strategy, a support tool to improve our diagnostic abilities,” Dr. Patel, a Mohs surgeon who is director of cutaneous oncology at the George Washington University Cancer Center, Washington, said during the ODAC Dermatology, Aesthetic & Surgical Conference. “Dermatologists should embrace AI and drive how it is utilized – be the captain of the plane (technology) and the passenger (patient). If we’re not in the forefront of the plane, we’re not to be able to dictate which way we are going with this.”

In 2019, a group of German researchers found that AI can improve accuracy and efficiency of specialists in classifying skin cancer based on dermoscopic images. “I really do believe this is going to be the future,” said Dr. Patel, who was not involved with the study. “Current research involves using supervised learning on known outcomes to determine inputs to predict them. In dermatology, think of identifying melanoma from clinical or dermoscopic images or predicting metastasis risk from digitized pathology slides.”

However, there are currently no universal guidelines on how large an AI dataset needs to be to yield accurate results. In the dermatology literature, most AI datasets range between 600 and 14,000 examples, Dr. Patel said, with a large study-specific variation in performance. “Misleading results can result from unanticipated training errors,” he said.

“The AI network may learn its intended task or an unrelated situational cue. For example, you can use great images to predict melanoma, but you may have an unintended poor outcome related to images that have, say, a ruler inside of them clustered within the melanoma diagnoses.” And unbeknown to the system’s developer, “the algorithm picks up that the ruler is predictive of an image being a melanoma and not the pigmented lesion itself.” In other words, the algorithm is only as good as the dataset being used, he said. “This is the key element, to ask what the dataset is that’s training the tool that you may one day use.”
 

Convolutional neural network

In 2017, a seminal study published in Nature showed that for classification of melanoma and epidermal lesions, a type of AI used in image processing known as a convolutional neural network (CNN) was on par with dermatologists and outperformed the average. For epidermal lesions, the network was one standard deviation higher above the average for dermatologists, while for melanocytic lesions, the network was just below one standard deviation above the average of the dermatologists. A CNN “clearly can perform well because it works on a different level than how our brains work,” Dr. Patel said.

In a separate study, a CNN trained to recognize melanoma in dermoscopic images was compared to 58 international dermatologists with varying levels of dermoscopy experience; 29% were “beginners,” with less than 2 years of experience; 19% were “skilled,” with 2-5 years of experience; and 52% were “experts,” with at least 5 years of experience. The analysis consisted of two experiments: In level I, dermatologists classified lesions based on dermoscopy only. In level II, dermatologists were provided dermoscopy, clinical images, and additional clinical information, while the CNN was trained on images only. The researchers found that most dermatologists were outperformed by the CNN. “Physicians of all different levels of training and experience may benefit from assistance by a CNN’s image classification,” they concluded.
 

Gene expression profiling

Another aspect of AI is gene expression profiling (GEP), which Dr. Patel defined as the evaluation of frequency and intensity of genetic activity at once to create a global picture of cellular function. “It’s AI that uses machine learning to evaluate genetic expression to assess lesion behavior,” he explained.

One GEP test on the market is the Pigmented Lesion Assay (PLA) from DermTech, a noninvasive test that looks at the expression of two genes to predict if a lesion is malignant or not. “Based on their validation set, they have shown some impressive numbers,” with sensitivities above 90%, and published registry data that have shown higher sensitivities “and even specificities above 90%,” he said.

“On the surface, it looks like this would be a useful test,” Dr. Patel said. A study published in 2021 looked at the evidence of applying real-world evidence with this test to see if results held up. Based on the authors’ analysis, he noted, “you would need a sensitivity and specificity of 95% to yield a positivity rate of 9.5% for the PLA test, which is what has been reported in real-world use. So, there’s a disconnect somewhere and we are not quite there yet.” That may be a result of the dataset itself not being as uniform between the validation and the training datasets, he continued. Also, the expression of certain genes is different “if you don’t have a clean input variable” of what the test is being used for, he added.

“If you’re not mirroring the dataset, you’re not going to get clean data,” he said. “So, if you’re using this on younger patients or for sun-damaged lesional skin or nonmelanocytic lesions around sun-damaged areas, there are variable expressions that may not be accurately captured by that algorithm. This might help explain the real-world variation that we’re seeing.”

Another GEP test in use is the 31-Gene Expression Profile Test for Melanoma, which evaluates gene expressions in melanoma tumors and what the behavior of that tumor may be. The test has been available for more than a decade “and there is a lot of speculation about its use,” Dr. Patel said. “A recent paper attempted to come up with an algorithm of how to use this, but there’s a lot of concern about the endpoints of what changes in management might result from this test. That is what we need to be thinking about. There’s a lot of back and forth about this.”

In 2020, authors of a consensus statement on prognostic GEP in cutaneous melanoma concluded that before GEP testing is routinely used, the clinical benefit in the management of patients with melanoma should be established through further clinical investigation. Dr. Patel recommended the accompanying editorial on GEP in melanoma, written by Hensin Tsao, MD, PhD, and Warren H. Chan, MS, in JAMA Dermatology.

In Dr. Patel’s opinion, T1a melanomas (0.8 mm, nonulcerated) do not need routine GEP, but the GEP test may be useful in cases that are in the “gray zone,” such as those with T1b or some borderline T2a melanomas (> 0.8 mm, < 1.2mm, nonulcerated, but with high mitosis, etc.); patients with unique coexisting conditions such as pregnancy, and patients who may not tolerate sentinel lymph node biopsy (SLNB) or adjuvant therapy.

Echoing sentiments expressed in the JAMA Dermatology editorial, he advised dermatologists to “remember your training and know the data. GEP predicting survival is not the same as SLNB positive rate. GEP should not replace standard guidelines in T2a and higher melanomas. Nodal sampling remains part of all major guidelines and determines adjuvant therapy.”

He cited the characterization of GEP in the editorial as “a powerful technology” that heralds the age of personalized medicine, but it is not ready for ubiquitous use. Prospective studies and time will lead to highly accurate tools.”

Dr. Patel disclosed that he is chief medical officer for Lazarus AI.

If you worry that artificial intelligence (AI) will one day replace your own clinical acumen as a dermatologist, Vishal A. Patel, MD, advises you to think differently.

“AI is meant to be an enhancement strategy, a support tool to improve our diagnostic abilities,” Dr. Patel, a Mohs surgeon who is director of cutaneous oncology at the George Washington University Cancer Center, Washington, said during the ODAC Dermatology, Aesthetic & Surgical Conference. “Dermatologists should embrace AI and drive how it is utilized – be the captain of the plane (technology) and the passenger (patient). If we’re not in the forefront of the plane, we’re not to be able to dictate which way we are going with this.”

In 2019, a group of German researchers found that AI can improve accuracy and efficiency of specialists in classifying skin cancer based on dermoscopic images. “I really do believe this is going to be the future,” said Dr. Patel, who was not involved with the study. “Current research involves using supervised learning on known outcomes to determine inputs to predict them. In dermatology, think of identifying melanoma from clinical or dermoscopic images or predicting metastasis risk from digitized pathology slides.”

However, there are currently no universal guidelines on how large an AI dataset needs to be to yield accurate results. In the dermatology literature, most AI datasets range between 600 and 14,000 examples, Dr. Patel said, with a large study-specific variation in performance. “Misleading results can result from unanticipated training errors,” he said.

“The AI network may learn its intended task or an unrelated situational cue. For example, you can use great images to predict melanoma, but you may have an unintended poor outcome related to images that have, say, a ruler inside of them clustered within the melanoma diagnoses.” And unbeknown to the system’s developer, “the algorithm picks up that the ruler is predictive of an image being a melanoma and not the pigmented lesion itself.” In other words, the algorithm is only as good as the dataset being used, he said. “This is the key element, to ask what the dataset is that’s training the tool that you may one day use.”
 

Convolutional neural network

In 2017, a seminal study published in Nature showed that for classification of melanoma and epidermal lesions, a type of AI used in image processing known as a convolutional neural network (CNN) was on par with dermatologists and outperformed the average. For epidermal lesions, the network was one standard deviation higher above the average for dermatologists, while for melanocytic lesions, the network was just below one standard deviation above the average of the dermatologists. A CNN “clearly can perform well because it works on a different level than how our brains work,” Dr. Patel said.

In a separate study, a CNN trained to recognize melanoma in dermoscopic images was compared to 58 international dermatologists with varying levels of dermoscopy experience; 29% were “beginners,” with less than 2 years of experience; 19% were “skilled,” with 2-5 years of experience; and 52% were “experts,” with at least 5 years of experience. The analysis consisted of two experiments: In level I, dermatologists classified lesions based on dermoscopy only. In level II, dermatologists were provided dermoscopy, clinical images, and additional clinical information, while the CNN was trained on images only. The researchers found that most dermatologists were outperformed by the CNN. “Physicians of all different levels of training and experience may benefit from assistance by a CNN’s image classification,” they concluded.
 

Gene expression profiling

Another aspect of AI is gene expression profiling (GEP), which Dr. Patel defined as the evaluation of frequency and intensity of genetic activity at once to create a global picture of cellular function. “It’s AI that uses machine learning to evaluate genetic expression to assess lesion behavior,” he explained.

One GEP test on the market is the Pigmented Lesion Assay (PLA) from DermTech, a noninvasive test that looks at the expression of two genes to predict if a lesion is malignant or not. “Based on their validation set, they have shown some impressive numbers,” with sensitivities above 90%, and published registry data that have shown higher sensitivities “and even specificities above 90%,” he said.

“On the surface, it looks like this would be a useful test,” Dr. Patel said. A study published in 2021 looked at the evidence of applying real-world evidence with this test to see if results held up. Based on the authors’ analysis, he noted, “you would need a sensitivity and specificity of 95% to yield a positivity rate of 9.5% for the PLA test, which is what has been reported in real-world use. So, there’s a disconnect somewhere and we are not quite there yet.” That may be a result of the dataset itself not being as uniform between the validation and the training datasets, he continued. Also, the expression of certain genes is different “if you don’t have a clean input variable” of what the test is being used for, he added.

“If you’re not mirroring the dataset, you’re not going to get clean data,” he said. “So, if you’re using this on younger patients or for sun-damaged lesional skin or nonmelanocytic lesions around sun-damaged areas, there are variable expressions that may not be accurately captured by that algorithm. This might help explain the real-world variation that we’re seeing.”

Another GEP test in use is the 31-Gene Expression Profile Test for Melanoma, which evaluates gene expressions in melanoma tumors and what the behavior of that tumor may be. The test has been available for more than a decade “and there is a lot of speculation about its use,” Dr. Patel said. “A recent paper attempted to come up with an algorithm of how to use this, but there’s a lot of concern about the endpoints of what changes in management might result from this test. That is what we need to be thinking about. There’s a lot of back and forth about this.”

In 2020, authors of a consensus statement on prognostic GEP in cutaneous melanoma concluded that before GEP testing is routinely used, the clinical benefit in the management of patients with melanoma should be established through further clinical investigation. Dr. Patel recommended the accompanying editorial on GEP in melanoma, written by Hensin Tsao, MD, PhD, and Warren H. Chan, MS, in JAMA Dermatology.

In Dr. Patel’s opinion, T1a melanomas (0.8 mm, nonulcerated) do not need routine GEP, but the GEP test may be useful in cases that are in the “gray zone,” such as those with T1b or some borderline T2a melanomas (> 0.8 mm, < 1.2mm, nonulcerated, but with high mitosis, etc.); patients with unique coexisting conditions such as pregnancy, and patients who may not tolerate sentinel lymph node biopsy (SLNB) or adjuvant therapy.

Echoing sentiments expressed in the JAMA Dermatology editorial, he advised dermatologists to “remember your training and know the data. GEP predicting survival is not the same as SLNB positive rate. GEP should not replace standard guidelines in T2a and higher melanomas. Nodal sampling remains part of all major guidelines and determines adjuvant therapy.”

He cited the characterization of GEP in the editorial as “a powerful technology” that heralds the age of personalized medicine, but it is not ready for ubiquitous use. Prospective studies and time will lead to highly accurate tools.”

Dr. Patel disclosed that he is chief medical officer for Lazarus AI.

If you worry that artificial intelligence (AI) will one day replace your own clinical acumen as a dermatologist, Vishal A. Patel, MD, advises you to think differently.

“AI is meant to be an enhancement strategy, a support tool to improve our diagnostic abilities,” Dr. Patel, a Mohs surgeon who is director of cutaneous oncology at the George Washington University Cancer Center, Washington, said during the ODAC Dermatology, Aesthetic & Surgical Conference. “Dermatologists should embrace AI and drive how it is utilized – be the captain of the plane (technology) and the passenger (patient). If we’re not in the forefront of the plane, we’re not to be able to dictate which way we are going with this.”

In 2019, a group of German researchers found that AI can improve accuracy and efficiency of specialists in classifying skin cancer based on dermoscopic images. “I really do believe this is going to be the future,” said Dr. Patel, who was not involved with the study. “Current research involves using supervised learning on known outcomes to determine inputs to predict them. In dermatology, think of identifying melanoma from clinical or dermoscopic images or predicting metastasis risk from digitized pathology slides.”

However, there are currently no universal guidelines on how large an AI dataset needs to be to yield accurate results. In the dermatology literature, most AI datasets range between 600 and 14,000 examples, Dr. Patel said, with a large study-specific variation in performance. “Misleading results can result from unanticipated training errors,” he said.

“The AI network may learn its intended task or an unrelated situational cue. For example, you can use great images to predict melanoma, but you may have an unintended poor outcome related to images that have, say, a ruler inside of them clustered within the melanoma diagnoses.” And unbeknown to the system’s developer, “the algorithm picks up that the ruler is predictive of an image being a melanoma and not the pigmented lesion itself.” In other words, the algorithm is only as good as the dataset being used, he said. “This is the key element, to ask what the dataset is that’s training the tool that you may one day use.”
 

Convolutional neural network

In 2017, a seminal study published in Nature showed that for classification of melanoma and epidermal lesions, a type of AI used in image processing known as a convolutional neural network (CNN) was on par with dermatologists and outperformed the average. For epidermal lesions, the network was one standard deviation higher above the average for dermatologists, while for melanocytic lesions, the network was just below one standard deviation above the average of the dermatologists. A CNN “clearly can perform well because it works on a different level than how our brains work,” Dr. Patel said.

In a separate study, a CNN trained to recognize melanoma in dermoscopic images was compared to 58 international dermatologists with varying levels of dermoscopy experience; 29% were “beginners,” with less than 2 years of experience; 19% were “skilled,” with 2-5 years of experience; and 52% were “experts,” with at least 5 years of experience. The analysis consisted of two experiments: In level I, dermatologists classified lesions based on dermoscopy only. In level II, dermatologists were provided dermoscopy, clinical images, and additional clinical information, while the CNN was trained on images only. The researchers found that most dermatologists were outperformed by the CNN. “Physicians of all different levels of training and experience may benefit from assistance by a CNN’s image classification,” they concluded.
 

Gene expression profiling

Another aspect of AI is gene expression profiling (GEP), which Dr. Patel defined as the evaluation of frequency and intensity of genetic activity at once to create a global picture of cellular function. “It’s AI that uses machine learning to evaluate genetic expression to assess lesion behavior,” he explained.

One GEP test on the market is the Pigmented Lesion Assay (PLA) from DermTech, a noninvasive test that looks at the expression of two genes to predict if a lesion is malignant or not. “Based on their validation set, they have shown some impressive numbers,” with sensitivities above 90%, and published registry data that have shown higher sensitivities “and even specificities above 90%,” he said.

“On the surface, it looks like this would be a useful test,” Dr. Patel said. A study published in 2021 looked at the evidence of applying real-world evidence with this test to see if results held up. Based on the authors’ analysis, he noted, “you would need a sensitivity and specificity of 95% to yield a positivity rate of 9.5% for the PLA test, which is what has been reported in real-world use. So, there’s a disconnect somewhere and we are not quite there yet.” That may be a result of the dataset itself not being as uniform between the validation and the training datasets, he continued. Also, the expression of certain genes is different “if you don’t have a clean input variable” of what the test is being used for, he added.

“If you’re not mirroring the dataset, you’re not going to get clean data,” he said. “So, if you’re using this on younger patients or for sun-damaged lesional skin or nonmelanocytic lesions around sun-damaged areas, there are variable expressions that may not be accurately captured by that algorithm. This might help explain the real-world variation that we’re seeing.”

Another GEP test in use is the 31-Gene Expression Profile Test for Melanoma, which evaluates gene expressions in melanoma tumors and what the behavior of that tumor may be. The test has been available for more than a decade “and there is a lot of speculation about its use,” Dr. Patel said. “A recent paper attempted to come up with an algorithm of how to use this, but there’s a lot of concern about the endpoints of what changes in management might result from this test. That is what we need to be thinking about. There’s a lot of back and forth about this.”

In 2020, authors of a consensus statement on prognostic GEP in cutaneous melanoma concluded that before GEP testing is routinely used, the clinical benefit in the management of patients with melanoma should be established through further clinical investigation. Dr. Patel recommended the accompanying editorial on GEP in melanoma, written by Hensin Tsao, MD, PhD, and Warren H. Chan, MS, in JAMA Dermatology.

In Dr. Patel’s opinion, T1a melanomas (0.8 mm, nonulcerated) do not need routine GEP, but the GEP test may be useful in cases that are in the “gray zone,” such as those with T1b or some borderline T2a melanomas (> 0.8 mm, < 1.2mm, nonulcerated, but with high mitosis, etc.); patients with unique coexisting conditions such as pregnancy, and patients who may not tolerate sentinel lymph node biopsy (SLNB) or adjuvant therapy.

Echoing sentiments expressed in the JAMA Dermatology editorial, he advised dermatologists to “remember your training and know the data. GEP predicting survival is not the same as SLNB positive rate. GEP should not replace standard guidelines in T2a and higher melanomas. Nodal sampling remains part of all major guidelines and determines adjuvant therapy.”

He cited the characterization of GEP in the editorial as “a powerful technology” that heralds the age of personalized medicine, but it is not ready for ubiquitous use. Prospective studies and time will lead to highly accurate tools.”

Dr. Patel disclosed that he is chief medical officer for Lazarus AI.

LAS VEGAS – In the opinion of Christoph U. Correll, MD, tardive dyskinesia (TD) “has been somewhat forgotten” by psychiatrists because the risk of patients developing the condition is considered to be significantly lower with second-generation antipsychotics compared with first-generation antipsychotics.

“But this does not seem to always be the case, because there is still a risk of TD, and we need to monitor for it,” Dr. Correll, professor of psychiatry and molecular medicine at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “It is important to minimize the risk of TD by educating patients and caregivers about the risks of and alternatives to antipsychotic medication and early signs of TD.”

First described in 1957, TD is characterized by involuntary repetitive but irregular movements, mostly in the oral, lingual, and buccal regions – such as tongue protruding, puckering, chewing, and grimacing. Less often, there are movements in the hands, legs, feet, and torso. Symptoms can include mannerisms, stereotypies, tics, myoclonus, dystonias, tremor, and akathisia. “TD can be severe, persistent, and have medical and psychosocial consequences,” Dr. Correll said. “It can occur in untreated patients, but treatment with dopamine blocking agents – antipsychotics and metoclopramide – increases risk for TD.”

Differential diagnoses to consider include morbus Huntington, benign familial Chorea, and Sydenham’s Chorea. Less frequent causes of TD include metabolic conditions such as uremia, hyponatremia, hypernatremia, hypoparathyroidism, and hyperparathyroidism. “Those would need to be ruled out during the physical exam,” he said. There can also be inflammatory causes of TD such as herpes simplex virus, varicella, measles, mumps, and rubella.

A standard measure for TD diagnosis is the Abnormal Involuntary Movement Scale (AIMS), an observer-rated 12-item anchored scale that takes 5-10 minutes to administer. However, the AIMS on its own does not diagnose TD. In 1982, researchers developed three diagnostic criteria for TD: At least 3 months of cumulative antipsychotic drug exposure; presence of at least moderate abnormal involuntary movements in one or more body area(s) or mild movements in two or more body areas, and absence of other conditions that might produce involuntary movements (Arch Gen Psychiatry 1982;39:486-7).

The impact of TD on everyday functioning depends on anatomic location as well as severity, Dr. Correll continued. The condition can cause impairments to speech, verbal communication, dentition, temporomandibular joint pain/myalgia, swallowing difficulties, and fine motor skills including instrumental activities of daily living and written communication. Truncal and lower extremity TD can affect gait, posture and postural stability, strength, power flexibility, physical capacity, and one’s ability to exercise. “There are also psychological impairments,” he said. “Patients can develop different awareness so they become self-conscious; there can be cognitive abnormalities, and they can become more anxious or [have an] increased sense of paranoia, isolation, stigma, social and/or educational/vocational impairment.”

According to research by Dr. Correll and colleagues, unmodifiable patient-related risk factors for TD include older age, female sex, and being of white or African descent (J Neurol Sci 2018 June 15; 389:21-7). Unmodifiable illness-related risk factors include longer duration of illness, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related factors include diabetes, smoking, and alcohol/substance abuse, while modifiable treatment-related factors include dopamine receptor blockers, higher cumulative and current antipsychotic dose or plasma levels, early parkinsonian side effects, treatment-emergent akathisia, and anticholinergic co-treatment. In a meta-analysis of 41 studies that aimed to determine the prevalence of TD, the mean age of the 11,493 patients was 43, 66% were male, and 77% had schizophrenia spectrum disorders (J Clin Psychiatry. 2017 Mar;78[3]:e264-78). The global mean TD prevalence was 25%, but the rates were lower with patients on current treatment with second-generation antipsychotics compared with those on first-generation antipsychotics (21% vs. 30%, respectively).

According to Dr. Correll, strategies for preventing TD include confirming and documenting the indication for dopamine antagonist antipsychotic medications, using conservative maintenance doses, and considering the use of SGAs, especially in those at high risk for EPS (extrapyramidal symptoms). “Don’t go too high [with the dose],” he said. “Stay below the EPS threshold. Inform patients and caregivers of the risk of TD and assess for incipient signs regularly using the AIMS.”

Treatment options include discontinuing antipsychotics, adjusting their dose, or switching patients from a first-generation antipsychotic to a second-generation antipsychotic. Supplementation with antioxidants/radical scavengers such as vitamin E, vitamin B₆, ginkgo biloba, and fish oil “can be tried, but have limited evidence, as is the case for melatonin.” Other options include clonazepam, amantadine, donepezil, and tetrabenazine, a reversible and specific inhibitor of vesicular monoamine transporter-2 (VMAT-2), a transporter that packages neurotransmitters (preferentially dopamine) into vesicles for release into the synapse and was approved in 2008 as an orphan drug for the treatment of choreiform movements associated with Huntington’s disease. “Neurologists have using tetrabenazine off-label for TD, but in schizophrenia and other psychiatric care, we rarely use it because it has to be given three times a day and it has a black box warning for depression and suicidality,” he said.

Dr. Correll noted that the Food and Drug Administration approval of two more recent VMAT-2 inhibitors – deutetrabenazine (Austedo) and valbenazine (Ingrezza) – provides an evidence-based care option for the effective management of TD. Deutetrabenazine requires titration over several weeks and twice-daily dosing, while valbenazine can reach the maximum dose by the beginning of week 2 and is dosed once daily. Deutetrabenazine should be taken with food, which is not required valbenazine.

“Both VMAT-2 inhibitors are generally well tolerated and have a positive benefit-risk ratio,” he said. “Both are recommended by the APA guidelines as the preferred and only evidence-based treatment for TD.”

Dr. Correll reported that he has received honoraria from and has been an advisory board member for numerous pharmaceutical companies. He has also received grant support from Janssen, the National Institute of Mental Health, the Patient Centered Outcomes Research Institute, Takeda, and the Thrasher Foundation.

LAS VEGAS – In the opinion of Christoph U. Correll, MD, tardive dyskinesia (TD) “has been somewhat forgotten” by psychiatrists because the risk of patients developing the condition is considered to be significantly lower with second-generation antipsychotics compared with first-generation antipsychotics.

“But this does not seem to always be the case, because there is still a risk of TD, and we need to monitor for it,” Dr. Correll, professor of psychiatry and molecular medicine at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “It is important to minimize the risk of TD by educating patients and caregivers about the risks of and alternatives to antipsychotic medication and early signs of TD.”

First described in 1957, TD is characterized by involuntary repetitive but irregular movements, mostly in the oral, lingual, and buccal regions – such as tongue protruding, puckering, chewing, and grimacing. Less often, there are movements in the hands, legs, feet, and torso. Symptoms can include mannerisms, stereotypies, tics, myoclonus, dystonias, tremor, and akathisia. “TD can be severe, persistent, and have medical and psychosocial consequences,” Dr. Correll said. “It can occur in untreated patients, but treatment with dopamine blocking agents – antipsychotics and metoclopramide – increases risk for TD.”

Differential diagnoses to consider include morbus Huntington, benign familial Chorea, and Sydenham’s Chorea. Less frequent causes of TD include metabolic conditions such as uremia, hyponatremia, hypernatremia, hypoparathyroidism, and hyperparathyroidism. “Those would need to be ruled out during the physical exam,” he said. There can also be inflammatory causes of TD such as herpes simplex virus, varicella, measles, mumps, and rubella.

A standard measure for TD diagnosis is the Abnormal Involuntary Movement Scale (AIMS), an observer-rated 12-item anchored scale that takes 5-10 minutes to administer. However, the AIMS on its own does not diagnose TD. In 1982, researchers developed three diagnostic criteria for TD: At least 3 months of cumulative antipsychotic drug exposure; presence of at least moderate abnormal involuntary movements in one or more body area(s) or mild movements in two or more body areas, and absence of other conditions that might produce involuntary movements (Arch Gen Psychiatry 1982;39:486-7).

The impact of TD on everyday functioning depends on anatomic location as well as severity, Dr. Correll continued. The condition can cause impairments to speech, verbal communication, dentition, temporomandibular joint pain/myalgia, swallowing difficulties, and fine motor skills including instrumental activities of daily living and written communication. Truncal and lower extremity TD can affect gait, posture and postural stability, strength, power flexibility, physical capacity, and one’s ability to exercise. “There are also psychological impairments,” he said. “Patients can develop different awareness so they become self-conscious; there can be cognitive abnormalities, and they can become more anxious or [have an] increased sense of paranoia, isolation, stigma, social and/or educational/vocational impairment.”

According to research by Dr. Correll and colleagues, unmodifiable patient-related risk factors for TD include older age, female sex, and being of white or African descent (J Neurol Sci 2018 June 15; 389:21-7). Unmodifiable illness-related risk factors include longer duration of illness, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related factors include diabetes, smoking, and alcohol/substance abuse, while modifiable treatment-related factors include dopamine receptor blockers, higher cumulative and current antipsychotic dose or plasma levels, early parkinsonian side effects, treatment-emergent akathisia, and anticholinergic co-treatment. In a meta-analysis of 41 studies that aimed to determine the prevalence of TD, the mean age of the 11,493 patients was 43, 66% were male, and 77% had schizophrenia spectrum disorders (J Clin Psychiatry. 2017 Mar;78[3]:e264-78). The global mean TD prevalence was 25%, but the rates were lower with patients on current treatment with second-generation antipsychotics compared with those on first-generation antipsychotics (21% vs. 30%, respectively).

According to Dr. Correll, strategies for preventing TD include confirming and documenting the indication for dopamine antagonist antipsychotic medications, using conservative maintenance doses, and considering the use of SGAs, especially in those at high risk for EPS (extrapyramidal symptoms). “Don’t go too high [with the dose],” he said. “Stay below the EPS threshold. Inform patients and caregivers of the risk of TD and assess for incipient signs regularly using the AIMS.”

Treatment options include discontinuing antipsychotics, adjusting their dose, or switching patients from a first-generation antipsychotic to a second-generation antipsychotic. Supplementation with antioxidants/radical scavengers such as vitamin E, vitamin B₆, ginkgo biloba, and fish oil “can be tried, but have limited evidence, as is the case for melatonin.” Other options include clonazepam, amantadine, donepezil, and tetrabenazine, a reversible and specific inhibitor of vesicular monoamine transporter-2 (VMAT-2), a transporter that packages neurotransmitters (preferentially dopamine) into vesicles for release into the synapse and was approved in 2008 as an orphan drug for the treatment of choreiform movements associated with Huntington’s disease. “Neurologists have using tetrabenazine off-label for TD, but in schizophrenia and other psychiatric care, we rarely use it because it has to be given three times a day and it has a black box warning for depression and suicidality,” he said.

Dr. Correll noted that the Food and Drug Administration approval of two more recent VMAT-2 inhibitors – deutetrabenazine (Austedo) and valbenazine (Ingrezza) – provides an evidence-based care option for the effective management of TD. Deutetrabenazine requires titration over several weeks and twice-daily dosing, while valbenazine can reach the maximum dose by the beginning of week 2 and is dosed once daily. Deutetrabenazine should be taken with food, which is not required valbenazine.

“Both VMAT-2 inhibitors are generally well tolerated and have a positive benefit-risk ratio,” he said. “Both are recommended by the APA guidelines as the preferred and only evidence-based treatment for TD.”

Dr. Correll reported that he has received honoraria from and has been an advisory board member for numerous pharmaceutical companies. He has also received grant support from Janssen, the National Institute of Mental Health, the Patient Centered Outcomes Research Institute, Takeda, and the Thrasher Foundation.

LAS VEGAS – In the opinion of Christoph U. Correll, MD, tardive dyskinesia (TD) “has been somewhat forgotten” by psychiatrists because the risk of patients developing the condition is considered to be significantly lower with second-generation antipsychotics compared with first-generation antipsychotics.

“But this does not seem to always be the case, because there is still a risk of TD, and we need to monitor for it,” Dr. Correll, professor of psychiatry and molecular medicine at The Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, New York, said during an annual psychopharmacology update held by the Nevada Psychiatric Association. “It is important to minimize the risk of TD by educating patients and caregivers about the risks of and alternatives to antipsychotic medication and early signs of TD.”

First described in 1957, TD is characterized by involuntary repetitive but irregular movements, mostly in the oral, lingual, and buccal regions – such as tongue protruding, puckering, chewing, and grimacing. Less often, there are movements in the hands, legs, feet, and torso. Symptoms can include mannerisms, stereotypies, tics, myoclonus, dystonias, tremor, and akathisia. “TD can be severe, persistent, and have medical and psychosocial consequences,” Dr. Correll said. “It can occur in untreated patients, but treatment with dopamine blocking agents – antipsychotics and metoclopramide – increases risk for TD.”

Differential diagnoses to consider include morbus Huntington, benign familial Chorea, and Sydenham’s Chorea. Less frequent causes of TD include metabolic conditions such as uremia, hyponatremia, hypernatremia, hypoparathyroidism, and hyperparathyroidism. “Those would need to be ruled out during the physical exam,” he said. There can also be inflammatory causes of TD such as herpes simplex virus, varicella, measles, mumps, and rubella.

A standard measure for TD diagnosis is the Abnormal Involuntary Movement Scale (AIMS), an observer-rated 12-item anchored scale that takes 5-10 minutes to administer. However, the AIMS on its own does not diagnose TD. In 1982, researchers developed three diagnostic criteria for TD: At least 3 months of cumulative antipsychotic drug exposure; presence of at least moderate abnormal involuntary movements in one or more body area(s) or mild movements in two or more body areas, and absence of other conditions that might produce involuntary movements (Arch Gen Psychiatry 1982;39:486-7).

The impact of TD on everyday functioning depends on anatomic location as well as severity, Dr. Correll continued. The condition can cause impairments to speech, verbal communication, dentition, temporomandibular joint pain/myalgia, swallowing difficulties, and fine motor skills including instrumental activities of daily living and written communication. Truncal and lower extremity TD can affect gait, posture and postural stability, strength, power flexibility, physical capacity, and one’s ability to exercise. “There are also psychological impairments,” he said. “Patients can develop different awareness so they become self-conscious; there can be cognitive abnormalities, and they can become more anxious or [have an] increased sense of paranoia, isolation, stigma, social and/or educational/vocational impairment.”

According to research by Dr. Correll and colleagues, unmodifiable patient-related risk factors for TD include older age, female sex, and being of white or African descent (J Neurol Sci 2018 June 15; 389:21-7). Unmodifiable illness-related risk factors include longer duration of illness, intellectual disability and brain damage, negative symptoms in schizophrenia, mood disorders, cognitive symptoms in mood disorders, and gene polymorphisms involving antipsychotic metabolism and dopamine functioning. Modifiable comorbidity-related factors include diabetes, smoking, and alcohol/substance abuse, while modifiable treatment-related factors include dopamine receptor blockers, higher cumulative and current antipsychotic dose or plasma levels, early parkinsonian side effects, treatment-emergent akathisia, and anticholinergic co-treatment. In a meta-analysis of 41 studies that aimed to determine the prevalence of TD, the mean age of the 11,493 patients was 43, 66% were male, and 77% had schizophrenia spectrum disorders (J Clin Psychiatry. 2017 Mar;78[3]:e264-78). The global mean TD prevalence was 25%, but the rates were lower with patients on current treatment with second-generation antipsychotics compared with those on first-generation antipsychotics (21% vs. 30%, respectively).

According to Dr. Correll, strategies for preventing TD include confirming and documenting the indication for dopamine antagonist antipsychotic medications, using conservative maintenance doses, and considering the use of SGAs, especially in those at high risk for EPS (extrapyramidal symptoms). “Don’t go too high [with the dose],” he said. “Stay below the EPS threshold. Inform patients and caregivers of the risk of TD and assess for incipient signs regularly using the AIMS.”

Treatment options include discontinuing antipsychotics, adjusting their dose, or switching patients from a first-generation antipsychotic to a second-generation antipsychotic. Supplementation with antioxidants/radical scavengers such as vitamin E, vitamin B₆, ginkgo biloba, and fish oil “can be tried, but have limited evidence, as is the case for melatonin.” Other options include clonazepam, amantadine, donepezil, and tetrabenazine, a reversible and specific inhibitor of vesicular monoamine transporter-2 (VMAT-2), a transporter that packages neurotransmitters (preferentially dopamine) into vesicles for release into the synapse and was approved in 2008 as an orphan drug for the treatment of choreiform movements associated with Huntington’s disease. “Neurologists have using tetrabenazine off-label for TD, but in schizophrenia and other psychiatric care, we rarely use it because it has to be given three times a day and it has a black box warning for depression and suicidality,” he said.

Dr. Correll noted that the Food and Drug Administration approval of two more recent VMAT-2 inhibitors – deutetrabenazine (Austedo) and valbenazine (Ingrezza) – provides an evidence-based care option for the effective management of TD. Deutetrabenazine requires titration over several weeks and twice-daily dosing, while valbenazine can reach the maximum dose by the beginning of week 2 and is dosed once daily. Deutetrabenazine should be taken with food, which is not required valbenazine.

“Both VMAT-2 inhibitors are generally well tolerated and have a positive benefit-risk ratio,” he said. “Both are recommended by the APA guidelines as the preferred and only evidence-based treatment for TD.”

Dr. Correll reported that he has received honoraria from and has been an advisory board member for numerous pharmaceutical companies. He has also received grant support from Janssen, the National Institute of Mental Health, the Patient Centered Outcomes Research Institute, Takeda, and the Thrasher Foundation.

In the clinical experience of Adam Friedman, MD, when patients present with acute urticaria, the culprit is usually food, a drug, or a bug.

But in some cases, the trigger remains elusive. “We don’t always find the source, but don’t beat yourself up about it,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said at the ODAC Dermatology, Aesthetic, and Surgical Conference. “The basic rule is to treat patients to clearance and keep them clear.”

Chronic urticaria is characterized by plaques with a burning/itch sensation that often “move” to different locations on the body over minutes to hours, and they typically last for less than 24 hours. The plaques are often oval, round, or irregular in shape and they typically leave no postinflammatory pigmentary alteration or scarring other than from scratching.

Urticaria affects an estimated 20% of the population, Dr. Friedman said, and is more common in females than males. More than two-thirds of cases are self-limiting but 10% can persist longer than 5 years. Acute episodes are more likely to have an identifiable trigger, while chronic episodes, which last more than six weeks, typically do not. The longer the duration, the lower the chance of identifying the root cause. The foods/food products most commonly affecting children with acute urticaria include milk, egg, peanut, wheat, and soy, while the common culprits in adults are tree nuts, peanuts, and shellfish. Other triggers include the yellow food dye annatto, the red food dye carmine, contact with raw fruits or vegetables, animal saliva, and certain detergents or perfume.

“When you have no idea what the cause is for acute urticaria, I think about viral or bacterial infections, especially in children,” Dr. Friedman said, particularly mycoplasma, adenovirus, enterovirus, rotavirus, respiratory syncytial virus, Epstein-Barr virus, and cytomegalovirus. COVID-19 has also been a new etiologic source for a recent rise in acute urticaria cases.

Other causes include certain medications such as antibiotics, opiates, muscle relaxants, salicylates, and NSAIDs; stinging insects; and exposure to latex products, which can cross react with passion fruit, banana, avocado, chestnut, and kiwi. Alcohol consumption can also trigger urticaria.

“Ask patients if they have joint discomfort or pain,” Dr. Friedman advised, referring to urticaria arthritis syndrome that is typically seen more often in women than in men. “It’s rare but important, because that may distinguish for you what is needed to get those patients under control.”

Chronic urticaria develops in 20%-45% of patients who present with acute urticaria. One form of chronic urticaria is inducible urticaria, which spontaneously occurs after an exposure to an external force. “The distinguishing feature here is that it doesn’t last long – 30 minutes or so – and is typically unresponsive to corticosteroids,” Dr. Friedman said. “It comes on quickly but disappears quickly whereas with chronic spontaneous urticaria, someone might be getting those wheals of flare for hours and hours.”

The most common form of physical urticaria is dermatographism, while other examples include physical urticaria resulting from exposure to cholinergic agents, heat, exercise, cold, water, sunlight, and pressure on the skin.

About half of patients with chronic urticaria are disease free within 1 year, but 20% continue to experience episodes for more than 10 years. One study found that patients with chronic spontaneous urticaria who were diagnosed at a younger age trended toward a longer disease course, and rates were higher in women, compared with men. “Perceived stress can make this worse,” Dr. Friedman added.

According to Dr. Friedman, it’s more important to ask patients targeted questions during office visits than it is to do a full workup. “I ask patients to keep a diary, which can help them identify triggers if there are any,” he said. “I also ask them to take a picture of the papules with their smartphone. There can be a genetic association, so it’s important to ask if anyone else in the family has urticaria. No routine lab tests are required unless there’s something in the history that suggests it’s worthwhile. Let the patient guide the diagnostic workup; don’t just order a million tests.”

That said, known comorbidities associated with urticaria include autoimmune disease, atopy, infections, metabolic conditions, and neoplastic disorders. “Biopsies are typically useless because this is an invisible dermatosis,” he said. “They’re useful when it’s urticarial, not urticaria, when you’re trying to figure out what it is.”

According to recently published international guidelines on urticaria, published in September 2021, the recommended first line of treatment for urticaria is with second-generation nonsedating antihistamines such as cetirizine and loratadine, up to four times the recommended dose.

Second-generation derivatives include desloratadine, levocetirizine, and fexofenadine. “I like using fexofenadine in the morning for folks who don’t tolerate cetirizine, then I’ll recommend something a little more sedating at night,” Dr. Friedman said. “We max out [the dose] by week 4. If it works, great. If not, we move on to something else.”

In late 2021, the British Association of Dermatologists also published guidelines on the treatment of chronic urticaria.

As for markers of treatment success, a study of 240 children with chronic spontaneous urticaria found that risk factors for a poor response included longer duration of disease, higher treatment step until initial disease control, and food sensitization.

Vitamin D supplementation may also add some benefit. One study of 42 adults with urticaria found that low and high doses of vitamin D added to antihistamine therapy can boost effectiveness. “This may be because vitamin D could be a marker of severity,” Dr. Friedman said. “The reality is, however, that a lot of patients don’t do well.”

Data from the large, prospective study known as AWARE (A World-Wide Antihistamine-Refractory Chronic Urticaria Patient Evaluation) found that 23% patients treated with nonsedating H1-antihistamines and 42% patients treated with up-dosed nonsedating H1-antihistamines had uncontrolled chronic spontaneous urticaria at month 24.

A second-line treatment option for patients aged 6 and older is the anti-IgE antibody omalizumab, 150-300 mg by subcutaneous injection every 4 weeks. Dr. Friedman typically uses only the 300-mg dose. “You do not need to take pretreatment serum IgE levels,” he said. “The most significant adverse event is anaphylaxis, which only affects 0.2% of patients.”

A third-line option is cyclosporine A. A dose of 3-5mg/kg per day appears to benefit about two-thirds of patients with antihistamine recalcitrant chronic urticaria. “It works fast but you can’t keep patients on it for very long,” he said.

Another third-line option is mycophenolate mofetil, which may work by inhibiting the production of autoantibodies to the high-affinity IgE receptor and/or IgE. “It does work well, especially in conjunction with antihistamines; it’s kind of a softer immunosuppressant,” he said. Methotrexate can also be used as an add-on therapy to H1 antihistamine therapy in difficult-to-treat cases.

“It’s great we have [a Food and Drug Administration]–approved biologic therapy in omalizumab and access to over-the-counter antihistamines, but there is a high unmet need for treatment,” and a need for new therapies, Dr. Friedman said. “Only about 39% achieve symptomatic control with conventional dosing of antihistamines, and 63% of nonresponders achieve symptom control with a fourfold increased dosing of antihistamines.” In addition, about 20% of patients will not respond to either standard or increased doses of antihistamines and are eligible for treatment with omalizumab. However, more than 50% of such patients experience a delay or lack of response to omalizumab. “We need innovation; we need to understand the disease better,” he said.

Dr. Friedman disclosed that he serves as a consultant and/or adviser for Loreal, La Roche Posay, Cerave, Galderma, Aveeno, Microcures, Pfizer, Novartis, Dermira, Brickell Biotech, Incyte, UCB, Janssen, Pfizer, Bristol-Myers Squibb, Almirall, Zylo Therapeutics, Hoth Therapeutics, Corbus, Greenway Therapeutics, TruPotency, and Dermavant. He is a speaker for Regeneron/Sanofi, AbbVie, Janssen, Brickell Biotech, and Incyte, and has received grants from Pfizer, the Dermatology Foundation, Incyte, and Galderma.

In the clinical experience of Adam Friedman, MD, when patients present with acute urticaria, the culprit is usually food, a drug, or a bug.

But in some cases, the trigger remains elusive. “We don’t always find the source, but don’t beat yourself up about it,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said at the ODAC Dermatology, Aesthetic, and Surgical Conference. “The basic rule is to treat patients to clearance and keep them clear.”

Chronic urticaria is characterized by plaques with a burning/itch sensation that often “move” to different locations on the body over minutes to hours, and they typically last for less than 24 hours. The plaques are often oval, round, or irregular in shape and they typically leave no postinflammatory pigmentary alteration or scarring other than from scratching.

Urticaria affects an estimated 20% of the population, Dr. Friedman said, and is more common in females than males. More than two-thirds of cases are self-limiting but 10% can persist longer than 5 years. Acute episodes are more likely to have an identifiable trigger, while chronic episodes, which last more than six weeks, typically do not. The longer the duration, the lower the chance of identifying the root cause. The foods/food products most commonly affecting children with acute urticaria include milk, egg, peanut, wheat, and soy, while the common culprits in adults are tree nuts, peanuts, and shellfish. Other triggers include the yellow food dye annatto, the red food dye carmine, contact with raw fruits or vegetables, animal saliva, and certain detergents or perfume.

“When you have no idea what the cause is for acute urticaria, I think about viral or bacterial infections, especially in children,” Dr. Friedman said, particularly mycoplasma, adenovirus, enterovirus, rotavirus, respiratory syncytial virus, Epstein-Barr virus, and cytomegalovirus. COVID-19 has also been a new etiologic source for a recent rise in acute urticaria cases.

Other causes include certain medications such as antibiotics, opiates, muscle relaxants, salicylates, and NSAIDs; stinging insects; and exposure to latex products, which can cross react with passion fruit, banana, avocado, chestnut, and kiwi. Alcohol consumption can also trigger urticaria.

“Ask patients if they have joint discomfort or pain,” Dr. Friedman advised, referring to urticaria arthritis syndrome that is typically seen more often in women than in men. “It’s rare but important, because that may distinguish for you what is needed to get those patients under control.”

Chronic urticaria develops in 20%-45% of patients who present with acute urticaria. One form of chronic urticaria is inducible urticaria, which spontaneously occurs after an exposure to an external force. “The distinguishing feature here is that it doesn’t last long – 30 minutes or so – and is typically unresponsive to corticosteroids,” Dr. Friedman said. “It comes on quickly but disappears quickly whereas with chronic spontaneous urticaria, someone might be getting those wheals of flare for hours and hours.”

The most common form of physical urticaria is dermatographism, while other examples include physical urticaria resulting from exposure to cholinergic agents, heat, exercise, cold, water, sunlight, and pressure on the skin.

About half of patients with chronic urticaria are disease free within 1 year, but 20% continue to experience episodes for more than 10 years. One study found that patients with chronic spontaneous urticaria who were diagnosed at a younger age trended toward a longer disease course, and rates were higher in women, compared with men. “Perceived stress can make this worse,” Dr. Friedman added.

According to Dr. Friedman, it’s more important to ask patients targeted questions during office visits than it is to do a full workup. “I ask patients to keep a diary, which can help them identify triggers if there are any,” he said. “I also ask them to take a picture of the papules with their smartphone. There can be a genetic association, so it’s important to ask if anyone else in the family has urticaria. No routine lab tests are required unless there’s something in the history that suggests it’s worthwhile. Let the patient guide the diagnostic workup; don’t just order a million tests.”

That said, known comorbidities associated with urticaria include autoimmune disease, atopy, infections, metabolic conditions, and neoplastic disorders. “Biopsies are typically useless because this is an invisible dermatosis,” he said. “They’re useful when it’s urticarial, not urticaria, when you’re trying to figure out what it is.”

According to recently published international guidelines on urticaria, published in September 2021, the recommended first line of treatment for urticaria is with second-generation nonsedating antihistamines such as cetirizine and loratadine, up to four times the recommended dose.

Second-generation derivatives include desloratadine, levocetirizine, and fexofenadine. “I like using fexofenadine in the morning for folks who don’t tolerate cetirizine, then I’ll recommend something a little more sedating at night,” Dr. Friedman said. “We max out [the dose] by week 4. If it works, great. If not, we move on to something else.”

In late 2021, the British Association of Dermatologists also published guidelines on the treatment of chronic urticaria.

As for markers of treatment success, a study of 240 children with chronic spontaneous urticaria found that risk factors for a poor response included longer duration of disease, higher treatment step until initial disease control, and food sensitization.

Vitamin D supplementation may also add some benefit. One study of 42 adults with urticaria found that low and high doses of vitamin D added to antihistamine therapy can boost effectiveness. “This may be because vitamin D could be a marker of severity,” Dr. Friedman said. “The reality is, however, that a lot of patients don’t do well.”

Data from the large, prospective study known as AWARE (A World-Wide Antihistamine-Refractory Chronic Urticaria Patient Evaluation) found that 23% patients treated with nonsedating H1-antihistamines and 42% patients treated with up-dosed nonsedating H1-antihistamines had uncontrolled chronic spontaneous urticaria at month 24.

A second-line treatment option for patients aged 6 and older is the anti-IgE antibody omalizumab, 150-300 mg by subcutaneous injection every 4 weeks. Dr. Friedman typically uses only the 300-mg dose. “You do not need to take pretreatment serum IgE levels,” he said. “The most significant adverse event is anaphylaxis, which only affects 0.2% of patients.”

A third-line option is cyclosporine A. A dose of 3-5mg/kg per day appears to benefit about two-thirds of patients with antihistamine recalcitrant chronic urticaria. “It works fast but you can’t keep patients on it for very long,” he said.

Another third-line option is mycophenolate mofetil, which may work by inhibiting the production of autoantibodies to the high-affinity IgE receptor and/or IgE. “It does work well, especially in conjunction with antihistamines; it’s kind of a softer immunosuppressant,” he said. Methotrexate can also be used as an add-on therapy to H1 antihistamine therapy in difficult-to-treat cases.

“It’s great we have [a Food and Drug Administration]–approved biologic therapy in omalizumab and access to over-the-counter antihistamines, but there is a high unmet need for treatment,” and a need for new therapies, Dr. Friedman said. “Only about 39% achieve symptomatic control with conventional dosing of antihistamines, and 63% of nonresponders achieve symptom control with a fourfold increased dosing of antihistamines.” In addition, about 20% of patients will not respond to either standard or increased doses of antihistamines and are eligible for treatment with omalizumab. However, more than 50% of such patients experience a delay or lack of response to omalizumab. “We need innovation; we need to understand the disease better,” he said.

Dr. Friedman disclosed that he serves as a consultant and/or adviser for Loreal, La Roche Posay, Cerave, Galderma, Aveeno, Microcures, Pfizer, Novartis, Dermira, Brickell Biotech, Incyte, UCB, Janssen, Pfizer, Bristol-Myers Squibb, Almirall, Zylo Therapeutics, Hoth Therapeutics, Corbus, Greenway Therapeutics, TruPotency, and Dermavant. He is a speaker for Regeneron/Sanofi, AbbVie, Janssen, Brickell Biotech, and Incyte, and has received grants from Pfizer, the Dermatology Foundation, Incyte, and Galderma.

In the clinical experience of Adam Friedman, MD, when patients present with acute urticaria, the culprit is usually food, a drug, or a bug.

But in some cases, the trigger remains elusive. “We don’t always find the source, but don’t beat yourself up about it,” Dr. Friedman, professor and chair of dermatology at George Washington University, Washington, said at the ODAC Dermatology, Aesthetic, and Surgical Conference. “The basic rule is to treat patients to clearance and keep them clear.”

Chronic urticaria is characterized by plaques with a burning/itch sensation that often “move” to different locations on the body over minutes to hours, and they typically last for less than 24 hours. The plaques are often oval, round, or irregular in shape and they typically leave no postinflammatory pigmentary alteration or scarring other than from scratching.

Urticaria affects an estimated 20% of the population, Dr. Friedman said, and is more common in females than males. More than two-thirds of cases are self-limiting but 10% can persist longer than 5 years. Acute episodes are more likely to have an identifiable trigger, while chronic episodes, which last more than six weeks, typically do not. The longer the duration, the lower the chance of identifying the root cause. The foods/food products most commonly affecting children with acute urticaria include milk, egg, peanut, wheat, and soy, while the common culprits in adults are tree nuts, peanuts, and shellfish. Other triggers include the yellow food dye annatto, the red food dye carmine, contact with raw fruits or vegetables, animal saliva, and certain detergents or perfume.

“When you have no idea what the cause is for acute urticaria, I think about viral or bacterial infections, especially in children,” Dr. Friedman said, particularly mycoplasma, adenovirus, enterovirus, rotavirus, respiratory syncytial virus, Epstein-Barr virus, and cytomegalovirus. COVID-19 has also been a new etiologic source for a recent rise in acute urticaria cases.

Other causes include certain medications such as antibiotics, opiates, muscle relaxants, salicylates, and NSAIDs; stinging insects; and exposure to latex products, which can cross react with passion fruit, banana, avocado, chestnut, and kiwi. Alcohol consumption can also trigger urticaria.

“Ask patients if they have joint discomfort or pain,” Dr. Friedman advised, referring to urticaria arthritis syndrome that is typically seen more often in women than in men. “It’s rare but important, because that may distinguish for you what is needed to get those patients under control.”

Chronic urticaria develops in 20%-45% of patients who present with acute urticaria. One form of chronic urticaria is inducible urticaria, which spontaneously occurs after an exposure to an external force. “The distinguishing feature here is that it doesn’t last long – 30 minutes or so – and is typically unresponsive to corticosteroids,” Dr. Friedman said. “It comes on quickly but disappears quickly whereas with chronic spontaneous urticaria, someone might be getting those wheals of flare for hours and hours.”

The most common form of physical urticaria is dermatographism, while other examples include physical urticaria resulting from exposure to cholinergic agents, heat, exercise, cold, water, sunlight, and pressure on the skin.

About half of patients with chronic urticaria are disease free within 1 year, but 20% continue to experience episodes for more than 10 years. One study found that patients with chronic spontaneous urticaria who were diagnosed at a younger age trended toward a longer disease course, and rates were higher in women, compared with men. “Perceived stress can make this worse,” Dr. Friedman added.

According to Dr. Friedman, it’s more important to ask patients targeted questions during office visits than it is to do a full workup. “I ask patients to keep a diary, which can help them identify triggers if there are any,” he said. “I also ask them to take a picture of the papules with their smartphone. There can be a genetic association, so it’s important to ask if anyone else in the family has urticaria. No routine lab tests are required unless there’s something in the history that suggests it’s worthwhile. Let the patient guide the diagnostic workup; don’t just order a million tests.”

That said, known comorbidities associated with urticaria include autoimmune disease, atopy, infections, metabolic conditions, and neoplastic disorders. “Biopsies are typically useless because this is an invisible dermatosis,” he said. “They’re useful when it’s urticarial, not urticaria, when you’re trying to figure out what it is.”

According to recently published international guidelines on urticaria, published in September 2021, the recommended first line of treatment for urticaria is with second-generation nonsedating antihistamines such as cetirizine and loratadine, up to four times the recommended dose.

Second-generation derivatives include desloratadine, levocetirizine, and fexofenadine. “I like using fexofenadine in the morning for folks who don’t tolerate cetirizine, then I’ll recommend something a little more sedating at night,” Dr. Friedman said. “We max out [the dose] by week 4. If it works, great. If not, we move on to something else.”

In late 2021, the British Association of Dermatologists also published guidelines on the treatment of chronic urticaria.

As for markers of treatment success, a study of 240 children with chronic spontaneous urticaria found that risk factors for a poor response included longer duration of disease, higher treatment step until initial disease control, and food sensitization.

Vitamin D supplementation may also add some benefit. One study of 42 adults with urticaria found that low and high doses of vitamin D added to antihistamine therapy can boost effectiveness. “This may be because vitamin D could be a marker of severity,” Dr. Friedman said. “The reality is, however, that a lot of patients don’t do well.”

Data from the large, prospective study known as AWARE (A World-Wide Antihistamine-Refractory Chronic Urticaria Patient Evaluation) found that 23% patients treated with nonsedating H1-antihistamines and 42% patients treated with up-dosed nonsedating H1-antihistamines had uncontrolled chronic spontaneous urticaria at month 24.

A second-line treatment option for patients aged 6 and older is the anti-IgE antibody omalizumab, 150-300 mg by subcutaneous injection every 4 weeks. Dr. Friedman typically uses only the 300-mg dose. “You do not need to take pretreatment serum IgE levels,” he said. “The most significant adverse event is anaphylaxis, which only affects 0.2% of patients.”

A third-line option is cyclosporine A. A dose of 3-5mg/kg per day appears to benefit about two-thirds of patients with antihistamine recalcitrant chronic urticaria. “It works fast but you can’t keep patients on it for very long,” he said.

Another third-line option is mycophenolate mofetil, which may work by inhibiting the production of autoantibodies to the high-affinity IgE receptor and/or IgE. “It does work well, especially in conjunction with antihistamines; it’s kind of a softer immunosuppressant,” he said. Methotrexate can also be used as an add-on therapy to H1 antihistamine therapy in difficult-to-treat cases.

“It’s great we have [a Food and Drug Administration]–approved biologic therapy in omalizumab and access to over-the-counter antihistamines, but there is a high unmet need for treatment,” and a need for new therapies, Dr. Friedman said. “Only about 39% achieve symptomatic control with conventional dosing of antihistamines, and 63% of nonresponders achieve symptom control with a fourfold increased dosing of antihistamines.” In addition, about 20% of patients will not respond to either standard or increased doses of antihistamines and are eligible for treatment with omalizumab. However, more than 50% of such patients experience a delay or lack of response to omalizumab. “We need innovation; we need to understand the disease better,” he said.

Dr. Friedman disclosed that he serves as a consultant and/or adviser for Loreal, La Roche Posay, Cerave, Galderma, Aveeno, Microcures, Pfizer, Novartis, Dermira, Brickell Biotech, Incyte, UCB, Janssen, Pfizer, Bristol-Myers Squibb, Almirall, Zylo Therapeutics, Hoth Therapeutics, Corbus, Greenway Therapeutics, TruPotency, and Dermavant. He is a speaker for Regeneron/Sanofi, AbbVie, Janssen, Brickell Biotech, and Incyte, and has received grants from Pfizer, the Dermatology Foundation, Incyte, and Galderma.