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Once-daily stimulant for ADHD safe, effective at 1 year
new research shows.
Results from a phase 3, multicenter, dose-optimization, open-label safety study of Azstarys (KemPharm) found that most treatment-emergent adverse events (TEAEs) were mild to moderate.
“This data show that Azstarys remains safe and effective for the treatment of ADHD when given for up to a year,” lead investigator Ann Childress, MD, president of the Center for Psychiatry and Behavioral Medicine, Las Vegas, said in an interview.
The study was published online in the Journal of Child and Adolescent Psychopharmacology.
Safety at 1 year
The drug is a combination of extended-release serdexmethylphenidate (SDX), KemPharm’s prodrug of dexmethylphenidate, coformulated with immediate-release d-MPH.
SDX is converted to d-MPH after it is absorbed in the gastrointestinal tract. The d-MPH is released gradually throughout the day, providing quick symptom control with the d-MPH and extended control with SDX.
Azstarys was approved by the Food and Drug Administration in 2021 on the basis of results from a laboratory classroom phase 3 trial, which showed significant improvement in ADHD symptoms, compared with placebo.
For this study, the second phase 3 trial of Azstarys, investigators analyzed data from 282 children aged 6-12 years in the United States, including 70 who participated in an earlier 1-month efficacy trial.
After screening and a 3-week dose-optimization phase for new participants, patients received once-daily treatment with doses of 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, or 52.3 mg/10.4 mg of SDX/d-MPH.
After 1 year of treatment, 60.1% of participants reported at least one TEAE, the majority of which were moderate. Twelve patients reported severe TEAEs. Six children (2.5%) discontinued the study because of a TEAE during the treatment phase.
The investigators also measured growth and changes in sleep with the Children’s Sleep Habits Questionnaire during the 12-month study. Sleep improved on most measures and the impact on growth was mild.
There were no life-threatening TEAEs and no deaths reported during the study.
The most common TEAEs during the treatment phase were decreased appetite, upper respiratory tract infection, nasopharyngitis, decreased weight, irritability, and increased weight.
Efficacy at 1 year
ADHD symptoms improved considerably after 1 month of treatment, with responses continuing at 1 year.
At baseline, participants’ mean ADHD Rating Scale–5 score was 41.5. After 1 month of treatment, scores averaged 16.1, a decline of –25.3 (P < .001).
The mean score stabilized in the 12-15 range for the remainder of the study. After 1 year of treatment, ADHD symptoms had decreased approximately 70% from baseline.
Investigators found similar results in clinical severity. After 1 month of treatment, the average Clinical Global Impressions–Severity (CGI-S) scale score was 2.5, a decline of –2.2 (P < .0001).
CGI-S scale scores remained in the 2.2-2.4 range for the remainder of the study.
These results, combined with the results of the original classroom trial, suggest Azstarys may offer advantages over other ADHD drugs, Dr. Childress said.
“In the laboratory classroom trial, subjects taking Azstarys completed significantly more math problems than subjects taking placebo beginning at 30 minutes and up to 13 hours after dosing,” Dr. Childress said. “No other methylphenidate extended-release product currently marketed in the United States has a 13-hour duration of effect.”
‘Reassuring data’
Commenting on the findings, Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, said that the study suggests the drug may be a valuable addition to ADHD treatment options for pediatric patients.
“The study provides reassuring data on the safety of stimulants in patients without significant history of cardiac events or blood pressure changes, which are usual concerns among patients and clinicians despite the evidence supporting safety, said Dr. Pawar, who was not part of the study.
“Additionally, the 1-year data on efficacy and safety of a new stimulant medication is valuable for clinicians looking for sustained relief for their patients, despite the limitations of an open-label trial,” she added.
Overall, the safety data reported in the study are fairly consistent with the safety profile of other methylphenidates used for treating ADHD, Dr. Pawar said.
However, she noted, the study does have some limitations, including its open-label design and lack of blinding. The research also excluded children with autism, disruptive mood dysregulation disorders, and other common comorbidities of ADHD, which may limit the generalizability of the results.
“These comorbidities often require stimulants as a part of treatment, and yet have a higher risk of side effects,” Dr. Pawar said. “Future studies with a broader population may be needed to better understand treatment effectiveness and potential risks.”
The study was funded by KemPharm. Dr. Childress serves as consultant for Aardvark, Arbor, Attentive, Cingulate, Ironshore, Neos Therapeutics, Neurocentria, Otsuka, Purdue, Rhodes, Sunovion, Tris Pharma, KemPharm, Supernus, Jazz, Corium, Tulex, and Lumos.
A version of this article first appeared on Medscape.com.
new research shows.
Results from a phase 3, multicenter, dose-optimization, open-label safety study of Azstarys (KemPharm) found that most treatment-emergent adverse events (TEAEs) were mild to moderate.
“This data show that Azstarys remains safe and effective for the treatment of ADHD when given for up to a year,” lead investigator Ann Childress, MD, president of the Center for Psychiatry and Behavioral Medicine, Las Vegas, said in an interview.
The study was published online in the Journal of Child and Adolescent Psychopharmacology.
Safety at 1 year
The drug is a combination of extended-release serdexmethylphenidate (SDX), KemPharm’s prodrug of dexmethylphenidate, coformulated with immediate-release d-MPH.
SDX is converted to d-MPH after it is absorbed in the gastrointestinal tract. The d-MPH is released gradually throughout the day, providing quick symptom control with the d-MPH and extended control with SDX.
Azstarys was approved by the Food and Drug Administration in 2021 on the basis of results from a laboratory classroom phase 3 trial, which showed significant improvement in ADHD symptoms, compared with placebo.
For this study, the second phase 3 trial of Azstarys, investigators analyzed data from 282 children aged 6-12 years in the United States, including 70 who participated in an earlier 1-month efficacy trial.
After screening and a 3-week dose-optimization phase for new participants, patients received once-daily treatment with doses of 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, or 52.3 mg/10.4 mg of SDX/d-MPH.
After 1 year of treatment, 60.1% of participants reported at least one TEAE, the majority of which were moderate. Twelve patients reported severe TEAEs. Six children (2.5%) discontinued the study because of a TEAE during the treatment phase.
The investigators also measured growth and changes in sleep with the Children’s Sleep Habits Questionnaire during the 12-month study. Sleep improved on most measures and the impact on growth was mild.
There were no life-threatening TEAEs and no deaths reported during the study.
The most common TEAEs during the treatment phase were decreased appetite, upper respiratory tract infection, nasopharyngitis, decreased weight, irritability, and increased weight.
Efficacy at 1 year
ADHD symptoms improved considerably after 1 month of treatment, with responses continuing at 1 year.
At baseline, participants’ mean ADHD Rating Scale–5 score was 41.5. After 1 month of treatment, scores averaged 16.1, a decline of –25.3 (P < .001).
The mean score stabilized in the 12-15 range for the remainder of the study. After 1 year of treatment, ADHD symptoms had decreased approximately 70% from baseline.
Investigators found similar results in clinical severity. After 1 month of treatment, the average Clinical Global Impressions–Severity (CGI-S) scale score was 2.5, a decline of –2.2 (P < .0001).
CGI-S scale scores remained in the 2.2-2.4 range for the remainder of the study.
These results, combined with the results of the original classroom trial, suggest Azstarys may offer advantages over other ADHD drugs, Dr. Childress said.
“In the laboratory classroom trial, subjects taking Azstarys completed significantly more math problems than subjects taking placebo beginning at 30 minutes and up to 13 hours after dosing,” Dr. Childress said. “No other methylphenidate extended-release product currently marketed in the United States has a 13-hour duration of effect.”
‘Reassuring data’
Commenting on the findings, Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, said that the study suggests the drug may be a valuable addition to ADHD treatment options for pediatric patients.
“The study provides reassuring data on the safety of stimulants in patients without significant history of cardiac events or blood pressure changes, which are usual concerns among patients and clinicians despite the evidence supporting safety, said Dr. Pawar, who was not part of the study.
“Additionally, the 1-year data on efficacy and safety of a new stimulant medication is valuable for clinicians looking for sustained relief for their patients, despite the limitations of an open-label trial,” she added.
Overall, the safety data reported in the study are fairly consistent with the safety profile of other methylphenidates used for treating ADHD, Dr. Pawar said.
However, she noted, the study does have some limitations, including its open-label design and lack of blinding. The research also excluded children with autism, disruptive mood dysregulation disorders, and other common comorbidities of ADHD, which may limit the generalizability of the results.
“These comorbidities often require stimulants as a part of treatment, and yet have a higher risk of side effects,” Dr. Pawar said. “Future studies with a broader population may be needed to better understand treatment effectiveness and potential risks.”
The study was funded by KemPharm. Dr. Childress serves as consultant for Aardvark, Arbor, Attentive, Cingulate, Ironshore, Neos Therapeutics, Neurocentria, Otsuka, Purdue, Rhodes, Sunovion, Tris Pharma, KemPharm, Supernus, Jazz, Corium, Tulex, and Lumos.
A version of this article first appeared on Medscape.com.
new research shows.
Results from a phase 3, multicenter, dose-optimization, open-label safety study of Azstarys (KemPharm) found that most treatment-emergent adverse events (TEAEs) were mild to moderate.
“This data show that Azstarys remains safe and effective for the treatment of ADHD when given for up to a year,” lead investigator Ann Childress, MD, president of the Center for Psychiatry and Behavioral Medicine, Las Vegas, said in an interview.
The study was published online in the Journal of Child and Adolescent Psychopharmacology.
Safety at 1 year
The drug is a combination of extended-release serdexmethylphenidate (SDX), KemPharm’s prodrug of dexmethylphenidate, coformulated with immediate-release d-MPH.
SDX is converted to d-MPH after it is absorbed in the gastrointestinal tract. The d-MPH is released gradually throughout the day, providing quick symptom control with the d-MPH and extended control with SDX.
Azstarys was approved by the Food and Drug Administration in 2021 on the basis of results from a laboratory classroom phase 3 trial, which showed significant improvement in ADHD symptoms, compared with placebo.
For this study, the second phase 3 trial of Azstarys, investigators analyzed data from 282 children aged 6-12 years in the United States, including 70 who participated in an earlier 1-month efficacy trial.
After screening and a 3-week dose-optimization phase for new participants, patients received once-daily treatment with doses of 26.1 mg/5.2 mg, 39.2 mg/7.8 mg, or 52.3 mg/10.4 mg of SDX/d-MPH.
After 1 year of treatment, 60.1% of participants reported at least one TEAE, the majority of which were moderate. Twelve patients reported severe TEAEs. Six children (2.5%) discontinued the study because of a TEAE during the treatment phase.
The investigators also measured growth and changes in sleep with the Children’s Sleep Habits Questionnaire during the 12-month study. Sleep improved on most measures and the impact on growth was mild.
There were no life-threatening TEAEs and no deaths reported during the study.
The most common TEAEs during the treatment phase were decreased appetite, upper respiratory tract infection, nasopharyngitis, decreased weight, irritability, and increased weight.
Efficacy at 1 year
ADHD symptoms improved considerably after 1 month of treatment, with responses continuing at 1 year.
At baseline, participants’ mean ADHD Rating Scale–5 score was 41.5. After 1 month of treatment, scores averaged 16.1, a decline of –25.3 (P < .001).
The mean score stabilized in the 12-15 range for the remainder of the study. After 1 year of treatment, ADHD symptoms had decreased approximately 70% from baseline.
Investigators found similar results in clinical severity. After 1 month of treatment, the average Clinical Global Impressions–Severity (CGI-S) scale score was 2.5, a decline of –2.2 (P < .0001).
CGI-S scale scores remained in the 2.2-2.4 range for the remainder of the study.
These results, combined with the results of the original classroom trial, suggest Azstarys may offer advantages over other ADHD drugs, Dr. Childress said.
“In the laboratory classroom trial, subjects taking Azstarys completed significantly more math problems than subjects taking placebo beginning at 30 minutes and up to 13 hours after dosing,” Dr. Childress said. “No other methylphenidate extended-release product currently marketed in the United States has a 13-hour duration of effect.”
‘Reassuring data’
Commenting on the findings, Aditya Pawar, MD, a child and adolescent psychiatrist with the Kennedy Krieger Institute and an assistant professor of psychiatry and behavioral sciences at Johns Hopkins University, Baltimore, said that the study suggests the drug may be a valuable addition to ADHD treatment options for pediatric patients.
“The study provides reassuring data on the safety of stimulants in patients without significant history of cardiac events or blood pressure changes, which are usual concerns among patients and clinicians despite the evidence supporting safety, said Dr. Pawar, who was not part of the study.
“Additionally, the 1-year data on efficacy and safety of a new stimulant medication is valuable for clinicians looking for sustained relief for their patients, despite the limitations of an open-label trial,” she added.
Overall, the safety data reported in the study are fairly consistent with the safety profile of other methylphenidates used for treating ADHD, Dr. Pawar said.
However, she noted, the study does have some limitations, including its open-label design and lack of blinding. The research also excluded children with autism, disruptive mood dysregulation disorders, and other common comorbidities of ADHD, which may limit the generalizability of the results.
“These comorbidities often require stimulants as a part of treatment, and yet have a higher risk of side effects,” Dr. Pawar said. “Future studies with a broader population may be needed to better understand treatment effectiveness and potential risks.”
The study was funded by KemPharm. Dr. Childress serves as consultant for Aardvark, Arbor, Attentive, Cingulate, Ironshore, Neos Therapeutics, Neurocentria, Otsuka, Purdue, Rhodes, Sunovion, Tris Pharma, KemPharm, Supernus, Jazz, Corium, Tulex, and Lumos.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
Depressive symptoms tied to higher stroke risk, worse outcomes
new research suggests.
Data from the international INTERSTROKE study also showed that those with depressive symptoms before a stroke had worse outcomes, including a significantly higher mortality rate in the first month after a stroke.
These findings build on prior research on the link between depression and stroke, including one study that showed an increased risk for incident stroke among those with a high number of depressive symptoms and another that found that worsening depression can precede stroke in older adults.
“Depression is an important risk factor for acute stroke and is potentially a modifiable contributor to the global burden of stroke,” lead investigator Robert Murphy, MB, a consultant in stroke and geriatric medicine and a researcher with the clinical research facility at the University of Galway, Ireland, told this news organization. “Even mild depressive symptoms were found in this study to be associated with increased risk of stroke and this adds to the literature that across the full range of depressive symptoms there is an association with increased risk of stroke.”
The findings were published online March 8 in Neurology.
Significant stroke risk
For the analysis, investigators collected data on 26,877 cases and controls across 32 countries who participated in INTERSTROKE, an international case-control study of risk factors for a first acute stroke. Participants were recruited between 2007 and 2015 and completed a series of questionnaires about stroke risk factors, including measures of depressive symptoms experienced in the past 12 months.
After adjustment for occupation, education, wealth index, diet, physical activity, alcohol consumption, and smoking history, having prestroke depressive symptoms was associated with greater odds for acute stroke (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.34-1.58), including both intracerebral hemorrhage (aOR, 1.56; 95% CI, 1.28-1.91) and ischemic stroke (aOR, 1.44; 95% CI, 1.31-1.58).
Stroke risk increased with increasing severity of depression, but even those with mild depression had a 35% increased risk (aOR, 1.35; 95% CI, 1.19-1.53).
The increased risk held even after the researchers adjusted further for diabetes, hypertension, atrial fibrillation, and body mass index, and work, home, and financial stress.
The association was consistent across geographical regions and age groups, but was stronger in men and in those without hypertension.
“This study looks at different constructs of depression and identifies that across the spectrum of mild, moderate, and severe depressive symptoms that there is an association present with acute stroke and that a biological gradient emerges with increasing burden of depressive symptoms associated with increasing risk,” Dr. Murphy said.
An antidepressant mediating effect?
While prestroke depressive symptoms were not associated with a greater odds of worse stroke severity, they were associated with worse outcomes (P < .001) and higher mortality (10% vs. 8.1%; P = .003) 1 month after a stroke.
In a subgroup analysis, researchers found no association between depressive symptoms and stroke risk in patients who were taking antidepressants.
While no assumptions of causality can be drawn from these findings, “this subgroup analysis does suggest that an increased risk of stroke in those with depression may be attenuated if a patient is on appropriate treatment,” Dr. Murphy said. “This is an area that warrants further exploration.”
The mechanisms that link depression to stroke are unclear, but these findings offer strong evidence that this link exists, Dr. Murphy said.
“We adjusted for potential confounders in sequential models and after adjusting for traditional cardiovascular risk factors there was a consistent association between depressive symptoms and stroke identifying that there is likely an independent association between depression and stroke,” Dr. Murphy said.
Questions remain
Commenting on the study, Daniel T. Lackland DrPH, professor, division of translational neurosciences and population studies, department of neurology, Medical University of South Carolina, Charleston, said it adds to a growing body of work on the association of stroke and depression.
“In this case, depression may be a risk factor for having a stroke,” said Dr. Lackland, who was not part of the study. In addition, the study suggests that “treating depression can have additional benefits beyond mental health, in this case, reduced stroke risks.”
However, it’s important, as with any observational study, that there may be confounding factors that may offer an alternative explanation for the findings.
“Further, it is often difficult to accurately assess depression in all individuals, and specifically in individuals who have had a stroke,” Dr. Lackland said. “While this particular study adds depression as a risk factor and suggests treatment of depression in reducing risks, it is important to emphasize that the traditional stroke risk factors including hypertension should [be] continually recognized and treat[ed] with high rigor.”
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Canadian Stroke Network, the Swedish Research Council, the Swedish Heart Lung Foundation, AFA Insurance, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), Merck Sharp & Dohme, the Swedish Heart Lung Foundation, Chest Heart & Stroke Scotland, and the Stroke Association (United Kingdom). Dr. Murphy and Dr. Lackland have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Data from the international INTERSTROKE study also showed that those with depressive symptoms before a stroke had worse outcomes, including a significantly higher mortality rate in the first month after a stroke.
These findings build on prior research on the link between depression and stroke, including one study that showed an increased risk for incident stroke among those with a high number of depressive symptoms and another that found that worsening depression can precede stroke in older adults.
“Depression is an important risk factor for acute stroke and is potentially a modifiable contributor to the global burden of stroke,” lead investigator Robert Murphy, MB, a consultant in stroke and geriatric medicine and a researcher with the clinical research facility at the University of Galway, Ireland, told this news organization. “Even mild depressive symptoms were found in this study to be associated with increased risk of stroke and this adds to the literature that across the full range of depressive symptoms there is an association with increased risk of stroke.”
The findings were published online March 8 in Neurology.
Significant stroke risk
For the analysis, investigators collected data on 26,877 cases and controls across 32 countries who participated in INTERSTROKE, an international case-control study of risk factors for a first acute stroke. Participants were recruited between 2007 and 2015 and completed a series of questionnaires about stroke risk factors, including measures of depressive symptoms experienced in the past 12 months.
After adjustment for occupation, education, wealth index, diet, physical activity, alcohol consumption, and smoking history, having prestroke depressive symptoms was associated with greater odds for acute stroke (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.34-1.58), including both intracerebral hemorrhage (aOR, 1.56; 95% CI, 1.28-1.91) and ischemic stroke (aOR, 1.44; 95% CI, 1.31-1.58).
Stroke risk increased with increasing severity of depression, but even those with mild depression had a 35% increased risk (aOR, 1.35; 95% CI, 1.19-1.53).
The increased risk held even after the researchers adjusted further for diabetes, hypertension, atrial fibrillation, and body mass index, and work, home, and financial stress.
The association was consistent across geographical regions and age groups, but was stronger in men and in those without hypertension.
“This study looks at different constructs of depression and identifies that across the spectrum of mild, moderate, and severe depressive symptoms that there is an association present with acute stroke and that a biological gradient emerges with increasing burden of depressive symptoms associated with increasing risk,” Dr. Murphy said.
An antidepressant mediating effect?
While prestroke depressive symptoms were not associated with a greater odds of worse stroke severity, they were associated with worse outcomes (P < .001) and higher mortality (10% vs. 8.1%; P = .003) 1 month after a stroke.
In a subgroup analysis, researchers found no association between depressive symptoms and stroke risk in patients who were taking antidepressants.
While no assumptions of causality can be drawn from these findings, “this subgroup analysis does suggest that an increased risk of stroke in those with depression may be attenuated if a patient is on appropriate treatment,” Dr. Murphy said. “This is an area that warrants further exploration.”
The mechanisms that link depression to stroke are unclear, but these findings offer strong evidence that this link exists, Dr. Murphy said.
“We adjusted for potential confounders in sequential models and after adjusting for traditional cardiovascular risk factors there was a consistent association between depressive symptoms and stroke identifying that there is likely an independent association between depression and stroke,” Dr. Murphy said.
Questions remain
Commenting on the study, Daniel T. Lackland DrPH, professor, division of translational neurosciences and population studies, department of neurology, Medical University of South Carolina, Charleston, said it adds to a growing body of work on the association of stroke and depression.
“In this case, depression may be a risk factor for having a stroke,” said Dr. Lackland, who was not part of the study. In addition, the study suggests that “treating depression can have additional benefits beyond mental health, in this case, reduced stroke risks.”
However, it’s important, as with any observational study, that there may be confounding factors that may offer an alternative explanation for the findings.
“Further, it is often difficult to accurately assess depression in all individuals, and specifically in individuals who have had a stroke,” Dr. Lackland said. “While this particular study adds depression as a risk factor and suggests treatment of depression in reducing risks, it is important to emphasize that the traditional stroke risk factors including hypertension should [be] continually recognized and treat[ed] with high rigor.”
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Canadian Stroke Network, the Swedish Research Council, the Swedish Heart Lung Foundation, AFA Insurance, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), Merck Sharp & Dohme, the Swedish Heart Lung Foundation, Chest Heart & Stroke Scotland, and the Stroke Association (United Kingdom). Dr. Murphy and Dr. Lackland have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Data from the international INTERSTROKE study also showed that those with depressive symptoms before a stroke had worse outcomes, including a significantly higher mortality rate in the first month after a stroke.
These findings build on prior research on the link between depression and stroke, including one study that showed an increased risk for incident stroke among those with a high number of depressive symptoms and another that found that worsening depression can precede stroke in older adults.
“Depression is an important risk factor for acute stroke and is potentially a modifiable contributor to the global burden of stroke,” lead investigator Robert Murphy, MB, a consultant in stroke and geriatric medicine and a researcher with the clinical research facility at the University of Galway, Ireland, told this news organization. “Even mild depressive symptoms were found in this study to be associated with increased risk of stroke and this adds to the literature that across the full range of depressive symptoms there is an association with increased risk of stroke.”
The findings were published online March 8 in Neurology.
Significant stroke risk
For the analysis, investigators collected data on 26,877 cases and controls across 32 countries who participated in INTERSTROKE, an international case-control study of risk factors for a first acute stroke. Participants were recruited between 2007 and 2015 and completed a series of questionnaires about stroke risk factors, including measures of depressive symptoms experienced in the past 12 months.
After adjustment for occupation, education, wealth index, diet, physical activity, alcohol consumption, and smoking history, having prestroke depressive symptoms was associated with greater odds for acute stroke (adjusted odds ratio [aOR], 1.46; 95% confidence interval [CI], 1.34-1.58), including both intracerebral hemorrhage (aOR, 1.56; 95% CI, 1.28-1.91) and ischemic stroke (aOR, 1.44; 95% CI, 1.31-1.58).
Stroke risk increased with increasing severity of depression, but even those with mild depression had a 35% increased risk (aOR, 1.35; 95% CI, 1.19-1.53).
The increased risk held even after the researchers adjusted further for diabetes, hypertension, atrial fibrillation, and body mass index, and work, home, and financial stress.
The association was consistent across geographical regions and age groups, but was stronger in men and in those without hypertension.
“This study looks at different constructs of depression and identifies that across the spectrum of mild, moderate, and severe depressive symptoms that there is an association present with acute stroke and that a biological gradient emerges with increasing burden of depressive symptoms associated with increasing risk,” Dr. Murphy said.
An antidepressant mediating effect?
While prestroke depressive symptoms were not associated with a greater odds of worse stroke severity, they were associated with worse outcomes (P < .001) and higher mortality (10% vs. 8.1%; P = .003) 1 month after a stroke.
In a subgroup analysis, researchers found no association between depressive symptoms and stroke risk in patients who were taking antidepressants.
While no assumptions of causality can be drawn from these findings, “this subgroup analysis does suggest that an increased risk of stroke in those with depression may be attenuated if a patient is on appropriate treatment,” Dr. Murphy said. “This is an area that warrants further exploration.”
The mechanisms that link depression to stroke are unclear, but these findings offer strong evidence that this link exists, Dr. Murphy said.
“We adjusted for potential confounders in sequential models and after adjusting for traditional cardiovascular risk factors there was a consistent association between depressive symptoms and stroke identifying that there is likely an independent association between depression and stroke,” Dr. Murphy said.
Questions remain
Commenting on the study, Daniel T. Lackland DrPH, professor, division of translational neurosciences and population studies, department of neurology, Medical University of South Carolina, Charleston, said it adds to a growing body of work on the association of stroke and depression.
“In this case, depression may be a risk factor for having a stroke,” said Dr. Lackland, who was not part of the study. In addition, the study suggests that “treating depression can have additional benefits beyond mental health, in this case, reduced stroke risks.”
However, it’s important, as with any observational study, that there may be confounding factors that may offer an alternative explanation for the findings.
“Further, it is often difficult to accurately assess depression in all individuals, and specifically in individuals who have had a stroke,” Dr. Lackland said. “While this particular study adds depression as a risk factor and suggests treatment of depression in reducing risks, it is important to emphasize that the traditional stroke risk factors including hypertension should [be] continually recognized and treat[ed] with high rigor.”
The INTERSTROKE study was funded by the Canadian Institutes of Health Research, the Heart and Stroke Foundation of Canada, the Canadian Stroke Network, the Swedish Research Council, the Swedish Heart Lung Foundation, AFA Insurance, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland, and through unrestricted grants from several pharmaceutical companies with major contributions from AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), Merck Sharp & Dohme, the Swedish Heart Lung Foundation, Chest Heart & Stroke Scotland, and the Stroke Association (United Kingdom). Dr. Murphy and Dr. Lackland have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
APA releases updated eating disorder guidelines
The updated guidelines focus primarily on anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) and include recommendations for screening and treatment.
“Eating disorders often are unrecognized and untreated,” Catherine Crone, MD, chair of the guideline writing group, said in a statement from APA. “This guideline and supplementary resources are intended to serve as a practical tool for clinicians, to help with screening, diagnosis, and providing evidence-based treatment for eating disorders.”
Approximately one in five children worldwide are at risk for developing an eating disorder and U.S. medical admissions for adolescents with restrictive eating disorders more than doubled during the pandemic.
The economic cost of eating disorders in the United States from 2018 to 2019 was an estimated $64.7 billion, the report notes, with an additional $326.5 billion attributable to reductions in well-being associated with eating disorders.
The executive summary of the updated guidelines was published online in The American Journal of Psychiatry.
The practice guideline, which was approved at the 2021 APA annual meeting, features 16 recommendations for clinicians, including screening patients for eating disorders as part of an initial psychiatric evaluation and conducting comprehensive patient evaluations that incorporate laboratory tests and electrocardiograms.
Recommendations also include setting individualized weight goals for patients with anorexia and incorporating family-based therapy as part of a treatment plan for adolescents with anorexia or bulimia.
“This practice guideline aims to help clinicians improve care for their patients by reviewing current evidence and providing evidence-based statements that are intended to enhance knowledge, increase assessment, and optimize treatment of eating disorders,” the authors wrote.
A range of other resources were released with the new guidelines to provide clinicians with support to implement the recommendations, including a pocket guide for clinicians, continuing medical education activities, and slides. The association is also launching a pocket guide for patients and families and an interactive tool kit with a screening assessment calculator.
The APA guidelines follow the 2021 release by the American Academy of Pediatrics on diagnosing and managing eating disorders in children and adolescents.
The development of the guidelines was supported by a grant from the Council of Medical Specialty Societies.
A version of this article first appeared on Medscape.com.
The updated guidelines focus primarily on anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) and include recommendations for screening and treatment.
“Eating disorders often are unrecognized and untreated,” Catherine Crone, MD, chair of the guideline writing group, said in a statement from APA. “This guideline and supplementary resources are intended to serve as a practical tool for clinicians, to help with screening, diagnosis, and providing evidence-based treatment for eating disorders.”
Approximately one in five children worldwide are at risk for developing an eating disorder and U.S. medical admissions for adolescents with restrictive eating disorders more than doubled during the pandemic.
The economic cost of eating disorders in the United States from 2018 to 2019 was an estimated $64.7 billion, the report notes, with an additional $326.5 billion attributable to reductions in well-being associated with eating disorders.
The executive summary of the updated guidelines was published online in The American Journal of Psychiatry.
The practice guideline, which was approved at the 2021 APA annual meeting, features 16 recommendations for clinicians, including screening patients for eating disorders as part of an initial psychiatric evaluation and conducting comprehensive patient evaluations that incorporate laboratory tests and electrocardiograms.
Recommendations also include setting individualized weight goals for patients with anorexia and incorporating family-based therapy as part of a treatment plan for adolescents with anorexia or bulimia.
“This practice guideline aims to help clinicians improve care for their patients by reviewing current evidence and providing evidence-based statements that are intended to enhance knowledge, increase assessment, and optimize treatment of eating disorders,” the authors wrote.
A range of other resources were released with the new guidelines to provide clinicians with support to implement the recommendations, including a pocket guide for clinicians, continuing medical education activities, and slides. The association is also launching a pocket guide for patients and families and an interactive tool kit with a screening assessment calculator.
The APA guidelines follow the 2021 release by the American Academy of Pediatrics on diagnosing and managing eating disorders in children and adolescents.
The development of the guidelines was supported by a grant from the Council of Medical Specialty Societies.
A version of this article first appeared on Medscape.com.
The updated guidelines focus primarily on anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) and include recommendations for screening and treatment.
“Eating disorders often are unrecognized and untreated,” Catherine Crone, MD, chair of the guideline writing group, said in a statement from APA. “This guideline and supplementary resources are intended to serve as a practical tool for clinicians, to help with screening, diagnosis, and providing evidence-based treatment for eating disorders.”
Approximately one in five children worldwide are at risk for developing an eating disorder and U.S. medical admissions for adolescents with restrictive eating disorders more than doubled during the pandemic.
The economic cost of eating disorders in the United States from 2018 to 2019 was an estimated $64.7 billion, the report notes, with an additional $326.5 billion attributable to reductions in well-being associated with eating disorders.
The executive summary of the updated guidelines was published online in The American Journal of Psychiatry.
The practice guideline, which was approved at the 2021 APA annual meeting, features 16 recommendations for clinicians, including screening patients for eating disorders as part of an initial psychiatric evaluation and conducting comprehensive patient evaluations that incorporate laboratory tests and electrocardiograms.
Recommendations also include setting individualized weight goals for patients with anorexia and incorporating family-based therapy as part of a treatment plan for adolescents with anorexia or bulimia.
“This practice guideline aims to help clinicians improve care for their patients by reviewing current evidence and providing evidence-based statements that are intended to enhance knowledge, increase assessment, and optimize treatment of eating disorders,” the authors wrote.
A range of other resources were released with the new guidelines to provide clinicians with support to implement the recommendations, including a pocket guide for clinicians, continuing medical education activities, and slides. The association is also launching a pocket guide for patients and families and an interactive tool kit with a screening assessment calculator.
The APA guidelines follow the 2021 release by the American Academy of Pediatrics on diagnosing and managing eating disorders in children and adolescents.
The development of the guidelines was supported by a grant from the Council of Medical Specialty Societies.
A version of this article first appeared on Medscape.com.
FROM THE AMERICAN JOURNAL OF PSYCHIATRY
Focused ultrasound ablation reduces dyskinesia in Parkinson’s disease
, new research shows.
The technique requires no sedation or brain implants. Surgeons use MRI to identify the globus pallidus internus, a part of the basal ganglia involved in movement disorders, and a focused ultrasound beam to heat and destroy the tissue.
Investigators performed the procedure with a device called Exablate Neuro, which was first approved by the Food and Drug Administration in 2016 to treat essential tremor.
On the basis of the results of a multicenter, randomized, sham-controlled trial, the agency expanded the indication in 2021 to include unilateral pallidotomy to treat advanced Parkinson’s disease for patients with mobility, rigidity, or dyskinesia symptoms.
“In some patients with Parkinson’s disease, you get dyskinesias, and ablation of the globus pallidus significantly reduces those dyskinesias and motor impairment,” said lead investigator Vibhor Krishna, MD, associate professor of neurosurgery at the University of North Carolina at Chapel Hill. “It could be used to treat patients when other surgical procedures can’t be applied.”
The study was published online in the New England Journal of Medicine.
Strong response
For the study, 94 patients with advanced Parkinson’s disease who had dyskinesias or motor fluctuations and motor impairment in the off-medication state wore transducer helmets while lying in an MRI scanner. Patients were awake during the entire procedure.
The treatment group received unilateral FUSA on the side of the brain with the greatest motor impairment. The device initially delivered target temperatures of 40°-45° C. Ablative temperatures were gradually increased following evaluations to test for improvement of motor symptoms. The maximum temperature used was 54.3° C.
Patients in the control group underwent an identical procedure with the sonication energy disabled.
The primary outcome was a response to therapy at 3 months, defined as a decrease of at least three points from baseline either in the score on the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), part III, while off medication or in the score on the Unified Dyskinesia Rating Scale (UDRS) while on medication.
At 3 months, 69% of the treatment group reported a response, compared with 32% of the control group (P = .003).
When researchers analyzed MDS-UPDRS scores, they found that 29% of the treatment group and 27% of the control group showed improvement. For UDRS scores, 12% of the treatment group demonstrated improvement. In the control group, there was no improvement on this score. Improvements in both scores were reported in 28% of the treatment group and 5% of the control group.
Among those who reported a response at 3 months, 77% continued to show a response at 12 months.
‘Unforgiving’ area of the brain
While the response rate was a promising sign of this finding, it was not what interested Dr. Krishna the most. “The most surprising finding of this trial is how safe focused ultrasound pallidotomy is in treating patients with Parkinson’s disease,” he said.
The globus pallidus internus is an area of the brain that Dr. Krishna calls “unforgiving.”
“One side is motor fibers, and any problem with that can paralyze the patient, and just below that is the optic tract, and any problem there, you would lose vision,” Dr. Krishna said. “It is a very tough neighborhood to be in.”
By using MRI-guided ultrasound, surgeons can change the target and temperature of the ultrasound beam during the procedure to allow more precise treatment.
Pallidotomy-related adverse events in the treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness. All were mild to moderate, Dr. Krishna said.
More study is needed
Dyskinesia is a challenge in the management of Parkinson’s disease. Patients need antiparkinsonian medications to slow deterioration of motor function, but those medications can cause the involuntary movements that are a hallmark of dyskinesia.
The most common treatment for this complication, deep-brain stimulation (DBS), has its own drawbacks. It’s an open procedure, and there is a low-level risk for intracranial bleeding and infection. In addition, the electrode implants require ongoing maintenance and adjustment.
But the findings of this study show that, for patients who aren’t candidates for other therapies, such as DBS and ablative radiofrequency, FUSA may be an alternative, wrote Anette Schrag, PhD, professor of clinical neurosciences at University College London, in an accompanying commentary.
“The results confirm that it is effective in reducing motor complications of Parkinson’s disease, at least in the short term,” Dr. Schrag wrote. However, more long-term studies are needed, she added.
One-third of patients in the treatment group had no response to the treatment, and investigators aren’t sure why. Dr. Krishna noted that the benefits of the procedure waned in about a quarter of patients within a year of treatment.
Investigators plan to probe these questions in future trials.
“The results of this trial are promising,” Dr. Schrag wrote, “but given the nonreversible nature of the intervention and the progressive nature of the disease, it will be important to establish whether improvements in motor complications are maintained over longer periods and whether treatment results in improved overall functioning and quality of life for patients.”
The study was funded by Insightec. Disclosure forms for Dr. Krishna and Dr. Schrag are provided on the journal’s website.
A version of this article originally appeared on Medscape.com.
, new research shows.
The technique requires no sedation or brain implants. Surgeons use MRI to identify the globus pallidus internus, a part of the basal ganglia involved in movement disorders, and a focused ultrasound beam to heat and destroy the tissue.
Investigators performed the procedure with a device called Exablate Neuro, which was first approved by the Food and Drug Administration in 2016 to treat essential tremor.
On the basis of the results of a multicenter, randomized, sham-controlled trial, the agency expanded the indication in 2021 to include unilateral pallidotomy to treat advanced Parkinson’s disease for patients with mobility, rigidity, or dyskinesia symptoms.
“In some patients with Parkinson’s disease, you get dyskinesias, and ablation of the globus pallidus significantly reduces those dyskinesias and motor impairment,” said lead investigator Vibhor Krishna, MD, associate professor of neurosurgery at the University of North Carolina at Chapel Hill. “It could be used to treat patients when other surgical procedures can’t be applied.”
The study was published online in the New England Journal of Medicine.
Strong response
For the study, 94 patients with advanced Parkinson’s disease who had dyskinesias or motor fluctuations and motor impairment in the off-medication state wore transducer helmets while lying in an MRI scanner. Patients were awake during the entire procedure.
The treatment group received unilateral FUSA on the side of the brain with the greatest motor impairment. The device initially delivered target temperatures of 40°-45° C. Ablative temperatures were gradually increased following evaluations to test for improvement of motor symptoms. The maximum temperature used was 54.3° C.
Patients in the control group underwent an identical procedure with the sonication energy disabled.
The primary outcome was a response to therapy at 3 months, defined as a decrease of at least three points from baseline either in the score on the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), part III, while off medication or in the score on the Unified Dyskinesia Rating Scale (UDRS) while on medication.
At 3 months, 69% of the treatment group reported a response, compared with 32% of the control group (P = .003).
When researchers analyzed MDS-UPDRS scores, they found that 29% of the treatment group and 27% of the control group showed improvement. For UDRS scores, 12% of the treatment group demonstrated improvement. In the control group, there was no improvement on this score. Improvements in both scores were reported in 28% of the treatment group and 5% of the control group.
Among those who reported a response at 3 months, 77% continued to show a response at 12 months.
‘Unforgiving’ area of the brain
While the response rate was a promising sign of this finding, it was not what interested Dr. Krishna the most. “The most surprising finding of this trial is how safe focused ultrasound pallidotomy is in treating patients with Parkinson’s disease,” he said.
The globus pallidus internus is an area of the brain that Dr. Krishna calls “unforgiving.”
“One side is motor fibers, and any problem with that can paralyze the patient, and just below that is the optic tract, and any problem there, you would lose vision,” Dr. Krishna said. “It is a very tough neighborhood to be in.”
By using MRI-guided ultrasound, surgeons can change the target and temperature of the ultrasound beam during the procedure to allow more precise treatment.
Pallidotomy-related adverse events in the treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness. All were mild to moderate, Dr. Krishna said.
More study is needed
Dyskinesia is a challenge in the management of Parkinson’s disease. Patients need antiparkinsonian medications to slow deterioration of motor function, but those medications can cause the involuntary movements that are a hallmark of dyskinesia.
The most common treatment for this complication, deep-brain stimulation (DBS), has its own drawbacks. It’s an open procedure, and there is a low-level risk for intracranial bleeding and infection. In addition, the electrode implants require ongoing maintenance and adjustment.
But the findings of this study show that, for patients who aren’t candidates for other therapies, such as DBS and ablative radiofrequency, FUSA may be an alternative, wrote Anette Schrag, PhD, professor of clinical neurosciences at University College London, in an accompanying commentary.
“The results confirm that it is effective in reducing motor complications of Parkinson’s disease, at least in the short term,” Dr. Schrag wrote. However, more long-term studies are needed, she added.
One-third of patients in the treatment group had no response to the treatment, and investigators aren’t sure why. Dr. Krishna noted that the benefits of the procedure waned in about a quarter of patients within a year of treatment.
Investigators plan to probe these questions in future trials.
“The results of this trial are promising,” Dr. Schrag wrote, “but given the nonreversible nature of the intervention and the progressive nature of the disease, it will be important to establish whether improvements in motor complications are maintained over longer periods and whether treatment results in improved overall functioning and quality of life for patients.”
The study was funded by Insightec. Disclosure forms for Dr. Krishna and Dr. Schrag are provided on the journal’s website.
A version of this article originally appeared on Medscape.com.
, new research shows.
The technique requires no sedation or brain implants. Surgeons use MRI to identify the globus pallidus internus, a part of the basal ganglia involved in movement disorders, and a focused ultrasound beam to heat and destroy the tissue.
Investigators performed the procedure with a device called Exablate Neuro, which was first approved by the Food and Drug Administration in 2016 to treat essential tremor.
On the basis of the results of a multicenter, randomized, sham-controlled trial, the agency expanded the indication in 2021 to include unilateral pallidotomy to treat advanced Parkinson’s disease for patients with mobility, rigidity, or dyskinesia symptoms.
“In some patients with Parkinson’s disease, you get dyskinesias, and ablation of the globus pallidus significantly reduces those dyskinesias and motor impairment,” said lead investigator Vibhor Krishna, MD, associate professor of neurosurgery at the University of North Carolina at Chapel Hill. “It could be used to treat patients when other surgical procedures can’t be applied.”
The study was published online in the New England Journal of Medicine.
Strong response
For the study, 94 patients with advanced Parkinson’s disease who had dyskinesias or motor fluctuations and motor impairment in the off-medication state wore transducer helmets while lying in an MRI scanner. Patients were awake during the entire procedure.
The treatment group received unilateral FUSA on the side of the brain with the greatest motor impairment. The device initially delivered target temperatures of 40°-45° C. Ablative temperatures were gradually increased following evaluations to test for improvement of motor symptoms. The maximum temperature used was 54.3° C.
Patients in the control group underwent an identical procedure with the sonication energy disabled.
The primary outcome was a response to therapy at 3 months, defined as a decrease of at least three points from baseline either in the score on the Movement Disorders Society–Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), part III, while off medication or in the score on the Unified Dyskinesia Rating Scale (UDRS) while on medication.
At 3 months, 69% of the treatment group reported a response, compared with 32% of the control group (P = .003).
When researchers analyzed MDS-UPDRS scores, they found that 29% of the treatment group and 27% of the control group showed improvement. For UDRS scores, 12% of the treatment group demonstrated improvement. In the control group, there was no improvement on this score. Improvements in both scores were reported in 28% of the treatment group and 5% of the control group.
Among those who reported a response at 3 months, 77% continued to show a response at 12 months.
‘Unforgiving’ area of the brain
While the response rate was a promising sign of this finding, it was not what interested Dr. Krishna the most. “The most surprising finding of this trial is how safe focused ultrasound pallidotomy is in treating patients with Parkinson’s disease,” he said.
The globus pallidus internus is an area of the brain that Dr. Krishna calls “unforgiving.”
“One side is motor fibers, and any problem with that can paralyze the patient, and just below that is the optic tract, and any problem there, you would lose vision,” Dr. Krishna said. “It is a very tough neighborhood to be in.”
By using MRI-guided ultrasound, surgeons can change the target and temperature of the ultrasound beam during the procedure to allow more precise treatment.
Pallidotomy-related adverse events in the treatment group included dysarthria, gait disturbance, loss of taste, visual disturbance, and facial weakness. All were mild to moderate, Dr. Krishna said.
More study is needed
Dyskinesia is a challenge in the management of Parkinson’s disease. Patients need antiparkinsonian medications to slow deterioration of motor function, but those medications can cause the involuntary movements that are a hallmark of dyskinesia.
The most common treatment for this complication, deep-brain stimulation (DBS), has its own drawbacks. It’s an open procedure, and there is a low-level risk for intracranial bleeding and infection. In addition, the electrode implants require ongoing maintenance and adjustment.
But the findings of this study show that, for patients who aren’t candidates for other therapies, such as DBS and ablative radiofrequency, FUSA may be an alternative, wrote Anette Schrag, PhD, professor of clinical neurosciences at University College London, in an accompanying commentary.
“The results confirm that it is effective in reducing motor complications of Parkinson’s disease, at least in the short term,” Dr. Schrag wrote. However, more long-term studies are needed, she added.
One-third of patients in the treatment group had no response to the treatment, and investigators aren’t sure why. Dr. Krishna noted that the benefits of the procedure waned in about a quarter of patients within a year of treatment.
Investigators plan to probe these questions in future trials.
“The results of this trial are promising,” Dr. Schrag wrote, “but given the nonreversible nature of the intervention and the progressive nature of the disease, it will be important to establish whether improvements in motor complications are maintained over longer periods and whether treatment results in improved overall functioning and quality of life for patients.”
The study was funded by Insightec. Disclosure forms for Dr. Krishna and Dr. Schrag are provided on the journal’s website.
A version of this article originally appeared on Medscape.com.
FROM THE NEW ENGLAND JOURNAL OF MEDICINE
Statin disappoints for treatment-resistant depression
The randomized clinical trial findings contradict earlier, smaller studies in patients with major depressive disorder (MDD) that suggested statins may reduce symptoms.
“Given the promising results from preliminary trials of statins in MDD, I was surprised that simvastatin did not separate from placebo in our trial,” lead author M. Ishrat Husain, MBBS, MD, associate professor of psychiatry and scientific head of the Centre for Addiction and Mental Health Clinical Trials Unit at the University of Toronto, told this news organization.
“I believe that our findings suggest that statins are not effective augmentation strategies in treatment-resistant depression,” Dr. Husain said.
The findings were published online in JAMA Network Open.
Disappointing results
The double-blind, placebo-controlled randomized clinical trial was conducted in five centers in Pakistan and included 150 patients with major depressive episode whose symptoms did not improve after treatment with at least two antidepressants.
In addition to their prescribed antidepressants, participants received 20 mg/day of simvastatin (n = 77) or placebo (n = 73).
At 12 weeks, both groups reported improvements in Montgomery-Åsberg Depression Rating Scale total scores, but there was no significant difference between groups. The estimated mean difference for simvastatin vs. placebo was −0.61 (P = .7).
Researchers found similar results when they compared scores from the Generalized Anxiety Disorder Scale and Morisky Medication Adherence Scale.
“Much like several other studies in mood disorders, our study results were impacted by a large placebo response,” Dr. Husain said.
The lack of inclusion of any participants under the age of 18 and the single-country cohort were limitations of the trial. Although it is possible that could have affected the outcome, Dr. Husain said it isn’t likely.
It is also unlikely that a different statin would yield different results, he added.
“Simvastatin was selected as it is believed to be most brain penetrant of the statins given its lipophilicity,” Dr. Husain said. “Clinical trials of other statins in major depressive disorder in other settings and populations have also been congruent with our results.”
The study was funded by NIHR Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London. Dr. Husain reports having received grants from Compass Pathways, holds stock options in Mindset, and previously served on the Board of Trustees of the Pakistan Institute of Living and Learning. Disclosures for the other investigators are fully listed in the original article.
A version of this article first appeared on Medscape.com.
The randomized clinical trial findings contradict earlier, smaller studies in patients with major depressive disorder (MDD) that suggested statins may reduce symptoms.
“Given the promising results from preliminary trials of statins in MDD, I was surprised that simvastatin did not separate from placebo in our trial,” lead author M. Ishrat Husain, MBBS, MD, associate professor of psychiatry and scientific head of the Centre for Addiction and Mental Health Clinical Trials Unit at the University of Toronto, told this news organization.
“I believe that our findings suggest that statins are not effective augmentation strategies in treatment-resistant depression,” Dr. Husain said.
The findings were published online in JAMA Network Open.
Disappointing results
The double-blind, placebo-controlled randomized clinical trial was conducted in five centers in Pakistan and included 150 patients with major depressive episode whose symptoms did not improve after treatment with at least two antidepressants.
In addition to their prescribed antidepressants, participants received 20 mg/day of simvastatin (n = 77) or placebo (n = 73).
At 12 weeks, both groups reported improvements in Montgomery-Åsberg Depression Rating Scale total scores, but there was no significant difference between groups. The estimated mean difference for simvastatin vs. placebo was −0.61 (P = .7).
Researchers found similar results when they compared scores from the Generalized Anxiety Disorder Scale and Morisky Medication Adherence Scale.
“Much like several other studies in mood disorders, our study results were impacted by a large placebo response,” Dr. Husain said.
The lack of inclusion of any participants under the age of 18 and the single-country cohort were limitations of the trial. Although it is possible that could have affected the outcome, Dr. Husain said it isn’t likely.
It is also unlikely that a different statin would yield different results, he added.
“Simvastatin was selected as it is believed to be most brain penetrant of the statins given its lipophilicity,” Dr. Husain said. “Clinical trials of other statins in major depressive disorder in other settings and populations have also been congruent with our results.”
The study was funded by NIHR Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London. Dr. Husain reports having received grants from Compass Pathways, holds stock options in Mindset, and previously served on the Board of Trustees of the Pakistan Institute of Living and Learning. Disclosures for the other investigators are fully listed in the original article.
A version of this article first appeared on Medscape.com.
The randomized clinical trial findings contradict earlier, smaller studies in patients with major depressive disorder (MDD) that suggested statins may reduce symptoms.
“Given the promising results from preliminary trials of statins in MDD, I was surprised that simvastatin did not separate from placebo in our trial,” lead author M. Ishrat Husain, MBBS, MD, associate professor of psychiatry and scientific head of the Centre for Addiction and Mental Health Clinical Trials Unit at the University of Toronto, told this news organization.
“I believe that our findings suggest that statins are not effective augmentation strategies in treatment-resistant depression,” Dr. Husain said.
The findings were published online in JAMA Network Open.
Disappointing results
The double-blind, placebo-controlled randomized clinical trial was conducted in five centers in Pakistan and included 150 patients with major depressive episode whose symptoms did not improve after treatment with at least two antidepressants.
In addition to their prescribed antidepressants, participants received 20 mg/day of simvastatin (n = 77) or placebo (n = 73).
At 12 weeks, both groups reported improvements in Montgomery-Åsberg Depression Rating Scale total scores, but there was no significant difference between groups. The estimated mean difference for simvastatin vs. placebo was −0.61 (P = .7).
Researchers found similar results when they compared scores from the Generalized Anxiety Disorder Scale and Morisky Medication Adherence Scale.
“Much like several other studies in mood disorders, our study results were impacted by a large placebo response,” Dr. Husain said.
The lack of inclusion of any participants under the age of 18 and the single-country cohort were limitations of the trial. Although it is possible that could have affected the outcome, Dr. Husain said it isn’t likely.
It is also unlikely that a different statin would yield different results, he added.
“Simvastatin was selected as it is believed to be most brain penetrant of the statins given its lipophilicity,” Dr. Husain said. “Clinical trials of other statins in major depressive disorder in other settings and populations have also been congruent with our results.”
The study was funded by NIHR Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London. Dr. Husain reports having received grants from Compass Pathways, holds stock options in Mindset, and previously served on the Board of Trustees of the Pakistan Institute of Living and Learning. Disclosures for the other investigators are fully listed in the original article.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Higher dementia risk in women explained?
a study suggests.
Prior research has found a higher lifetime dementia risk in women, and one explanation cited has been that women tend to live longer than men.
However, this new analysis of data from nearly 30,000 people in 18 countries found almost no evidence of sex differences in most known risk factors for dementia, including age.
The risk of dementia among women was significantly higher in poorer countries, pointing to economic disadvantages as a possible explanation.
“In general, we found that the greater dementia risk found in women compared to men was more pronounced in poorer countries, which points to the need for greater efforts to narrow the gaps in health disparities between women and men in these countries,” lead investigator Jessica Gong, MSc, a doctoral student at the George Institute for Global Health, Newtown, Australia, told this news organization. “It is likely that socioeconomic factors are potentially more important than biological factors when assessing dementia risk.”
The findings were published online in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Global data
Most previous studies that examined sex differences in dementia risk were conducted in high-income countries, Ms. Gong noted, leaving a gap in the literature on risk in low- and middle-income countries.
To address this issue, researchers conducted an individual participant meta-analysis of 21 studies from the Cohort Studies of Memory in an International Consortium. Data analysis included information on 29,850 people from 18 countries on six continents. None of the participants had dementia at baseline, and the average age was 71.6 years.
Over a median of 4.6 years, incident dementia was reported in 2,089 people, 66% of whom were women.
Overall, women had higher dementia risk (hazard ratio, 1.12; 95% confidence interval, 1.02-1.23) than men, but the rates were highest in low- to middle-income economies (HR, 1.73; P = .03).
Dementia risk in women was higher than in men in 14 countries. Risk was highest in Nigeria, where dementia risk was more than double in women (aHR, 2.11; 95% CI, 1.46-3.04), and lowest in Brazil, where risk was 46% lower in women than in men (aHR, 0.54; 95% CI, 0.29-1.00).
In the United States, dementia risk was 7% higher in women than men (aHR, 1.07; 0.73-1.57).
Similar risk factors
In both women and men, older age, diabetes, depression, hearing impairment, and apo E–epsilon 4 carriage were associated with a greater risk of dementia, and more years of education, higher hip circumference, current alcohol use (vs. never), and high physical activity (vs. none to minimal) were associated with a lower risk of dementia.
Among all these risk factors, sex differences were only significant for longer education and former alcohol use, with both demonstrating a stronger association in men than women.
Global dementia rates are expected to triple over the next 25 years unless steps are taken to reduce risk factors. A 2020 report found that dementia risk could be reduced by addressing 12 modifiable risk factors, including obesity, air pollution, diabetes, social isolation, and hypertension. All of these risk factors are more common in low- to middle-income countries, Ms. Gong noted.
“These findings justify ongoing efforts to support programs to improve sex and gender equity in brain health, particularly in underrepresented and underserved populations, in turn to narrow the gaps within and between country,” Ms. Gong said.
Understanding the puzzle
Commenting on the findings for Medscape Medical News, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, said the findings add to the body of work about sex differences in dementia risk.
“This is an interesting study looking at risk factors for dementia and suggests that, while some risk factors are more pronounced in men than in women, women may be more at risk of progressing to dementia,” Dr. Snyder said. “The findings outline the importance of understanding how the underlying biology, particularly biology that differs in males and females, may be contributing to risk.”
Data on the country and geographical variations highlighted in the study also point to a potential risk influencer, she said.
“Studying geography-specific risk factors is important because it helps us understand the ‘why’ behind geographic differences in dementia risk,” Dr. Snyder said. “This type of collaboration among countries and researchers is essential for us to understand these puzzle pieces.”
Funding for the study was provided by the U.K. Medical Research Council Skills Development Fellowship, Australian National Health and Medical Research Council Investigator Grant, National Institute on Aging, among others. See the original article for full funding sources. Ms. Gong reported no relevant financial conflicts. Dr. Snyder is employed by the Alzheimer’s Association.
A version of this article originally appeared on Medscape.com.
a study suggests.
Prior research has found a higher lifetime dementia risk in women, and one explanation cited has been that women tend to live longer than men.
However, this new analysis of data from nearly 30,000 people in 18 countries found almost no evidence of sex differences in most known risk factors for dementia, including age.
The risk of dementia among women was significantly higher in poorer countries, pointing to economic disadvantages as a possible explanation.
“In general, we found that the greater dementia risk found in women compared to men was more pronounced in poorer countries, which points to the need for greater efforts to narrow the gaps in health disparities between women and men in these countries,” lead investigator Jessica Gong, MSc, a doctoral student at the George Institute for Global Health, Newtown, Australia, told this news organization. “It is likely that socioeconomic factors are potentially more important than biological factors when assessing dementia risk.”
The findings were published online in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Global data
Most previous studies that examined sex differences in dementia risk were conducted in high-income countries, Ms. Gong noted, leaving a gap in the literature on risk in low- and middle-income countries.
To address this issue, researchers conducted an individual participant meta-analysis of 21 studies from the Cohort Studies of Memory in an International Consortium. Data analysis included information on 29,850 people from 18 countries on six continents. None of the participants had dementia at baseline, and the average age was 71.6 years.
Over a median of 4.6 years, incident dementia was reported in 2,089 people, 66% of whom were women.
Overall, women had higher dementia risk (hazard ratio, 1.12; 95% confidence interval, 1.02-1.23) than men, but the rates were highest in low- to middle-income economies (HR, 1.73; P = .03).
Dementia risk in women was higher than in men in 14 countries. Risk was highest in Nigeria, where dementia risk was more than double in women (aHR, 2.11; 95% CI, 1.46-3.04), and lowest in Brazil, where risk was 46% lower in women than in men (aHR, 0.54; 95% CI, 0.29-1.00).
In the United States, dementia risk was 7% higher in women than men (aHR, 1.07; 0.73-1.57).
Similar risk factors
In both women and men, older age, diabetes, depression, hearing impairment, and apo E–epsilon 4 carriage were associated with a greater risk of dementia, and more years of education, higher hip circumference, current alcohol use (vs. never), and high physical activity (vs. none to minimal) were associated with a lower risk of dementia.
Among all these risk factors, sex differences were only significant for longer education and former alcohol use, with both demonstrating a stronger association in men than women.
Global dementia rates are expected to triple over the next 25 years unless steps are taken to reduce risk factors. A 2020 report found that dementia risk could be reduced by addressing 12 modifiable risk factors, including obesity, air pollution, diabetes, social isolation, and hypertension. All of these risk factors are more common in low- to middle-income countries, Ms. Gong noted.
“These findings justify ongoing efforts to support programs to improve sex and gender equity in brain health, particularly in underrepresented and underserved populations, in turn to narrow the gaps within and between country,” Ms. Gong said.
Understanding the puzzle
Commenting on the findings for Medscape Medical News, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, said the findings add to the body of work about sex differences in dementia risk.
“This is an interesting study looking at risk factors for dementia and suggests that, while some risk factors are more pronounced in men than in women, women may be more at risk of progressing to dementia,” Dr. Snyder said. “The findings outline the importance of understanding how the underlying biology, particularly biology that differs in males and females, may be contributing to risk.”
Data on the country and geographical variations highlighted in the study also point to a potential risk influencer, she said.
“Studying geography-specific risk factors is important because it helps us understand the ‘why’ behind geographic differences in dementia risk,” Dr. Snyder said. “This type of collaboration among countries and researchers is essential for us to understand these puzzle pieces.”
Funding for the study was provided by the U.K. Medical Research Council Skills Development Fellowship, Australian National Health and Medical Research Council Investigator Grant, National Institute on Aging, among others. See the original article for full funding sources. Ms. Gong reported no relevant financial conflicts. Dr. Snyder is employed by the Alzheimer’s Association.
A version of this article originally appeared on Medscape.com.
a study suggests.
Prior research has found a higher lifetime dementia risk in women, and one explanation cited has been that women tend to live longer than men.
However, this new analysis of data from nearly 30,000 people in 18 countries found almost no evidence of sex differences in most known risk factors for dementia, including age.
The risk of dementia among women was significantly higher in poorer countries, pointing to economic disadvantages as a possible explanation.
“In general, we found that the greater dementia risk found in women compared to men was more pronounced in poorer countries, which points to the need for greater efforts to narrow the gaps in health disparities between women and men in these countries,” lead investigator Jessica Gong, MSc, a doctoral student at the George Institute for Global Health, Newtown, Australia, told this news organization. “It is likely that socioeconomic factors are potentially more important than biological factors when assessing dementia risk.”
The findings were published online in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
Global data
Most previous studies that examined sex differences in dementia risk were conducted in high-income countries, Ms. Gong noted, leaving a gap in the literature on risk in low- and middle-income countries.
To address this issue, researchers conducted an individual participant meta-analysis of 21 studies from the Cohort Studies of Memory in an International Consortium. Data analysis included information on 29,850 people from 18 countries on six continents. None of the participants had dementia at baseline, and the average age was 71.6 years.
Over a median of 4.6 years, incident dementia was reported in 2,089 people, 66% of whom were women.
Overall, women had higher dementia risk (hazard ratio, 1.12; 95% confidence interval, 1.02-1.23) than men, but the rates were highest in low- to middle-income economies (HR, 1.73; P = .03).
Dementia risk in women was higher than in men in 14 countries. Risk was highest in Nigeria, where dementia risk was more than double in women (aHR, 2.11; 95% CI, 1.46-3.04), and lowest in Brazil, where risk was 46% lower in women than in men (aHR, 0.54; 95% CI, 0.29-1.00).
In the United States, dementia risk was 7% higher in women than men (aHR, 1.07; 0.73-1.57).
Similar risk factors
In both women and men, older age, diabetes, depression, hearing impairment, and apo E–epsilon 4 carriage were associated with a greater risk of dementia, and more years of education, higher hip circumference, current alcohol use (vs. never), and high physical activity (vs. none to minimal) were associated with a lower risk of dementia.
Among all these risk factors, sex differences were only significant for longer education and former alcohol use, with both demonstrating a stronger association in men than women.
Global dementia rates are expected to triple over the next 25 years unless steps are taken to reduce risk factors. A 2020 report found that dementia risk could be reduced by addressing 12 modifiable risk factors, including obesity, air pollution, diabetes, social isolation, and hypertension. All of these risk factors are more common in low- to middle-income countries, Ms. Gong noted.
“These findings justify ongoing efforts to support programs to improve sex and gender equity in brain health, particularly in underrepresented and underserved populations, in turn to narrow the gaps within and between country,” Ms. Gong said.
Understanding the puzzle
Commenting on the findings for Medscape Medical News, Heather Snyder, PhD, Alzheimer’s Association vice president of medical and scientific relations, said the findings add to the body of work about sex differences in dementia risk.
“This is an interesting study looking at risk factors for dementia and suggests that, while some risk factors are more pronounced in men than in women, women may be more at risk of progressing to dementia,” Dr. Snyder said. “The findings outline the importance of understanding how the underlying biology, particularly biology that differs in males and females, may be contributing to risk.”
Data on the country and geographical variations highlighted in the study also point to a potential risk influencer, she said.
“Studying geography-specific risk factors is important because it helps us understand the ‘why’ behind geographic differences in dementia risk,” Dr. Snyder said. “This type of collaboration among countries and researchers is essential for us to understand these puzzle pieces.”
Funding for the study was provided by the U.K. Medical Research Council Skills Development Fellowship, Australian National Health and Medical Research Council Investigator Grant, National Institute on Aging, among others. See the original article for full funding sources. Ms. Gong reported no relevant financial conflicts. Dr. Snyder is employed by the Alzheimer’s Association.
A version of this article originally appeared on Medscape.com.
FROM ALZHEIMER’S & DEMENTIA
Slowing, not stopping, Alzheimer’s a better goal for clinical trials?
and may be a more realistic goal for clinical AD drug trials, a new report suggests.
The report is a yearlong undertaking by an expert work group convened by the Alzheimer’s Association and was prompted, in part, by the fallout from the U.S. Food and Drug Administration’s controversial decision to grant aducanumab (Aduhelm) accelerated approval, which came over the objection of an advisory panel that found the drug was ineffective.
The report’s authors call for a “reframing” of how researchers define “clinically meaningful” in randomized controlled trials (RCTs), noting that it’s time to adjust expectations of outcomes from relatively short clinical trials.
“Without lowering the bar, are we expecting too much from a clinical trial by expecting that unless the disease is halted in its tracks and there’s no progression, we failed at treatment?” the report’s lead author and group leader Ronald C. Petersen, MD, PhD, lead author, chair of the work group, and professor of neurology at the Mayo Clinic, Rochester, Minn., told this news organization.
Interpretations of clinical meaningfulness are used in the drug approval process and in decisions about whether an insurer will cover the cost of treatment, the authors note.
While the report doesn’t provide a consensus definition of clinically meaningful benefit, it does offer a starting point for a conversation about how the phrase should be defined in the context of RCTs for disease-modifying therapies (DMTs) in AD, Dr. Petersen said.
“What we tried to do was to put it into some kind of perspective and at least have people reflect on this: If you’re going to design the perfect drug trial in Alzheimer’s disease, what would it be? We wanted to get people to think about it without digging in their heels for or against,” he added.
The report was published online in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.
A proactive measure
The expert group began its work in January 2022, less than a year after the FDA approved aducanumab. Since the panel began its work, the FDA has approved a second AD drug, lecanemab (Leqembi), and denied accelerated approval of a third medication, donanemab.
“At the time we started this group, we had one approved treatment, and we just knew that there were others on the way, and we needed to be prepared to have this conversation and be more proactive than reactive,” Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association and co-author of the report, said in an interview.
The work group suggests that simply slowing disease progression might be a desired goal for drug trials, especially early on, before cognition and memory are affected.
They also note that a benefit identified during an 18-month clinical trial may ultimately lead to even more meaningful changes over coming years, well beyond the trial’s end.
In addition, the report authors call for the development of better research tools to more accurately assess meaningful change. The Clinical Dementia Rating (CDR) scale is currently the key instrument used as a primary outcome measure in RCTs. However, the report’s authors note that it may not be adequate to measure meaningful change in early-stage disease.
“Developing better tools certainly should be on the radar screen for all of us, because I think we can do better,” Dr. Petersen said. “The CDR, as good as it is and as long as it’s been used in the field, is a pretty blunt instrument, and it’s the result of subjective ratings.”
‘Quality of mind’
Jason Karlawish, MD, professor of medicine, medical ethics, health policy, and neurology at the University of Pennsylvania, Philadelphia, said measuring the actual impact of a drug on a patient’s disease and quality of life has been a hot topic in the AD field for some time, but settling on a definition of “clinically meaningful” that everyone agrees upon will be a challenge.
“I think the idea of ‘clinically meaningful’ is truly a socially constructed idea,” said Dr. Karlawish, co-director of Penn’s Memory Center, who did not work on the report.
“You can come up with objective measures of cognition, but a measure to call something ‘clinically meaningful’ ultimately requires some sort of negotiated social order among clinicians and patients and others who have immediate interest in the health and well-being of the patient.”
Dr. Karlawish added that he’s interested in the conversations the report might prompt and the challenges it could highlight, especially when it comes to how meaningful clinical benefit can be measured, regardless of how it’s defined.
“Hidden in this conversation about clinically meaningful treatments in Alzheimer’s disease is, frankly, not quality of life, but quality of mind,” said Dr. Karlawish. “No measure captures acceptably the very thing that everyone actually cares a lot about and why we view this disease as so dreadful, which is damage to our mind.”
More evidence needed
The development of such tools will take time. What does that mean for drugs already in the pipeline? Members of the work group argue that those trials must move forward at the same time new tools are being created.
“We need to continue to refine, develop better instruments, [and] develop tools that are going to assess the disease in its more subtle features early on, even in the so-called ‘pre-symptomatic’ stage of the disease,” said lead author Dr. Petersen. “We shouldn’t wait for the development of that before intervening if we have a drug that seems to work.”
However, not everyone who agrees with the premise of the report agrees with this position, including Joel S. Perlmutter, MD, professor of neurology, Washington University School of Medicine, St. Louis, who also commented on the report.
As reported by this news organization, Dr. Perlmutter was one of three physicians who resigned from the FDA advisory panel that voted against approving aducanumab after the agency moved forward anyway.
“We have to be careful not to recommend DMTs that we hope will help without strong evidence, especially when potential side effects are not trivial,” Dr. Perlmutter said. “We have to have evidence before making these recommendations so we don’t end up harming people more than helping them.”
The report received no specific funding. Dr. Petersen received consulting fees from Roche, Nestle, Merck, Biogen, Eisai, and Genentech. Full disclosures are included in the original article. Dr. Perlmutter and Dr. Karlawish report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
and may be a more realistic goal for clinical AD drug trials, a new report suggests.
The report is a yearlong undertaking by an expert work group convened by the Alzheimer’s Association and was prompted, in part, by the fallout from the U.S. Food and Drug Administration’s controversial decision to grant aducanumab (Aduhelm) accelerated approval, which came over the objection of an advisory panel that found the drug was ineffective.
The report’s authors call for a “reframing” of how researchers define “clinically meaningful” in randomized controlled trials (RCTs), noting that it’s time to adjust expectations of outcomes from relatively short clinical trials.
“Without lowering the bar, are we expecting too much from a clinical trial by expecting that unless the disease is halted in its tracks and there’s no progression, we failed at treatment?” the report’s lead author and group leader Ronald C. Petersen, MD, PhD, lead author, chair of the work group, and professor of neurology at the Mayo Clinic, Rochester, Minn., told this news organization.
Interpretations of clinical meaningfulness are used in the drug approval process and in decisions about whether an insurer will cover the cost of treatment, the authors note.
While the report doesn’t provide a consensus definition of clinically meaningful benefit, it does offer a starting point for a conversation about how the phrase should be defined in the context of RCTs for disease-modifying therapies (DMTs) in AD, Dr. Petersen said.
“What we tried to do was to put it into some kind of perspective and at least have people reflect on this: If you’re going to design the perfect drug trial in Alzheimer’s disease, what would it be? We wanted to get people to think about it without digging in their heels for or against,” he added.
The report was published online in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.
A proactive measure
The expert group began its work in January 2022, less than a year after the FDA approved aducanumab. Since the panel began its work, the FDA has approved a second AD drug, lecanemab (Leqembi), and denied accelerated approval of a third medication, donanemab.
“At the time we started this group, we had one approved treatment, and we just knew that there were others on the way, and we needed to be prepared to have this conversation and be more proactive than reactive,” Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association and co-author of the report, said in an interview.
The work group suggests that simply slowing disease progression might be a desired goal for drug trials, especially early on, before cognition and memory are affected.
They also note that a benefit identified during an 18-month clinical trial may ultimately lead to even more meaningful changes over coming years, well beyond the trial’s end.
In addition, the report authors call for the development of better research tools to more accurately assess meaningful change. The Clinical Dementia Rating (CDR) scale is currently the key instrument used as a primary outcome measure in RCTs. However, the report’s authors note that it may not be adequate to measure meaningful change in early-stage disease.
“Developing better tools certainly should be on the radar screen for all of us, because I think we can do better,” Dr. Petersen said. “The CDR, as good as it is and as long as it’s been used in the field, is a pretty blunt instrument, and it’s the result of subjective ratings.”
‘Quality of mind’
Jason Karlawish, MD, professor of medicine, medical ethics, health policy, and neurology at the University of Pennsylvania, Philadelphia, said measuring the actual impact of a drug on a patient’s disease and quality of life has been a hot topic in the AD field for some time, but settling on a definition of “clinically meaningful” that everyone agrees upon will be a challenge.
“I think the idea of ‘clinically meaningful’ is truly a socially constructed idea,” said Dr. Karlawish, co-director of Penn’s Memory Center, who did not work on the report.
“You can come up with objective measures of cognition, but a measure to call something ‘clinically meaningful’ ultimately requires some sort of negotiated social order among clinicians and patients and others who have immediate interest in the health and well-being of the patient.”
Dr. Karlawish added that he’s interested in the conversations the report might prompt and the challenges it could highlight, especially when it comes to how meaningful clinical benefit can be measured, regardless of how it’s defined.
“Hidden in this conversation about clinically meaningful treatments in Alzheimer’s disease is, frankly, not quality of life, but quality of mind,” said Dr. Karlawish. “No measure captures acceptably the very thing that everyone actually cares a lot about and why we view this disease as so dreadful, which is damage to our mind.”
More evidence needed
The development of such tools will take time. What does that mean for drugs already in the pipeline? Members of the work group argue that those trials must move forward at the same time new tools are being created.
“We need to continue to refine, develop better instruments, [and] develop tools that are going to assess the disease in its more subtle features early on, even in the so-called ‘pre-symptomatic’ stage of the disease,” said lead author Dr. Petersen. “We shouldn’t wait for the development of that before intervening if we have a drug that seems to work.”
However, not everyone who agrees with the premise of the report agrees with this position, including Joel S. Perlmutter, MD, professor of neurology, Washington University School of Medicine, St. Louis, who also commented on the report.
As reported by this news organization, Dr. Perlmutter was one of three physicians who resigned from the FDA advisory panel that voted against approving aducanumab after the agency moved forward anyway.
“We have to be careful not to recommend DMTs that we hope will help without strong evidence, especially when potential side effects are not trivial,” Dr. Perlmutter said. “We have to have evidence before making these recommendations so we don’t end up harming people more than helping them.”
The report received no specific funding. Dr. Petersen received consulting fees from Roche, Nestle, Merck, Biogen, Eisai, and Genentech. Full disclosures are included in the original article. Dr. Perlmutter and Dr. Karlawish report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
and may be a more realistic goal for clinical AD drug trials, a new report suggests.
The report is a yearlong undertaking by an expert work group convened by the Alzheimer’s Association and was prompted, in part, by the fallout from the U.S. Food and Drug Administration’s controversial decision to grant aducanumab (Aduhelm) accelerated approval, which came over the objection of an advisory panel that found the drug was ineffective.
The report’s authors call for a “reframing” of how researchers define “clinically meaningful” in randomized controlled trials (RCTs), noting that it’s time to adjust expectations of outcomes from relatively short clinical trials.
“Without lowering the bar, are we expecting too much from a clinical trial by expecting that unless the disease is halted in its tracks and there’s no progression, we failed at treatment?” the report’s lead author and group leader Ronald C. Petersen, MD, PhD, lead author, chair of the work group, and professor of neurology at the Mayo Clinic, Rochester, Minn., told this news organization.
Interpretations of clinical meaningfulness are used in the drug approval process and in decisions about whether an insurer will cover the cost of treatment, the authors note.
While the report doesn’t provide a consensus definition of clinically meaningful benefit, it does offer a starting point for a conversation about how the phrase should be defined in the context of RCTs for disease-modifying therapies (DMTs) in AD, Dr. Petersen said.
“What we tried to do was to put it into some kind of perspective and at least have people reflect on this: If you’re going to design the perfect drug trial in Alzheimer’s disease, what would it be? We wanted to get people to think about it without digging in their heels for or against,” he added.
The report was published online in Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.
A proactive measure
The expert group began its work in January 2022, less than a year after the FDA approved aducanumab. Since the panel began its work, the FDA has approved a second AD drug, lecanemab (Leqembi), and denied accelerated approval of a third medication, donanemab.
“At the time we started this group, we had one approved treatment, and we just knew that there were others on the way, and we needed to be prepared to have this conversation and be more proactive than reactive,” Christopher Weber, PhD, director of global science initiatives for the Alzheimer’s Association and co-author of the report, said in an interview.
The work group suggests that simply slowing disease progression might be a desired goal for drug trials, especially early on, before cognition and memory are affected.
They also note that a benefit identified during an 18-month clinical trial may ultimately lead to even more meaningful changes over coming years, well beyond the trial’s end.
In addition, the report authors call for the development of better research tools to more accurately assess meaningful change. The Clinical Dementia Rating (CDR) scale is currently the key instrument used as a primary outcome measure in RCTs. However, the report’s authors note that it may not be adequate to measure meaningful change in early-stage disease.
“Developing better tools certainly should be on the radar screen for all of us, because I think we can do better,” Dr. Petersen said. “The CDR, as good as it is and as long as it’s been used in the field, is a pretty blunt instrument, and it’s the result of subjective ratings.”
‘Quality of mind’
Jason Karlawish, MD, professor of medicine, medical ethics, health policy, and neurology at the University of Pennsylvania, Philadelphia, said measuring the actual impact of a drug on a patient’s disease and quality of life has been a hot topic in the AD field for some time, but settling on a definition of “clinically meaningful” that everyone agrees upon will be a challenge.
“I think the idea of ‘clinically meaningful’ is truly a socially constructed idea,” said Dr. Karlawish, co-director of Penn’s Memory Center, who did not work on the report.
“You can come up with objective measures of cognition, but a measure to call something ‘clinically meaningful’ ultimately requires some sort of negotiated social order among clinicians and patients and others who have immediate interest in the health and well-being of the patient.”
Dr. Karlawish added that he’s interested in the conversations the report might prompt and the challenges it could highlight, especially when it comes to how meaningful clinical benefit can be measured, regardless of how it’s defined.
“Hidden in this conversation about clinically meaningful treatments in Alzheimer’s disease is, frankly, not quality of life, but quality of mind,” said Dr. Karlawish. “No measure captures acceptably the very thing that everyone actually cares a lot about and why we view this disease as so dreadful, which is damage to our mind.”
More evidence needed
The development of such tools will take time. What does that mean for drugs already in the pipeline? Members of the work group argue that those trials must move forward at the same time new tools are being created.
“We need to continue to refine, develop better instruments, [and] develop tools that are going to assess the disease in its more subtle features early on, even in the so-called ‘pre-symptomatic’ stage of the disease,” said lead author Dr. Petersen. “We shouldn’t wait for the development of that before intervening if we have a drug that seems to work.”
However, not everyone who agrees with the premise of the report agrees with this position, including Joel S. Perlmutter, MD, professor of neurology, Washington University School of Medicine, St. Louis, who also commented on the report.
As reported by this news organization, Dr. Perlmutter was one of three physicians who resigned from the FDA advisory panel that voted against approving aducanumab after the agency moved forward anyway.
“We have to be careful not to recommend DMTs that we hope will help without strong evidence, especially when potential side effects are not trivial,” Dr. Perlmutter said. “We have to have evidence before making these recommendations so we don’t end up harming people more than helping them.”
The report received no specific funding. Dr. Petersen received consulting fees from Roche, Nestle, Merck, Biogen, Eisai, and Genentech. Full disclosures are included in the original article. Dr. Perlmutter and Dr. Karlawish report no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
FROM ALZHEIMER’S AND DEMENTIA
Time for a national ketamine registry, experts say
The number of ketamine clinics has risen dramatically, with little to no oversight. Prescriptions are being written by providers who lack training in safe ketamine use and online startups are selling the drug for at-home use, taking advantage of a temporary federal regulation that makes it easier to prescribe controlled substances without an in-person patient assessment.
All of this comes at a time when recreational use of ketamine, known on the street as “Special K,” is rising, and reports to poison control centers and drug seizures by the U.S. Drug Enforcement Agency (DEA) are climbing.
In a scenario where enthusiasm for the drug is larger than the body of evidence supporting its clinical use, support is growing for the creation of a ketamine registry to collect data on dosage, treatment frequency, adverse events, and long-term outcomes in patients receiving the therapy for depression and other mental health conditions.
“In the past, there was this question of whether a registry was even needed,” said Gerard Sanacora, MD, PhD, a professor of psychiatry at Yale University, New Haven, Conn., who has pushed for a registry for more than 5 years.
“Now, not only are people being treated with this in large numbers, but it’s also started to push the envelope with at-home dosing,” Dr. Sanacora said in an interview. “It’s come to the point that everybody agrees we do need some way to track it.”
An idea whose time has come
Interest in ketamine’s antidepressant effects has grown since 2000, when a small study suggested the drug rapidly improved depressive symptoms. Research now suggests ketamine reduces symptoms in patients with treatment-resistant depression (TRD).
Studies linking ketamine to relief of depressive symptoms are small and mostly retrospective, and none has offered longitudinal information on long-term outcomes, including side effects and the risk of addiction.
Still, clinicians desperate to help the one-third of patients with major depression who fail to respond to first-line treatments often prescribe the drug anyway.
In 2017, Dr. Sanacora, who also is director of the Yale Depression Research Program at the Yale School of Medicine, was the lead author of a consensus statement that sought to help physicians administer ketamine safely and appropriately in patients with severe depression and other mood disorders.
In that paper, Dr. Sanacora and his coauthors advocated for the creation of a ketamine registry. Such a database, they argued, would provide much-needed data for large, long-term studies, which could be used to develop treatment guidelines, certification programs, and possibly even accreditation standards for providers. Meanwhile, researchers and clinicians in the United Kingdom were also calling for a ketamine registry.
While there seemed to be wide consensus that such a registry was needed, there was no clear path to creating one and no clear line to an agency that would take responsibility for maintaining it.
Because the registry wouldn’t be tied to a drug indication, Dr. Sanacora was told the U.S. Food and Drug Administration wouldn’t take it on. The project also fell outside the purview of the U.S. Department of Health & Human Services, the National Institute of Mental Health (NIMH), and the DEA.
“I haven’t met anybody who has said this is a terrible idea, but nobody seems to have a clear mechanism of doing it, and it doesn’t seem to fall directly under anybody’s jurisdiction,” Dr. Sanacora said.
Dr. Sanacora and other ketamine registry advocates were met with an endless stream of questions. Who would pay for it? How would they get providers to participate? Who would run it and how would the data be shared? The barriers to implementation seemed insurmountable.
A changing landscape
Five years later, these barriers remain. However, advocates note support for a registry is growing, due in large part to a series of developments over the past 6 years that they believe have altered the ketamine landscape.
Chief among these was the 2019 FDA approval of esketamine, a nasal formulation of ketamine, for the treatment of resistant depression. The drug’s indication was expanded in 2020 to include major depressive disorder and acute suicidal ideation or behavior. The drug is only available through a restricted distribution system – the Spravato Risk Evaluation and Mitigation Strategy (REMS) – because of the risk for serious adverse events, including sedation and dissociation, as well as the potential for abuse or misuse.
A sharp increase in the number of ketamine prescribers and clinics has also heightened interest in a ketamine registry. In the last year alone, membership in the American Society of Ketamine Physicians, Psychotherapists, and Practitioners (ASKP) – a nonprofit trade organization for clinicians who prescribe ketamine for mental health disorders and pain conditions – swelled from 300 individual providers to more than 500.
The number of ketamine clinics in the United States has also grown exponentially and is estimated to be anywhere from 500 to 750. A spokesperson with HHS said such clinics are not regulated by the department or any other federal agency but instead are subject to oversight by individual states.
Although recreational use of ketamine remains low overall, there are signs that illicit use is rising, including an increase in DEA seizures of illicit ketamine and reports of ketamine-related poisonings to the nation’s poison control centers. Data on recreational use is spotty, at best. The Centers for Disease Control and Prevention National Vital Statistics System – the primary source of information on drug-related mortality in the United States – does not report on ketamine.
At-home ketamine use soars
Perhaps the most significant development came in March 2020 in the early days of the pandemic. To ease access to therapeutic schedule II-V controlled substances, the DEA issued a waiver that relaxed restrictions in the Ryan Haight Act, legislation that requires that patients be seen at least once in person before receiving a prescription for this class of drugs.
Under the waiver, DEA-registered practitioners are allowed to prescribe these substances – including ketamine, a schedule III substance – via telemedicine, without an in-person exam.
Startup companies cropped up almost overnight to prescribe oral ketamine online for at-home use, with almost no oversight. A spokesperson with the DEA told this news organization that the agency is working to make these “temporary” regulations permanent.
Under the relaxed DEA guidelines, a prescriber only needs to have a DEA license to dispense a ketamine prescription. An alarming number of clinics and online startups are staffed by individuals with no training in ketamine use and, in some cases, no formal mental health training at all, said Lisa Harding, MD, vice president of ASKP and a clinical instructor of psychiatry at Yale School of Medicine.
“The biggest problem is not the ketamine itself, it’s that the majority of practitioners are not psychiatrists, so they don’t have mental health training,” Dr. Harding said. “The fact that an untrained person, any practitioner with no mental health training, can administer this treatment once they have a state license to give ketamine ... then how are you protecting the patients?”
That question prompted ASKP to create the first known program to train psychiatrists, and other qualified mental health practitioners who prescribe ketamine, how to use the drug safely and effectively. The program, scheduled for June, will also include discussion by leaders in the field about how a ketamine registry might address these and other patient safety concerns.
“Nobody is really investigating the standard to which these clinics and online companies should be held, and I think a registry would help with that,” she said in an interview.
The path forward
While ASKP leadership supports the idea of a ketamine registry, Dr. Harding said the organization would need assurances the effort would not create a barrier to treatment.
“It will take somebody bringing all of us to the table and figuring that out,” Dr. Harding said.
Conversations like that with stakeholders would be one of the first steps toward creating a registry, Dr. Sanacora said.
“The more complicated we make this registry, the less compliance we’re going to get,” Dr. Sanacora said. “Our first step is to understand the major impediments and figure out how we can make this easier for people.”
Ideally, the registry would take advantage of existing data-collection tools, such as electronic health records (EHR), and include some sort of patient data entry mechanism, Dr. Sanacora said. The effort will also require skilled biostatisticians and a database system that is easy to manage.
And, of course, the registry will need a large number of patients to gather sufficient data to conduct high-quality research to develop treatment guidelines, training, and accreditation standards. A good target would be about 10,000 patients, Dr. Sanacora said.
All of this requires funding, which is the first hurdle registry advocates must clear. Dr. Sanacora is working on identifying funding sources and said that after working on this for years, he is hopeful that progress can be made.
“I had reached a point where it felt like there was no path forward,” Dr. Sanacora said. “But now I have renewed optimism that something can be done. And something does need to be done, largely for public health reasons but also to optimize the treatment.”
A version of this article first appeared on Medscape.com.
The number of ketamine clinics has risen dramatically, with little to no oversight. Prescriptions are being written by providers who lack training in safe ketamine use and online startups are selling the drug for at-home use, taking advantage of a temporary federal regulation that makes it easier to prescribe controlled substances without an in-person patient assessment.
All of this comes at a time when recreational use of ketamine, known on the street as “Special K,” is rising, and reports to poison control centers and drug seizures by the U.S. Drug Enforcement Agency (DEA) are climbing.
In a scenario where enthusiasm for the drug is larger than the body of evidence supporting its clinical use, support is growing for the creation of a ketamine registry to collect data on dosage, treatment frequency, adverse events, and long-term outcomes in patients receiving the therapy for depression and other mental health conditions.
“In the past, there was this question of whether a registry was even needed,” said Gerard Sanacora, MD, PhD, a professor of psychiatry at Yale University, New Haven, Conn., who has pushed for a registry for more than 5 years.
“Now, not only are people being treated with this in large numbers, but it’s also started to push the envelope with at-home dosing,” Dr. Sanacora said in an interview. “It’s come to the point that everybody agrees we do need some way to track it.”
An idea whose time has come
Interest in ketamine’s antidepressant effects has grown since 2000, when a small study suggested the drug rapidly improved depressive symptoms. Research now suggests ketamine reduces symptoms in patients with treatment-resistant depression (TRD).
Studies linking ketamine to relief of depressive symptoms are small and mostly retrospective, and none has offered longitudinal information on long-term outcomes, including side effects and the risk of addiction.
Still, clinicians desperate to help the one-third of patients with major depression who fail to respond to first-line treatments often prescribe the drug anyway.
In 2017, Dr. Sanacora, who also is director of the Yale Depression Research Program at the Yale School of Medicine, was the lead author of a consensus statement that sought to help physicians administer ketamine safely and appropriately in patients with severe depression and other mood disorders.
In that paper, Dr. Sanacora and his coauthors advocated for the creation of a ketamine registry. Such a database, they argued, would provide much-needed data for large, long-term studies, which could be used to develop treatment guidelines, certification programs, and possibly even accreditation standards for providers. Meanwhile, researchers and clinicians in the United Kingdom were also calling for a ketamine registry.
While there seemed to be wide consensus that such a registry was needed, there was no clear path to creating one and no clear line to an agency that would take responsibility for maintaining it.
Because the registry wouldn’t be tied to a drug indication, Dr. Sanacora was told the U.S. Food and Drug Administration wouldn’t take it on. The project also fell outside the purview of the U.S. Department of Health & Human Services, the National Institute of Mental Health (NIMH), and the DEA.
“I haven’t met anybody who has said this is a terrible idea, but nobody seems to have a clear mechanism of doing it, and it doesn’t seem to fall directly under anybody’s jurisdiction,” Dr. Sanacora said.
Dr. Sanacora and other ketamine registry advocates were met with an endless stream of questions. Who would pay for it? How would they get providers to participate? Who would run it and how would the data be shared? The barriers to implementation seemed insurmountable.
A changing landscape
Five years later, these barriers remain. However, advocates note support for a registry is growing, due in large part to a series of developments over the past 6 years that they believe have altered the ketamine landscape.
Chief among these was the 2019 FDA approval of esketamine, a nasal formulation of ketamine, for the treatment of resistant depression. The drug’s indication was expanded in 2020 to include major depressive disorder and acute suicidal ideation or behavior. The drug is only available through a restricted distribution system – the Spravato Risk Evaluation and Mitigation Strategy (REMS) – because of the risk for serious adverse events, including sedation and dissociation, as well as the potential for abuse or misuse.
A sharp increase in the number of ketamine prescribers and clinics has also heightened interest in a ketamine registry. In the last year alone, membership in the American Society of Ketamine Physicians, Psychotherapists, and Practitioners (ASKP) – a nonprofit trade organization for clinicians who prescribe ketamine for mental health disorders and pain conditions – swelled from 300 individual providers to more than 500.
The number of ketamine clinics in the United States has also grown exponentially and is estimated to be anywhere from 500 to 750. A spokesperson with HHS said such clinics are not regulated by the department or any other federal agency but instead are subject to oversight by individual states.
Although recreational use of ketamine remains low overall, there are signs that illicit use is rising, including an increase in DEA seizures of illicit ketamine and reports of ketamine-related poisonings to the nation’s poison control centers. Data on recreational use is spotty, at best. The Centers for Disease Control and Prevention National Vital Statistics System – the primary source of information on drug-related mortality in the United States – does not report on ketamine.
At-home ketamine use soars
Perhaps the most significant development came in March 2020 in the early days of the pandemic. To ease access to therapeutic schedule II-V controlled substances, the DEA issued a waiver that relaxed restrictions in the Ryan Haight Act, legislation that requires that patients be seen at least once in person before receiving a prescription for this class of drugs.
Under the waiver, DEA-registered practitioners are allowed to prescribe these substances – including ketamine, a schedule III substance – via telemedicine, without an in-person exam.
Startup companies cropped up almost overnight to prescribe oral ketamine online for at-home use, with almost no oversight. A spokesperson with the DEA told this news organization that the agency is working to make these “temporary” regulations permanent.
Under the relaxed DEA guidelines, a prescriber only needs to have a DEA license to dispense a ketamine prescription. An alarming number of clinics and online startups are staffed by individuals with no training in ketamine use and, in some cases, no formal mental health training at all, said Lisa Harding, MD, vice president of ASKP and a clinical instructor of psychiatry at Yale School of Medicine.
“The biggest problem is not the ketamine itself, it’s that the majority of practitioners are not psychiatrists, so they don’t have mental health training,” Dr. Harding said. “The fact that an untrained person, any practitioner with no mental health training, can administer this treatment once they have a state license to give ketamine ... then how are you protecting the patients?”
That question prompted ASKP to create the first known program to train psychiatrists, and other qualified mental health practitioners who prescribe ketamine, how to use the drug safely and effectively. The program, scheduled for June, will also include discussion by leaders in the field about how a ketamine registry might address these and other patient safety concerns.
“Nobody is really investigating the standard to which these clinics and online companies should be held, and I think a registry would help with that,” she said in an interview.
The path forward
While ASKP leadership supports the idea of a ketamine registry, Dr. Harding said the organization would need assurances the effort would not create a barrier to treatment.
“It will take somebody bringing all of us to the table and figuring that out,” Dr. Harding said.
Conversations like that with stakeholders would be one of the first steps toward creating a registry, Dr. Sanacora said.
“The more complicated we make this registry, the less compliance we’re going to get,” Dr. Sanacora said. “Our first step is to understand the major impediments and figure out how we can make this easier for people.”
Ideally, the registry would take advantage of existing data-collection tools, such as electronic health records (EHR), and include some sort of patient data entry mechanism, Dr. Sanacora said. The effort will also require skilled biostatisticians and a database system that is easy to manage.
And, of course, the registry will need a large number of patients to gather sufficient data to conduct high-quality research to develop treatment guidelines, training, and accreditation standards. A good target would be about 10,000 patients, Dr. Sanacora said.
All of this requires funding, which is the first hurdle registry advocates must clear. Dr. Sanacora is working on identifying funding sources and said that after working on this for years, he is hopeful that progress can be made.
“I had reached a point where it felt like there was no path forward,” Dr. Sanacora said. “But now I have renewed optimism that something can be done. And something does need to be done, largely for public health reasons but also to optimize the treatment.”
A version of this article first appeared on Medscape.com.
The number of ketamine clinics has risen dramatically, with little to no oversight. Prescriptions are being written by providers who lack training in safe ketamine use and online startups are selling the drug for at-home use, taking advantage of a temporary federal regulation that makes it easier to prescribe controlled substances without an in-person patient assessment.
All of this comes at a time when recreational use of ketamine, known on the street as “Special K,” is rising, and reports to poison control centers and drug seizures by the U.S. Drug Enforcement Agency (DEA) are climbing.
In a scenario where enthusiasm for the drug is larger than the body of evidence supporting its clinical use, support is growing for the creation of a ketamine registry to collect data on dosage, treatment frequency, adverse events, and long-term outcomes in patients receiving the therapy for depression and other mental health conditions.
“In the past, there was this question of whether a registry was even needed,” said Gerard Sanacora, MD, PhD, a professor of psychiatry at Yale University, New Haven, Conn., who has pushed for a registry for more than 5 years.
“Now, not only are people being treated with this in large numbers, but it’s also started to push the envelope with at-home dosing,” Dr. Sanacora said in an interview. “It’s come to the point that everybody agrees we do need some way to track it.”
An idea whose time has come
Interest in ketamine’s antidepressant effects has grown since 2000, when a small study suggested the drug rapidly improved depressive symptoms. Research now suggests ketamine reduces symptoms in patients with treatment-resistant depression (TRD).
Studies linking ketamine to relief of depressive symptoms are small and mostly retrospective, and none has offered longitudinal information on long-term outcomes, including side effects and the risk of addiction.
Still, clinicians desperate to help the one-third of patients with major depression who fail to respond to first-line treatments often prescribe the drug anyway.
In 2017, Dr. Sanacora, who also is director of the Yale Depression Research Program at the Yale School of Medicine, was the lead author of a consensus statement that sought to help physicians administer ketamine safely and appropriately in patients with severe depression and other mood disorders.
In that paper, Dr. Sanacora and his coauthors advocated for the creation of a ketamine registry. Such a database, they argued, would provide much-needed data for large, long-term studies, which could be used to develop treatment guidelines, certification programs, and possibly even accreditation standards for providers. Meanwhile, researchers and clinicians in the United Kingdom were also calling for a ketamine registry.
While there seemed to be wide consensus that such a registry was needed, there was no clear path to creating one and no clear line to an agency that would take responsibility for maintaining it.
Because the registry wouldn’t be tied to a drug indication, Dr. Sanacora was told the U.S. Food and Drug Administration wouldn’t take it on. The project also fell outside the purview of the U.S. Department of Health & Human Services, the National Institute of Mental Health (NIMH), and the DEA.
“I haven’t met anybody who has said this is a terrible idea, but nobody seems to have a clear mechanism of doing it, and it doesn’t seem to fall directly under anybody’s jurisdiction,” Dr. Sanacora said.
Dr. Sanacora and other ketamine registry advocates were met with an endless stream of questions. Who would pay for it? How would they get providers to participate? Who would run it and how would the data be shared? The barriers to implementation seemed insurmountable.
A changing landscape
Five years later, these barriers remain. However, advocates note support for a registry is growing, due in large part to a series of developments over the past 6 years that they believe have altered the ketamine landscape.
Chief among these was the 2019 FDA approval of esketamine, a nasal formulation of ketamine, for the treatment of resistant depression. The drug’s indication was expanded in 2020 to include major depressive disorder and acute suicidal ideation or behavior. The drug is only available through a restricted distribution system – the Spravato Risk Evaluation and Mitigation Strategy (REMS) – because of the risk for serious adverse events, including sedation and dissociation, as well as the potential for abuse or misuse.
A sharp increase in the number of ketamine prescribers and clinics has also heightened interest in a ketamine registry. In the last year alone, membership in the American Society of Ketamine Physicians, Psychotherapists, and Practitioners (ASKP) – a nonprofit trade organization for clinicians who prescribe ketamine for mental health disorders and pain conditions – swelled from 300 individual providers to more than 500.
The number of ketamine clinics in the United States has also grown exponentially and is estimated to be anywhere from 500 to 750. A spokesperson with HHS said such clinics are not regulated by the department or any other federal agency but instead are subject to oversight by individual states.
Although recreational use of ketamine remains low overall, there are signs that illicit use is rising, including an increase in DEA seizures of illicit ketamine and reports of ketamine-related poisonings to the nation’s poison control centers. Data on recreational use is spotty, at best. The Centers for Disease Control and Prevention National Vital Statistics System – the primary source of information on drug-related mortality in the United States – does not report on ketamine.
At-home ketamine use soars
Perhaps the most significant development came in March 2020 in the early days of the pandemic. To ease access to therapeutic schedule II-V controlled substances, the DEA issued a waiver that relaxed restrictions in the Ryan Haight Act, legislation that requires that patients be seen at least once in person before receiving a prescription for this class of drugs.
Under the waiver, DEA-registered practitioners are allowed to prescribe these substances – including ketamine, a schedule III substance – via telemedicine, without an in-person exam.
Startup companies cropped up almost overnight to prescribe oral ketamine online for at-home use, with almost no oversight. A spokesperson with the DEA told this news organization that the agency is working to make these “temporary” regulations permanent.
Under the relaxed DEA guidelines, a prescriber only needs to have a DEA license to dispense a ketamine prescription. An alarming number of clinics and online startups are staffed by individuals with no training in ketamine use and, in some cases, no formal mental health training at all, said Lisa Harding, MD, vice president of ASKP and a clinical instructor of psychiatry at Yale School of Medicine.
“The biggest problem is not the ketamine itself, it’s that the majority of practitioners are not psychiatrists, so they don’t have mental health training,” Dr. Harding said. “The fact that an untrained person, any practitioner with no mental health training, can administer this treatment once they have a state license to give ketamine ... then how are you protecting the patients?”
That question prompted ASKP to create the first known program to train psychiatrists, and other qualified mental health practitioners who prescribe ketamine, how to use the drug safely and effectively. The program, scheduled for June, will also include discussion by leaders in the field about how a ketamine registry might address these and other patient safety concerns.
“Nobody is really investigating the standard to which these clinics and online companies should be held, and I think a registry would help with that,” she said in an interview.
The path forward
While ASKP leadership supports the idea of a ketamine registry, Dr. Harding said the organization would need assurances the effort would not create a barrier to treatment.
“It will take somebody bringing all of us to the table and figuring that out,” Dr. Harding said.
Conversations like that with stakeholders would be one of the first steps toward creating a registry, Dr. Sanacora said.
“The more complicated we make this registry, the less compliance we’re going to get,” Dr. Sanacora said. “Our first step is to understand the major impediments and figure out how we can make this easier for people.”
Ideally, the registry would take advantage of existing data-collection tools, such as electronic health records (EHR), and include some sort of patient data entry mechanism, Dr. Sanacora said. The effort will also require skilled biostatisticians and a database system that is easy to manage.
And, of course, the registry will need a large number of patients to gather sufficient data to conduct high-quality research to develop treatment guidelines, training, and accreditation standards. A good target would be about 10,000 patients, Dr. Sanacora said.
All of this requires funding, which is the first hurdle registry advocates must clear. Dr. Sanacora is working on identifying funding sources and said that after working on this for years, he is hopeful that progress can be made.
“I had reached a point where it felt like there was no path forward,” Dr. Sanacora said. “But now I have renewed optimism that something can be done. And something does need to be done, largely for public health reasons but also to optimize the treatment.”
A version of this article first appeared on Medscape.com.
Unexpected link between light drinking and dementia risk
new research suggests.
Investigators assessed dementia risk using changes in alcohol consumption over a 2-year period in nearly 4 million people in South Korea. After about 7 years, dementia was 21% less likely in mild drinkers and 17% less likely in moderate drinkers. Heavy drinking was linked to an 8% increased risk.
Other studies of the relationship between alcohol and dementia have yielded mixed results, and this study does little to clear those murky waters. Nor do the results mean that drinking is recommended, the investigators note.
But the study does offer new information on how risk changes over time as people change their drinking habits, lead investigator Keun Hye Jeon, MD, assistant professor of family medicine at Cha Gumi Medical Center at Cha University, Gumi, South Korea, told this news organization.
“Although numerous studies have shown a relationship between alcohol consumption and dementia, there is a paucity of understanding as to how the incidence of dementia changes with changes in drinking habits,” Dr. Jeon said.
“By measuring alcohol consumption at two time points, we were able to study the relationship between reducing, ceasing, maintaining, and increasing alcohol consumption and incident dementia,” he added.
The findings were published online in JAMA Network Open.
Tracking drinking habits
Researchers analyzed data from nearly 4 million individuals aged 40 years and older in the Korean National Health Insurance Service who completed questionnaires and underwent physical exams in 2009 and 2011.
Study participants completed questionnaires on their drinking habits and were assigned to one of five groups according to change in alcohol consumption during the study period. These groups consisted of sustained nondrinkers; those who stopped drinking (quitters); those who reduced their consumption of alcohol but did not stop drinking (reducers); those who maintained the same level of consumption (sustainers); and those who increased their level of consumption (increasers).
A standard drink in the United States contains 14 g of alcohol. For this study, mild drinking was defined as less than 15 g/day, or one drink; moderate consumption as 15-29.9 g/day, or one to two drinks; and heavy drinking as 30 g/day or more, or three or more drinks.
At baseline, 54.8% of participants were nondrinkers, 26.7% were mild drinkers, 11.0% were moderate drinkers, and 7.5% were heavy drinkers.
From 2009 to 2011, 24.2% of mild drinkers, 8.4% of moderate drinkers, and 7.6% of heavy drinkers became quitters. In the same period, 13.9% of nondrinkers, 16.1% of mild drinkers, and 17.4% of moderate drinkers increased their drinking level.
After a mean follow-up of 6.3 years, 2.5% of participants were diagnosed with dementia, 2.0% with Alzheimer’s disease, and 0.3% with vascular dementia.
Unexpected finding
Compared with consistently not drinking, mild and moderate alcohol consumption was associated with a 21% (adjust hazard ratio, 0.79; 95% confidence interval, 0.77-0.81) and 17% (aHR, 0.83; 95% CI, 0.79-0.88) decreased risk for dementia, respectively.
Heavy drinking was linked to an 8% increased risk (aHR, 1.08; 95% CI, 1.03-1.12).
Similar associations were found between alcohol consumption and risk for Alzheimer’s disease and vascular dementia.
Reducing drinking habits from heavy to moderate led to a reduction in risk for dementia and Alzheimer’s, and increasing drinking levels led to an increase in risk for both conditions.
But when the researchers analyzed dementia risk for nondrinkers who began drinking at mild levels during the study period, they found something unexpected – the risk in this group decreased by 7% for dementia (aHR, 0.93; 95% CI, 0.90-0.96) and by 8% for Alzheimer’s (aHR, 0.92; 95% CI, 0.89-0.95), compared with sustained mild drinkers.
“Our study showed that initiation of mild alcohol consumption leads to a reduced risk of all-cause dementia and Alzheimer’s disease, which has never been reported in previous studies,” Dr. Jeon said.
However, Dr. Jeon was quick to point out that this doesn’t mean that people who don’t drink should start.
Previous studies have shown that heavy alcohol use can triple an individual’s dementia risk, while other studies have shown that no amount of alcohol consumption is good for the brain.
“None of the existing health guidelines recommend starting alcohol drinking,” Dr. Jeon said. “Our findings regarding an initiation of mild alcohol consumption cannot be directly translated into clinical recommendations,” but the findings do warrant additional study, he added.
Risks persist
Commenting on the findings, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association in Chicago, agrees.
“While this study is interesting, and this topic deserves further study, no one should drink alcohol as a method of reducing risk of Alzheimer’s disease or other dementia based on this study,” said Dr. Griffin, who was not part of the study.
The exact tipping point in alcohol consumption that can lead to problems with cognition or increased dementia risk is unknown, Dr. Griffin said. Nor do researchers understand why mild drinking may have a protective effect.
“We do know, however, that excessive alcohol consumption has negative effects on heart health and general health, which can lead to problems with brain function,” he said. “Clinicians should have discussions with their patients around their alcohol consumption patterns and the risks associated with drinking in excess, including potential damage to their cognition.”
Funding for the study was not disclosed. Dr. Jeon and Dr. Griffin report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Investigators assessed dementia risk using changes in alcohol consumption over a 2-year period in nearly 4 million people in South Korea. After about 7 years, dementia was 21% less likely in mild drinkers and 17% less likely in moderate drinkers. Heavy drinking was linked to an 8% increased risk.
Other studies of the relationship between alcohol and dementia have yielded mixed results, and this study does little to clear those murky waters. Nor do the results mean that drinking is recommended, the investigators note.
But the study does offer new information on how risk changes over time as people change their drinking habits, lead investigator Keun Hye Jeon, MD, assistant professor of family medicine at Cha Gumi Medical Center at Cha University, Gumi, South Korea, told this news organization.
“Although numerous studies have shown a relationship between alcohol consumption and dementia, there is a paucity of understanding as to how the incidence of dementia changes with changes in drinking habits,” Dr. Jeon said.
“By measuring alcohol consumption at two time points, we were able to study the relationship between reducing, ceasing, maintaining, and increasing alcohol consumption and incident dementia,” he added.
The findings were published online in JAMA Network Open.
Tracking drinking habits
Researchers analyzed data from nearly 4 million individuals aged 40 years and older in the Korean National Health Insurance Service who completed questionnaires and underwent physical exams in 2009 and 2011.
Study participants completed questionnaires on their drinking habits and were assigned to one of five groups according to change in alcohol consumption during the study period. These groups consisted of sustained nondrinkers; those who stopped drinking (quitters); those who reduced their consumption of alcohol but did not stop drinking (reducers); those who maintained the same level of consumption (sustainers); and those who increased their level of consumption (increasers).
A standard drink in the United States contains 14 g of alcohol. For this study, mild drinking was defined as less than 15 g/day, or one drink; moderate consumption as 15-29.9 g/day, or one to two drinks; and heavy drinking as 30 g/day or more, or three or more drinks.
At baseline, 54.8% of participants were nondrinkers, 26.7% were mild drinkers, 11.0% were moderate drinkers, and 7.5% were heavy drinkers.
From 2009 to 2011, 24.2% of mild drinkers, 8.4% of moderate drinkers, and 7.6% of heavy drinkers became quitters. In the same period, 13.9% of nondrinkers, 16.1% of mild drinkers, and 17.4% of moderate drinkers increased their drinking level.
After a mean follow-up of 6.3 years, 2.5% of participants were diagnosed with dementia, 2.0% with Alzheimer’s disease, and 0.3% with vascular dementia.
Unexpected finding
Compared with consistently not drinking, mild and moderate alcohol consumption was associated with a 21% (adjust hazard ratio, 0.79; 95% confidence interval, 0.77-0.81) and 17% (aHR, 0.83; 95% CI, 0.79-0.88) decreased risk for dementia, respectively.
Heavy drinking was linked to an 8% increased risk (aHR, 1.08; 95% CI, 1.03-1.12).
Similar associations were found between alcohol consumption and risk for Alzheimer’s disease and vascular dementia.
Reducing drinking habits from heavy to moderate led to a reduction in risk for dementia and Alzheimer’s, and increasing drinking levels led to an increase in risk for both conditions.
But when the researchers analyzed dementia risk for nondrinkers who began drinking at mild levels during the study period, they found something unexpected – the risk in this group decreased by 7% for dementia (aHR, 0.93; 95% CI, 0.90-0.96) and by 8% for Alzheimer’s (aHR, 0.92; 95% CI, 0.89-0.95), compared with sustained mild drinkers.
“Our study showed that initiation of mild alcohol consumption leads to a reduced risk of all-cause dementia and Alzheimer’s disease, which has never been reported in previous studies,” Dr. Jeon said.
However, Dr. Jeon was quick to point out that this doesn’t mean that people who don’t drink should start.
Previous studies have shown that heavy alcohol use can triple an individual’s dementia risk, while other studies have shown that no amount of alcohol consumption is good for the brain.
“None of the existing health guidelines recommend starting alcohol drinking,” Dr. Jeon said. “Our findings regarding an initiation of mild alcohol consumption cannot be directly translated into clinical recommendations,” but the findings do warrant additional study, he added.
Risks persist
Commenting on the findings, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association in Chicago, agrees.
“While this study is interesting, and this topic deserves further study, no one should drink alcohol as a method of reducing risk of Alzheimer’s disease or other dementia based on this study,” said Dr. Griffin, who was not part of the study.
The exact tipping point in alcohol consumption that can lead to problems with cognition or increased dementia risk is unknown, Dr. Griffin said. Nor do researchers understand why mild drinking may have a protective effect.
“We do know, however, that excessive alcohol consumption has negative effects on heart health and general health, which can lead to problems with brain function,” he said. “Clinicians should have discussions with their patients around their alcohol consumption patterns and the risks associated with drinking in excess, including potential damage to their cognition.”
Funding for the study was not disclosed. Dr. Jeon and Dr. Griffin report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
Investigators assessed dementia risk using changes in alcohol consumption over a 2-year period in nearly 4 million people in South Korea. After about 7 years, dementia was 21% less likely in mild drinkers and 17% less likely in moderate drinkers. Heavy drinking was linked to an 8% increased risk.
Other studies of the relationship between alcohol and dementia have yielded mixed results, and this study does little to clear those murky waters. Nor do the results mean that drinking is recommended, the investigators note.
But the study does offer new information on how risk changes over time as people change their drinking habits, lead investigator Keun Hye Jeon, MD, assistant professor of family medicine at Cha Gumi Medical Center at Cha University, Gumi, South Korea, told this news organization.
“Although numerous studies have shown a relationship between alcohol consumption and dementia, there is a paucity of understanding as to how the incidence of dementia changes with changes in drinking habits,” Dr. Jeon said.
“By measuring alcohol consumption at two time points, we were able to study the relationship between reducing, ceasing, maintaining, and increasing alcohol consumption and incident dementia,” he added.
The findings were published online in JAMA Network Open.
Tracking drinking habits
Researchers analyzed data from nearly 4 million individuals aged 40 years and older in the Korean National Health Insurance Service who completed questionnaires and underwent physical exams in 2009 and 2011.
Study participants completed questionnaires on their drinking habits and were assigned to one of five groups according to change in alcohol consumption during the study period. These groups consisted of sustained nondrinkers; those who stopped drinking (quitters); those who reduced their consumption of alcohol but did not stop drinking (reducers); those who maintained the same level of consumption (sustainers); and those who increased their level of consumption (increasers).
A standard drink in the United States contains 14 g of alcohol. For this study, mild drinking was defined as less than 15 g/day, or one drink; moderate consumption as 15-29.9 g/day, or one to two drinks; and heavy drinking as 30 g/day or more, or three or more drinks.
At baseline, 54.8% of participants were nondrinkers, 26.7% were mild drinkers, 11.0% were moderate drinkers, and 7.5% were heavy drinkers.
From 2009 to 2011, 24.2% of mild drinkers, 8.4% of moderate drinkers, and 7.6% of heavy drinkers became quitters. In the same period, 13.9% of nondrinkers, 16.1% of mild drinkers, and 17.4% of moderate drinkers increased their drinking level.
After a mean follow-up of 6.3 years, 2.5% of participants were diagnosed with dementia, 2.0% with Alzheimer’s disease, and 0.3% with vascular dementia.
Unexpected finding
Compared with consistently not drinking, mild and moderate alcohol consumption was associated with a 21% (adjust hazard ratio, 0.79; 95% confidence interval, 0.77-0.81) and 17% (aHR, 0.83; 95% CI, 0.79-0.88) decreased risk for dementia, respectively.
Heavy drinking was linked to an 8% increased risk (aHR, 1.08; 95% CI, 1.03-1.12).
Similar associations were found between alcohol consumption and risk for Alzheimer’s disease and vascular dementia.
Reducing drinking habits from heavy to moderate led to a reduction in risk for dementia and Alzheimer’s, and increasing drinking levels led to an increase in risk for both conditions.
But when the researchers analyzed dementia risk for nondrinkers who began drinking at mild levels during the study period, they found something unexpected – the risk in this group decreased by 7% for dementia (aHR, 0.93; 95% CI, 0.90-0.96) and by 8% for Alzheimer’s (aHR, 0.92; 95% CI, 0.89-0.95), compared with sustained mild drinkers.
“Our study showed that initiation of mild alcohol consumption leads to a reduced risk of all-cause dementia and Alzheimer’s disease, which has never been reported in previous studies,” Dr. Jeon said.
However, Dr. Jeon was quick to point out that this doesn’t mean that people who don’t drink should start.
Previous studies have shown that heavy alcohol use can triple an individual’s dementia risk, while other studies have shown that no amount of alcohol consumption is good for the brain.
“None of the existing health guidelines recommend starting alcohol drinking,” Dr. Jeon said. “Our findings regarding an initiation of mild alcohol consumption cannot be directly translated into clinical recommendations,” but the findings do warrant additional study, he added.
Risks persist
Commenting on the findings, Percy Griffin, PhD, director of scientific engagement for the Alzheimer’s Association in Chicago, agrees.
“While this study is interesting, and this topic deserves further study, no one should drink alcohol as a method of reducing risk of Alzheimer’s disease or other dementia based on this study,” said Dr. Griffin, who was not part of the study.
The exact tipping point in alcohol consumption that can lead to problems with cognition or increased dementia risk is unknown, Dr. Griffin said. Nor do researchers understand why mild drinking may have a protective effect.
“We do know, however, that excessive alcohol consumption has negative effects on heart health and general health, which can lead to problems with brain function,” he said. “Clinicians should have discussions with their patients around their alcohol consumption patterns and the risks associated with drinking in excess, including potential damage to their cognition.”
Funding for the study was not disclosed. Dr. Jeon and Dr. Griffin report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
Nature, not nurture, the culprit in OCD
new research suggests.
This finding from a large, register-based study is particularly surprising because results from previous studies of major depression and anxiety disorder have shown a significant effect of parenting and a child’s home environment on the risk for these disorders, the investigators noted.
While the results likely won’t change patient treatment, one expert said it could alleviate concerns of some parents with OCD who fear that witnessing their obsessive behaviors might put their children at higher risk for the disorder.
“The evidence is consistent with the idea that the psychological transmission of OCD from parent to child, if it exists, is really pretty weak,” lead author Kenneth S. Kendler, MD, professor of psychiatry and director of the Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, said in an interview.
The findings were published online in JAMA Psychiatry.
Family analysis
The study is the first to include adoptive parents in an analysis of OCD transmission, which allowed investigators to answer the nature versus nurture question that is often difficult to decipher.
Working with Swedish population registries, researchers identified more than 2.4 million offspring. Of these, 27,141 individuals (1.1%) had a lifetime diagnosis of OCD.
Families were divided into four types: intact families, with kids who lived at home with their biological parents from birth to at least age 15 years; families with kids who never lived with their biological father; families with children who did not live with their biological fathers between birth and age 15 years but who lived with a stepfather for at least 10 of those years; and families with children who were adopted before the age of 5 by people with no biological connection to the child.
After analyzing data from all parent-child relationships, researchers found that genes plus rearing (odds ratio, 3.94; 95% confidence interval, 3.58-4.33) and genes only (OR, 3.34; 95% CI, 2.27-4.93) were significantly more likely to be correlated to transmission of OCD from parent to offspring than rearing alone. Rearing only (OR, 1.4; 95% CI, 0.45-4.39) was not significantly correlated with OCD transmission
“It appears from our data that the only substantial transmission that occurs is in the genes parents transmit, not by the modeling of behavior,” Dr. Kendler said.
“There’s an idea that you can learn some things from your parents from psychopathology, but we didn’t see that kids picked that up much in the case of OCD,” he added.
However, there was one outlier: Children raised by stepparents or adoptive parents with an anxiety disorder had a greater risk of developing OCD.
Given the lack of evidence of a strong rearing effect in other analyses, Dr. Kendler noted that this rogue finding could be caused by an underpowered sample; the researchers plan to study the data further.
“Psychiatric disorders, like many other conditions, are often correlated with neighboring conditions,” he said. “Our study would suggest that some of the molecular genetic variants between OCD and generalized anxiety disorder or other anxiety disorders would be shared, but some would be unique.”
Answers an old question
In a comment, Jon Grant, JD, MD, MPH, professor of psychiatry and director of the Addictive, Compulsive, and Impulsive Disorders Research Lab at the University of Chicago, said the findings fill an important gap in what is known about OCD.
“I think the findings are really answering this old question of: ‘Is OCD due to the rearing patterns in a family versus genetics?’ This was able to get at that information showing that it’s virtually all due to genetics within families, and that’s really good to know,” said Dr. Grant, who was not a part of the study.
He was also struck by the finding of a strong genetic relationship between OCD and generalized anxiety disorder (GAD).
While identifying that OCD and GAD are genetically linked likely won’t change clinical care, “I think it at least allows clinicians to know when we see that comorbidity that it may be much more genetically linked in the case of GAD,” Dr. Grant said.
The study was funded by the Swedish Research Council, as well as Avtal om Läkarutbildning och Forskning funding from Region Skåne. Dr. Kendler and Dr. Grant reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
This finding from a large, register-based study is particularly surprising because results from previous studies of major depression and anxiety disorder have shown a significant effect of parenting and a child’s home environment on the risk for these disorders, the investigators noted.
While the results likely won’t change patient treatment, one expert said it could alleviate concerns of some parents with OCD who fear that witnessing their obsessive behaviors might put their children at higher risk for the disorder.
“The evidence is consistent with the idea that the psychological transmission of OCD from parent to child, if it exists, is really pretty weak,” lead author Kenneth S. Kendler, MD, professor of psychiatry and director of the Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, said in an interview.
The findings were published online in JAMA Psychiatry.
Family analysis
The study is the first to include adoptive parents in an analysis of OCD transmission, which allowed investigators to answer the nature versus nurture question that is often difficult to decipher.
Working with Swedish population registries, researchers identified more than 2.4 million offspring. Of these, 27,141 individuals (1.1%) had a lifetime diagnosis of OCD.
Families were divided into four types: intact families, with kids who lived at home with their biological parents from birth to at least age 15 years; families with kids who never lived with their biological father; families with children who did not live with their biological fathers between birth and age 15 years but who lived with a stepfather for at least 10 of those years; and families with children who were adopted before the age of 5 by people with no biological connection to the child.
After analyzing data from all parent-child relationships, researchers found that genes plus rearing (odds ratio, 3.94; 95% confidence interval, 3.58-4.33) and genes only (OR, 3.34; 95% CI, 2.27-4.93) were significantly more likely to be correlated to transmission of OCD from parent to offspring than rearing alone. Rearing only (OR, 1.4; 95% CI, 0.45-4.39) was not significantly correlated with OCD transmission
“It appears from our data that the only substantial transmission that occurs is in the genes parents transmit, not by the modeling of behavior,” Dr. Kendler said.
“There’s an idea that you can learn some things from your parents from psychopathology, but we didn’t see that kids picked that up much in the case of OCD,” he added.
However, there was one outlier: Children raised by stepparents or adoptive parents with an anxiety disorder had a greater risk of developing OCD.
Given the lack of evidence of a strong rearing effect in other analyses, Dr. Kendler noted that this rogue finding could be caused by an underpowered sample; the researchers plan to study the data further.
“Psychiatric disorders, like many other conditions, are often correlated with neighboring conditions,” he said. “Our study would suggest that some of the molecular genetic variants between OCD and generalized anxiety disorder or other anxiety disorders would be shared, but some would be unique.”
Answers an old question
In a comment, Jon Grant, JD, MD, MPH, professor of psychiatry and director of the Addictive, Compulsive, and Impulsive Disorders Research Lab at the University of Chicago, said the findings fill an important gap in what is known about OCD.
“I think the findings are really answering this old question of: ‘Is OCD due to the rearing patterns in a family versus genetics?’ This was able to get at that information showing that it’s virtually all due to genetics within families, and that’s really good to know,” said Dr. Grant, who was not a part of the study.
He was also struck by the finding of a strong genetic relationship between OCD and generalized anxiety disorder (GAD).
While identifying that OCD and GAD are genetically linked likely won’t change clinical care, “I think it at least allows clinicians to know when we see that comorbidity that it may be much more genetically linked in the case of GAD,” Dr. Grant said.
The study was funded by the Swedish Research Council, as well as Avtal om Läkarutbildning och Forskning funding from Region Skåne. Dr. Kendler and Dr. Grant reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
new research suggests.
This finding from a large, register-based study is particularly surprising because results from previous studies of major depression and anxiety disorder have shown a significant effect of parenting and a child’s home environment on the risk for these disorders, the investigators noted.
While the results likely won’t change patient treatment, one expert said it could alleviate concerns of some parents with OCD who fear that witnessing their obsessive behaviors might put their children at higher risk for the disorder.
“The evidence is consistent with the idea that the psychological transmission of OCD from parent to child, if it exists, is really pretty weak,” lead author Kenneth S. Kendler, MD, professor of psychiatry and director of the Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, said in an interview.
The findings were published online in JAMA Psychiatry.
Family analysis
The study is the first to include adoptive parents in an analysis of OCD transmission, which allowed investigators to answer the nature versus nurture question that is often difficult to decipher.
Working with Swedish population registries, researchers identified more than 2.4 million offspring. Of these, 27,141 individuals (1.1%) had a lifetime diagnosis of OCD.
Families were divided into four types: intact families, with kids who lived at home with their biological parents from birth to at least age 15 years; families with kids who never lived with their biological father; families with children who did not live with their biological fathers between birth and age 15 years but who lived with a stepfather for at least 10 of those years; and families with children who were adopted before the age of 5 by people with no biological connection to the child.
After analyzing data from all parent-child relationships, researchers found that genes plus rearing (odds ratio, 3.94; 95% confidence interval, 3.58-4.33) and genes only (OR, 3.34; 95% CI, 2.27-4.93) were significantly more likely to be correlated to transmission of OCD from parent to offspring than rearing alone. Rearing only (OR, 1.4; 95% CI, 0.45-4.39) was not significantly correlated with OCD transmission
“It appears from our data that the only substantial transmission that occurs is in the genes parents transmit, not by the modeling of behavior,” Dr. Kendler said.
“There’s an idea that you can learn some things from your parents from psychopathology, but we didn’t see that kids picked that up much in the case of OCD,” he added.
However, there was one outlier: Children raised by stepparents or adoptive parents with an anxiety disorder had a greater risk of developing OCD.
Given the lack of evidence of a strong rearing effect in other analyses, Dr. Kendler noted that this rogue finding could be caused by an underpowered sample; the researchers plan to study the data further.
“Psychiatric disorders, like many other conditions, are often correlated with neighboring conditions,” he said. “Our study would suggest that some of the molecular genetic variants between OCD and generalized anxiety disorder or other anxiety disorders would be shared, but some would be unique.”
Answers an old question
In a comment, Jon Grant, JD, MD, MPH, professor of psychiatry and director of the Addictive, Compulsive, and Impulsive Disorders Research Lab at the University of Chicago, said the findings fill an important gap in what is known about OCD.
“I think the findings are really answering this old question of: ‘Is OCD due to the rearing patterns in a family versus genetics?’ This was able to get at that information showing that it’s virtually all due to genetics within families, and that’s really good to know,” said Dr. Grant, who was not a part of the study.
He was also struck by the finding of a strong genetic relationship between OCD and generalized anxiety disorder (GAD).
While identifying that OCD and GAD are genetically linked likely won’t change clinical care, “I think it at least allows clinicians to know when we see that comorbidity that it may be much more genetically linked in the case of GAD,” Dr. Grant said.
The study was funded by the Swedish Research Council, as well as Avtal om Läkarutbildning och Forskning funding from Region Skåne. Dr. Kendler and Dr. Grant reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA PSYCHIATRY