Clinical Psychiatry News

Women with polycystic ovary syndrome (PCOS) may be as much as eight times more likely to attempt suicide than are those without the disorder, according to a new study published in the Annals of Internal Medicine on February 5.

The results point to the importance of mental health screening for all patients who may have syndrome, the researchers concluded.

“If we can know such conditions earlier in our clinical practice, we may reduce the subsequence risk and bad consequences,” said Mu-Hong Chen, MD, PhD, an attending psychiatrist at the Department of Psychiatry at Taipei Veterans General Hospital in Taiwan, a coauthor of the study. 

PCOS affects as many as 15% of reproductive-age women in the United States, or approximately six million people. The condition is associated with an increased risk for metabolic disorders, like diabetes and metabolic syndrome, and cardiovascular problems, like hypertension and stroke. The disorder is associated with infertility, weight gain, hirsutism, and skin changes. Evidence also shows that these changes can lead to poorer self-image and mental health conditions like depression and anxiety. 

Dr. Chen and his coauthors compared the records of nearly 19,000 women between ages 12 and 64 years who had a PCOS diagnosis with a matched control group of 189,600 women and girls without PCOS using data from 1997 to 2012 in the Taiwan National Health Insurance Research Database. Cohorts were matched by age, income, urbanization level, and mental health conditions.

The researchers found that the women diagnosed with PCOS were at an 8.47 times higher risk for suicide attempt over the 16-year follow-up period than were women without the condition. Older women with PCOS had slightly lower risk compared with younger women, but the risk was higher compared with older women without PCOS. Studies in other countries have shown similar results.

Adolescents with PCOS had more than five times the risk for attempted suicide than did the control group (hazard ratio [HR], 5.38; 95% CI, 3.93-7.3). Those between ages 20 and 40 years had more than nine times the risk for attempted suicide (HR, 9.15; 95% CI, 8.03-10.42), and those older than 40 years had the lowest risk (HR, 3.75; 95% CI, 2.23-6.28). 

The number of women with PCOS in the study was likely underreported, and those who were included likely had more serious cases, according to Ricardo Azziz, MD, MPH, MBA, professor in the Department of Obstetrics & Gynecology and the Department of Medicine at the University of Alabama at Birmingham. 

The findings, “speak to the fact that women with PCOS do have a greater incidence of mental health disorders and do require clinicians and patients themselves and their families to be aware of these risks,” said Dr. Azziz, former CEO of the American Society for Reproductive Medicine. 

Clinicians should ask their patients with PCOS about suicide risk and mental health, according to Dr. Azziz. 

“It’s not infrequent that those of us in clinical practice see patients who are significantly depressed, and we need to ask the right questions,” he said.

Though he was only aware of a few patients with PCOS who have attempted suicide, he said that clinicians should be prepared to refer these patients to another professional who can address mental health concerns if they express any signs of distress. 

“Simply asking and inviting patients to speak about this will allow physicians to identify patients who may need to be referred,” Dr. Azziz said. 

The study was funded by grants from the Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and the Ministry of Science and Technology of Taiwan. 

The study authors report no relevant financial relationships. 

A version of this article appeared on Medscape.com.

Women with polycystic ovary syndrome (PCOS) may be as much as eight times more likely to attempt suicide than are those without the disorder, according to a new study published in the Annals of Internal Medicine on February 5.

The results point to the importance of mental health screening for all patients who may have syndrome, the researchers concluded.

“If we can know such conditions earlier in our clinical practice, we may reduce the subsequence risk and bad consequences,” said Mu-Hong Chen, MD, PhD, an attending psychiatrist at the Department of Psychiatry at Taipei Veterans General Hospital in Taiwan, a coauthor of the study. 

PCOS affects as many as 15% of reproductive-age women in the United States, or approximately six million people. The condition is associated with an increased risk for metabolic disorders, like diabetes and metabolic syndrome, and cardiovascular problems, like hypertension and stroke. The disorder is associated with infertility, weight gain, hirsutism, and skin changes. Evidence also shows that these changes can lead to poorer self-image and mental health conditions like depression and anxiety. 

Dr. Chen and his coauthors compared the records of nearly 19,000 women between ages 12 and 64 years who had a PCOS diagnosis with a matched control group of 189,600 women and girls without PCOS using data from 1997 to 2012 in the Taiwan National Health Insurance Research Database. Cohorts were matched by age, income, urbanization level, and mental health conditions.

The researchers found that the women diagnosed with PCOS were at an 8.47 times higher risk for suicide attempt over the 16-year follow-up period than were women without the condition. Older women with PCOS had slightly lower risk compared with younger women, but the risk was higher compared with older women without PCOS. Studies in other countries have shown similar results.

Adolescents with PCOS had more than five times the risk for attempted suicide than did the control group (hazard ratio [HR], 5.38; 95% CI, 3.93-7.3). Those between ages 20 and 40 years had more than nine times the risk for attempted suicide (HR, 9.15; 95% CI, 8.03-10.42), and those older than 40 years had the lowest risk (HR, 3.75; 95% CI, 2.23-6.28). 

The number of women with PCOS in the study was likely underreported, and those who were included likely had more serious cases, according to Ricardo Azziz, MD, MPH, MBA, professor in the Department of Obstetrics & Gynecology and the Department of Medicine at the University of Alabama at Birmingham. 

The findings, “speak to the fact that women with PCOS do have a greater incidence of mental health disorders and do require clinicians and patients themselves and their families to be aware of these risks,” said Dr. Azziz, former CEO of the American Society for Reproductive Medicine. 

Clinicians should ask their patients with PCOS about suicide risk and mental health, according to Dr. Azziz. 

“It’s not infrequent that those of us in clinical practice see patients who are significantly depressed, and we need to ask the right questions,” he said.

Though he was only aware of a few patients with PCOS who have attempted suicide, he said that clinicians should be prepared to refer these patients to another professional who can address mental health concerns if they express any signs of distress. 

“Simply asking and inviting patients to speak about this will allow physicians to identify patients who may need to be referred,” Dr. Azziz said. 

The study was funded by grants from the Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and the Ministry of Science and Technology of Taiwan. 

The study authors report no relevant financial relationships. 

A version of this article appeared on Medscape.com.

Women with polycystic ovary syndrome (PCOS) may be as much as eight times more likely to attempt suicide than are those without the disorder, according to a new study published in the Annals of Internal Medicine on February 5.

The results point to the importance of mental health screening for all patients who may have syndrome, the researchers concluded.

“If we can know such conditions earlier in our clinical practice, we may reduce the subsequence risk and bad consequences,” said Mu-Hong Chen, MD, PhD, an attending psychiatrist at the Department of Psychiatry at Taipei Veterans General Hospital in Taiwan, a coauthor of the study. 

PCOS affects as many as 15% of reproductive-age women in the United States, or approximately six million people. The condition is associated with an increased risk for metabolic disorders, like diabetes and metabolic syndrome, and cardiovascular problems, like hypertension and stroke. The disorder is associated with infertility, weight gain, hirsutism, and skin changes. Evidence also shows that these changes can lead to poorer self-image and mental health conditions like depression and anxiety. 

Dr. Chen and his coauthors compared the records of nearly 19,000 women between ages 12 and 64 years who had a PCOS diagnosis with a matched control group of 189,600 women and girls without PCOS using data from 1997 to 2012 in the Taiwan National Health Insurance Research Database. Cohorts were matched by age, income, urbanization level, and mental health conditions.

The researchers found that the women diagnosed with PCOS were at an 8.47 times higher risk for suicide attempt over the 16-year follow-up period than were women without the condition. Older women with PCOS had slightly lower risk compared with younger women, but the risk was higher compared with older women without PCOS. Studies in other countries have shown similar results.

Adolescents with PCOS had more than five times the risk for attempted suicide than did the control group (hazard ratio [HR], 5.38; 95% CI, 3.93-7.3). Those between ages 20 and 40 years had more than nine times the risk for attempted suicide (HR, 9.15; 95% CI, 8.03-10.42), and those older than 40 years had the lowest risk (HR, 3.75; 95% CI, 2.23-6.28). 

The number of women with PCOS in the study was likely underreported, and those who were included likely had more serious cases, according to Ricardo Azziz, MD, MPH, MBA, professor in the Department of Obstetrics & Gynecology and the Department of Medicine at the University of Alabama at Birmingham. 

The findings, “speak to the fact that women with PCOS do have a greater incidence of mental health disorders and do require clinicians and patients themselves and their families to be aware of these risks,” said Dr. Azziz, former CEO of the American Society for Reproductive Medicine. 

Clinicians should ask their patients with PCOS about suicide risk and mental health, according to Dr. Azziz. 

“It’s not infrequent that those of us in clinical practice see patients who are significantly depressed, and we need to ask the right questions,” he said.

Though he was only aware of a few patients with PCOS who have attempted suicide, he said that clinicians should be prepared to refer these patients to another professional who can address mental health concerns if they express any signs of distress. 

“Simply asking and inviting patients to speak about this will allow physicians to identify patients who may need to be referred,” Dr. Azziz said. 

The study was funded by grants from the Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and the Ministry of Science and Technology of Taiwan. 

The study authors report no relevant financial relationships. 

A version of this article appeared on Medscape.com.

Recent research highlights the potential role of an atypical antipsychotic to treat anxiety, a prevalent and undertreated symptom in bipolar I disorder (BPD). Notably, investigators said, the drug comes without the typical metabolic side effects, including weight gain, associated with this drug class.

A post hoc analysis of pooled data from two trials comparing two different doses of cariprazine (Vraylar) to placebo showed it was consistently effective not only in alleviating bipolar depression but also in improving symptoms of anxiety.

“Since this was a post hoc analysis, one has to be careful about not overstating the findings,” said study investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit.

“But what we can say is that anxiety has been an under-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are very promising,” said Dr. McIntyre, chair and executive director of the Brain and Cognition Discovery Foundation, also in Toronto.

The analysis was published in International Clinical Psychopharmacology) and was presented as a poster at the 2023 Neuroscience Education Institute, Colorado Springs, Colorado.
 

Ubiquitous, Common, Hazardous

Anxiety in BPD is “ubiquitous, common, and hazardous,” Dr. McIntyre said. “We talk so much about depression and mania as cardinal presentations, but someone could make a case that in that trifecta, we’re missing anxiety.”

In patients with BPD and anxiety, “the index episode is much more difficult to treat, there’s a longer time to remission, lower rates of recovery, and a shorter time to recurrence,” noted Dr. McIntyre, chair of the board of the Depression and Bipolar Support Alliance.

Anxiety also may “represent a portent of other things that can add more to the trouble, like alcohol, illicit drugs, or cannabis use — especially now that cannabis is no longer illegal,” Dr. McIntyre said.

Unfortunately, he said, “there hasn’t been an organized, systematic approach to developing a therapy for anxiety in BPD.” Rather, patients are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have limitations, he added.

Some atypical antipsychotics such as quetiapine have been shown to be helpful with anxiety but “have a lot of baggage and side effects — especially sedation, somnolence, weight gain, and metabolic problems,” Dr. McIntyre noted.

Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has shown anxiolytic-like activity in rodent models.

It was approved by the US Food and Drug Administration to treat mania, depression, and mixed episodes of BPD in 2015 and BPD in 2019.

Dr. McIntyre and his team believed there was an opportunity in the completed randomized controlled trials of cariprazine in BPD to conduct a post hoc analysis of its impact on anxiety.
 

‘Cornerstone Mood Stabilizer’

The researchers pooled data from two phase 3, randomized, double-blind, placebo-controlled studies in adults with BPD experiencing a current major depressive episode.

The pooled intention-to-treat population consisted of 952 patients with BPD (mean age, ~43 years; 62% female) randomized to receive either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Patients were divided into two subsets: Lower or higher anxiety (defined as a Hamilton Anxiety Rating Scale [HAM-A] total score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS).

A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets.

Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The rate of remission was significantly greater for cariprazine 1.5 mg/d in the higher and lower anxiety subsets (P = .0172 and P = .0004, respectively).

In addition, the change in HAM-A total score change was statistically significant for cariprazine 1.5 mg/d in the higher anxiety subgroup (P = .0105) and the 3 mg/d dose in the lower anxiety subgroup (P = .0441).

Dr. McIntyre hopes these findings can be replicated in other trials.

“Clinically, I find that many patients who take cariprazine don’t require as many benzodiazepines or other medications for anxiety, and it’s one of the better-tolerated medications without metabolic complications or weight gain, so it’s become a cornerstone mood stabilizer,” he said.
 

Polypharmacy Avoided

Another recent study retrospectively analyzed medical records of close to 40 adult patients with BPD I who were receiving treatment with aripiprazole for bipolar depression and then switched to cariprazine.

“We wanted to conduct a study in depressed patients who had gained weight on aripiprazole and then directly switched to cariprazine. It improved their mood and helped mitigate weight gain, thereby avoiding polypharmacy of additional antidepressants and weight loss agents,” said study investigator Maxwell Zachary Price, a medical student at Hackensack Meridian School of Medicine, Nutley, New Jersey.

“In our general outpatient psychiatry practice, we’ve treated many adult patients with oral aripiprazole for maintenance of BPD,” the study’s senior investigator, Richard Price, MD, clinical assistant professor of psychiatry at Weill Cornell Medical College, New York City, added.

Aripiprazole is associated with weight gain. Moreover, aripiprazole “hasn’t shown efficacy in managing BPD,” he said.

Most patients in Dr. Price’s practice are insured through Medicaid, which mandates treatment with aripiprazole before covering cariprazine. “We noticed their weight had been creeping up over the years, and they also were experiencing depressive symptoms,” he said.

The requirement to initiate treatment with aripiprazole before switching to cariprazine offered Dr. Price an opportunity to compare the two agents in this real-world setting by retrospectively reviewing the charts of 37 patients with BPD (23 females and 14 males who made the switch). The patients had been taking aripiprazole for a mean duration of 94.9 weeks and had experienced a mean increase in body weight of 16.1% ± 12.3% on aripiprazole before switching.

Patients who were taking 2 mg-10 mg of aripiprazole were switched to 1.5 mg of cariprazine, while those taking ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine.

“Patients tolerated the switch well and maintained stability during the transition,” and “no patients discontinued cariprazine during the study,” Dr. Price said.

After a mean duration of 36.7 weeks (range, 1-127 weeks), the patients showed a decrease in Clinical Global Impression-Bipolar Severity of Illness Scale score from a mean of 5.0 ± 0.9 to a mean of 2.8 ± 0.7 (t = −12.75, P < .00001).

The patients’ weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001).

Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction.

“We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well,” said Dr. Price. He hopes that further research in randomized blinded trials will corroborate the findings.
 

Hypothesis-Generating Research

Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are “hypothesis-generating.”

Dr. Ciremele, who wasn’t involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, “help us all ask questions related to concurrent symptoms in bipolar depression.”

However, the post hoc analysis was a secondary analysis of an efficacy trial where individuals with concurrent anxiety disorders were excluded. “So, a next step might be to evaluate this and other treatments in individuals with BPD and concurrent anxiety disorders,” he said.

The study by Jain et al was funded by AbbVie. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. McIntyre is the CEO of Braxia Scientific Corp. His coauthors’ disclosures are listed in the original paper. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Mr. Price and Dr. Cerimele reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recent research highlights the potential role of an atypical antipsychotic to treat anxiety, a prevalent and undertreated symptom in bipolar I disorder (BPD). Notably, investigators said, the drug comes without the typical metabolic side effects, including weight gain, associated with this drug class.

A post hoc analysis of pooled data from two trials comparing two different doses of cariprazine (Vraylar) to placebo showed it was consistently effective not only in alleviating bipolar depression but also in improving symptoms of anxiety.

“Since this was a post hoc analysis, one has to be careful about not overstating the findings,” said study investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit.

“But what we can say is that anxiety has been an under-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are very promising,” said Dr. McIntyre, chair and executive director of the Brain and Cognition Discovery Foundation, also in Toronto.

The analysis was published in International Clinical Psychopharmacology) and was presented as a poster at the 2023 Neuroscience Education Institute, Colorado Springs, Colorado.
 

Ubiquitous, Common, Hazardous

Anxiety in BPD is “ubiquitous, common, and hazardous,” Dr. McIntyre said. “We talk so much about depression and mania as cardinal presentations, but someone could make a case that in that trifecta, we’re missing anxiety.”

In patients with BPD and anxiety, “the index episode is much more difficult to treat, there’s a longer time to remission, lower rates of recovery, and a shorter time to recurrence,” noted Dr. McIntyre, chair of the board of the Depression and Bipolar Support Alliance.

Anxiety also may “represent a portent of other things that can add more to the trouble, like alcohol, illicit drugs, or cannabis use — especially now that cannabis is no longer illegal,” Dr. McIntyre said.

Unfortunately, he said, “there hasn’t been an organized, systematic approach to developing a therapy for anxiety in BPD.” Rather, patients are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have limitations, he added.

Some atypical antipsychotics such as quetiapine have been shown to be helpful with anxiety but “have a lot of baggage and side effects — especially sedation, somnolence, weight gain, and metabolic problems,” Dr. McIntyre noted.

Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has shown anxiolytic-like activity in rodent models.

It was approved by the US Food and Drug Administration to treat mania, depression, and mixed episodes of BPD in 2015 and BPD in 2019.

Dr. McIntyre and his team believed there was an opportunity in the completed randomized controlled trials of cariprazine in BPD to conduct a post hoc analysis of its impact on anxiety.
 

‘Cornerstone Mood Stabilizer’

The researchers pooled data from two phase 3, randomized, double-blind, placebo-controlled studies in adults with BPD experiencing a current major depressive episode.

The pooled intention-to-treat population consisted of 952 patients with BPD (mean age, ~43 years; 62% female) randomized to receive either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Patients were divided into two subsets: Lower or higher anxiety (defined as a Hamilton Anxiety Rating Scale [HAM-A] total score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS).

A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets.

Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The rate of remission was significantly greater for cariprazine 1.5 mg/d in the higher and lower anxiety subsets (P = .0172 and P = .0004, respectively).

In addition, the change in HAM-A total score change was statistically significant for cariprazine 1.5 mg/d in the higher anxiety subgroup (P = .0105) and the 3 mg/d dose in the lower anxiety subgroup (P = .0441).

Dr. McIntyre hopes these findings can be replicated in other trials.

“Clinically, I find that many patients who take cariprazine don’t require as many benzodiazepines or other medications for anxiety, and it’s one of the better-tolerated medications without metabolic complications or weight gain, so it’s become a cornerstone mood stabilizer,” he said.
 

Polypharmacy Avoided

Another recent study retrospectively analyzed medical records of close to 40 adult patients with BPD I who were receiving treatment with aripiprazole for bipolar depression and then switched to cariprazine.

“We wanted to conduct a study in depressed patients who had gained weight on aripiprazole and then directly switched to cariprazine. It improved their mood and helped mitigate weight gain, thereby avoiding polypharmacy of additional antidepressants and weight loss agents,” said study investigator Maxwell Zachary Price, a medical student at Hackensack Meridian School of Medicine, Nutley, New Jersey.

“In our general outpatient psychiatry practice, we’ve treated many adult patients with oral aripiprazole for maintenance of BPD,” the study’s senior investigator, Richard Price, MD, clinical assistant professor of psychiatry at Weill Cornell Medical College, New York City, added.

Aripiprazole is associated with weight gain. Moreover, aripiprazole “hasn’t shown efficacy in managing BPD,” he said.

Most patients in Dr. Price’s practice are insured through Medicaid, which mandates treatment with aripiprazole before covering cariprazine. “We noticed their weight had been creeping up over the years, and they also were experiencing depressive symptoms,” he said.

The requirement to initiate treatment with aripiprazole before switching to cariprazine offered Dr. Price an opportunity to compare the two agents in this real-world setting by retrospectively reviewing the charts of 37 patients with BPD (23 females and 14 males who made the switch). The patients had been taking aripiprazole for a mean duration of 94.9 weeks and had experienced a mean increase in body weight of 16.1% ± 12.3% on aripiprazole before switching.

Patients who were taking 2 mg-10 mg of aripiprazole were switched to 1.5 mg of cariprazine, while those taking ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine.

“Patients tolerated the switch well and maintained stability during the transition,” and “no patients discontinued cariprazine during the study,” Dr. Price said.

After a mean duration of 36.7 weeks (range, 1-127 weeks), the patients showed a decrease in Clinical Global Impression-Bipolar Severity of Illness Scale score from a mean of 5.0 ± 0.9 to a mean of 2.8 ± 0.7 (t = −12.75, P < .00001).

The patients’ weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001).

Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction.

“We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well,” said Dr. Price. He hopes that further research in randomized blinded trials will corroborate the findings.
 

Hypothesis-Generating Research

Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are “hypothesis-generating.”

Dr. Ciremele, who wasn’t involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, “help us all ask questions related to concurrent symptoms in bipolar depression.”

However, the post hoc analysis was a secondary analysis of an efficacy trial where individuals with concurrent anxiety disorders were excluded. “So, a next step might be to evaluate this and other treatments in individuals with BPD and concurrent anxiety disorders,” he said.

The study by Jain et al was funded by AbbVie. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. McIntyre is the CEO of Braxia Scientific Corp. His coauthors’ disclosures are listed in the original paper. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Mr. Price and Dr. Cerimele reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Recent research highlights the potential role of an atypical antipsychotic to treat anxiety, a prevalent and undertreated symptom in bipolar I disorder (BPD). Notably, investigators said, the drug comes without the typical metabolic side effects, including weight gain, associated with this drug class.

A post hoc analysis of pooled data from two trials comparing two different doses of cariprazine (Vraylar) to placebo showed it was consistently effective not only in alleviating bipolar depression but also in improving symptoms of anxiety.

“Since this was a post hoc analysis, one has to be careful about not overstating the findings,” said study investigator Roger McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, and head of the Mood Disorders Psychopharmacology Unit.

“But what we can say is that anxiety has been an under-researched, undertreated symptom dimension in BPD, and these findings about cariprazine are very promising,” said Dr. McIntyre, chair and executive director of the Brain and Cognition Discovery Foundation, also in Toronto.

The analysis was published in International Clinical Psychopharmacology) and was presented as a poster at the 2023 Neuroscience Education Institute, Colorado Springs, Colorado.
 

Ubiquitous, Common, Hazardous

Anxiety in BPD is “ubiquitous, common, and hazardous,” Dr. McIntyre said. “We talk so much about depression and mania as cardinal presentations, but someone could make a case that in that trifecta, we’re missing anxiety.”

In patients with BPD and anxiety, “the index episode is much more difficult to treat, there’s a longer time to remission, lower rates of recovery, and a shorter time to recurrence,” noted Dr. McIntyre, chair of the board of the Depression and Bipolar Support Alliance.

Anxiety also may “represent a portent of other things that can add more to the trouble, like alcohol, illicit drugs, or cannabis use — especially now that cannabis is no longer illegal,” Dr. McIntyre said.

Unfortunately, he said, “there hasn’t been an organized, systematic approach to developing a therapy for anxiety in BPD.” Rather, patients are prescribed benzodiazepines, gabapentinoids, or selective serotonin reuptake inhibitors, all of which have limitations, he added.

Some atypical antipsychotics such as quetiapine have been shown to be helpful with anxiety but “have a lot of baggage and side effects — especially sedation, somnolence, weight gain, and metabolic problems,” Dr. McIntyre noted.

Cariprazine is a dopamine D3-preferring D3/D2 partial agonist, a serotonin 5-HT1A receptor partial agonist, and 5-HT2B receptor antagonist, which has shown anxiolytic-like activity in rodent models.

It was approved by the US Food and Drug Administration to treat mania, depression, and mixed episodes of BPD in 2015 and BPD in 2019.

Dr. McIntyre and his team believed there was an opportunity in the completed randomized controlled trials of cariprazine in BPD to conduct a post hoc analysis of its impact on anxiety.
 

‘Cornerstone Mood Stabilizer’

The researchers pooled data from two phase 3, randomized, double-blind, placebo-controlled studies in adults with BPD experiencing a current major depressive episode.

The pooled intention-to-treat population consisted of 952 patients with BPD (mean age, ~43 years; 62% female) randomized to receive either 1.5 mg/d, 3 mg/d of cariprazine, or placebo. Patients were divided into two subsets: Lower or higher anxiety (defined as a Hamilton Anxiety Rating Scale [HAM-A] total score of < 18 and ≥ 18, respectively). Patients also completed the Montgomery-Åsberg Rating Scale (MADRS).

A third of the patients received a placebo, a third received the 1.5 mg/d dose, and a third received the 3 mg/d dose. Demographic and baseline characteristics were similar between the subsets.

Results showed there was a statistically significant change in HAM-A total score for cariprazine 1.5 mg/d (P = .0027). The investigators also found a statistically significant change in MADRS total score change for cariprazine 1.5 mg (P = .0200) in the higher anxiety subset. The rate of remission was significantly greater for cariprazine 1.5 mg/d in the higher and lower anxiety subsets (P = .0172 and P = .0004, respectively).

In addition, the change in HAM-A total score change was statistically significant for cariprazine 1.5 mg/d in the higher anxiety subgroup (P = .0105) and the 3 mg/d dose in the lower anxiety subgroup (P = .0441).

Dr. McIntyre hopes these findings can be replicated in other trials.

“Clinically, I find that many patients who take cariprazine don’t require as many benzodiazepines or other medications for anxiety, and it’s one of the better-tolerated medications without metabolic complications or weight gain, so it’s become a cornerstone mood stabilizer,” he said.
 

Polypharmacy Avoided

Another recent study retrospectively analyzed medical records of close to 40 adult patients with BPD I who were receiving treatment with aripiprazole for bipolar depression and then switched to cariprazine.

“We wanted to conduct a study in depressed patients who had gained weight on aripiprazole and then directly switched to cariprazine. It improved their mood and helped mitigate weight gain, thereby avoiding polypharmacy of additional antidepressants and weight loss agents,” said study investigator Maxwell Zachary Price, a medical student at Hackensack Meridian School of Medicine, Nutley, New Jersey.

“In our general outpatient psychiatry practice, we’ve treated many adult patients with oral aripiprazole for maintenance of BPD,” the study’s senior investigator, Richard Price, MD, clinical assistant professor of psychiatry at Weill Cornell Medical College, New York City, added.

Aripiprazole is associated with weight gain. Moreover, aripiprazole “hasn’t shown efficacy in managing BPD,” he said.

Most patients in Dr. Price’s practice are insured through Medicaid, which mandates treatment with aripiprazole before covering cariprazine. “We noticed their weight had been creeping up over the years, and they also were experiencing depressive symptoms,” he said.

The requirement to initiate treatment with aripiprazole before switching to cariprazine offered Dr. Price an opportunity to compare the two agents in this real-world setting by retrospectively reviewing the charts of 37 patients with BPD (23 females and 14 males who made the switch). The patients had been taking aripiprazole for a mean duration of 94.9 weeks and had experienced a mean increase in body weight of 16.1% ± 12.3% on aripiprazole before switching.

Patients who were taking 2 mg-10 mg of aripiprazole were switched to 1.5 mg of cariprazine, while those taking ≥ 15 mg of aripiprazole were switched to 3 mg of cariprazine.

“Patients tolerated the switch well and maintained stability during the transition,” and “no patients discontinued cariprazine during the study,” Dr. Price said.

After a mean duration of 36.7 weeks (range, 1-127 weeks), the patients showed a decrease in Clinical Global Impression-Bipolar Severity of Illness Scale score from a mean of 5.0 ± 0.9 to a mean of 2.8 ± 0.7 (t = −12.75, P < .00001).

The patients’ weight dropped from a mean of 90.3± 21.5 kg on aripiprazole to a mean of 83.9 ± 19.2 kg on cariprazine (t = −4.22, P < .001).

Two patients experienced initial nausea that resolved by taking the medication with food, and two experienced initial restlessness that resolved with dosage reduction.

“We found that the patients were lighter in mood, body habitus and weight, and less agitated and their mental alertness and concentration improved as well,” said Dr. Price. He hopes that further research in randomized blinded trials will corroborate the findings.
 

Hypothesis-Generating Research

Joseph Cerimele, MD, MPH, associate professor of psychiatry and behavioral sciences, University of Washington, Division of Population Health, UW Medicine, Seattle, Washington, said the research findings are “hypothesis-generating.”

Dr. Ciremele, who wasn’t involved with either study, said many clinicians and researchers are trying to tailor treatment options to match patient characteristics, and these studies and other similar research, “help us all ask questions related to concurrent symptoms in bipolar depression.”

However, the post hoc analysis was a secondary analysis of an efficacy trial where individuals with concurrent anxiety disorders were excluded. “So, a next step might be to evaluate this and other treatments in individuals with BPD and concurrent anxiety disorders,” he said.

The study by Jain et al was funded by AbbVie. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics Inc., Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies, NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. Dr. McIntyre is the CEO of Braxia Scientific Corp. His coauthors’ disclosures are listed in the original paper. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus. Mr. Price and Dr. Cerimele reported no relevant financial relationships.

A version of this article appeared on Medscape.com.

Iloperidone, a second-generation antipsychotic used to treat schizophrenia, appears to be safe and effective in the treatment of bipolar mania, new research suggested.

Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.

The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.

“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.

The study was published online in the Journal of Clinical Psychiatry.
 

Early Improvement

Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.

The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).

Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.

The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).

Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).

Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.

Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
 

Favorable Akathisia Profile

As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.

Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.

The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).

Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.

Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.

Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”

Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.

One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
 

Potential Second-Line Treatment

Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.

“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.

Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT_2A and dopamine D₂ and D₃ receptors, as well as the noradrenergic α₁ receptors.

The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.

Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.

“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.

This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.

A version of this article appeared on Medscape.com.

Iloperidone, a second-generation antipsychotic used to treat schizophrenia, appears to be safe and effective in the treatment of bipolar mania, new research suggested.

Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.

The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.

“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.

The study was published online in the Journal of Clinical Psychiatry.
 

Early Improvement

Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.

The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).

Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.

The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).

Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).

Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.

Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
 

Favorable Akathisia Profile

As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.

Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.

The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).

Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.

Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.

Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”

Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.

One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
 

Potential Second-Line Treatment

Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.

“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.

Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT_2A and dopamine D₂ and D₃ receptors, as well as the noradrenergic α₁ receptors.

The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.

Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.

“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.

This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.

A version of this article appeared on Medscape.com.

Iloperidone, a second-generation antipsychotic used to treat schizophrenia, appears to be safe and effective in the treatment of bipolar mania, new research suggested.

Results of the phase 3 randomized double-blind placebo-controlled trial show patients with bipolar mania who received iloperidone had significantly greater change from baseline to 4 weeks on the Young Mania Rating Scale (YMRS) compared with placebo, an improvement detected as early as 14 days from the initial dose.

The incidence of akathisia and extrapyramidal symptoms (EPS) was low in the treatment group, and the medication was well-tolerated.

“This study provides evidence that iloperidone improves the symptoms of bipolar mania in adults and can be a useful treatment option for people with bipolar disorder,” the investigators, led by Rosarelis Torres, PhD, of Vanda Pharmaceuticals, and colleagues wrote.

The study was published online in the Journal of Clinical Psychiatry.
 

Early Improvement

Iloperidone was first approved by the US Food and Drug Administration in 2009 for treatment of schizophrenia.

The current study included 414 participants (mean age, 43 years; 56% male) across 17 US and international sites. Patients with psychotic features received a fixed daily dose of 24 mg of iloperidone (n = 206) or placebo (n = 208).

Participants completed a screening period of up to 7 days before randomization, followed by a 1-day baseline evaluation period and a 28-day treatment phase.

The primary efficacy endpoint was change from baseline to week 4 on the YMRS (vs placebo), while secondary efficacy endpoints included change from baseline on the Clinical Global Impressions-Severity and Clinical Global Impression of Change scales (CGI-S and CGI-C, respectively).

Compared with placebo, iloperidone was associated with significant improvement of mania symptoms at week 4, with a mean reduction on the YMRS scale of −4.0 (P = .000008), and significant decreases on the CGI-S (mean, −0.4; P = .0005) and CGI-C scales (mean, −0.5; P = .0002).

Statistically significant differences between iloperidone and placebo were observed as early as day 14 and continued through days 21 and 28.

Post hoc analyses found no difference in efficacy even when patients who had received benzodiazepines were excluded, regardless of the presence or absence of psychotic features at baseline.
 

Favorable Akathisia Profile

As for safety, 68% of patients in the iloperidone group experienced at least one adverse event, compared with 49% of patients in the placebo group.

Patients in the treatment group had a higher rate of withdrawal from the study than those in the placebo group (32.9% vs 27.1%), and more patients in the iloperidone group experienced treatment-emergent adverse events (TEAEs) leading to study drug discontinuation (8.7% vs 5.3%). However, no TEAEs associated with discontinuation occurred in more than two patients in either group, and none of the participants experienced any AE leading to death.

The most common adverse events (AEs) were tachycardia (18%), dizziness (11%), dry mouth (9%), increased alanine aminotransferase (7%), nasal congestion (6%), weight gain (6%), and somnolence (5%).

Five serious AEs were reported in four participants in the treatment group and one in the placebo group. Two were identified as related to the study medication. These included sedation and spontaneous penile erection.

Changes from baseline in clinical laboratory parameters were not largely different between the groups, but there were post-randomization changes in QT interval in three iloperidone patients. The incidence of orthostatic response was also higher for iloperidone vs placebo.

Although “much improved compared to early antipsychotics, SGAs can still cause considerable adverse motor side effects,” the authors wrote. “However, among all SGAs, iloperidone’s akathisia profile is favorable.”

Antipsychotic-induced akathisia has been reported more frequently in patients with bipolar disorder than in those with schizophrenia treated with the same medication, investigators noted.

One study limitation is the fact that long-term efficacy in the prevention of manic or depressive episodes was not assessed.
 

Potential Second-Line Treatment

Commenting on the study, Richard Louis Price, MD, assistant professor of psychiatry, at Weill Cornell Medical College, New York City, said the findings suggest iloperidone may be “modestly effective” for patients with bipolar 1 mania or mixed episodes.

“It’s helpful to have new treatment options, especially for patients who have difficulty tolerating other agents,” said Dr. Price, who was not involved with the study.

Also commenting on the research, Roger S. McIntyre, MD, professor of psychiatry and pharmacology, University of Toronto, Toronto, Ontario, Canada, noted iloperidone’s “interesting antipsychotic pharmacodynamic,” highlighting the drug’s high-binding affinity for serotonin 5HT_2A and dopamine D₂ and D₃ receptors, as well as the noradrenergic α₁ receptors.

The drug’s profile “suggests benefit in manic features and agitation, perhaps with a lower propensity to EPS, which is especially important in persons at higher risk, like persons living with bipolar disorder,” Dr. McIntyre said.

Dr. McIntyre, who was not involved with the study, added iloperidone could be a second-line therapy because of its tolerability profile, provided the study results can be replicated.

“When considering alternatives with similar efficacy, absence of titration (or simple titration) minimal to no weight gain, no orthostatic hypotension, and no potential concerns with QT, those alternatives would have to be considered first-line, assuming that the study results are replicated,” he said.

This study was funded by Vanda Pharmaceuticals. The authors’ disclosures are listed in the original paper. Dr. McIntyre had received research grant support from CIHR/GACD/National Natural Science Foundation of China and the Milken Institute; speaker/consultation fees from Lundbeck, Janssen, Alkermes, Neumora Therapeutics, Boehringer Ingelheim, Sage, Biogen, Mitsubishi Tanabe, Purdue, Pfizer, Otsuka, Takeda, Neurocrine Biosciences, Sunovion, Bausch Health, Axsome Therapeutics, Novo Nordisk, Kris, Sanofi, Eisai, Intra-Cellular Therapies Inc., NewBridge Pharmaceuticals, Viatris, Abbvie, and Atai Life Sciences. McIntyre is the CEO of Braxia Scientific Corp. Dr. Price had received honoraria from AbbVie, Alkermes, Allergan, Intra-Cellular Therapies, Janssen, Jazz, Lundbeck, Neuronetics, Otsuka, and Supernus.

A version of this article appeared on Medscape.com.

Biogen’s announcement on January 31 that it will discontinue development and commercialization of the anti-amyloid agent, aducanumab (Aduhelm), for Alzheimer’s disease came as no surprise to many experts in the field. 

“Clearly, the drug was a commercial failure,” Dave Knopman, MD, professor of neurology, Mayo Clinic, Rochester, Minnesota, said. “Despite the accelerated approval, the uncertainty of clinical benefits was transparent, and the public failed to generate any enthusiasm for the drug.”

Aducanumab received accelerated approval from the US Food and Drug Administration (FDA) in June 2021 despite a recommendation by its own advisory panel not to approve the drug. Dr. Knopman was a member of that panel and one of three members who resigned after the agency’s decision to approve the drug. 

“The decision by Biogen to cancel the aducanumab program was not surprising, as the company steadily withdrew their engagement in the program over the past year,” Dr. Knopman noted. 

“This was a commercial decision — not so much a scientific decision,” Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, said. 

“The process by which the [aducanumab] program was handled and some of the conflicting opinions at the FDA led to uncertainty about the efficacy of the drug, and it wasn’t being prescribed,” Dr. Fillit said. 

After its approval, the Centers for Medicare & Medicaid Services restricted coverage of aducanumab to patients enrolled in clinical trials, which experts say likely contributed to Biogen’s decision to ditch the drug. 

It also limited the number of people living with Alzheimer’s disease who could get access to the treatment and “created significant confusion for patients and doctors,” the Alzheimer’s Association said in a statement on Biogen’s decision. 

Biogen will also terminate the post-approval clinical trial known as ENVISION, which sought to confirm aducanumab’s benefits in patients with early Alzheimer’s disease. 

Going forward, Biogen said that it will now focus on advancing lecanemab (Leqembi), the first anti-amyloid to receive traditional FDA approval.

“We have learned much from the mistakes and misjudgments that plagued aducanumab, but the field has moved on and is a little the wiser,” Dr. Knopman said. “With the standard approval of lecanemab, which showed clear, albeit modest, clinical benefits, we are focusing on providing safe and efficient access to lecanemab.” 

Biogen plans to accelerate the development of potential new treatment modalities. These include BIIB080, an investigational antisense oligonucleotide therapy targeting tau, and BIIB113, an oral small-molecule inhibitor of tau aggregation.

Dr. Fillit said that he’s “very excited” about the current pipeline of Alzheimer’s disease drugs, starting with donanemab, which is currently under review at the FDA, and “looks like it has somewhat better efficacy data than lecanemab.”

A version of this article appeared on Medscape.com.

Biogen’s announcement on January 31 that it will discontinue development and commercialization of the anti-amyloid agent, aducanumab (Aduhelm), for Alzheimer’s disease came as no surprise to many experts in the field. 

“Clearly, the drug was a commercial failure,” Dave Knopman, MD, professor of neurology, Mayo Clinic, Rochester, Minnesota, said. “Despite the accelerated approval, the uncertainty of clinical benefits was transparent, and the public failed to generate any enthusiasm for the drug.”

Aducanumab received accelerated approval from the US Food and Drug Administration (FDA) in June 2021 despite a recommendation by its own advisory panel not to approve the drug. Dr. Knopman was a member of that panel and one of three members who resigned after the agency’s decision to approve the drug. 

“The decision by Biogen to cancel the aducanumab program was not surprising, as the company steadily withdrew their engagement in the program over the past year,” Dr. Knopman noted. 

“This was a commercial decision — not so much a scientific decision,” Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, said. 

“The process by which the [aducanumab] program was handled and some of the conflicting opinions at the FDA led to uncertainty about the efficacy of the drug, and it wasn’t being prescribed,” Dr. Fillit said. 

After its approval, the Centers for Medicare & Medicaid Services restricted coverage of aducanumab to patients enrolled in clinical trials, which experts say likely contributed to Biogen’s decision to ditch the drug. 

It also limited the number of people living with Alzheimer’s disease who could get access to the treatment and “created significant confusion for patients and doctors,” the Alzheimer’s Association said in a statement on Biogen’s decision. 

Biogen will also terminate the post-approval clinical trial known as ENVISION, which sought to confirm aducanumab’s benefits in patients with early Alzheimer’s disease. 

Going forward, Biogen said that it will now focus on advancing lecanemab (Leqembi), the first anti-amyloid to receive traditional FDA approval.

“We have learned much from the mistakes and misjudgments that plagued aducanumab, but the field has moved on and is a little the wiser,” Dr. Knopman said. “With the standard approval of lecanemab, which showed clear, albeit modest, clinical benefits, we are focusing on providing safe and efficient access to lecanemab.” 

Biogen plans to accelerate the development of potential new treatment modalities. These include BIIB080, an investigational antisense oligonucleotide therapy targeting tau, and BIIB113, an oral small-molecule inhibitor of tau aggregation.

Dr. Fillit said that he’s “very excited” about the current pipeline of Alzheimer’s disease drugs, starting with donanemab, which is currently under review at the FDA, and “looks like it has somewhat better efficacy data than lecanemab.”

A version of this article appeared on Medscape.com.

Biogen’s announcement on January 31 that it will discontinue development and commercialization of the anti-amyloid agent, aducanumab (Aduhelm), for Alzheimer’s disease came as no surprise to many experts in the field. 

“Clearly, the drug was a commercial failure,” Dave Knopman, MD, professor of neurology, Mayo Clinic, Rochester, Minnesota, said. “Despite the accelerated approval, the uncertainty of clinical benefits was transparent, and the public failed to generate any enthusiasm for the drug.”

Aducanumab received accelerated approval from the US Food and Drug Administration (FDA) in June 2021 despite a recommendation by its own advisory panel not to approve the drug. Dr. Knopman was a member of that panel and one of three members who resigned after the agency’s decision to approve the drug. 

“The decision by Biogen to cancel the aducanumab program was not surprising, as the company steadily withdrew their engagement in the program over the past year,” Dr. Knopman noted. 

“This was a commercial decision — not so much a scientific decision,” Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, said. 

“The process by which the [aducanumab] program was handled and some of the conflicting opinions at the FDA led to uncertainty about the efficacy of the drug, and it wasn’t being prescribed,” Dr. Fillit said. 

After its approval, the Centers for Medicare & Medicaid Services restricted coverage of aducanumab to patients enrolled in clinical trials, which experts say likely contributed to Biogen’s decision to ditch the drug. 

It also limited the number of people living with Alzheimer’s disease who could get access to the treatment and “created significant confusion for patients and doctors,” the Alzheimer’s Association said in a statement on Biogen’s decision. 

Biogen will also terminate the post-approval clinical trial known as ENVISION, which sought to confirm aducanumab’s benefits in patients with early Alzheimer’s disease. 

Going forward, Biogen said that it will now focus on advancing lecanemab (Leqembi), the first anti-amyloid to receive traditional FDA approval.

“We have learned much from the mistakes and misjudgments that plagued aducanumab, but the field has moved on and is a little the wiser,” Dr. Knopman said. “With the standard approval of lecanemab, which showed clear, albeit modest, clinical benefits, we are focusing on providing safe and efficient access to lecanemab.” 

Biogen plans to accelerate the development of potential new treatment modalities. These include BIIB080, an investigational antisense oligonucleotide therapy targeting tau, and BIIB113, an oral small-molecule inhibitor of tau aggregation.

Dr. Fillit said that he’s “very excited” about the current pipeline of Alzheimer’s disease drugs, starting with donanemab, which is currently under review at the FDA, and “looks like it has somewhat better efficacy data than lecanemab.”

A version of this article appeared on Medscape.com.

TOPLINE:

People with polycystic ovary syndrome (PCOS) may score lower on cognitive tests than people without the condition, a research showed. They also may have worse integrity of brain tissue as evident on an MRI.

METHODOLOGY:

• Researchers used data from the Coronary Artery Risk Development in Young Adults Women’s Study; individuals were 18-30 years old at the beginning of the study and were followed over 30 years.
• A little over 900 women were included in the study, of which 66 had PCOS, which was defined as having elevated androgen levels or self-reported hirsutism and irregular menstrual cycles more than 32 days apart.
• Study participants completed tests measuring verbal learning and memory, processing speed and executive function, attention and cognitive control, and semantics and attention.
• Researchers analyzed brain white matter integrity for 291 of the individuals, including 25 with PCOS, who underwent MRI.

TAKEAWAY:

• Individuals with PCOS had worse memory, attention, and verbal ability scores than those without the disorder.
• MRI scans showed that those with PCOS had lower white matter integrity, an indicator of cognitive deficits, including poorer decision-making abilities.
• Those in the PCOS group were more likely to be White and have diabetes than those in the control group.

IN PRACTICE:

“This report of midlife cognition in PCOS raises a new concern about another potential comorbidity for individuals with this common disorder; given that up to 10% of women may be affected by PCOS, these results have important implications for public health at large,” the authors concluded.

SOURCE:

Heather G. Huddleston, MD, director of the PCOS Clinic at the UCSF Health, San Francisco, California, is the lead author of the study published in Neurology.

LIMITATIONS:

PCOS was determined on the basis of serum androgen levels and self-reporting of hirsutism and oligomenorrhea, so some cases may have been misclassified without the official diagnosis of a clinician.

DISCLOSURES:

The authors did not report any relevant financial conflicts. The study was funded by a grant from the University of California, San Francisco, California.

A version of this article appeared on Medscape.com.

TOPLINE:

People with polycystic ovary syndrome (PCOS) may score lower on cognitive tests than people without the condition, a research showed. They also may have worse integrity of brain tissue as evident on an MRI.

METHODOLOGY:

• Researchers used data from the Coronary Artery Risk Development in Young Adults Women’s Study; individuals were 18-30 years old at the beginning of the study and were followed over 30 years.
• A little over 900 women were included in the study, of which 66 had PCOS, which was defined as having elevated androgen levels or self-reported hirsutism and irregular menstrual cycles more than 32 days apart.
• Study participants completed tests measuring verbal learning and memory, processing speed and executive function, attention and cognitive control, and semantics and attention.
• Researchers analyzed brain white matter integrity for 291 of the individuals, including 25 with PCOS, who underwent MRI.

TAKEAWAY:

• Individuals with PCOS had worse memory, attention, and verbal ability scores than those without the disorder.
• MRI scans showed that those with PCOS had lower white matter integrity, an indicator of cognitive deficits, including poorer decision-making abilities.
• Those in the PCOS group were more likely to be White and have diabetes than those in the control group.

IN PRACTICE:

“This report of midlife cognition in PCOS raises a new concern about another potential comorbidity for individuals with this common disorder; given that up to 10% of women may be affected by PCOS, these results have important implications for public health at large,” the authors concluded.

SOURCE:

Heather G. Huddleston, MD, director of the PCOS Clinic at the UCSF Health, San Francisco, California, is the lead author of the study published in Neurology.

LIMITATIONS:

PCOS was determined on the basis of serum androgen levels and self-reporting of hirsutism and oligomenorrhea, so some cases may have been misclassified without the official diagnosis of a clinician.

DISCLOSURES:

The authors did not report any relevant financial conflicts. The study was funded by a grant from the University of California, San Francisco, California.

A version of this article appeared on Medscape.com.

TOPLINE:

People with polycystic ovary syndrome (PCOS) may score lower on cognitive tests than people without the condition, a research showed. They also may have worse integrity of brain tissue as evident on an MRI.

METHODOLOGY:

• Researchers used data from the Coronary Artery Risk Development in Young Adults Women’s Study; individuals were 18-30 years old at the beginning of the study and were followed over 30 years.
• A little over 900 women were included in the study, of which 66 had PCOS, which was defined as having elevated androgen levels or self-reported hirsutism and irregular menstrual cycles more than 32 days apart.
• Study participants completed tests measuring verbal learning and memory, processing speed and executive function, attention and cognitive control, and semantics and attention.
• Researchers analyzed brain white matter integrity for 291 of the individuals, including 25 with PCOS, who underwent MRI.

TAKEAWAY:

• Individuals with PCOS had worse memory, attention, and verbal ability scores than those without the disorder.
• MRI scans showed that those with PCOS had lower white matter integrity, an indicator of cognitive deficits, including poorer decision-making abilities.
• Those in the PCOS group were more likely to be White and have diabetes than those in the control group.

IN PRACTICE:

“This report of midlife cognition in PCOS raises a new concern about another potential comorbidity for individuals with this common disorder; given that up to 10% of women may be affected by PCOS, these results have important implications for public health at large,” the authors concluded.

SOURCE:

Heather G. Huddleston, MD, director of the PCOS Clinic at the UCSF Health, San Francisco, California, is the lead author of the study published in Neurology.

LIMITATIONS:

PCOS was determined on the basis of serum androgen levels and self-reporting of hirsutism and oligomenorrhea, so some cases may have been misclassified without the official diagnosis of a clinician.

DISCLOSURES:

The authors did not report any relevant financial conflicts. The study was funded by a grant from the University of California, San Francisco, California.

A version of this article appeared on Medscape.com.

The United States Medical Licensing Examination (USMLE) program is invalidating scores attained by some examinees after an investigation revealed a pattern of anomalous exam performance associated with test-takers from Nepal. 

In a January 31 announcement, the USMLE program said that officials are in the process of notifying examinees with results in question and that the examinees will be required to take validation exams. The program did not offer further details about its investigation or how the questionable performance was identified. 

“The USMLE program regularly monitors and analyzes examinees’ test performances for unusual score patterns or variations, and other information that could raise questions about the validity of an examinee’s results,” the program said in a statement. “Highly irregular patterns can be indicative of prior unauthorized access to secure exam content.”

Some medical graduates say the action against students cheating on the USMLE is long overdue. 

The selling and buying of USMLE questions online have become rampant in recent years, particularly by groups within the international medical graduate (IMG) community, according to multiple IMGs who shared their concerns with this news organization. Sellers operate under pseudonyms across social media platforms and charge anywhere from $300 to $2000 for questions, Medscape research shows. 

Facebook posts often advertise questions for sale, said Saqib Gul, MD, an IMG from Pakistan who has voiced concerns about the practice on social media. 

“People make up fake profiles and tell others to [direct message] them for recalls,” he told this news organization. “There was a dedicated Facebook page that was doing this. In other cases, a couple of friends that took the exam remember a certain number of questions and write them down after the test.”

Ahmad Ozair, MD, an IMG from Lucknow, Uttar Pradesh, India, said that he has come across many groups online sharing or selling USMLE recalls. He first became suspicious when he saw several students, all from a few medical schools in Nepal, posting on social media about scoring in the 270 and 280-plus range. 

“The statistical probability that you would have three or more candidates in the same year, scoring in the 99th percentile worldwide, belonging to a small geographical area is extremely low.” 

Dr. Ozair, who now is studying public health at Johns Hopkins University in Baltimore, said that the issue is important for “all stakeholders” who care about patient safety: “Would you want a doctor who has cheated on the medical licensing exam to take care of you?” 

In an interview, USMLE program spokesman Joe Knickrehm said that the program relies on multiple processes to detect and respond to claims that exam integrity is being compromised. The process includes monitoring performance data, an anonymous tip line for reporting suspicious behavior, and a thorough investigative process. 

“The USMLE program regularly monitors social media channels for comments relating to exam security and irregular behavior and will initiate an investigation if warranted,” Mr. Knickrehm told this news organization. “ The covert nature of this activity does not lend itself to a definitive statement regarding whether the problem has increased or decreased in recent years.” 

Mr. Knickrehm said that the program’s STOPit app allows people to report suspicious behavior electronically to the USMLE program. Since its launch in 2021, the program has received more than 80 tips per year through the app, according to Mr. Knickrehm. Security violations are investigated by USMLE staff and reviewed by the USMLE Committee for Individualized Review (CIR). Anyone found to have engaged in irregular behavior by the CIR for activities undermining exam integrity are typically barred from access to the USMLE for multiple years. 
 

How Easy Is It to Buy Recalls?

Two years ago, Dr B was approached by a former study partner who had just completed Step 2 of the USMLE. She asked whether Dr B wanted to buy recalled questions to help her pass. 

“She paid this guy almost $2000 for recalls and told me if I pay this money, he’ll give me the recalls,” said Dr B, who asked to remain anonymous for fear of being associated with students cheating on the USMLE. “I told her I was not interested, and she said the guy would lower the price. I broke contact with her.”

Dr B, an IMG from Pakistan, was appalled. But she said that the episode was not the first time she has come across groups selling USMLE recalls or heard peers brag about having access to exam content. 

“I am baffled at how many [groups] post on social media and brazenly advertise their ‘services,’” she told this news organization. “No one arrests them, their customers go on to score abnormally high on the boards, making it unachievable for people who take the honest route, plus giving IMGs a bad rep.” 

Groups offering recalls are easily findable on sites such as Telegram and Signal. Telegram is a cloud-based messaging app that focuses on security, and Signal is an encrypted messaging service. 

The website recallmastery.com purports to offer a range of USMLE recall packages, from a free, unsorted version to Step 1 and Step 2 packages that include “fresh updates,” and sections with “mostly repeated topics. Prices range from the free version to the $799 VIP package. 

Another site called MedPox.com boasts 2024 Step 2 recalls, advertising “ actual exam questions to get HIGH scores.” The website’s owner states that the recalls were collected “by my friends,” and to message the them to be added to the “recalls group.”

A reporter was able to easily download a free version of alleged USMLE questions and answers from recallmastery.com. The document was a combination of typed and handwritten notes about medical questions, with red circles around recalled answers. 

J. Bryan Carmody, MD, who blogs about medical education, reviewed a copy of the document. He said that the content appeared “credible” and was in fact recalled USMLE questions. However, the extent of which the question stem was recalled was incomplete at best, and there was little production value to the document, said Dr. Carmody, a nephrologist and associate professor of pediatrics at the Eastern Virgina Medical School in Norfolk. 

The person selling the recall packages states on the website that the free version is not organized or sorted, but it allows viewers to “see how this works before paying for premium recalls.” 

Mr. Knickrehm said that the program could not comment on the document, but that “whenever the USMLE program receives or locates information about a potential security violation, we investigate and take necessary action.” 

When asked about the specific websites noted above, Knickrehm said that the program routinely monitors a wide array of websites, message boards, and chat rooms for USMLE-related materials. Though many sites advertise having USMLE recalls for sale, it’s more likely they are selling non-USMLE content, he said. 

Using past content to cheat on medical exams is an old problem. In 2010, for example, the American Board of Internal Medicine suspended 139 physicians after they were caught cheating on the board exams. The scandal involved a vast cheating ring that included physicians memorizing questions and reproducing them after the tests. The board later sued a gastroenterologist for her part in the scandal. 

In 2012, a CNN investigation exposed doctors who were memorizing test questions and creating sophisticated recall banks to cheat on radiology boards. The Association of American Medical Colleges sued a medical student in 2017 for attempting to secretly record content on the MCAT using spyglasses. 

In recent years, Dr. Carmody said that he has received multiple messages and screenshots from concerned students and residents who were offered or encountered recalls. 

“One thing that’s unclear is how legitimate the claims are,” he said. “Many of these recalls may be faulty or outdated. It could be someone who took the exam yesterday and has a photographic memory or it could be some sparsely recalled or mis-recalled information. Unless you’re willing to pay these people, you can’t inspect the quality, or even if you did, you wouldn’t know if the information was current or not.”
 

‘As an IMG, There Is So Much at Stake’

Whether recall sellers — and those buying them — are more frequently IMGs has fostered heated debate on social media. 

On a Reddit thread devoted to IMG issues, posters expressed frustration about being bombarded with recall advertisements and unwanted messages about buying USMLE questions while trying to find study materials. One poster called the practices a “huge slap to all those IMGs who are struggling day and night, just to get a good score.”

In an X thread about the same subject, however, some self-described IMGs took offense to claims that IMGs might score higher because they have access to recalls. The allegations are “incendiary” and “malign hardworking IMGs,” posters wrote.

When Dr. Gul spoke out online about the “biopsy” culture, he received multiple private messages from fellow IMGs telling him to remove his comments, he said. 

“I received a lot of backlash on social media,” he told this news organization. “Some IMGs asked me to take down my posts because they thought I was making IMGs look bad, and it might prompt authorities to take action or shut down international examination centers for IMGs.”

Most of the IMGs who spoke to this news organization were afraid to be publicly identified. Several IMG advocates and IMG associations contacted for the story did not respond. One medical education expert said that his institution advised him to “steer clear” of commenting because the issue was “controversial.” 

“As an IMG, there is so much at stake,” Dr B said. “Any association with shady operations like these is an absolute suicide. I’m personally afraid of any repercussions of the sort.”

USMLE officials declined to comment on whether the buying or selling of recalls appears to be more prevalent among the IMG community, saying it is “difficult to generalize this behavior as ‘prevalent’ simply due to the clandestine nature of this activity.”
 

Cheat-Proofing the USMLE

The USMLE program has taken several steps intended to prevent cheating, but more needs to be done, medical education advocates say. 

For example, Dr. Carmody called the recent change in the attempt limit for taking USMLE exams from six to four times a good move. 

“The reality is, if you’re taking a USMLE exam five-plus times, you’re far more likely to be memorizing questions and selling them for shady test prep operations than you are to be legitimately pursuing U.S. residency training or licensure,” he wrote on X. 

The 2022 move to make USMLE Step 1 pass or fail is another positive change, said Dr. Gul, who added that US programs should also put less weight on test scores and focus more on clinical experience. 

“Many programs in the US prioritize scores rather than clinical experiences in home countries,” he said. “If program directors would remove these criteria, probably the cheating practices would stop. Clinical practice matters. When a doctor gets matched, they have to be good at seeing and treating patients, not just good at sitting in front of a screen and taking an exam.”

Turning over questions more rapidly would help curb the practices, Dr. Carmody said. Another strategy is using math techniques to identify unusual deviations that suggest cheating, he said. 

A blueprint for the strategy was created after a cheating scandal involving Canada’s Medical Council of Canada Qualifying Examination (MCCQE) in 2004. After learning which questions were circulated, MCCQE administrators evaluated exams by comparing answers of compromised questions with the answers of noncompromised questions. 

“For a person who was not cheating, the error of performance should be pretty similar on those two groups of questions,” Dr. Carmody said. “But if you were given the questions in advance, you might have very poor performance on questions that had not been compromised, and very high performance on those that had been compromised. That disparity is very unlikely to occur just by chance alone.” 

Based on his research, Dr. Ozair is working on an academic review paper about cheating on the USMLE and on the Medical Council of Canada Qualification Examination. He said that he hopes the paper will raise more awareness about the problem and drive more action. 

He and others interviewed for this story shared that the websites they’ve reported to the USMLE program are still active and offering recalls to buyers. 

“Even if they are not actually offering something tangible or true, appearance matters,” Dr. Ozair said. “I think it’s worth the USMLE sending cease and desist letters and getting these websites taken down. This would restore faith in the process and underscore that this issue is being taken seriously.”
 

A version of this article appeared on Medscape.com.

The United States Medical Licensing Examination (USMLE) program is invalidating scores attained by some examinees after an investigation revealed a pattern of anomalous exam performance associated with test-takers from Nepal. 

In a January 31 announcement, the USMLE program said that officials are in the process of notifying examinees with results in question and that the examinees will be required to take validation exams. The program did not offer further details about its investigation or how the questionable performance was identified. 

“The USMLE program regularly monitors and analyzes examinees’ test performances for unusual score patterns or variations, and other information that could raise questions about the validity of an examinee’s results,” the program said in a statement. “Highly irregular patterns can be indicative of prior unauthorized access to secure exam content.”

Some medical graduates say the action against students cheating on the USMLE is long overdue. 

The selling and buying of USMLE questions online have become rampant in recent years, particularly by groups within the international medical graduate (IMG) community, according to multiple IMGs who shared their concerns with this news organization. Sellers operate under pseudonyms across social media platforms and charge anywhere from $300 to $2000 for questions, Medscape research shows. 

Facebook posts often advertise questions for sale, said Saqib Gul, MD, an IMG from Pakistan who has voiced concerns about the practice on social media. 

“People make up fake profiles and tell others to [direct message] them for recalls,” he told this news organization. “There was a dedicated Facebook page that was doing this. In other cases, a couple of friends that took the exam remember a certain number of questions and write them down after the test.”

Ahmad Ozair, MD, an IMG from Lucknow, Uttar Pradesh, India, said that he has come across many groups online sharing or selling USMLE recalls. He first became suspicious when he saw several students, all from a few medical schools in Nepal, posting on social media about scoring in the 270 and 280-plus range. 

“The statistical probability that you would have three or more candidates in the same year, scoring in the 99th percentile worldwide, belonging to a small geographical area is extremely low.” 

Dr. Ozair, who now is studying public health at Johns Hopkins University in Baltimore, said that the issue is important for “all stakeholders” who care about patient safety: “Would you want a doctor who has cheated on the medical licensing exam to take care of you?” 

In an interview, USMLE program spokesman Joe Knickrehm said that the program relies on multiple processes to detect and respond to claims that exam integrity is being compromised. The process includes monitoring performance data, an anonymous tip line for reporting suspicious behavior, and a thorough investigative process. 

“The USMLE program regularly monitors social media channels for comments relating to exam security and irregular behavior and will initiate an investigation if warranted,” Mr. Knickrehm told this news organization. “ The covert nature of this activity does not lend itself to a definitive statement regarding whether the problem has increased or decreased in recent years.” 

Mr. Knickrehm said that the program’s STOPit app allows people to report suspicious behavior electronically to the USMLE program. Since its launch in 2021, the program has received more than 80 tips per year through the app, according to Mr. Knickrehm. Security violations are investigated by USMLE staff and reviewed by the USMLE Committee for Individualized Review (CIR). Anyone found to have engaged in irregular behavior by the CIR for activities undermining exam integrity are typically barred from access to the USMLE for multiple years. 
 

How Easy Is It to Buy Recalls?

Two years ago, Dr B was approached by a former study partner who had just completed Step 2 of the USMLE. She asked whether Dr B wanted to buy recalled questions to help her pass. 

“She paid this guy almost $2000 for recalls and told me if I pay this money, he’ll give me the recalls,” said Dr B, who asked to remain anonymous for fear of being associated with students cheating on the USMLE. “I told her I was not interested, and she said the guy would lower the price. I broke contact with her.”

Dr B, an IMG from Pakistan, was appalled. But she said that the episode was not the first time she has come across groups selling USMLE recalls or heard peers brag about having access to exam content. 

“I am baffled at how many [groups] post on social media and brazenly advertise their ‘services,’” she told this news organization. “No one arrests them, their customers go on to score abnormally high on the boards, making it unachievable for people who take the honest route, plus giving IMGs a bad rep.” 

Groups offering recalls are easily findable on sites such as Telegram and Signal. Telegram is a cloud-based messaging app that focuses on security, and Signal is an encrypted messaging service. 

The website recallmastery.com purports to offer a range of USMLE recall packages, from a free, unsorted version to Step 1 and Step 2 packages that include “fresh updates,” and sections with “mostly repeated topics. Prices range from the free version to the $799 VIP package. 

Another site called MedPox.com boasts 2024 Step 2 recalls, advertising “ actual exam questions to get HIGH scores.” The website’s owner states that the recalls were collected “by my friends,” and to message the them to be added to the “recalls group.”

A reporter was able to easily download a free version of alleged USMLE questions and answers from recallmastery.com. The document was a combination of typed and handwritten notes about medical questions, with red circles around recalled answers. 

J. Bryan Carmody, MD, who blogs about medical education, reviewed a copy of the document. He said that the content appeared “credible” and was in fact recalled USMLE questions. However, the extent of which the question stem was recalled was incomplete at best, and there was little production value to the document, said Dr. Carmody, a nephrologist and associate professor of pediatrics at the Eastern Virgina Medical School in Norfolk. 

The person selling the recall packages states on the website that the free version is not organized or sorted, but it allows viewers to “see how this works before paying for premium recalls.” 

Mr. Knickrehm said that the program could not comment on the document, but that “whenever the USMLE program receives or locates information about a potential security violation, we investigate and take necessary action.” 

When asked about the specific websites noted above, Knickrehm said that the program routinely monitors a wide array of websites, message boards, and chat rooms for USMLE-related materials. Though many sites advertise having USMLE recalls for sale, it’s more likely they are selling non-USMLE content, he said. 

Using past content to cheat on medical exams is an old problem. In 2010, for example, the American Board of Internal Medicine suspended 139 physicians after they were caught cheating on the board exams. The scandal involved a vast cheating ring that included physicians memorizing questions and reproducing them after the tests. The board later sued a gastroenterologist for her part in the scandal. 

In 2012, a CNN investigation exposed doctors who were memorizing test questions and creating sophisticated recall banks to cheat on radiology boards. The Association of American Medical Colleges sued a medical student in 2017 for attempting to secretly record content on the MCAT using spyglasses. 

In recent years, Dr. Carmody said that he has received multiple messages and screenshots from concerned students and residents who were offered or encountered recalls. 

“One thing that’s unclear is how legitimate the claims are,” he said. “Many of these recalls may be faulty or outdated. It could be someone who took the exam yesterday and has a photographic memory or it could be some sparsely recalled or mis-recalled information. Unless you’re willing to pay these people, you can’t inspect the quality, or even if you did, you wouldn’t know if the information was current or not.”
 

‘As an IMG, There Is So Much at Stake’

Whether recall sellers — and those buying them — are more frequently IMGs has fostered heated debate on social media. 

On a Reddit thread devoted to IMG issues, posters expressed frustration about being bombarded with recall advertisements and unwanted messages about buying USMLE questions while trying to find study materials. One poster called the practices a “huge slap to all those IMGs who are struggling day and night, just to get a good score.”

In an X thread about the same subject, however, some self-described IMGs took offense to claims that IMGs might score higher because they have access to recalls. The allegations are “incendiary” and “malign hardworking IMGs,” posters wrote.

When Dr. Gul spoke out online about the “biopsy” culture, he received multiple private messages from fellow IMGs telling him to remove his comments, he said. 

“I received a lot of backlash on social media,” he told this news organization. “Some IMGs asked me to take down my posts because they thought I was making IMGs look bad, and it might prompt authorities to take action or shut down international examination centers for IMGs.”

Most of the IMGs who spoke to this news organization were afraid to be publicly identified. Several IMG advocates and IMG associations contacted for the story did not respond. One medical education expert said that his institution advised him to “steer clear” of commenting because the issue was “controversial.” 

“As an IMG, there is so much at stake,” Dr B said. “Any association with shady operations like these is an absolute suicide. I’m personally afraid of any repercussions of the sort.”

USMLE officials declined to comment on whether the buying or selling of recalls appears to be more prevalent among the IMG community, saying it is “difficult to generalize this behavior as ‘prevalent’ simply due to the clandestine nature of this activity.”
 

Cheat-Proofing the USMLE

The USMLE program has taken several steps intended to prevent cheating, but more needs to be done, medical education advocates say. 

For example, Dr. Carmody called the recent change in the attempt limit for taking USMLE exams from six to four times a good move. 

“The reality is, if you’re taking a USMLE exam five-plus times, you’re far more likely to be memorizing questions and selling them for shady test prep operations than you are to be legitimately pursuing U.S. residency training or licensure,” he wrote on X. 

The 2022 move to make USMLE Step 1 pass or fail is another positive change, said Dr. Gul, who added that US programs should also put less weight on test scores and focus more on clinical experience. 

“Many programs in the US prioritize scores rather than clinical experiences in home countries,” he said. “If program directors would remove these criteria, probably the cheating practices would stop. Clinical practice matters. When a doctor gets matched, they have to be good at seeing and treating patients, not just good at sitting in front of a screen and taking an exam.”

Turning over questions more rapidly would help curb the practices, Dr. Carmody said. Another strategy is using math techniques to identify unusual deviations that suggest cheating, he said. 

A blueprint for the strategy was created after a cheating scandal involving Canada’s Medical Council of Canada Qualifying Examination (MCCQE) in 2004. After learning which questions were circulated, MCCQE administrators evaluated exams by comparing answers of compromised questions with the answers of noncompromised questions. 

“For a person who was not cheating, the error of performance should be pretty similar on those two groups of questions,” Dr. Carmody said. “But if you were given the questions in advance, you might have very poor performance on questions that had not been compromised, and very high performance on those that had been compromised. That disparity is very unlikely to occur just by chance alone.” 

Based on his research, Dr. Ozair is working on an academic review paper about cheating on the USMLE and on the Medical Council of Canada Qualification Examination. He said that he hopes the paper will raise more awareness about the problem and drive more action. 

He and others interviewed for this story shared that the websites they’ve reported to the USMLE program are still active and offering recalls to buyers. 

“Even if they are not actually offering something tangible or true, appearance matters,” Dr. Ozair said. “I think it’s worth the USMLE sending cease and desist letters and getting these websites taken down. This would restore faith in the process and underscore that this issue is being taken seriously.”
 

A version of this article appeared on Medscape.com.

The United States Medical Licensing Examination (USMLE) program is invalidating scores attained by some examinees after an investigation revealed a pattern of anomalous exam performance associated with test-takers from Nepal. 

In a January 31 announcement, the USMLE program said that officials are in the process of notifying examinees with results in question and that the examinees will be required to take validation exams. The program did not offer further details about its investigation or how the questionable performance was identified. 

“The USMLE program regularly monitors and analyzes examinees’ test performances for unusual score patterns or variations, and other information that could raise questions about the validity of an examinee’s results,” the program said in a statement. “Highly irregular patterns can be indicative of prior unauthorized access to secure exam content.”

Some medical graduates say the action against students cheating on the USMLE is long overdue. 

The selling and buying of USMLE questions online have become rampant in recent years, particularly by groups within the international medical graduate (IMG) community, according to multiple IMGs who shared their concerns with this news organization. Sellers operate under pseudonyms across social media platforms and charge anywhere from $300 to $2000 for questions, Medscape research shows. 

Facebook posts often advertise questions for sale, said Saqib Gul, MD, an IMG from Pakistan who has voiced concerns about the practice on social media. 

“People make up fake profiles and tell others to [direct message] them for recalls,” he told this news organization. “There was a dedicated Facebook page that was doing this. In other cases, a couple of friends that took the exam remember a certain number of questions and write them down after the test.”

Ahmad Ozair, MD, an IMG from Lucknow, Uttar Pradesh, India, said that he has come across many groups online sharing or selling USMLE recalls. He first became suspicious when he saw several students, all from a few medical schools in Nepal, posting on social media about scoring in the 270 and 280-plus range. 

“The statistical probability that you would have three or more candidates in the same year, scoring in the 99th percentile worldwide, belonging to a small geographical area is extremely low.” 

Dr. Ozair, who now is studying public health at Johns Hopkins University in Baltimore, said that the issue is important for “all stakeholders” who care about patient safety: “Would you want a doctor who has cheated on the medical licensing exam to take care of you?” 

In an interview, USMLE program spokesman Joe Knickrehm said that the program relies on multiple processes to detect and respond to claims that exam integrity is being compromised. The process includes monitoring performance data, an anonymous tip line for reporting suspicious behavior, and a thorough investigative process. 

“The USMLE program regularly monitors social media channels for comments relating to exam security and irregular behavior and will initiate an investigation if warranted,” Mr. Knickrehm told this news organization. “ The covert nature of this activity does not lend itself to a definitive statement regarding whether the problem has increased or decreased in recent years.” 

Mr. Knickrehm said that the program’s STOPit app allows people to report suspicious behavior electronically to the USMLE program. Since its launch in 2021, the program has received more than 80 tips per year through the app, according to Mr. Knickrehm. Security violations are investigated by USMLE staff and reviewed by the USMLE Committee for Individualized Review (CIR). Anyone found to have engaged in irregular behavior by the CIR for activities undermining exam integrity are typically barred from access to the USMLE for multiple years. 
 

How Easy Is It to Buy Recalls?

Two years ago, Dr B was approached by a former study partner who had just completed Step 2 of the USMLE. She asked whether Dr B wanted to buy recalled questions to help her pass. 

“She paid this guy almost $2000 for recalls and told me if I pay this money, he’ll give me the recalls,” said Dr B, who asked to remain anonymous for fear of being associated with students cheating on the USMLE. “I told her I was not interested, and she said the guy would lower the price. I broke contact with her.”

Dr B, an IMG from Pakistan, was appalled. But she said that the episode was not the first time she has come across groups selling USMLE recalls or heard peers brag about having access to exam content. 

“I am baffled at how many [groups] post on social media and brazenly advertise their ‘services,’” she told this news organization. “No one arrests them, their customers go on to score abnormally high on the boards, making it unachievable for people who take the honest route, plus giving IMGs a bad rep.” 

Groups offering recalls are easily findable on sites such as Telegram and Signal. Telegram is a cloud-based messaging app that focuses on security, and Signal is an encrypted messaging service. 

The website recallmastery.com purports to offer a range of USMLE recall packages, from a free, unsorted version to Step 1 and Step 2 packages that include “fresh updates,” and sections with “mostly repeated topics. Prices range from the free version to the $799 VIP package. 

Another site called MedPox.com boasts 2024 Step 2 recalls, advertising “ actual exam questions to get HIGH scores.” The website’s owner states that the recalls were collected “by my friends,” and to message the them to be added to the “recalls group.”

A reporter was able to easily download a free version of alleged USMLE questions and answers from recallmastery.com. The document was a combination of typed and handwritten notes about medical questions, with red circles around recalled answers. 

J. Bryan Carmody, MD, who blogs about medical education, reviewed a copy of the document. He said that the content appeared “credible” and was in fact recalled USMLE questions. However, the extent of which the question stem was recalled was incomplete at best, and there was little production value to the document, said Dr. Carmody, a nephrologist and associate professor of pediatrics at the Eastern Virgina Medical School in Norfolk. 

The person selling the recall packages states on the website that the free version is not organized or sorted, but it allows viewers to “see how this works before paying for premium recalls.” 

Mr. Knickrehm said that the program could not comment on the document, but that “whenever the USMLE program receives or locates information about a potential security violation, we investigate and take necessary action.” 

When asked about the specific websites noted above, Knickrehm said that the program routinely monitors a wide array of websites, message boards, and chat rooms for USMLE-related materials. Though many sites advertise having USMLE recalls for sale, it’s more likely they are selling non-USMLE content, he said. 

Using past content to cheat on medical exams is an old problem. In 2010, for example, the American Board of Internal Medicine suspended 139 physicians after they were caught cheating on the board exams. The scandal involved a vast cheating ring that included physicians memorizing questions and reproducing them after the tests. The board later sued a gastroenterologist for her part in the scandal. 

In 2012, a CNN investigation exposed doctors who were memorizing test questions and creating sophisticated recall banks to cheat on radiology boards. The Association of American Medical Colleges sued a medical student in 2017 for attempting to secretly record content on the MCAT using spyglasses. 

In recent years, Dr. Carmody said that he has received multiple messages and screenshots from concerned students and residents who were offered or encountered recalls. 

“One thing that’s unclear is how legitimate the claims are,” he said. “Many of these recalls may be faulty or outdated. It could be someone who took the exam yesterday and has a photographic memory or it could be some sparsely recalled or mis-recalled information. Unless you’re willing to pay these people, you can’t inspect the quality, or even if you did, you wouldn’t know if the information was current or not.”
 

‘As an IMG, There Is So Much at Stake’

Whether recall sellers — and those buying them — are more frequently IMGs has fostered heated debate on social media. 

On a Reddit thread devoted to IMG issues, posters expressed frustration about being bombarded with recall advertisements and unwanted messages about buying USMLE questions while trying to find study materials. One poster called the practices a “huge slap to all those IMGs who are struggling day and night, just to get a good score.”

In an X thread about the same subject, however, some self-described IMGs took offense to claims that IMGs might score higher because they have access to recalls. The allegations are “incendiary” and “malign hardworking IMGs,” posters wrote.

When Dr. Gul spoke out online about the “biopsy” culture, he received multiple private messages from fellow IMGs telling him to remove his comments, he said. 

“I received a lot of backlash on social media,” he told this news organization. “Some IMGs asked me to take down my posts because they thought I was making IMGs look bad, and it might prompt authorities to take action or shut down international examination centers for IMGs.”

Most of the IMGs who spoke to this news organization were afraid to be publicly identified. Several IMG advocates and IMG associations contacted for the story did not respond. One medical education expert said that his institution advised him to “steer clear” of commenting because the issue was “controversial.” 

“As an IMG, there is so much at stake,” Dr B said. “Any association with shady operations like these is an absolute suicide. I’m personally afraid of any repercussions of the sort.”

USMLE officials declined to comment on whether the buying or selling of recalls appears to be more prevalent among the IMG community, saying it is “difficult to generalize this behavior as ‘prevalent’ simply due to the clandestine nature of this activity.”
 

Cheat-Proofing the USMLE

The USMLE program has taken several steps intended to prevent cheating, but more needs to be done, medical education advocates say. 

For example, Dr. Carmody called the recent change in the attempt limit for taking USMLE exams from six to four times a good move. 

“The reality is, if you’re taking a USMLE exam five-plus times, you’re far more likely to be memorizing questions and selling them for shady test prep operations than you are to be legitimately pursuing U.S. residency training or licensure,” he wrote on X. 

The 2022 move to make USMLE Step 1 pass or fail is another positive change, said Dr. Gul, who added that US programs should also put less weight on test scores and focus more on clinical experience. 

“Many programs in the US prioritize scores rather than clinical experiences in home countries,” he said. “If program directors would remove these criteria, probably the cheating practices would stop. Clinical practice matters. When a doctor gets matched, they have to be good at seeing and treating patients, not just good at sitting in front of a screen and taking an exam.”

Turning over questions more rapidly would help curb the practices, Dr. Carmody said. Another strategy is using math techniques to identify unusual deviations that suggest cheating, he said. 

A blueprint for the strategy was created after a cheating scandal involving Canada’s Medical Council of Canada Qualifying Examination (MCCQE) in 2004. After learning which questions were circulated, MCCQE administrators evaluated exams by comparing answers of compromised questions with the answers of noncompromised questions. 

“For a person who was not cheating, the error of performance should be pretty similar on those two groups of questions,” Dr. Carmody said. “But if you were given the questions in advance, you might have very poor performance on questions that had not been compromised, and very high performance on those that had been compromised. That disparity is very unlikely to occur just by chance alone.” 

Based on his research, Dr. Ozair is working on an academic review paper about cheating on the USMLE and on the Medical Council of Canada Qualification Examination. He said that he hopes the paper will raise more awareness about the problem and drive more action. 

He and others interviewed for this story shared that the websites they’ve reported to the USMLE program are still active and offering recalls to buyers. 

“Even if they are not actually offering something tangible or true, appearance matters,” Dr. Ozair said. “I think it’s worth the USMLE sending cease and desist letters and getting these websites taken down. This would restore faith in the process and underscore that this issue is being taken seriously.”
 

A version of this article appeared on Medscape.com.

A new Senate bill would require Medicare to test two tools routinely used by credit card companies to prevent fraud: Artificial intelligence (AI)-trained algorithms to detect suspicious activity and a system to quickly alert Medicare patients on whose behalf payment is being sought.

Senator Mike Braun (R-IN) recently introduced the Medicare Transaction Fraud Prevention Act, which calls for a 2-year test of this approach.

The experiment, targeted to start in 2025, would focus on durable medical equipment and clinical diagnostic laboratory tests and cover Medicare beneficiaries who receive electronic notices about claims.

The legislation would direct the Center for Medicare and Medicaid Services (CMS) to test the use of predictive risk-scoring algorithms in finding fraud. The program would be modeled on the systems that credit card companies already use. Transactions could be scored from 1 (least risky) to 99 (most risky).

CMS would then check directly by email or phone call with selected Medicare enrollees about transactions considered to present a high risk for fraud.

Many consumers have benefited from this approach when used to check for fraud on their credit cards, Braun noted during a November hearing of the Senate Special Committee on Aging. Credit card companies often can intervene before a fraudulent transaction is cleared.

“There’s no reason we wouldn’t want to minimally at least mimic that,” Braun said at the hearing.

Asking Medicare enrollees to verify certain purchases could give CMS increased access to vital predictive data, test proof of concept, and save hundreds of millions of dollars, Braun said.

Concerns Raised

So far, Braun has only one cosponsor for the bill, Senator Bill Cassidy, MD (R-LA), and the bill has drawn some criticism.

Brett Meeks, executive director of the Health Innovation Alliance, a trade group representing technology companies, insurers, and consumer organizations, objected to requiring Medicare enrollees to verify flagged orders. CMS should internally root out fraud through technology, not burden seniors, Meeks told this news organization.

Meeks said he has been following the discussion about the use of AI in addressing Medicare fraud. Had a bill broadly targeted Medicare fraud through AI, his alliance might have backed it, he said. But the current proposed legislation has a narrower focus.

Focusing on durable medical equipment, for example, could have unintended consequences like denying power wheelchairs to people with debilitating conditions like multiple sclerosis, Meeks said.

But Braun’s bill won a quick nod of approval from a researcher who studies the use of AI to detect Medicare fraud. Taghi M. Khoshgoftaar, PhD, director of the Data Mining and Machine Learning Lab at Florida Atlantic University, Boca Raton, Florida, said he sees an advantage to Braun’s approach of involving Medicare enrollees in the protection of their benefits.

The bill does not authorize funding for the pilot project, and it’s unclear what it would cost.

Detecting Medicare Fraud

The federal government has stepped up Medicare fraud investigations in recent years, and more doctors are getting caught.

A study published in 2018 examined cases of physicians excluded from Medicare using data from the US Office of Inspector General (OIG) at the Department of Health and Human Services.

The OIG has the right to exclude clinicians from Medicare for fraud or other reasons. Chen and coauthors looked at Medicare physician exclusions from 2007 to 2017. They found that exclusions due to fraud increased an estimated 14% per year on average from a base level of 139 exclusions in 2007.

In 2019, CMS sought feedback on new ways to use AI to detect fraud. In a public request for information, the agency said Medicare scrutinizes fewer claims for payment than commercial insurers do.

About 99.7% of Medicare fee-for-service claims are processed and paid within 17 days without any medical review, CMS said at the time.

A version of this article appeared on Medscape.com .

A new Senate bill would require Medicare to test two tools routinely used by credit card companies to prevent fraud: Artificial intelligence (AI)-trained algorithms to detect suspicious activity and a system to quickly alert Medicare patients on whose behalf payment is being sought.

Senator Mike Braun (R-IN) recently introduced the Medicare Transaction Fraud Prevention Act, which calls for a 2-year test of this approach.

The experiment, targeted to start in 2025, would focus on durable medical equipment and clinical diagnostic laboratory tests and cover Medicare beneficiaries who receive electronic notices about claims.

The legislation would direct the Center for Medicare and Medicaid Services (CMS) to test the use of predictive risk-scoring algorithms in finding fraud. The program would be modeled on the systems that credit card companies already use. Transactions could be scored from 1 (least risky) to 99 (most risky).

CMS would then check directly by email or phone call with selected Medicare enrollees about transactions considered to present a high risk for fraud.

Many consumers have benefited from this approach when used to check for fraud on their credit cards, Braun noted during a November hearing of the Senate Special Committee on Aging. Credit card companies often can intervene before a fraudulent transaction is cleared.

“There’s no reason we wouldn’t want to minimally at least mimic that,” Braun said at the hearing.

Asking Medicare enrollees to verify certain purchases could give CMS increased access to vital predictive data, test proof of concept, and save hundreds of millions of dollars, Braun said.

Concerns Raised

So far, Braun has only one cosponsor for the bill, Senator Bill Cassidy, MD (R-LA), and the bill has drawn some criticism.

Brett Meeks, executive director of the Health Innovation Alliance, a trade group representing technology companies, insurers, and consumer organizations, objected to requiring Medicare enrollees to verify flagged orders. CMS should internally root out fraud through technology, not burden seniors, Meeks told this news organization.

Meeks said he has been following the discussion about the use of AI in addressing Medicare fraud. Had a bill broadly targeted Medicare fraud through AI, his alliance might have backed it, he said. But the current proposed legislation has a narrower focus.

Focusing on durable medical equipment, for example, could have unintended consequences like denying power wheelchairs to people with debilitating conditions like multiple sclerosis, Meeks said.

But Braun’s bill won a quick nod of approval from a researcher who studies the use of AI to detect Medicare fraud. Taghi M. Khoshgoftaar, PhD, director of the Data Mining and Machine Learning Lab at Florida Atlantic University, Boca Raton, Florida, said he sees an advantage to Braun’s approach of involving Medicare enrollees in the protection of their benefits.

The bill does not authorize funding for the pilot project, and it’s unclear what it would cost.

Detecting Medicare Fraud

The federal government has stepped up Medicare fraud investigations in recent years, and more doctors are getting caught.

A study published in 2018 examined cases of physicians excluded from Medicare using data from the US Office of Inspector General (OIG) at the Department of Health and Human Services.

The OIG has the right to exclude clinicians from Medicare for fraud or other reasons. Chen and coauthors looked at Medicare physician exclusions from 2007 to 2017. They found that exclusions due to fraud increased an estimated 14% per year on average from a base level of 139 exclusions in 2007.

In 2019, CMS sought feedback on new ways to use AI to detect fraud. In a public request for information, the agency said Medicare scrutinizes fewer claims for payment than commercial insurers do.

About 99.7% of Medicare fee-for-service claims are processed and paid within 17 days without any medical review, CMS said at the time.

A version of this article appeared on Medscape.com .

A new Senate bill would require Medicare to test two tools routinely used by credit card companies to prevent fraud: Artificial intelligence (AI)-trained algorithms to detect suspicious activity and a system to quickly alert Medicare patients on whose behalf payment is being sought.

Senator Mike Braun (R-IN) recently introduced the Medicare Transaction Fraud Prevention Act, which calls for a 2-year test of this approach.

The experiment, targeted to start in 2025, would focus on durable medical equipment and clinical diagnostic laboratory tests and cover Medicare beneficiaries who receive electronic notices about claims.

The legislation would direct the Center for Medicare and Medicaid Services (CMS) to test the use of predictive risk-scoring algorithms in finding fraud. The program would be modeled on the systems that credit card companies already use. Transactions could be scored from 1 (least risky) to 99 (most risky).

CMS would then check directly by email or phone call with selected Medicare enrollees about transactions considered to present a high risk for fraud.

Many consumers have benefited from this approach when used to check for fraud on their credit cards, Braun noted during a November hearing of the Senate Special Committee on Aging. Credit card companies often can intervene before a fraudulent transaction is cleared.

“There’s no reason we wouldn’t want to minimally at least mimic that,” Braun said at the hearing.

Asking Medicare enrollees to verify certain purchases could give CMS increased access to vital predictive data, test proof of concept, and save hundreds of millions of dollars, Braun said.

Concerns Raised

So far, Braun has only one cosponsor for the bill, Senator Bill Cassidy, MD (R-LA), and the bill has drawn some criticism.

Brett Meeks, executive director of the Health Innovation Alliance, a trade group representing technology companies, insurers, and consumer organizations, objected to requiring Medicare enrollees to verify flagged orders. CMS should internally root out fraud through technology, not burden seniors, Meeks told this news organization.

Meeks said he has been following the discussion about the use of AI in addressing Medicare fraud. Had a bill broadly targeted Medicare fraud through AI, his alliance might have backed it, he said. But the current proposed legislation has a narrower focus.

Focusing on durable medical equipment, for example, could have unintended consequences like denying power wheelchairs to people with debilitating conditions like multiple sclerosis, Meeks said.

But Braun’s bill won a quick nod of approval from a researcher who studies the use of AI to detect Medicare fraud. Taghi M. Khoshgoftaar, PhD, director of the Data Mining and Machine Learning Lab at Florida Atlantic University, Boca Raton, Florida, said he sees an advantage to Braun’s approach of involving Medicare enrollees in the protection of their benefits.

The bill does not authorize funding for the pilot project, and it’s unclear what it would cost.

Detecting Medicare Fraud

The federal government has stepped up Medicare fraud investigations in recent years, and more doctors are getting caught.

A study published in 2018 examined cases of physicians excluded from Medicare using data from the US Office of Inspector General (OIG) at the Department of Health and Human Services.

The OIG has the right to exclude clinicians from Medicare for fraud or other reasons. Chen and coauthors looked at Medicare physician exclusions from 2007 to 2017. They found that exclusions due to fraud increased an estimated 14% per year on average from a base level of 139 exclusions in 2007.

In 2019, CMS sought feedback on new ways to use AI to detect fraud. In a public request for information, the agency said Medicare scrutinizes fewer claims for payment than commercial insurers do.

About 99.7% of Medicare fee-for-service claims are processed and paid within 17 days without any medical review, CMS said at the time.

A version of this article appeared on Medscape.com .

In patients with stimulant use disorder (SUD), even slight reductions in drug use can lessen depression and reduce cravings, a new analysis showed.

Abstinence has long been the overall goal of SUD treatment, the investigators noted. The findings from this pooled analysis of randomized clinical trials support what investigators noted was a growing recognition that reducing stimulant use can lead to better outcomes.

“This study provides evidence that reducing the overall use of drugs is important and clinically meaningful,” study author Mehdi Farokhnia, MD, MPH, of the National Institute on Drug Abuse, North Bethesda, Maryland, wrote in a press release. “This shift may open opportunities for medication development that can help individuals achieve these improved outcomes, even if complete abstinence is not immediately achievable or wanted.”

The findings were published online on January 10, 2024, in Addiction.
 

Not the Only Indicator of Success

To compare clinical indicators of improvement among those with SUDs who achieved abstinence or reduced their use, investigators pooled data from 13 randomized clinical trials with more than 2000 patients seeking treatment for cocaine or methamphetamine use disorders at centers in the United States from 2001 to 2017.

The trials used similar study protocols, including similar eligibility criteria, recruitment methods, and outcome measures. Participants were 18 or older and met criteria for methamphetamine or cocaine dependence at the beginning of each trial.

Among the participants, 1196 sought treatment for cocaine use disorder and 866 for methamphetamine use disorder. Of those, just 1487 had outcomes available by the end of the trial.

Most participants had no change in the level of use or increased their use through the trial (68%) or transitioned from low (1-4 days a month) to high (5 or more days a month) frequency use.

Nearly one third of participants (32%) stopped or reduced drug use, including 18% who cut down on stimulant use and 14% who abstained altogether.

Participants using methamphetamine were more likely to be in the abstinence vs reduced use category (21.3% vs 13.9%, respectively), whereas participants using cocaine were less likely to be in the abstinence vs reduced use category (9.1% vs 20.9%).

Those who reached abstinence showed better clinical improvement than those who reduced use on most clinical measures (P < .009).

However, there were no significant differences between groups on the Addiction Severity Index (ASI) psychiatric problems subscale and cravings for secondary drugs.

“Our findings suggest that reduced frequency of stimulant use is also associated with improved psychosocial functioning,” the authors wrote. “These findings suggest the need to re-evaluate the traditional approach of exclusively relying on total abstinence as the only indicator of successful treatment, a goal that may not be achievable for all patients, especially after one treatment episode.”

Those who reduced drug intake showed a significant association with nearly all clinical indicators of improvement (P < .010) compared with those who didn’t, except for the ASI psychiatric problems subscale and family/social relationship domains of the Problem Free Functioning scale, and HIV risk behavior.

Study limitations included short follow-up time in most trials and follow-up measures were based only on urine drug screens. There were also a substantial number of missing assessment points.

The study was funded by the National Institute on Drug Abuse and the National Institute of Health. There were no reported disclosures.
 

A version of this article appeared on Medscape.com.

In patients with stimulant use disorder (SUD), even slight reductions in drug use can lessen depression and reduce cravings, a new analysis showed.

Abstinence has long been the overall goal of SUD treatment, the investigators noted. The findings from this pooled analysis of randomized clinical trials support what investigators noted was a growing recognition that reducing stimulant use can lead to better outcomes.

“This study provides evidence that reducing the overall use of drugs is important and clinically meaningful,” study author Mehdi Farokhnia, MD, MPH, of the National Institute on Drug Abuse, North Bethesda, Maryland, wrote in a press release. “This shift may open opportunities for medication development that can help individuals achieve these improved outcomes, even if complete abstinence is not immediately achievable or wanted.”

The findings were published online on January 10, 2024, in Addiction.
 

Not the Only Indicator of Success

To compare clinical indicators of improvement among those with SUDs who achieved abstinence or reduced their use, investigators pooled data from 13 randomized clinical trials with more than 2000 patients seeking treatment for cocaine or methamphetamine use disorders at centers in the United States from 2001 to 2017.

The trials used similar study protocols, including similar eligibility criteria, recruitment methods, and outcome measures. Participants were 18 or older and met criteria for methamphetamine or cocaine dependence at the beginning of each trial.

Among the participants, 1196 sought treatment for cocaine use disorder and 866 for methamphetamine use disorder. Of those, just 1487 had outcomes available by the end of the trial.

Most participants had no change in the level of use or increased their use through the trial (68%) or transitioned from low (1-4 days a month) to high (5 or more days a month) frequency use.

Nearly one third of participants (32%) stopped or reduced drug use, including 18% who cut down on stimulant use and 14% who abstained altogether.

Participants using methamphetamine were more likely to be in the abstinence vs reduced use category (21.3% vs 13.9%, respectively), whereas participants using cocaine were less likely to be in the abstinence vs reduced use category (9.1% vs 20.9%).

Those who reached abstinence showed better clinical improvement than those who reduced use on most clinical measures (P < .009).

However, there were no significant differences between groups on the Addiction Severity Index (ASI) psychiatric problems subscale and cravings for secondary drugs.

“Our findings suggest that reduced frequency of stimulant use is also associated with improved psychosocial functioning,” the authors wrote. “These findings suggest the need to re-evaluate the traditional approach of exclusively relying on total abstinence as the only indicator of successful treatment, a goal that may not be achievable for all patients, especially after one treatment episode.”

Those who reduced drug intake showed a significant association with nearly all clinical indicators of improvement (P < .010) compared with those who didn’t, except for the ASI psychiatric problems subscale and family/social relationship domains of the Problem Free Functioning scale, and HIV risk behavior.

Study limitations included short follow-up time in most trials and follow-up measures were based only on urine drug screens. There were also a substantial number of missing assessment points.

The study was funded by the National Institute on Drug Abuse and the National Institute of Health. There were no reported disclosures.
 

A version of this article appeared on Medscape.com.

In patients with stimulant use disorder (SUD), even slight reductions in drug use can lessen depression and reduce cravings, a new analysis showed.

Abstinence has long been the overall goal of SUD treatment, the investigators noted. The findings from this pooled analysis of randomized clinical trials support what investigators noted was a growing recognition that reducing stimulant use can lead to better outcomes.

“This study provides evidence that reducing the overall use of drugs is important and clinically meaningful,” study author Mehdi Farokhnia, MD, MPH, of the National Institute on Drug Abuse, North Bethesda, Maryland, wrote in a press release. “This shift may open opportunities for medication development that can help individuals achieve these improved outcomes, even if complete abstinence is not immediately achievable or wanted.”

The findings were published online on January 10, 2024, in Addiction.
 

Not the Only Indicator of Success

To compare clinical indicators of improvement among those with SUDs who achieved abstinence or reduced their use, investigators pooled data from 13 randomized clinical trials with more than 2000 patients seeking treatment for cocaine or methamphetamine use disorders at centers in the United States from 2001 to 2017.

The trials used similar study protocols, including similar eligibility criteria, recruitment methods, and outcome measures. Participants were 18 or older and met criteria for methamphetamine or cocaine dependence at the beginning of each trial.

Among the participants, 1196 sought treatment for cocaine use disorder and 866 for methamphetamine use disorder. Of those, just 1487 had outcomes available by the end of the trial.

Most participants had no change in the level of use or increased their use through the trial (68%) or transitioned from low (1-4 days a month) to high (5 or more days a month) frequency use.

Nearly one third of participants (32%) stopped or reduced drug use, including 18% who cut down on stimulant use and 14% who abstained altogether.

Participants using methamphetamine were more likely to be in the abstinence vs reduced use category (21.3% vs 13.9%, respectively), whereas participants using cocaine were less likely to be in the abstinence vs reduced use category (9.1% vs 20.9%).

Those who reached abstinence showed better clinical improvement than those who reduced use on most clinical measures (P < .009).

However, there were no significant differences between groups on the Addiction Severity Index (ASI) psychiatric problems subscale and cravings for secondary drugs.

“Our findings suggest that reduced frequency of stimulant use is also associated with improved psychosocial functioning,” the authors wrote. “These findings suggest the need to re-evaluate the traditional approach of exclusively relying on total abstinence as the only indicator of successful treatment, a goal that may not be achievable for all patients, especially after one treatment episode.”

Those who reduced drug intake showed a significant association with nearly all clinical indicators of improvement (P < .010) compared with those who didn’t, except for the ASI psychiatric problems subscale and family/social relationship domains of the Problem Free Functioning scale, and HIV risk behavior.

Study limitations included short follow-up time in most trials and follow-up measures were based only on urine drug screens. There were also a substantial number of missing assessment points.

The study was funded by the National Institute on Drug Abuse and the National Institute of Health. There were no reported disclosures.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.

METHODOLOGY:

• The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
• Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
• Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
• Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
• Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.

TAKEAWAY:

• During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
• After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
• Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
• Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.

IN PRACTICE:

The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”

SOURCE:

The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.

LIMITATIONS:

The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.

METHODOLOGY:

• The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
• Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
• Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
• Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
• Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.

TAKEAWAY:

• During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
• After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
• Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
• Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.

IN PRACTICE:

The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”

SOURCE:

The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.

LIMITATIONS:

The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Social frailty, the lack of resources to meet basic social needs, is associated with an increased risk for motoric cognitive risk syndrome (MCR), a predementia syndrome characterized by cognitive complaints and slow gait, results of a large, population-based study suggested.

METHODOLOGY:

• The study used 2011 (Round 1) to 2018 (Round 8) data on a discovery sample of 4657 individuals without MCR or dementia at baseline from the National Health and Aging Trends Study (NHATS), a longitudinal survey of older adult Medicare beneficiaries.
• Researchers also collected data on 3075 newly recruited individuals in Round 5 and followed to Round 8 as an independent validation sample to create a pooled sample of 7732 older adults, mean age 76.06, without MCR at baseline.
• Social frailty, assessed at baseline, included five social items: Going out less, not feeling confident, rarely visiting friends/family, not talking with others, and without live-in partner/spouse (researchers divided participants into normal [zero to one items] and social frailty [two to five items] groups).
• Individuals were considered to have MCR if they had both subjective cognitive complaints and slow gait speed (greater than 1 standard deviation below age-specific level) without dementia or mobility disability.
• Covariates included demographic and lifestyle data, presence of depression and/or anxiety symptoms, and number of chronic diseases.

TAKEAWAY:

• During a median follow-up period of 4 years, 10.35% individuals were diagnosed with MCR.
• After the researchers controlled for confounding factors, those with social frailty had an increased risk for MCR compared with the normal group (pooled sample: hazard ratio [HR], 1.57; 95% CI, 1.34-1.84; P < .001).
• Each additional unfavorable social item was associated with an increased risk for MCR (pooled sample: HR, 1.32; 95% CI, 1.22-1.43; P < .001).
• Results of stratified analyses across subgroups suggested individuals with social frailty had a significantly higher risk for incident MCR than that of those without social frailty, regardless of socioeconomic status, lifestyle factors, chronic diseases, and mental health.

IN PRACTICE:

The findings suggest assessing social frailty using simple questions “is an efficient tool for detecting older individuals with a high risk of MCR,” the authors wrote. They noted that the addition of such a tool in clinical practice may facilitate “timely implementation of prevention strategies.”

SOURCE:

The research was led by Hui Zhang, Human Phenome Institute, Zhangjiang Fudan International Innovation Centre, Fudan University, Shanghai, China. It was published online on January 29, 2024, in Alzheimer’s & Dementia.

LIMITATIONS:

The study was observational, so the association between social frailty and MCR is merely correlational. Due to the lack of genetic information in NHATS data, researchers didn’t evaluate the effect of genetic factors such as apolipoprotein E on the association between social frailty and MCR. Social frailty was assessed at a single time point. In addition, the researchers were unable examine the time sequence between social frailty and MCR and so could not determine the cause of this association.

DISCLOSURES:

The study was supported by the National Natural Science Foundation of China-Youth Science Fund, Shanghai Rising-Star Program, Shanghai Municipal Health Commission and Key Discipline Construction Project of Pudong Health, and Family Planning Commission of Shanghai. The authors reported no relevant conflicts of interest.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Legalization of recreational and medical cannabis is not associated with a reduction in opioid prescriptions or overall opioid overdose mortality, a new study suggested. However, investigators did find that recreational cannabis laws may be tied to a potential reduction in synthetic opioid deaths.

METHODOLOGY:

• Investigators analyzed state-level data from the US Centers for Disease Control and Prevention and other databases (2006-2020) on the number of opioid prescriptions (per 100,000 persons).
• Prescription opioids included buprenorphine (except products to treat opioid use disorder), codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, propoxyphene, tapentadol, and tramadol.
• Researchers used regression analyses to account for poverty rates and real gross domestic product and a generalized difference-in-differences method that accounted for staggered implementation of cannabis laws.

TAKEAWAY:

• During the full study period, 13 states legalized recreational cannabis and 23 legalized medical cannabis.
• No statistically significant association was found between recreational cannabis laws and opioid prescriptions (3.08 fewer prescriptions per 100 persons; P = .17) or overall opioid overdose mortality (3.05 fewer deaths per 100,000; P = .24).
• The changes in outcomes associated with medical cannabis laws were larger in magnitude than those for recreational cannabis laws but also not statistically significant (3.54 additional prescriptions per 100 persons; P = .17 and 3.09 additional deaths per 100,000; P = .07).
• A potential reduction was found in synthetic opioid deaths associated specifically with states that had recreational cannabis laws (4.9 fewer deaths per 100,000; P = .04), but there were no differences in overdose deaths with other opioids.

IN PRACTICE:

“These results contrast with recent studies that suggested that recreational and medical cannabis legalization are associated with reductions in opioid prescriptions and medical cannabis legalization is associated with an increase in opioid mortality,” the authors wrote.

SOURCE:

Hai V. Nguyen, PhD, of the School of Pharmacy, Memorial University of Newfoundland, St. John’s, Canada, was the lead and corresponding author of the study. It was published online on January 19, 2024, in JAMA Health Forum.

A version of this article appeared on Medscape.com.

TOPLINE:

Legalization of recreational and medical cannabis is not associated with a reduction in opioid prescriptions or overall opioid overdose mortality, a new study suggested. However, investigators did find that recreational cannabis laws may be tied to a potential reduction in synthetic opioid deaths.

METHODOLOGY:

• Investigators analyzed state-level data from the US Centers for Disease Control and Prevention and other databases (2006-2020) on the number of opioid prescriptions (per 100,000 persons).
• Prescription opioids included buprenorphine (except products to treat opioid use disorder), codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, propoxyphene, tapentadol, and tramadol.
• Researchers used regression analyses to account for poverty rates and real gross domestic product and a generalized difference-in-differences method that accounted for staggered implementation of cannabis laws.

TAKEAWAY:

• During the full study period, 13 states legalized recreational cannabis and 23 legalized medical cannabis.
• No statistically significant association was found between recreational cannabis laws and opioid prescriptions (3.08 fewer prescriptions per 100 persons; P = .17) or overall opioid overdose mortality (3.05 fewer deaths per 100,000; P = .24).
• The changes in outcomes associated with medical cannabis laws were larger in magnitude than those for recreational cannabis laws but also not statistically significant (3.54 additional prescriptions per 100 persons; P = .17 and 3.09 additional deaths per 100,000; P = .07).
• A potential reduction was found in synthetic opioid deaths associated specifically with states that had recreational cannabis laws (4.9 fewer deaths per 100,000; P = .04), but there were no differences in overdose deaths with other opioids.

IN PRACTICE:

“These results contrast with recent studies that suggested that recreational and medical cannabis legalization are associated with reductions in opioid prescriptions and medical cannabis legalization is associated with an increase in opioid mortality,” the authors wrote.

SOURCE:

Hai V. Nguyen, PhD, of the School of Pharmacy, Memorial University of Newfoundland, St. John’s, Canada, was the lead and corresponding author of the study. It was published online on January 19, 2024, in JAMA Health Forum.

A version of this article appeared on Medscape.com.

TOPLINE:

Legalization of recreational and medical cannabis is not associated with a reduction in opioid prescriptions or overall opioid overdose mortality, a new study suggested. However, investigators did find that recreational cannabis laws may be tied to a potential reduction in synthetic opioid deaths.

METHODOLOGY:

• Investigators analyzed state-level data from the US Centers for Disease Control and Prevention and other databases (2006-2020) on the number of opioid prescriptions (per 100,000 persons).
• Prescription opioids included buprenorphine (except products to treat opioid use disorder), codeine, fentanyl, hydrocodone, hydromorphone, methadone, morphine, oxycodone, oxymorphone, propoxyphene, tapentadol, and tramadol.
• Researchers used regression analyses to account for poverty rates and real gross domestic product and a generalized difference-in-differences method that accounted for staggered implementation of cannabis laws.

TAKEAWAY:

• During the full study period, 13 states legalized recreational cannabis and 23 legalized medical cannabis.
• No statistically significant association was found between recreational cannabis laws and opioid prescriptions (3.08 fewer prescriptions per 100 persons; P = .17) or overall opioid overdose mortality (3.05 fewer deaths per 100,000; P = .24).
• The changes in outcomes associated with medical cannabis laws were larger in magnitude than those for recreational cannabis laws but also not statistically significant (3.54 additional prescriptions per 100 persons; P = .17 and 3.09 additional deaths per 100,000; P = .07).
• A potential reduction was found in synthetic opioid deaths associated specifically with states that had recreational cannabis laws (4.9 fewer deaths per 100,000; P = .04), but there were no differences in overdose deaths with other opioids.

IN PRACTICE:

“These results contrast with recent studies that suggested that recreational and medical cannabis legalization are associated with reductions in opioid prescriptions and medical cannabis legalization is associated with an increase in opioid mortality,” the authors wrote.

SOURCE:

Hai V. Nguyen, PhD, of the School of Pharmacy, Memorial University of Newfoundland, St. John’s, Canada, was the lead and corresponding author of the study. It was published online on January 19, 2024, in JAMA Health Forum.

A version of this article appeared on Medscape.com.