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Beyond One-Size-Fits-All: Precision Psychiatry Is Here
The field of psychiatry is experiencing a transformative shift toward precision medicine, a paradigm that tailors treatment to the unique characteristics of individual patients. This approach echoes advances in fields like oncology and cardiology, where precision tools have already revolutionized patient care.
But what exactly is precision psychiatry? How does it differ from traditional psychiatry? What will it look like in clinical practice? And are we there yet?
Beyond One-Size-Fits-All
The prevailing “one-size-fits-all” approach in psychiatry, which relies heavily on subjective symptom reporting, often proves ineffective due to the broad heterogeneity of diagnostic categories. This can lead to a “trial-and-error” cycle in treatment, which is time-consuming, costly, and frustrating for both doctors and patients.
In contrast, precision psychiatry has the potential to identify subtypes of psychiatric disorders and tailor treatments using measurable, objective data.
“The data supporting the use of precision psychiatry are very promising, particularly for treatment-resistant depression,” Leanne Williams, PhD, professor in the Department of Psychiatry and Behavioral Sciences at Stanford University, Stanford, and director of the Stanford Center for Precision Mental Health and Wellness, Palo Alto, California, said in an interview with this news organization.
Using functional MRI (fMRI), Dr. Williams and her team have mapped and measured patients’ brain circuitry to identify eight “biotypes” of depression that reflect combinations of dysfunction in six different circuits of the brain.
They are using these biotypes to guide treatment decisions in the clinic, matching individual patients to more targeted and effective therapies.
“We’re offering functional MRI to directly assess brain function along with other measures, so precision psychiatry is happening, and it’s really wanted by patients and their families. And the data suggest that we can double the rate of good outcomes,” said Dr. Williams.
“Neuroimaging techniques, particularly fMRI, have revolutionized our ability to map and quantify circuit abnormalities. Neural circuit measurements potentially offer the most direct window into the neural bases of psychiatric symptoms and, crucially, their modulation by treatment,” Teddy Akiki, MD, clinical scholar, Department of Psychiatry and Behavioral Sciences at Stanford, California, who works with Dr. Williams, told this news organization.
Blood-based biomarkers can complement brain imaging by providing additional information to better target treatment, help predict side effects, and guide dosage adjustments.
Precision Tools
A team led by Alexander B. Niculescu, III, MD, PhD, has found that a panel of blood-based biomarkers can distinguish between depression and bipolar disorder, predict a person’s future risk for these disorders, and inform more tailored medication choices.
Dr. Niculescu is currently a professor of psychiatry and medical neuroscience at the Indiana University School of Medicine, Indianapolis. He will head west in September to direct the newly created Center for Precision Psychiatry at the University of Arizona College of Medicine–Phoenix.
MindX Sciences, the start-up company Dr. Niculescu cofounded, has been providing blood biomarker reports to “early adopting” doctors and patients.
“We are in the process of collecting and writing up the outcome data on the first 100 cases. The feedback we have received so far from the doctors and patients who have used it, as well as biopharma companies who have used it, has been very positive,” Dr. Niculescu told this news organization.
Another benefit of precision psychiatry lies in its potential to significantly accelerate drug development.
“By identifying specific neural circuits involved in subtypes of psychiatric conditions, we can repurpose or develop drugs that target these circuits more precisely. This approach allows for smaller, more focused trials with potentially higher success rates, which could speed up the typically slow and costly process of psychiatric drug development,” said Dr. Akiki.
Dr. Niculescu agreed. With precision psychiatry tools, “psychiatric drug development will become faster, cheaper, and more successful with the use of biomarkers and other precision tools,” he said.
The Future Is Already Here
The implementation and widespread adoption of precision psychiatry have several challenges.
It requires sophisticated technology and expertise, which may not be readily available in all clinical settings. Moreover, while evidence supports its use in conditions like major depression, there are fewer data on its efficacy in other psychiatric disorders, like schizophrenia.
Dr. Williams said future research should focus on expanding the evidence base for precision psychiatry across a broader range of psychiatric conditions.
Efforts to make precision tools more accessible and scalable, such as developing portable imaging technologies or more readily available biomarker tests, are also critical.
Integrating these precision tools into routine psychiatric practice will also require training and education for clinicians, as well as cost-effective solutions to make these approaches widely available.
“Mental health clinicians throughout the country are starting to employ semi-objective and objective measures in their practices, particularly self-report symptom questionnaires and pharmacogenomic assessment,” Laura Hack, MD, PhD, assistant professor, Department of Psychiatry and Behavioral Sciences, Stanford University, told this news organization.
“For precision psychiatry measures to be widely implemented, it is essential to demonstrate their reliability, clinical validity, clinical utility, and cost-effectiveness. Additionally, there is a need to develop clinical guidelines for their use, ensure that measurement tools are accessible, and educate all relevant stakeholders,” said Dr. Hack.
Right now, functional neuroimaging is used “only on a very limited basis in current clinical psychiatric practice,” Dr. Hack noted.
“We are developing standardized systems that will require less specialized expertise in functional neuroimaging and can be readily integrated into routine clinical care,” Dr. Akiki added.
Quoting William Gibson, “The future [of precision psychiatry] is already here; it’s just not evenly distributed,” said Dr. Niculescu.
Dr. Williams has disclosed relationships with One Mind PsyberGuide, Laureate Institute for Brain Research, and Et Cere Inc. Dr. Niculescu is a cofounder of MindX Sciences and is listed as inventor on a patent application filed by Indiana University. Dr. Akiki and Dr. Hack had no relevant disclosures.
A version of this article first appeared on Medscape.com.
The field of psychiatry is experiencing a transformative shift toward precision medicine, a paradigm that tailors treatment to the unique characteristics of individual patients. This approach echoes advances in fields like oncology and cardiology, where precision tools have already revolutionized patient care.
But what exactly is precision psychiatry? How does it differ from traditional psychiatry? What will it look like in clinical practice? And are we there yet?
Beyond One-Size-Fits-All
The prevailing “one-size-fits-all” approach in psychiatry, which relies heavily on subjective symptom reporting, often proves ineffective due to the broad heterogeneity of diagnostic categories. This can lead to a “trial-and-error” cycle in treatment, which is time-consuming, costly, and frustrating for both doctors and patients.
In contrast, precision psychiatry has the potential to identify subtypes of psychiatric disorders and tailor treatments using measurable, objective data.
“The data supporting the use of precision psychiatry are very promising, particularly for treatment-resistant depression,” Leanne Williams, PhD, professor in the Department of Psychiatry and Behavioral Sciences at Stanford University, Stanford, and director of the Stanford Center for Precision Mental Health and Wellness, Palo Alto, California, said in an interview with this news organization.
Using functional MRI (fMRI), Dr. Williams and her team have mapped and measured patients’ brain circuitry to identify eight “biotypes” of depression that reflect combinations of dysfunction in six different circuits of the brain.
They are using these biotypes to guide treatment decisions in the clinic, matching individual patients to more targeted and effective therapies.
“We’re offering functional MRI to directly assess brain function along with other measures, so precision psychiatry is happening, and it’s really wanted by patients and their families. And the data suggest that we can double the rate of good outcomes,” said Dr. Williams.
“Neuroimaging techniques, particularly fMRI, have revolutionized our ability to map and quantify circuit abnormalities. Neural circuit measurements potentially offer the most direct window into the neural bases of psychiatric symptoms and, crucially, their modulation by treatment,” Teddy Akiki, MD, clinical scholar, Department of Psychiatry and Behavioral Sciences at Stanford, California, who works with Dr. Williams, told this news organization.
Blood-based biomarkers can complement brain imaging by providing additional information to better target treatment, help predict side effects, and guide dosage adjustments.
Precision Tools
A team led by Alexander B. Niculescu, III, MD, PhD, has found that a panel of blood-based biomarkers can distinguish between depression and bipolar disorder, predict a person’s future risk for these disorders, and inform more tailored medication choices.
Dr. Niculescu is currently a professor of psychiatry and medical neuroscience at the Indiana University School of Medicine, Indianapolis. He will head west in September to direct the newly created Center for Precision Psychiatry at the University of Arizona College of Medicine–Phoenix.
MindX Sciences, the start-up company Dr. Niculescu cofounded, has been providing blood biomarker reports to “early adopting” doctors and patients.
“We are in the process of collecting and writing up the outcome data on the first 100 cases. The feedback we have received so far from the doctors and patients who have used it, as well as biopharma companies who have used it, has been very positive,” Dr. Niculescu told this news organization.
Another benefit of precision psychiatry lies in its potential to significantly accelerate drug development.
“By identifying specific neural circuits involved in subtypes of psychiatric conditions, we can repurpose or develop drugs that target these circuits more precisely. This approach allows for smaller, more focused trials with potentially higher success rates, which could speed up the typically slow and costly process of psychiatric drug development,” said Dr. Akiki.
Dr. Niculescu agreed. With precision psychiatry tools, “psychiatric drug development will become faster, cheaper, and more successful with the use of biomarkers and other precision tools,” he said.
The Future Is Already Here
The implementation and widespread adoption of precision psychiatry have several challenges.
It requires sophisticated technology and expertise, which may not be readily available in all clinical settings. Moreover, while evidence supports its use in conditions like major depression, there are fewer data on its efficacy in other psychiatric disorders, like schizophrenia.
Dr. Williams said future research should focus on expanding the evidence base for precision psychiatry across a broader range of psychiatric conditions.
Efforts to make precision tools more accessible and scalable, such as developing portable imaging technologies or more readily available biomarker tests, are also critical.
Integrating these precision tools into routine psychiatric practice will also require training and education for clinicians, as well as cost-effective solutions to make these approaches widely available.
“Mental health clinicians throughout the country are starting to employ semi-objective and objective measures in their practices, particularly self-report symptom questionnaires and pharmacogenomic assessment,” Laura Hack, MD, PhD, assistant professor, Department of Psychiatry and Behavioral Sciences, Stanford University, told this news organization.
“For precision psychiatry measures to be widely implemented, it is essential to demonstrate their reliability, clinical validity, clinical utility, and cost-effectiveness. Additionally, there is a need to develop clinical guidelines for their use, ensure that measurement tools are accessible, and educate all relevant stakeholders,” said Dr. Hack.
Right now, functional neuroimaging is used “only on a very limited basis in current clinical psychiatric practice,” Dr. Hack noted.
“We are developing standardized systems that will require less specialized expertise in functional neuroimaging and can be readily integrated into routine clinical care,” Dr. Akiki added.
Quoting William Gibson, “The future [of precision psychiatry] is already here; it’s just not evenly distributed,” said Dr. Niculescu.
Dr. Williams has disclosed relationships with One Mind PsyberGuide, Laureate Institute for Brain Research, and Et Cere Inc. Dr. Niculescu is a cofounder of MindX Sciences and is listed as inventor on a patent application filed by Indiana University. Dr. Akiki and Dr. Hack had no relevant disclosures.
A version of this article first appeared on Medscape.com.
The field of psychiatry is experiencing a transformative shift toward precision medicine, a paradigm that tailors treatment to the unique characteristics of individual patients. This approach echoes advances in fields like oncology and cardiology, where precision tools have already revolutionized patient care.
But what exactly is precision psychiatry? How does it differ from traditional psychiatry? What will it look like in clinical practice? And are we there yet?
Beyond One-Size-Fits-All
The prevailing “one-size-fits-all” approach in psychiatry, which relies heavily on subjective symptom reporting, often proves ineffective due to the broad heterogeneity of diagnostic categories. This can lead to a “trial-and-error” cycle in treatment, which is time-consuming, costly, and frustrating for both doctors and patients.
In contrast, precision psychiatry has the potential to identify subtypes of psychiatric disorders and tailor treatments using measurable, objective data.
“The data supporting the use of precision psychiatry are very promising, particularly for treatment-resistant depression,” Leanne Williams, PhD, professor in the Department of Psychiatry and Behavioral Sciences at Stanford University, Stanford, and director of the Stanford Center for Precision Mental Health and Wellness, Palo Alto, California, said in an interview with this news organization.
Using functional MRI (fMRI), Dr. Williams and her team have mapped and measured patients’ brain circuitry to identify eight “biotypes” of depression that reflect combinations of dysfunction in six different circuits of the brain.
They are using these biotypes to guide treatment decisions in the clinic, matching individual patients to more targeted and effective therapies.
“We’re offering functional MRI to directly assess brain function along with other measures, so precision psychiatry is happening, and it’s really wanted by patients and their families. And the data suggest that we can double the rate of good outcomes,” said Dr. Williams.
“Neuroimaging techniques, particularly fMRI, have revolutionized our ability to map and quantify circuit abnormalities. Neural circuit measurements potentially offer the most direct window into the neural bases of psychiatric symptoms and, crucially, their modulation by treatment,” Teddy Akiki, MD, clinical scholar, Department of Psychiatry and Behavioral Sciences at Stanford, California, who works with Dr. Williams, told this news organization.
Blood-based biomarkers can complement brain imaging by providing additional information to better target treatment, help predict side effects, and guide dosage adjustments.
Precision Tools
A team led by Alexander B. Niculescu, III, MD, PhD, has found that a panel of blood-based biomarkers can distinguish between depression and bipolar disorder, predict a person’s future risk for these disorders, and inform more tailored medication choices.
Dr. Niculescu is currently a professor of psychiatry and medical neuroscience at the Indiana University School of Medicine, Indianapolis. He will head west in September to direct the newly created Center for Precision Psychiatry at the University of Arizona College of Medicine–Phoenix.
MindX Sciences, the start-up company Dr. Niculescu cofounded, has been providing blood biomarker reports to “early adopting” doctors and patients.
“We are in the process of collecting and writing up the outcome data on the first 100 cases. The feedback we have received so far from the doctors and patients who have used it, as well as biopharma companies who have used it, has been very positive,” Dr. Niculescu told this news organization.
Another benefit of precision psychiatry lies in its potential to significantly accelerate drug development.
“By identifying specific neural circuits involved in subtypes of psychiatric conditions, we can repurpose or develop drugs that target these circuits more precisely. This approach allows for smaller, more focused trials with potentially higher success rates, which could speed up the typically slow and costly process of psychiatric drug development,” said Dr. Akiki.
Dr. Niculescu agreed. With precision psychiatry tools, “psychiatric drug development will become faster, cheaper, and more successful with the use of biomarkers and other precision tools,” he said.
The Future Is Already Here
The implementation and widespread adoption of precision psychiatry have several challenges.
It requires sophisticated technology and expertise, which may not be readily available in all clinical settings. Moreover, while evidence supports its use in conditions like major depression, there are fewer data on its efficacy in other psychiatric disorders, like schizophrenia.
Dr. Williams said future research should focus on expanding the evidence base for precision psychiatry across a broader range of psychiatric conditions.
Efforts to make precision tools more accessible and scalable, such as developing portable imaging technologies or more readily available biomarker tests, are also critical.
Integrating these precision tools into routine psychiatric practice will also require training and education for clinicians, as well as cost-effective solutions to make these approaches widely available.
“Mental health clinicians throughout the country are starting to employ semi-objective and objective measures in their practices, particularly self-report symptom questionnaires and pharmacogenomic assessment,” Laura Hack, MD, PhD, assistant professor, Department of Psychiatry and Behavioral Sciences, Stanford University, told this news organization.
“For precision psychiatry measures to be widely implemented, it is essential to demonstrate their reliability, clinical validity, clinical utility, and cost-effectiveness. Additionally, there is a need to develop clinical guidelines for their use, ensure that measurement tools are accessible, and educate all relevant stakeholders,” said Dr. Hack.
Right now, functional neuroimaging is used “only on a very limited basis in current clinical psychiatric practice,” Dr. Hack noted.
“We are developing standardized systems that will require less specialized expertise in functional neuroimaging and can be readily integrated into routine clinical care,” Dr. Akiki added.
Quoting William Gibson, “The future [of precision psychiatry] is already here; it’s just not evenly distributed,” said Dr. Niculescu.
Dr. Williams has disclosed relationships with One Mind PsyberGuide, Laureate Institute for Brain Research, and Et Cere Inc. Dr. Niculescu is a cofounder of MindX Sciences and is listed as inventor on a patent application filed by Indiana University. Dr. Akiki and Dr. Hack had no relevant disclosures.
A version of this article first appeared on Medscape.com.
Evidence Growing for Inflammation’s Role in Elevating Risk for Psychiatric Illness
New research provides more evidence that inflammation may contribute to the development of psychiatric disorders and suggests that measuring certain inflammatory biomarkers may aid in the early identification of individuals at high risk.
Using large-scale datasets, researchers found that elevated levels of certain inflammatory biomarkers, particularly leukocytes, haptoglobin, and C-reactive protein (CRP), and lower levels of anti-inflammatory immunoglobulin G (IgG) were associated with an increased risk for psychiatric disorders.
Individuals with psychiatric disorders had persistently higher levels of leukocytes and haptoglobin, as well as persistently lower levels of IgG, than controls during the 30 years before diagnosis, which suggest “long-term processes and may aid in the identification of individuals at high risk,” the researchers wrote.
In addition, a higher level of leukocytes was consistently associated with increased odds of depression across different methods of Mendelian randomization (MR) analysis, “indicating a possible causal relationship between leukocytes and depression,” they said.
The study, with first author Yu Zeng, MSc, with the Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China, was published online on August 21 in JAMA Psychiatry.
Inflammatory Phenotype
Individuals with psychiatric disorders have been found to have elevated levels of inflammatory biomarkers, but prospective evidence is limited regarding the association between inflammatory biomarkers and subsequent psychiatric disorders risk.
To investigate further, the researchers employed a “triangulation” approach consisting of an exploration dataset of 585,279 adults in the Swedish AMORIS cohort with no prior psychiatric diagnoses and a measurement of at least one inflammatory biomarker, a validation dataset of 485,620 UK Biobank participants, and genetic and MR analyses using genome-wide association study summary statistics.
In the AMORIS cohort, individuals with a higher than median level of leukocytes (hazard ratio [HR], 1.11), haptoglobin (HR, 1.13), or CRP (HR, 1.02) had an elevated risk for any psychiatric disorder. In contrast, there was an inverse association for IgG level (HR, 0.92).
“The estimates were comparable for depression, anxiety, and stress-related disorders, specifically, and these results were largely validated in the UK Biobank,” the authors reported.
In trajectory analyses, compared with controls, individuals with psychiatric disorders had higher leukocyte and haptoglobin levels and lower IgG up to three decades before being diagnosed.
The MR analysis suggested a possible causal relationship between leukocytes and depression.
The underlying mechanisms for the associations of serum leukocytes, haptoglobin, CRP, and IgG with psychiatry disorders remain unclear.
“Possible explanations mainly include blood-brain barrier disruption, microglia activation, neurotransmission impairment, and other interactions between inflammations and neuropathology,” the researchers wrote.
A related paper published online on August 21 in JAMA Psychiatry looked at trajectories of inflammation in childhood and risk for mental and cardiometabolic disorders in adulthood.
This longitudinal cohort study found that having persistently raised levels of inflammation as measured by CRP throughout childhood and adolescence, peaking at age 9 years, were associated with an increased risk of developing psychosis disorder, severe depression, and higher levels of insulin resistance.
Support for Precision Psychiatry
This study is “another strong indication that inflammation plays a role in depression,” Andrew H. Miller, MD, professor of psychiatry and behavioral sciences and director of the behavioral immunology program, Emory University School of Medicine, Atlanta, Georgia, who wasn’t involved in the study, told this news organization.
“The work adds to the mounting data that there exists an inflammatory phenotype of depression that may uniquely respond to treatment and may have a unique trajectory,” Dr. Miller said.
“Eventually the field will want to embrace this novel phenotype and better understand how to recognize it and treat it. This is our entrée into precision psychiatry where we identify the right treatment for the right patient at the right time based on an understanding of the underlying cause of their illness,” Dr. Miller added.
Also weighing in, Alexander B. Niculescu III, MD, PhD, professor of psychiatry and medical neuroscience, Indiana University School of Medicine, Indianapolis, cautioned that these biomarkers are “very nonspecific and are likely related to these subjects that go on to develop psychiatric disorders having more stressful, adverse life trajectories.”
“There are better, more specific blood biomarkers for psychiatric disorders already available,” Dr. Niculescu told this news organization.
His group recently reported that a panel of blood-based biomarkers can distinguish between depression and bipolar disorder, predict a person’s future risk for these disorders, and inform more tailored medication choices.
Notably, they observed a strong circadian clock gene component to mood disorders, which helps explain why some patients’ conditions become worse with seasonal changes. It also explains the sleep alterations that occur among patients with mood disorders, they said.
This study had no commercial funding. Yu Zeng and Dr. Miller had no relevant disclosures. Dr. Niculescu is a cofounder of MindX Sciences and is listed as inventor on a patent application filed by Indiana University.
A version of this article first appeared on Medscape.com.
New research provides more evidence that inflammation may contribute to the development of psychiatric disorders and suggests that measuring certain inflammatory biomarkers may aid in the early identification of individuals at high risk.
Using large-scale datasets, researchers found that elevated levels of certain inflammatory biomarkers, particularly leukocytes, haptoglobin, and C-reactive protein (CRP), and lower levels of anti-inflammatory immunoglobulin G (IgG) were associated with an increased risk for psychiatric disorders.
Individuals with psychiatric disorders had persistently higher levels of leukocytes and haptoglobin, as well as persistently lower levels of IgG, than controls during the 30 years before diagnosis, which suggest “long-term processes and may aid in the identification of individuals at high risk,” the researchers wrote.
In addition, a higher level of leukocytes was consistently associated with increased odds of depression across different methods of Mendelian randomization (MR) analysis, “indicating a possible causal relationship between leukocytes and depression,” they said.
The study, with first author Yu Zeng, MSc, with the Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China, was published online on August 21 in JAMA Psychiatry.
Inflammatory Phenotype
Individuals with psychiatric disorders have been found to have elevated levels of inflammatory biomarkers, but prospective evidence is limited regarding the association between inflammatory biomarkers and subsequent psychiatric disorders risk.
To investigate further, the researchers employed a “triangulation” approach consisting of an exploration dataset of 585,279 adults in the Swedish AMORIS cohort with no prior psychiatric diagnoses and a measurement of at least one inflammatory biomarker, a validation dataset of 485,620 UK Biobank participants, and genetic and MR analyses using genome-wide association study summary statistics.
In the AMORIS cohort, individuals with a higher than median level of leukocytes (hazard ratio [HR], 1.11), haptoglobin (HR, 1.13), or CRP (HR, 1.02) had an elevated risk for any psychiatric disorder. In contrast, there was an inverse association for IgG level (HR, 0.92).
“The estimates were comparable for depression, anxiety, and stress-related disorders, specifically, and these results were largely validated in the UK Biobank,” the authors reported.
In trajectory analyses, compared with controls, individuals with psychiatric disorders had higher leukocyte and haptoglobin levels and lower IgG up to three decades before being diagnosed.
The MR analysis suggested a possible causal relationship between leukocytes and depression.
The underlying mechanisms for the associations of serum leukocytes, haptoglobin, CRP, and IgG with psychiatry disorders remain unclear.
“Possible explanations mainly include blood-brain barrier disruption, microglia activation, neurotransmission impairment, and other interactions between inflammations and neuropathology,” the researchers wrote.
A related paper published online on August 21 in JAMA Psychiatry looked at trajectories of inflammation in childhood and risk for mental and cardiometabolic disorders in adulthood.
This longitudinal cohort study found that having persistently raised levels of inflammation as measured by CRP throughout childhood and adolescence, peaking at age 9 years, were associated with an increased risk of developing psychosis disorder, severe depression, and higher levels of insulin resistance.
Support for Precision Psychiatry
This study is “another strong indication that inflammation plays a role in depression,” Andrew H. Miller, MD, professor of psychiatry and behavioral sciences and director of the behavioral immunology program, Emory University School of Medicine, Atlanta, Georgia, who wasn’t involved in the study, told this news organization.
“The work adds to the mounting data that there exists an inflammatory phenotype of depression that may uniquely respond to treatment and may have a unique trajectory,” Dr. Miller said.
“Eventually the field will want to embrace this novel phenotype and better understand how to recognize it and treat it. This is our entrée into precision psychiatry where we identify the right treatment for the right patient at the right time based on an understanding of the underlying cause of their illness,” Dr. Miller added.
Also weighing in, Alexander B. Niculescu III, MD, PhD, professor of psychiatry and medical neuroscience, Indiana University School of Medicine, Indianapolis, cautioned that these biomarkers are “very nonspecific and are likely related to these subjects that go on to develop psychiatric disorders having more stressful, adverse life trajectories.”
“There are better, more specific blood biomarkers for psychiatric disorders already available,” Dr. Niculescu told this news organization.
His group recently reported that a panel of blood-based biomarkers can distinguish between depression and bipolar disorder, predict a person’s future risk for these disorders, and inform more tailored medication choices.
Notably, they observed a strong circadian clock gene component to mood disorders, which helps explain why some patients’ conditions become worse with seasonal changes. It also explains the sleep alterations that occur among patients with mood disorders, they said.
This study had no commercial funding. Yu Zeng and Dr. Miller had no relevant disclosures. Dr. Niculescu is a cofounder of MindX Sciences and is listed as inventor on a patent application filed by Indiana University.
A version of this article first appeared on Medscape.com.
New research provides more evidence that inflammation may contribute to the development of psychiatric disorders and suggests that measuring certain inflammatory biomarkers may aid in the early identification of individuals at high risk.
Using large-scale datasets, researchers found that elevated levels of certain inflammatory biomarkers, particularly leukocytes, haptoglobin, and C-reactive protein (CRP), and lower levels of anti-inflammatory immunoglobulin G (IgG) were associated with an increased risk for psychiatric disorders.
Individuals with psychiatric disorders had persistently higher levels of leukocytes and haptoglobin, as well as persistently lower levels of IgG, than controls during the 30 years before diagnosis, which suggest “long-term processes and may aid in the identification of individuals at high risk,” the researchers wrote.
In addition, a higher level of leukocytes was consistently associated with increased odds of depression across different methods of Mendelian randomization (MR) analysis, “indicating a possible causal relationship between leukocytes and depression,” they said.
The study, with first author Yu Zeng, MSc, with the Mental Health Center and West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China, was published online on August 21 in JAMA Psychiatry.
Inflammatory Phenotype
Individuals with psychiatric disorders have been found to have elevated levels of inflammatory biomarkers, but prospective evidence is limited regarding the association between inflammatory biomarkers and subsequent psychiatric disorders risk.
To investigate further, the researchers employed a “triangulation” approach consisting of an exploration dataset of 585,279 adults in the Swedish AMORIS cohort with no prior psychiatric diagnoses and a measurement of at least one inflammatory biomarker, a validation dataset of 485,620 UK Biobank participants, and genetic and MR analyses using genome-wide association study summary statistics.
In the AMORIS cohort, individuals with a higher than median level of leukocytes (hazard ratio [HR], 1.11), haptoglobin (HR, 1.13), or CRP (HR, 1.02) had an elevated risk for any psychiatric disorder. In contrast, there was an inverse association for IgG level (HR, 0.92).
“The estimates were comparable for depression, anxiety, and stress-related disorders, specifically, and these results were largely validated in the UK Biobank,” the authors reported.
In trajectory analyses, compared with controls, individuals with psychiatric disorders had higher leukocyte and haptoglobin levels and lower IgG up to three decades before being diagnosed.
The MR analysis suggested a possible causal relationship between leukocytes and depression.
The underlying mechanisms for the associations of serum leukocytes, haptoglobin, CRP, and IgG with psychiatry disorders remain unclear.
“Possible explanations mainly include blood-brain barrier disruption, microglia activation, neurotransmission impairment, and other interactions between inflammations and neuropathology,” the researchers wrote.
A related paper published online on August 21 in JAMA Psychiatry looked at trajectories of inflammation in childhood and risk for mental and cardiometabolic disorders in adulthood.
This longitudinal cohort study found that having persistently raised levels of inflammation as measured by CRP throughout childhood and adolescence, peaking at age 9 years, were associated with an increased risk of developing psychosis disorder, severe depression, and higher levels of insulin resistance.
Support for Precision Psychiatry
This study is “another strong indication that inflammation plays a role in depression,” Andrew H. Miller, MD, professor of psychiatry and behavioral sciences and director of the behavioral immunology program, Emory University School of Medicine, Atlanta, Georgia, who wasn’t involved in the study, told this news organization.
“The work adds to the mounting data that there exists an inflammatory phenotype of depression that may uniquely respond to treatment and may have a unique trajectory,” Dr. Miller said.
“Eventually the field will want to embrace this novel phenotype and better understand how to recognize it and treat it. This is our entrée into precision psychiatry where we identify the right treatment for the right patient at the right time based on an understanding of the underlying cause of their illness,” Dr. Miller added.
Also weighing in, Alexander B. Niculescu III, MD, PhD, professor of psychiatry and medical neuroscience, Indiana University School of Medicine, Indianapolis, cautioned that these biomarkers are “very nonspecific and are likely related to these subjects that go on to develop psychiatric disorders having more stressful, adverse life trajectories.”
“There are better, more specific blood biomarkers for psychiatric disorders already available,” Dr. Niculescu told this news organization.
His group recently reported that a panel of blood-based biomarkers can distinguish between depression and bipolar disorder, predict a person’s future risk for these disorders, and inform more tailored medication choices.
Notably, they observed a strong circadian clock gene component to mood disorders, which helps explain why some patients’ conditions become worse with seasonal changes. It also explains the sleep alterations that occur among patients with mood disorders, they said.
This study had no commercial funding. Yu Zeng and Dr. Miller had no relevant disclosures. Dr. Niculescu is a cofounder of MindX Sciences and is listed as inventor on a patent application filed by Indiana University.
A version of this article first appeared on Medscape.com.
Severe COVID-19 Tied to Increased Risk for Mental Illness
New research adds to a growing body of evidence suggesting that COVID-19 infection can be hard on mental health.
, particularly in those with severe COVID who had not been vaccinated.
Importantly, vaccination appeared to mitigate the adverse effects of COVID-19 on mental health, the investigators found.
“Our results highlight the importance COVID-19 vaccination in the general population and particularly among those with mental illnesses, who may be at higher risk of both SARS-CoV-2 infection and adverse outcomes following COVID-19,” first author Venexia Walker, PhD, with University of Bristol, United Kingdom, said in a news release.
The study was published online on August 21 in JAMA Psychiatry.
Novel Data
“Before this study, a number of papers had looked at associations of COVID diagnosis with mental ill health, and broadly speaking, they had reported associations of different magnitudes,” study author Jonathan A. C. Sterne, PhD, with University of Bristol, noted in a journal podcast.
“Some studies were restricted to patients who were hospitalized with COVID-19 and some not and the duration of follow-up varied. And importantly, the nature of COVID-19 changed profoundly as vaccination became available and there was little data on the impact of vaccination on associations of COVID-19 with subsequent mental ill health,” Dr. Sterne said.
The UK study was conducted in three cohorts — a cohort of about 18.6 million people who were diagnosed with COVID-19 before a vaccine was available, a cohort of about 14 million adults who were vaccinated, and a cohort of about 3.2 million people who were unvaccinated.
The researchers compared rates of various mental illnesses after COVID-19 with rates before or without COVID-19 and by vaccination status.
Across all cohorts, rates of most mental illnesses examined were “markedly elevated” during the first month following a COVID-19 diagnosis compared with rates before or without COVID-19.
For example, the adjusted hazard ratios for depression (the most common illness) and serious mental illness in the month after COVID-19 were 1.93 and 1.49, respectively, in the prevaccination cohort and 1.79 and 1.45, respectively, in the unvaccinated cohort compared with 1.16 and 0.91 in the vaccinated cohort.
This elevation in the rate of mental illnesses was mainly seen after severe COVID-19 that led to hospitalization and remained higher for up to a year following severe COVID-19 in unvaccinated adults.
For severe COVID-19 with hospitalization, the adjusted hazard ratio for depression in the month following admission was 16.3 in the prevaccine cohort, 15.6 in the unvaccinated cohort, and 12.9 in the vaccinated cohort.
The adjusted hazard ratios for serious mental illness in the month after COVID hospitalization was 9.71 in the prevaccine cohort, 8.75 with no vaccination, and 6.52 with vaccination.
“Incidences of other mental illnesses were broadly similar to those of depression and serious mental illness, both overall and for COVID-19 with and without hospitalization,” the authors report in their paper.
Consistent with prior research, subgroup analyzes found the association of COVID-19 and mental illness was stronger among older adults and men, with no marked differences by ethnic group.
“We should be concerned about continuing consequences in people who experienced severe COVID-19 early in the pandemic, and they may include a continuing higher incidence of mental ill health, such as depression and serious mental illness,” Dr. Sterne said in the podcast.
In terms of ongoing booster vaccinations, “people who are advised that they are under vaccinated or recommended for further COVID-19 vaccination, should take those invitations seriously, because by preventing severe COVID-19, which is what vaccination does, you can prevent consequences such as mental illness,” Dr. Sterne added.
The study was supported by the COVID-19 Longitudinal Health and Wellbeing National Core Study, which is funded by the Medical Research Council and National Institute for Health and Care Research. The authors had no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
New research adds to a growing body of evidence suggesting that COVID-19 infection can be hard on mental health.
, particularly in those with severe COVID who had not been vaccinated.
Importantly, vaccination appeared to mitigate the adverse effects of COVID-19 on mental health, the investigators found.
“Our results highlight the importance COVID-19 vaccination in the general population and particularly among those with mental illnesses, who may be at higher risk of both SARS-CoV-2 infection and adverse outcomes following COVID-19,” first author Venexia Walker, PhD, with University of Bristol, United Kingdom, said in a news release.
The study was published online on August 21 in JAMA Psychiatry.
Novel Data
“Before this study, a number of papers had looked at associations of COVID diagnosis with mental ill health, and broadly speaking, they had reported associations of different magnitudes,” study author Jonathan A. C. Sterne, PhD, with University of Bristol, noted in a journal podcast.
“Some studies were restricted to patients who were hospitalized with COVID-19 and some not and the duration of follow-up varied. And importantly, the nature of COVID-19 changed profoundly as vaccination became available and there was little data on the impact of vaccination on associations of COVID-19 with subsequent mental ill health,” Dr. Sterne said.
The UK study was conducted in three cohorts — a cohort of about 18.6 million people who were diagnosed with COVID-19 before a vaccine was available, a cohort of about 14 million adults who were vaccinated, and a cohort of about 3.2 million people who were unvaccinated.
The researchers compared rates of various mental illnesses after COVID-19 with rates before or without COVID-19 and by vaccination status.
Across all cohorts, rates of most mental illnesses examined were “markedly elevated” during the first month following a COVID-19 diagnosis compared with rates before or without COVID-19.
For example, the adjusted hazard ratios for depression (the most common illness) and serious mental illness in the month after COVID-19 were 1.93 and 1.49, respectively, in the prevaccination cohort and 1.79 and 1.45, respectively, in the unvaccinated cohort compared with 1.16 and 0.91 in the vaccinated cohort.
This elevation in the rate of mental illnesses was mainly seen after severe COVID-19 that led to hospitalization and remained higher for up to a year following severe COVID-19 in unvaccinated adults.
For severe COVID-19 with hospitalization, the adjusted hazard ratio for depression in the month following admission was 16.3 in the prevaccine cohort, 15.6 in the unvaccinated cohort, and 12.9 in the vaccinated cohort.
The adjusted hazard ratios for serious mental illness in the month after COVID hospitalization was 9.71 in the prevaccine cohort, 8.75 with no vaccination, and 6.52 with vaccination.
“Incidences of other mental illnesses were broadly similar to those of depression and serious mental illness, both overall and for COVID-19 with and without hospitalization,” the authors report in their paper.
Consistent with prior research, subgroup analyzes found the association of COVID-19 and mental illness was stronger among older adults and men, with no marked differences by ethnic group.
“We should be concerned about continuing consequences in people who experienced severe COVID-19 early in the pandemic, and they may include a continuing higher incidence of mental ill health, such as depression and serious mental illness,” Dr. Sterne said in the podcast.
In terms of ongoing booster vaccinations, “people who are advised that they are under vaccinated or recommended for further COVID-19 vaccination, should take those invitations seriously, because by preventing severe COVID-19, which is what vaccination does, you can prevent consequences such as mental illness,” Dr. Sterne added.
The study was supported by the COVID-19 Longitudinal Health and Wellbeing National Core Study, which is funded by the Medical Research Council and National Institute for Health and Care Research. The authors had no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
New research adds to a growing body of evidence suggesting that COVID-19 infection can be hard on mental health.
, particularly in those with severe COVID who had not been vaccinated.
Importantly, vaccination appeared to mitigate the adverse effects of COVID-19 on mental health, the investigators found.
“Our results highlight the importance COVID-19 vaccination in the general population and particularly among those with mental illnesses, who may be at higher risk of both SARS-CoV-2 infection and adverse outcomes following COVID-19,” first author Venexia Walker, PhD, with University of Bristol, United Kingdom, said in a news release.
The study was published online on August 21 in JAMA Psychiatry.
Novel Data
“Before this study, a number of papers had looked at associations of COVID diagnosis with mental ill health, and broadly speaking, they had reported associations of different magnitudes,” study author Jonathan A. C. Sterne, PhD, with University of Bristol, noted in a journal podcast.
“Some studies were restricted to patients who were hospitalized with COVID-19 and some not and the duration of follow-up varied. And importantly, the nature of COVID-19 changed profoundly as vaccination became available and there was little data on the impact of vaccination on associations of COVID-19 with subsequent mental ill health,” Dr. Sterne said.
The UK study was conducted in three cohorts — a cohort of about 18.6 million people who were diagnosed with COVID-19 before a vaccine was available, a cohort of about 14 million adults who were vaccinated, and a cohort of about 3.2 million people who were unvaccinated.
The researchers compared rates of various mental illnesses after COVID-19 with rates before or without COVID-19 and by vaccination status.
Across all cohorts, rates of most mental illnesses examined were “markedly elevated” during the first month following a COVID-19 diagnosis compared with rates before or without COVID-19.
For example, the adjusted hazard ratios for depression (the most common illness) and serious mental illness in the month after COVID-19 were 1.93 and 1.49, respectively, in the prevaccination cohort and 1.79 and 1.45, respectively, in the unvaccinated cohort compared with 1.16 and 0.91 in the vaccinated cohort.
This elevation in the rate of mental illnesses was mainly seen after severe COVID-19 that led to hospitalization and remained higher for up to a year following severe COVID-19 in unvaccinated adults.
For severe COVID-19 with hospitalization, the adjusted hazard ratio for depression in the month following admission was 16.3 in the prevaccine cohort, 15.6 in the unvaccinated cohort, and 12.9 in the vaccinated cohort.
The adjusted hazard ratios for serious mental illness in the month after COVID hospitalization was 9.71 in the prevaccine cohort, 8.75 with no vaccination, and 6.52 with vaccination.
“Incidences of other mental illnesses were broadly similar to those of depression and serious mental illness, both overall and for COVID-19 with and without hospitalization,” the authors report in their paper.
Consistent with prior research, subgroup analyzes found the association of COVID-19 and mental illness was stronger among older adults and men, with no marked differences by ethnic group.
“We should be concerned about continuing consequences in people who experienced severe COVID-19 early in the pandemic, and they may include a continuing higher incidence of mental ill health, such as depression and serious mental illness,” Dr. Sterne said in the podcast.
In terms of ongoing booster vaccinations, “people who are advised that they are under vaccinated or recommended for further COVID-19 vaccination, should take those invitations seriously, because by preventing severe COVID-19, which is what vaccination does, you can prevent consequences such as mental illness,” Dr. Sterne added.
The study was supported by the COVID-19 Longitudinal Health and Wellbeing National Core Study, which is funded by the Medical Research Council and National Institute for Health and Care Research. The authors had no relevant conflicts of interest.
A version of this article first appeared on Medscape.com.
Which Medications Can Cause Edema?
Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.
Therefore, it is important to know how to treat or prevent medication-induced edema.
There are four main causes of edema, and all can facilitate medication-induced edema.
- Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
- Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
- Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
- Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.
Medications That Can Cause Edema
- Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
- Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
- Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
- Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
- New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
- Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
- Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
- ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
- Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
- Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.
Implications
Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.
The key takeaways from this review are:
- Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
- Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
- Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.
Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.
This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.
Therefore, it is important to know how to treat or prevent medication-induced edema.
There are four main causes of edema, and all can facilitate medication-induced edema.
- Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
- Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
- Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
- Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.
Medications That Can Cause Edema
- Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
- Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
- Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
- Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
- New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
- Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
- Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
- ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
- Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
- Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.
Implications
Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.
The key takeaways from this review are:
- Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
- Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
- Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.
Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.
This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.
Therefore, it is important to know how to treat or prevent medication-induced edema.
There are four main causes of edema, and all can facilitate medication-induced edema.
- Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
- Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
- Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
- Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.
Medications That Can Cause Edema
- Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
- Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
- Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
- Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
- New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
- Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
- Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
- ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
- Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
- Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.
Implications
Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.
The key takeaways from this review are:
- Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
- Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
- Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.
Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.
This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.
Early-Life Exposure to Pollution Linked to Psychosis, Anxiety, Depression
Early-life exposure to air and noise pollution is associated with a higher risk for psychosis, depression, and anxiety in adolescence and early adulthood, results from a longitudinal birth cohort study showed.
While air pollution was associated primarily with psychotic experiences and depression, noise pollution was more likely to be associated with anxiety in adolescence and early adulthood.
“Early-life exposure could be detrimental to mental health given the extensive brain development and epigenetic processes that occur in utero and during infancy,” the researchers, led by Joanne Newbury, PhD, of Bristol Medical School, University of Bristol, England, wrote, adding that “the results of this cohort study provide novel evidence that early-life exposure to particulate matter is prospectively associated with the development of psychotic experiences and depression in youth.”
The findings were published online on May 28 in JAMA Network Open.
Large, Longitudinal Study
To learn more about how air and noise pollution may affect the brain from an early age, the investigators used data from the Avon Longitudinal Study of Parents and Children, an ongoing longitudinal birth cohort capturing data on new births in Southwest England from 1991 to 1992.
Investigators captured levels of air pollutants, which included nitrogen dioxide and fine particulate matter with a diameter smaller than 2.5 µm (PM2.5), in the areas where expectant mothers lived and where their children lived until age 12.
They also collected decibel levels of noise pollution in neighborhoods where expectant mothers and their children lived.
Participants were assessed for psychotic experiences, depression, and anxiety when they were 13, 18, and 24 years old.
Among the 9065 participants who had mental health data, 20% reported psychotic experiences, 11% reported depression, and 10% reported anxiety. About 60% of the participants had a family history of mental illness.
When they were age 13, 13.6% of participants reported psychotic experiences; 9.2% reported them at age 18, and 12.6% at age 24.
A lower number of participants reported feeling depressed and anxious at 13 years (5.6% for depression and 3.6% for anxiety) and 18 years (7.9% for depression and 5.7% for anxiety).
After adjusting for individual and family-level variables, including family psychiatric history, maternal social class, and neighborhood deprivation, elevated PM2.5 levels during pregnancy (P = .002) and childhood (P = .04) were associated with a significantly increased risk for psychotic experiences later in life. Pregnancy PM2.5 exposure was also associated with depression (P = .01).
Participants exposed to higher noise pollution in childhood and adolescence had an increased risk for anxiety (P = .03) as teenagers.
Vulnerability of the Developing Brain
The investigators noted that more information is needed to understand the underlying mechanisms behind these associations but noted that early-life exposure could be detrimental to mental health given “extensive brain development and epigenetic processes that occur in utero.”
They also noted that air pollution could lead to restricted fetal growth and premature birth, both of which are risk factors for psychopathology.
Martin Clift, PhD, of Swansea University in Swansea, Wales, who was not involved in the study, said that the paper highlights the need for more consideration of health consequences related to these exposures.
“As noted by the authors, this is an area that has received a lot of recent attention, yet there remains a large void of knowledge,” Dr. Clift said in a UK Science Media Centre release. “It highlights that some of the most dominant air pollutants can impact different mental health diagnoses, but that time-of-life is particularly important as to how each individual air pollutant may impact this diagnosis.”
Study limitations included limitations to generalizability of the data — the families in the study were more affluent and less diverse than the UK population overall.
The study was funded by the UK Medical Research Council, Wellcome Trust, and University of Bristol. Disclosures were noted in the original article.
A version of this article appeared on Medscape.com.
Early-life exposure to air and noise pollution is associated with a higher risk for psychosis, depression, and anxiety in adolescence and early adulthood, results from a longitudinal birth cohort study showed.
While air pollution was associated primarily with psychotic experiences and depression, noise pollution was more likely to be associated with anxiety in adolescence and early adulthood.
“Early-life exposure could be detrimental to mental health given the extensive brain development and epigenetic processes that occur in utero and during infancy,” the researchers, led by Joanne Newbury, PhD, of Bristol Medical School, University of Bristol, England, wrote, adding that “the results of this cohort study provide novel evidence that early-life exposure to particulate matter is prospectively associated with the development of psychotic experiences and depression in youth.”
The findings were published online on May 28 in JAMA Network Open.
Large, Longitudinal Study
To learn more about how air and noise pollution may affect the brain from an early age, the investigators used data from the Avon Longitudinal Study of Parents and Children, an ongoing longitudinal birth cohort capturing data on new births in Southwest England from 1991 to 1992.
Investigators captured levels of air pollutants, which included nitrogen dioxide and fine particulate matter with a diameter smaller than 2.5 µm (PM2.5), in the areas where expectant mothers lived and where their children lived until age 12.
They also collected decibel levels of noise pollution in neighborhoods where expectant mothers and their children lived.
Participants were assessed for psychotic experiences, depression, and anxiety when they were 13, 18, and 24 years old.
Among the 9065 participants who had mental health data, 20% reported psychotic experiences, 11% reported depression, and 10% reported anxiety. About 60% of the participants had a family history of mental illness.
When they were age 13, 13.6% of participants reported psychotic experiences; 9.2% reported them at age 18, and 12.6% at age 24.
A lower number of participants reported feeling depressed and anxious at 13 years (5.6% for depression and 3.6% for anxiety) and 18 years (7.9% for depression and 5.7% for anxiety).
After adjusting for individual and family-level variables, including family psychiatric history, maternal social class, and neighborhood deprivation, elevated PM2.5 levels during pregnancy (P = .002) and childhood (P = .04) were associated with a significantly increased risk for psychotic experiences later in life. Pregnancy PM2.5 exposure was also associated with depression (P = .01).
Participants exposed to higher noise pollution in childhood and adolescence had an increased risk for anxiety (P = .03) as teenagers.
Vulnerability of the Developing Brain
The investigators noted that more information is needed to understand the underlying mechanisms behind these associations but noted that early-life exposure could be detrimental to mental health given “extensive brain development and epigenetic processes that occur in utero.”
They also noted that air pollution could lead to restricted fetal growth and premature birth, both of which are risk factors for psychopathology.
Martin Clift, PhD, of Swansea University in Swansea, Wales, who was not involved in the study, said that the paper highlights the need for more consideration of health consequences related to these exposures.
“As noted by the authors, this is an area that has received a lot of recent attention, yet there remains a large void of knowledge,” Dr. Clift said in a UK Science Media Centre release. “It highlights that some of the most dominant air pollutants can impact different mental health diagnoses, but that time-of-life is particularly important as to how each individual air pollutant may impact this diagnosis.”
Study limitations included limitations to generalizability of the data — the families in the study were more affluent and less diverse than the UK population overall.
The study was funded by the UK Medical Research Council, Wellcome Trust, and University of Bristol. Disclosures were noted in the original article.
A version of this article appeared on Medscape.com.
Early-life exposure to air and noise pollution is associated with a higher risk for psychosis, depression, and anxiety in adolescence and early adulthood, results from a longitudinal birth cohort study showed.
While air pollution was associated primarily with psychotic experiences and depression, noise pollution was more likely to be associated with anxiety in adolescence and early adulthood.
“Early-life exposure could be detrimental to mental health given the extensive brain development and epigenetic processes that occur in utero and during infancy,” the researchers, led by Joanne Newbury, PhD, of Bristol Medical School, University of Bristol, England, wrote, adding that “the results of this cohort study provide novel evidence that early-life exposure to particulate matter is prospectively associated with the development of psychotic experiences and depression in youth.”
The findings were published online on May 28 in JAMA Network Open.
Large, Longitudinal Study
To learn more about how air and noise pollution may affect the brain from an early age, the investigators used data from the Avon Longitudinal Study of Parents and Children, an ongoing longitudinal birth cohort capturing data on new births in Southwest England from 1991 to 1992.
Investigators captured levels of air pollutants, which included nitrogen dioxide and fine particulate matter with a diameter smaller than 2.5 µm (PM2.5), in the areas where expectant mothers lived and where their children lived until age 12.
They also collected decibel levels of noise pollution in neighborhoods where expectant mothers and their children lived.
Participants were assessed for psychotic experiences, depression, and anxiety when they were 13, 18, and 24 years old.
Among the 9065 participants who had mental health data, 20% reported psychotic experiences, 11% reported depression, and 10% reported anxiety. About 60% of the participants had a family history of mental illness.
When they were age 13, 13.6% of participants reported psychotic experiences; 9.2% reported them at age 18, and 12.6% at age 24.
A lower number of participants reported feeling depressed and anxious at 13 years (5.6% for depression and 3.6% for anxiety) and 18 years (7.9% for depression and 5.7% for anxiety).
After adjusting for individual and family-level variables, including family psychiatric history, maternal social class, and neighborhood deprivation, elevated PM2.5 levels during pregnancy (P = .002) and childhood (P = .04) were associated with a significantly increased risk for psychotic experiences later in life. Pregnancy PM2.5 exposure was also associated with depression (P = .01).
Participants exposed to higher noise pollution in childhood and adolescence had an increased risk for anxiety (P = .03) as teenagers.
Vulnerability of the Developing Brain
The investigators noted that more information is needed to understand the underlying mechanisms behind these associations but noted that early-life exposure could be detrimental to mental health given “extensive brain development and epigenetic processes that occur in utero.”
They also noted that air pollution could lead to restricted fetal growth and premature birth, both of which are risk factors for psychopathology.
Martin Clift, PhD, of Swansea University in Swansea, Wales, who was not involved in the study, said that the paper highlights the need for more consideration of health consequences related to these exposures.
“As noted by the authors, this is an area that has received a lot of recent attention, yet there remains a large void of knowledge,” Dr. Clift said in a UK Science Media Centre release. “It highlights that some of the most dominant air pollutants can impact different mental health diagnoses, but that time-of-life is particularly important as to how each individual air pollutant may impact this diagnosis.”
Study limitations included limitations to generalizability of the data — the families in the study were more affluent and less diverse than the UK population overall.
The study was funded by the UK Medical Research Council, Wellcome Trust, and University of Bristol. Disclosures were noted in the original article.
A version of this article appeared on Medscape.com.
Teen Cannabis Use Tied to Dramatic Increased Risk for Psychosis
, new research showed.
Investigators at the University of Toronto, The Centre for Addiction and Mental Health (CAMH), and the Institute for Clinical Evaluative Sciences (ICES), in Canada, linked recent population-based survey data from more than 11,000 youngsters to health service use records, including hospitalizations, emergency department (ED) visits, and outpatient visits.
“We found a very strong association between cannabis use and risk of psychotic disorder in adolescence [although] surprisingly, we didn’t find evidence of association in young adulthood,” lead author André J. McDonald, PhD, currently a postdoctoral fellow at the Peter Boris Centre for Addictions Research and the Michael G. DeGroote Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ontario, Canada, said in a news release.
“These findings are consistent with the neurodevelopmental theory that teens are especially vulnerable to the effects of cannabis,” said Dr. McDonald, who conducted the research.
The study was published online in Psychological Medicine.
Increased Potency
“Epidemiologic research suggests that cannabis use may be a significant risk factor for psychotic disorders,” the authors wrote. However, methodological limitations of previous studies make it difficult to estimate the strength of association, with the current evidence base relying largely on cannabis use during the twentieth century, when the drug was “significantly less potent.” It’s plausible that the strength of association has increased due to increased cannabis potency.
The researchers believe youth cannabis use and psychotic disorders is “a critical public health issue,” especially as more jurisdictions liberalize cannabis use and the perception of harm declines among youth.
To estimate the association between cannabis use during youth and the risk for a psychotic disorder diagnosis, using recent population-based data, they used data from the 2009-2012 cycles of the Canadian Community Health Survey (CCHS) linked to administrative health data at ICES to study noninstitutionalized Ontario residents, aged 12-24 years, who had completed the CCHS during that period.
They excluded respondents who used health services for psychotic disorders during the 6 years prior to their CCHS interview date.
Respondents (n = 11,363; 51% men; mean age [SD], 18.3 [15.2-21.3] years) were followed for 6-9 years, with days to first hospitalization, ED visit, or outpatient visit related to a psychotic disorder as the primary outcome.
The researchers estimated age-specific hazard ratios during adolescence (12-19 years) and young adulthood (20-33 years) and conducted sensitivity analyses to explore alternative model conditions, including restricting the outcome to hospitalizations and ED visits, to increase specificity.
Compared with no cannabis use, cannabis use was significantly associated with an 11-fold increased risk for psychotic disorders during adolescence, although not during young adulthood (adjusted hazard ratio [aHR], 11.2; 95% CI, 4.6-27.3 and aHR, 1.3; 95% CI, 0.6-2.6, respectively).
Perception of Harm Declining
When the researchers restricted the outcome to hospitalizations and ED visits only, the strength of association “increased markedly” during adolescence, with a 26-fold higher association in cannabis users than in nonusers (aHR, 26.7; 95% CI, 7.7-92.8). However, there was no meaningful change during young adulthood (aHR, 1.8; 95% CI, 0.6-5.4).
“Many have hypothesized that adolescence is a more sensitive risk period than adulthood for the effect of cannabis use on psychotic disorder development, yet prior to this study, little epidemiologic evidence existed to support this view,” the authors wrote.
The data also suggest that cannabis use is “more strongly associated with more severe psychotic outcomes, as the strength of association during adolescence increased markedly when we restricted the outcome to hospitalizations and ED visits (the most severe types of health service use),” the investigators noted.
The authors noted several limitations. For instance, it’s unclear to what extent unmeasured confounders including genetic predisposition, family history of psychotic disorders, and trauma might have biased the results. In addition, they could not assess the potential confounding impact of genetic predisposition to psychotic disorders. The possibility of reverse causality also cannot be ruled out. It’s possible, they noted, that individuals with “psychotic dispositions” may self-medicate or show greater disposition to cannabis use.
Moreover, the dataset neither captured important factors regarding the cannabis itself, including delta-9-tetrahydrocannabinol potency, mode of use, product type, or cannabis dependence, nor captured institutionalized and homeless youth.
Nevertheless, they pointed to the findings as supporting a “precautionary principle” — as more jurisdictions move to liberalize cannabis use and perception of harm declines among youth, the findings suggest that evidence-based cannabis prevention strategies for adolescents are warranted.
This study was supported by CAMH, the University of Toronto, and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. The authors declared no relevant financial relationships.
A version of this article appeared on Medscape.com.
, new research showed.
Investigators at the University of Toronto, The Centre for Addiction and Mental Health (CAMH), and the Institute for Clinical Evaluative Sciences (ICES), in Canada, linked recent population-based survey data from more than 11,000 youngsters to health service use records, including hospitalizations, emergency department (ED) visits, and outpatient visits.
“We found a very strong association between cannabis use and risk of psychotic disorder in adolescence [although] surprisingly, we didn’t find evidence of association in young adulthood,” lead author André J. McDonald, PhD, currently a postdoctoral fellow at the Peter Boris Centre for Addictions Research and the Michael G. DeGroote Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ontario, Canada, said in a news release.
“These findings are consistent with the neurodevelopmental theory that teens are especially vulnerable to the effects of cannabis,” said Dr. McDonald, who conducted the research.
The study was published online in Psychological Medicine.
Increased Potency
“Epidemiologic research suggests that cannabis use may be a significant risk factor for psychotic disorders,” the authors wrote. However, methodological limitations of previous studies make it difficult to estimate the strength of association, with the current evidence base relying largely on cannabis use during the twentieth century, when the drug was “significantly less potent.” It’s plausible that the strength of association has increased due to increased cannabis potency.
The researchers believe youth cannabis use and psychotic disorders is “a critical public health issue,” especially as more jurisdictions liberalize cannabis use and the perception of harm declines among youth.
To estimate the association between cannabis use during youth and the risk for a psychotic disorder diagnosis, using recent population-based data, they used data from the 2009-2012 cycles of the Canadian Community Health Survey (CCHS) linked to administrative health data at ICES to study noninstitutionalized Ontario residents, aged 12-24 years, who had completed the CCHS during that period.
They excluded respondents who used health services for psychotic disorders during the 6 years prior to their CCHS interview date.
Respondents (n = 11,363; 51% men; mean age [SD], 18.3 [15.2-21.3] years) were followed for 6-9 years, with days to first hospitalization, ED visit, or outpatient visit related to a psychotic disorder as the primary outcome.
The researchers estimated age-specific hazard ratios during adolescence (12-19 years) and young adulthood (20-33 years) and conducted sensitivity analyses to explore alternative model conditions, including restricting the outcome to hospitalizations and ED visits, to increase specificity.
Compared with no cannabis use, cannabis use was significantly associated with an 11-fold increased risk for psychotic disorders during adolescence, although not during young adulthood (adjusted hazard ratio [aHR], 11.2; 95% CI, 4.6-27.3 and aHR, 1.3; 95% CI, 0.6-2.6, respectively).
Perception of Harm Declining
When the researchers restricted the outcome to hospitalizations and ED visits only, the strength of association “increased markedly” during adolescence, with a 26-fold higher association in cannabis users than in nonusers (aHR, 26.7; 95% CI, 7.7-92.8). However, there was no meaningful change during young adulthood (aHR, 1.8; 95% CI, 0.6-5.4).
“Many have hypothesized that adolescence is a more sensitive risk period than adulthood for the effect of cannabis use on psychotic disorder development, yet prior to this study, little epidemiologic evidence existed to support this view,” the authors wrote.
The data also suggest that cannabis use is “more strongly associated with more severe psychotic outcomes, as the strength of association during adolescence increased markedly when we restricted the outcome to hospitalizations and ED visits (the most severe types of health service use),” the investigators noted.
The authors noted several limitations. For instance, it’s unclear to what extent unmeasured confounders including genetic predisposition, family history of psychotic disorders, and trauma might have biased the results. In addition, they could not assess the potential confounding impact of genetic predisposition to psychotic disorders. The possibility of reverse causality also cannot be ruled out. It’s possible, they noted, that individuals with “psychotic dispositions” may self-medicate or show greater disposition to cannabis use.
Moreover, the dataset neither captured important factors regarding the cannabis itself, including delta-9-tetrahydrocannabinol potency, mode of use, product type, or cannabis dependence, nor captured institutionalized and homeless youth.
Nevertheless, they pointed to the findings as supporting a “precautionary principle” — as more jurisdictions move to liberalize cannabis use and perception of harm declines among youth, the findings suggest that evidence-based cannabis prevention strategies for adolescents are warranted.
This study was supported by CAMH, the University of Toronto, and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. The authors declared no relevant financial relationships.
A version of this article appeared on Medscape.com.
, new research showed.
Investigators at the University of Toronto, The Centre for Addiction and Mental Health (CAMH), and the Institute for Clinical Evaluative Sciences (ICES), in Canada, linked recent population-based survey data from more than 11,000 youngsters to health service use records, including hospitalizations, emergency department (ED) visits, and outpatient visits.
“We found a very strong association between cannabis use and risk of psychotic disorder in adolescence [although] surprisingly, we didn’t find evidence of association in young adulthood,” lead author André J. McDonald, PhD, currently a postdoctoral fellow at the Peter Boris Centre for Addictions Research and the Michael G. DeGroote Centre for Medicinal Cannabis Research, McMaster University, Hamilton, Ontario, Canada, said in a news release.
“These findings are consistent with the neurodevelopmental theory that teens are especially vulnerable to the effects of cannabis,” said Dr. McDonald, who conducted the research.
The study was published online in Psychological Medicine.
Increased Potency
“Epidemiologic research suggests that cannabis use may be a significant risk factor for psychotic disorders,” the authors wrote. However, methodological limitations of previous studies make it difficult to estimate the strength of association, with the current evidence base relying largely on cannabis use during the twentieth century, when the drug was “significantly less potent.” It’s plausible that the strength of association has increased due to increased cannabis potency.
The researchers believe youth cannabis use and psychotic disorders is “a critical public health issue,” especially as more jurisdictions liberalize cannabis use and the perception of harm declines among youth.
To estimate the association between cannabis use during youth and the risk for a psychotic disorder diagnosis, using recent population-based data, they used data from the 2009-2012 cycles of the Canadian Community Health Survey (CCHS) linked to administrative health data at ICES to study noninstitutionalized Ontario residents, aged 12-24 years, who had completed the CCHS during that period.
They excluded respondents who used health services for psychotic disorders during the 6 years prior to their CCHS interview date.
Respondents (n = 11,363; 51% men; mean age [SD], 18.3 [15.2-21.3] years) were followed for 6-9 years, with days to first hospitalization, ED visit, or outpatient visit related to a psychotic disorder as the primary outcome.
The researchers estimated age-specific hazard ratios during adolescence (12-19 years) and young adulthood (20-33 years) and conducted sensitivity analyses to explore alternative model conditions, including restricting the outcome to hospitalizations and ED visits, to increase specificity.
Compared with no cannabis use, cannabis use was significantly associated with an 11-fold increased risk for psychotic disorders during adolescence, although not during young adulthood (adjusted hazard ratio [aHR], 11.2; 95% CI, 4.6-27.3 and aHR, 1.3; 95% CI, 0.6-2.6, respectively).
Perception of Harm Declining
When the researchers restricted the outcome to hospitalizations and ED visits only, the strength of association “increased markedly” during adolescence, with a 26-fold higher association in cannabis users than in nonusers (aHR, 26.7; 95% CI, 7.7-92.8). However, there was no meaningful change during young adulthood (aHR, 1.8; 95% CI, 0.6-5.4).
“Many have hypothesized that adolescence is a more sensitive risk period than adulthood for the effect of cannabis use on psychotic disorder development, yet prior to this study, little epidemiologic evidence existed to support this view,” the authors wrote.
The data also suggest that cannabis use is “more strongly associated with more severe psychotic outcomes, as the strength of association during adolescence increased markedly when we restricted the outcome to hospitalizations and ED visits (the most severe types of health service use),” the investigators noted.
The authors noted several limitations. For instance, it’s unclear to what extent unmeasured confounders including genetic predisposition, family history of psychotic disorders, and trauma might have biased the results. In addition, they could not assess the potential confounding impact of genetic predisposition to psychotic disorders. The possibility of reverse causality also cannot be ruled out. It’s possible, they noted, that individuals with “psychotic dispositions” may self-medicate or show greater disposition to cannabis use.
Moreover, the dataset neither captured important factors regarding the cannabis itself, including delta-9-tetrahydrocannabinol potency, mode of use, product type, or cannabis dependence, nor captured institutionalized and homeless youth.
Nevertheless, they pointed to the findings as supporting a “precautionary principle” — as more jurisdictions move to liberalize cannabis use and perception of harm declines among youth, the findings suggest that evidence-based cannabis prevention strategies for adolescents are warranted.
This study was supported by CAMH, the University of Toronto, and ICES, which is funded by an annual grant from the Ontario Ministry of Health and the Ministry of Long-Term Care. The authors declared no relevant financial relationships.
A version of this article appeared on Medscape.com.
Do Antipsychotic Overprescribing Warning Letters Work?
Warning letters to primary care physicians (PCPs) regarding overprescription of quetiapine were helpful in reducing overprescribing of this agent, new research suggested.
Investigators analyzed data from an earlier trial that compared prescribing patterns in 5055 PCPs who receive a placebo letter or three warning letters informing them that their prescribing of quetiapine was high and under review by Medicare. Patients in question all had dementia and were either living in nursing homes or in the community.
The intervention reduced quetiapine use among all patients with dementia, with no detectable adverse effects on cognitive function, behavioral symptoms, depression, metabolic diagnoses, hospitalization, or death.
“This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia,” wrote investigators led by Adam Sacarny, PhD, of the Department of Health Policy and Management, Mailman School of Public Health, Columbia University, New York.
“This intervention and other[s] like it may be useful for future efforts to promote guideline-concordant care,” they added.
The study was published online in JAMA Network Open.
Off-Label Prescribing Common
The off-label use of antipsychotics in patients with dementia is fairly common, the investigators noted, affecting roughly one in seven nursing home residents and a similar number of community-dwelling older adults with dementia.
The agents are often prescribed to treat behavioral symptoms associated with dementia, including agitation and aggression. Although some evidence supports this use, antipsychotics in dementia patients can also cause an increased risk for weight gain, cognitive decline, falls and other injuries, cerebrovascular events, and mortality.
While some professional societies have called for “judicious use of antipsychotics in dementia care,” there is little evidence that reducing antipsychotic use in people with dementia might result in a benefit, investigators wrote.
The researchers analyzed data from a previous trial that focused on quetiapine, which is the most prescribed antipsychotic in the United States and is frequently used for patients with dementia.
In the original study, 2528 PCPs received a placebo letter and 2527 received three warning letters sent by the Centers for Medicare & Medicaid Services (CMS), which identified the highest-volume PCP prescribers of quetiapine.
The warning letters stated that the recipient’s quetiapine prescribing was high relative to their peers and was under review by Medicare. The placebo letter clarified an unrelated regulation.
The current secondary analysis followed the providers and a cohort of their patients from their first receipt of the letters in 2015 through April 2017. The current evaluation analyzes patients’ outcomes through December 2018, utilizing Medicare fee-for-service claims, Minimum Data Set nursing home assessment, and Medicare enrollment data.
Low-Cost, Effective Intervention
While the original study focused on total quetiapine prescribing by study PCPs, the current analysis focused on patients’ total quetiapine use per 90-day period. Additional secondary outcomes included measures of cognitive function and behavioral symptoms, indicators of depression, metabolic diagnoses, indicators of use of hospital and healthcare services, and death.
PCPs in the study had a total of 84,881 patients with dementia living in nursing homes and 261,288 living in the community. At baseline, there were 92,874 patients (mean age, 82 years; 69% female).
The warning letters were associated with reduced quetiapine use among both nursing home patients and community-dwelling patients (adjusted difference, –0.7 days; P = .02 and adjusted difference, −1.5 days; P < .001, respectively).
Among nursing home patients, there were no statistically significant adverse changes in cognitive of behavioral health measures that coincided with reduction in quetiapine use.
Although a higher percentage of treatment vs control patients reported weight loss, the difference was not significant, and rates of metabolic diagnoses were similar in both groups. There were also no significant differences between the groups in emergency department use, inpatient hospital admission, or use of restraints.
Results were similar for patients living in the community.
Additionally, no adverse effects on more severe health endpoints, including rates of hospital use or entry to nursing facilities, were detected. Importantly, the risk for death was statistically significantly lower for patients whose PCPs had received warning letters vs control patients (P = .04).
The analysis “provides evidence that a low-cost letter intervention informed by behavioral science can reduce prescribing of quetiapine to patients with dementia in nursing home and community settings,” the authors wrote.
Researchers did not directly observe the administration of the medication but instead used prescription drug fills as a proxy. Moreover, they could not observe results for patients enrolled in Medicare Advantage, and claims-based and assessment-based outcomes might have been subject to measurement errors and under-ascertainment of diagnoses.
The authors received support from the National Institute on Aging. They reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Warning letters to primary care physicians (PCPs) regarding overprescription of quetiapine were helpful in reducing overprescribing of this agent, new research suggested.
Investigators analyzed data from an earlier trial that compared prescribing patterns in 5055 PCPs who receive a placebo letter or three warning letters informing them that their prescribing of quetiapine was high and under review by Medicare. Patients in question all had dementia and were either living in nursing homes or in the community.
The intervention reduced quetiapine use among all patients with dementia, with no detectable adverse effects on cognitive function, behavioral symptoms, depression, metabolic diagnoses, hospitalization, or death.
“This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia,” wrote investigators led by Adam Sacarny, PhD, of the Department of Health Policy and Management, Mailman School of Public Health, Columbia University, New York.
“This intervention and other[s] like it may be useful for future efforts to promote guideline-concordant care,” they added.
The study was published online in JAMA Network Open.
Off-Label Prescribing Common
The off-label use of antipsychotics in patients with dementia is fairly common, the investigators noted, affecting roughly one in seven nursing home residents and a similar number of community-dwelling older adults with dementia.
The agents are often prescribed to treat behavioral symptoms associated with dementia, including agitation and aggression. Although some evidence supports this use, antipsychotics in dementia patients can also cause an increased risk for weight gain, cognitive decline, falls and other injuries, cerebrovascular events, and mortality.
While some professional societies have called for “judicious use of antipsychotics in dementia care,” there is little evidence that reducing antipsychotic use in people with dementia might result in a benefit, investigators wrote.
The researchers analyzed data from a previous trial that focused on quetiapine, which is the most prescribed antipsychotic in the United States and is frequently used for patients with dementia.
In the original study, 2528 PCPs received a placebo letter and 2527 received three warning letters sent by the Centers for Medicare & Medicaid Services (CMS), which identified the highest-volume PCP prescribers of quetiapine.
The warning letters stated that the recipient’s quetiapine prescribing was high relative to their peers and was under review by Medicare. The placebo letter clarified an unrelated regulation.
The current secondary analysis followed the providers and a cohort of their patients from their first receipt of the letters in 2015 through April 2017. The current evaluation analyzes patients’ outcomes through December 2018, utilizing Medicare fee-for-service claims, Minimum Data Set nursing home assessment, and Medicare enrollment data.
Low-Cost, Effective Intervention
While the original study focused on total quetiapine prescribing by study PCPs, the current analysis focused on patients’ total quetiapine use per 90-day period. Additional secondary outcomes included measures of cognitive function and behavioral symptoms, indicators of depression, metabolic diagnoses, indicators of use of hospital and healthcare services, and death.
PCPs in the study had a total of 84,881 patients with dementia living in nursing homes and 261,288 living in the community. At baseline, there were 92,874 patients (mean age, 82 years; 69% female).
The warning letters were associated with reduced quetiapine use among both nursing home patients and community-dwelling patients (adjusted difference, –0.7 days; P = .02 and adjusted difference, −1.5 days; P < .001, respectively).
Among nursing home patients, there were no statistically significant adverse changes in cognitive of behavioral health measures that coincided with reduction in quetiapine use.
Although a higher percentage of treatment vs control patients reported weight loss, the difference was not significant, and rates of metabolic diagnoses were similar in both groups. There were also no significant differences between the groups in emergency department use, inpatient hospital admission, or use of restraints.
Results were similar for patients living in the community.
Additionally, no adverse effects on more severe health endpoints, including rates of hospital use or entry to nursing facilities, were detected. Importantly, the risk for death was statistically significantly lower for patients whose PCPs had received warning letters vs control patients (P = .04).
The analysis “provides evidence that a low-cost letter intervention informed by behavioral science can reduce prescribing of quetiapine to patients with dementia in nursing home and community settings,” the authors wrote.
Researchers did not directly observe the administration of the medication but instead used prescription drug fills as a proxy. Moreover, they could not observe results for patients enrolled in Medicare Advantage, and claims-based and assessment-based outcomes might have been subject to measurement errors and under-ascertainment of diagnoses.
The authors received support from the National Institute on Aging. They reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Warning letters to primary care physicians (PCPs) regarding overprescription of quetiapine were helpful in reducing overprescribing of this agent, new research suggested.
Investigators analyzed data from an earlier trial that compared prescribing patterns in 5055 PCPs who receive a placebo letter or three warning letters informing them that their prescribing of quetiapine was high and under review by Medicare. Patients in question all had dementia and were either living in nursing homes or in the community.
The intervention reduced quetiapine use among all patients with dementia, with no detectable adverse effects on cognitive function, behavioral symptoms, depression, metabolic diagnoses, hospitalization, or death.
“This study found that overprescribing warning letters to PCPs safely reduced quetiapine prescribing to their patients with dementia,” wrote investigators led by Adam Sacarny, PhD, of the Department of Health Policy and Management, Mailman School of Public Health, Columbia University, New York.
“This intervention and other[s] like it may be useful for future efforts to promote guideline-concordant care,” they added.
The study was published online in JAMA Network Open.
Off-Label Prescribing Common
The off-label use of antipsychotics in patients with dementia is fairly common, the investigators noted, affecting roughly one in seven nursing home residents and a similar number of community-dwelling older adults with dementia.
The agents are often prescribed to treat behavioral symptoms associated with dementia, including agitation and aggression. Although some evidence supports this use, antipsychotics in dementia patients can also cause an increased risk for weight gain, cognitive decline, falls and other injuries, cerebrovascular events, and mortality.
While some professional societies have called for “judicious use of antipsychotics in dementia care,” there is little evidence that reducing antipsychotic use in people with dementia might result in a benefit, investigators wrote.
The researchers analyzed data from a previous trial that focused on quetiapine, which is the most prescribed antipsychotic in the United States and is frequently used for patients with dementia.
In the original study, 2528 PCPs received a placebo letter and 2527 received three warning letters sent by the Centers for Medicare & Medicaid Services (CMS), which identified the highest-volume PCP prescribers of quetiapine.
The warning letters stated that the recipient’s quetiapine prescribing was high relative to their peers and was under review by Medicare. The placebo letter clarified an unrelated regulation.
The current secondary analysis followed the providers and a cohort of their patients from their first receipt of the letters in 2015 through April 2017. The current evaluation analyzes patients’ outcomes through December 2018, utilizing Medicare fee-for-service claims, Minimum Data Set nursing home assessment, and Medicare enrollment data.
Low-Cost, Effective Intervention
While the original study focused on total quetiapine prescribing by study PCPs, the current analysis focused on patients’ total quetiapine use per 90-day period. Additional secondary outcomes included measures of cognitive function and behavioral symptoms, indicators of depression, metabolic diagnoses, indicators of use of hospital and healthcare services, and death.
PCPs in the study had a total of 84,881 patients with dementia living in nursing homes and 261,288 living in the community. At baseline, there were 92,874 patients (mean age, 82 years; 69% female).
The warning letters were associated with reduced quetiapine use among both nursing home patients and community-dwelling patients (adjusted difference, –0.7 days; P = .02 and adjusted difference, −1.5 days; P < .001, respectively).
Among nursing home patients, there were no statistically significant adverse changes in cognitive of behavioral health measures that coincided with reduction in quetiapine use.
Although a higher percentage of treatment vs control patients reported weight loss, the difference was not significant, and rates of metabolic diagnoses were similar in both groups. There were also no significant differences between the groups in emergency department use, inpatient hospital admission, or use of restraints.
Results were similar for patients living in the community.
Additionally, no adverse effects on more severe health endpoints, including rates of hospital use or entry to nursing facilities, were detected. Importantly, the risk for death was statistically significantly lower for patients whose PCPs had received warning letters vs control patients (P = .04).
The analysis “provides evidence that a low-cost letter intervention informed by behavioral science can reduce prescribing of quetiapine to patients with dementia in nursing home and community settings,” the authors wrote.
Researchers did not directly observe the administration of the medication but instead used prescription drug fills as a proxy. Moreover, they could not observe results for patients enrolled in Medicare Advantage, and claims-based and assessment-based outcomes might have been subject to measurement errors and under-ascertainment of diagnoses.
The authors received support from the National Institute on Aging. They reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
The DEA Plans to Reschedule Marijuana: What Happens Next?
The US Drug Enforcement Agency (DEA) is moving forward with plans to move marijuana from a Schedule I to a Schedule III controlled substance under the Controlled Substance Act (CSA), the US Department of Justice officials announced this week.
First reported by the Associated Press and since confirmed by this news organization through a US Department of Justice spokesperson, the news made international headlines. Despite the media splash, the final rule is still months away.
How did we get here? What happens next? What impact might rescheduling have on clinicians, patients, researchers, and the medical cannabis industry?
Why Reschedule? Why Now?
The DEA’s decision is based on a 2023 determination from the US Food and Drug Administration (FDA) that marijuana has a legitimate medical use and should be moved to Schedule III.
This class includes ketamine, acetaminophen with codeine, and buprenorphine.
Even though the manufacturing, distribution, sale, and use of marijuana has long violated federal law, 38 states and Washington, DC, have legalized medical cannabis, and 24 states and DC have legalized its recreational use.
Congress has allowed states leeway for the distribution and use of medical marijuana, and current and previous presidential administrations have chosen not to aggressively pursue prosecution of state-allowed marijuana use, the Congressional Research Service (CRS) reports.
Pressure to address the conflict between federal and state laws and an increasing interest in drug development of cannabis and cannabis-derived products probably contributed to the DEA’s decision, said Stephen Strakowski, MD, professor, and vice chair of psychiatry at Indiana University in Indianapolis, and professor and associate vice president at University of Texas in Austin.
“The trend toward legalization is everywhere and even though nationally the feds in this instance are lagging the states, the pressure to legalize has been intense for 50 years and it’s not surprising that the DEA is finally following that lead,” Dr. Strakowski told this news organization.
How Does Rescheduling Work? What’s the Timeline?
The DEA will submit a formal rule proposing that marijuana be moved from Schedule I to Schedule III to the White House Office of Management and Budget. The timing of the submission is unclear.
Once the proposed rule is posted to the Federal Register, there will be a public comment period, which usually lasts 30-60 days.
“This will likely generate a lot of public comment,” Robert Mikos, JD, LaRoche Family Chair in Law at Vanderbilt University Law School in Nashville, Tennessee, told this news organization. “Then the agency has to go back and wade through those comments and decide if they want to proceed with the rule as proposed or modify it.”
A final rule will probably be posted before the end of the current presidential term in January, Mr. Mikos said. While a lawsuit blocking its implementation is possible, there is a “low chance that a court would block this,” he added.
How Will Rescheduling Affect Medical Marijuana?
For medical marijuana, changing the drug to a Schedule III means that it can legally be prescribed but only in states that have legalized medical cannabis, Mr. Mikos said.
“If you’re a patient in a state with a medical marijuana law and your physician gives you a prescription for medical marijuana and you possess it, you will no longer be guilty of a federal crime,” he said.
Rescheduling could also benefit patients who receive care through the Veterans Administration (VA), Mr. Mikos said. For several years, the VA has had a policy that blocked clinicians from prescribing medical marijuana because as a Schedule I drug, it was determined to have no accepted medical use.
“It’s possible the VA may drop that policy once the drug gets rescheduled. If you’re in a medical marijuana state, if you’re a VA patient, and you don’t want to spend the extra money to go outside that system, this will have meaningful impact on their lives,” Mr. Mikos said.
But what about patients living in states that have not legalized medical cannabis?
“You still wouldn’t be committing a federal crime, but you could be violating state law,” Mr. Mikos said. “That’s a much more salient consideration because if you look at who goes after individuals who possess small amounts of drugs, the state handles 99% of those cases.”
The manufacture, distribution, and possession of recreational marijuana would remain illegal under federal law.
What Does It Mean for Medical Marijuana Dispensaries?
Though rescheduling makes it legal for clinicians to prescribe medical marijuana and for patients to use it, the actual sale of the drug will remain illegal under federal law because rescheduling only changes prescribing under the CSA, Mr. Mikos said.
“If you’re a dispensary and you sell it, even if it’s to somebody who’s got a prescription, you’re still probably violating the Food, Drug and Cosmetics Act. Rescheduling doesn’t change that,” he said.
“Even assuming the DEA follows through with this and it doesn’t come undone at some future date, the industry is still going struggle to comply with the Controlled Substances Act post rescheduling because that statute is going to continue to impose a number of regulations on the industry,” Mr. Mikos added.
However, rescheduling would change the tax status of the estimated 12,000-15,000 state-licensed cannabis dispensaries in the United States, allowing access to certain tax deductions that are unavailable to sales involving Schedule I controlled substances, James Daily, JD, MS, with Center for Empirical Research in the Law at Washington University School of Law in St. Louis, told this news organization.
“Many cannabis businesses do in fact pay federal taxes, but the inability to take any federal tax credits or deductions means that their effective tax rate is much higher than it would otherwise be,” Mr. Daily said.
Although new federal tax deductions would likely available to cannabis businesses if marijuana were rescheduled to Schedule III, “their business would still be in violation of federal law,” he said.
“This creates a further tension between state and federal law, which could be resolved by further legalization or it could be resolved by extending the prohibition on tax deductions to include cannabis and not just Schedule I and II drugs,” he added.
Will Rescheduling Make It Easier to Conduct Cannabis-Related Research?
Research on medical cannabis has been stymied by FDA and DEA regulations regarding the study of Schedule I controlled substances. Although rescheduling could lift that barrier, other challenges would remain.
“Schedule III drugs can be more easily researched, but it’s unclear if, for example, a clinical trial could lawfully obtain the cannabis from a dispensary or if they would still have to go through the one legal federal supplier of cannabis,” Daily said.
The FDA reports having received more than 800 investigational new drug applications for and pre-investigational new drug applications related to cannabis and cannabis-derived products since the 1970s, the agency reports. To date, the FDA has not approved any marketing drug applications for cannabis for the treatment of any disease or condition.
In January 2023, the agency published updated guidelines for researchers and sponsors interested in developing drugs containing cannabis or cannabis-derived compounds.
It’s unclear whether those guidelines would be updated if the rescheduling moves forward.
Does Rescheduling Marijuana Pose Any Risk?
In its report to the DEA that marijuana be rescheduled, the FDA was careful to note that the agency’s recommendation is “not meant to imply that safety and effectiveness have been established for marijuana that would support FDA approval of a marijuana drug product for a particular indication.”
That’s a notation that clinicians and patients should take to heart, Dr. Strakowski said.
“It’s important to remind people that Schedule III drugs, by definition, have addiction and other side effect risks,” he said. “The celebrity marketing that sits behind a lot of this is incompletely informed. It’s portrayed as fun and harmless in almost every movie and conversation you see, and we know that’s not true.”
Previous studies have linked cannabis to increased risk for mania, anxiety disorders, and schizophrenia.
“It is increasingly clear that marijuana use is linked to poor outcomes in people who struggle with mental illness,” Dr. Strakowski said. “We have no evidence that it can help you but there is evidence that it can harm you.”
Dr. Strakowski likens cannabis use to alcohol, which is a known depressant that is associated with worse outcomes in people with mental illness.
“I think with cannabis, we don’t know enough about it yet, but we do know that it does have some anxiety risks,” he said. “The risks in people with mental illness are simply different than in people who don’t have mental illness.”
Dr. Strakowski, Mr. Mikos, and Mr. Daily report no relevant disclosures.
A version of this article appeared on Medscape.com.
The US Drug Enforcement Agency (DEA) is moving forward with plans to move marijuana from a Schedule I to a Schedule III controlled substance under the Controlled Substance Act (CSA), the US Department of Justice officials announced this week.
First reported by the Associated Press and since confirmed by this news organization through a US Department of Justice spokesperson, the news made international headlines. Despite the media splash, the final rule is still months away.
How did we get here? What happens next? What impact might rescheduling have on clinicians, patients, researchers, and the medical cannabis industry?
Why Reschedule? Why Now?
The DEA’s decision is based on a 2023 determination from the US Food and Drug Administration (FDA) that marijuana has a legitimate medical use and should be moved to Schedule III.
This class includes ketamine, acetaminophen with codeine, and buprenorphine.
Even though the manufacturing, distribution, sale, and use of marijuana has long violated federal law, 38 states and Washington, DC, have legalized medical cannabis, and 24 states and DC have legalized its recreational use.
Congress has allowed states leeway for the distribution and use of medical marijuana, and current and previous presidential administrations have chosen not to aggressively pursue prosecution of state-allowed marijuana use, the Congressional Research Service (CRS) reports.
Pressure to address the conflict between federal and state laws and an increasing interest in drug development of cannabis and cannabis-derived products probably contributed to the DEA’s decision, said Stephen Strakowski, MD, professor, and vice chair of psychiatry at Indiana University in Indianapolis, and professor and associate vice president at University of Texas in Austin.
“The trend toward legalization is everywhere and even though nationally the feds in this instance are lagging the states, the pressure to legalize has been intense for 50 years and it’s not surprising that the DEA is finally following that lead,” Dr. Strakowski told this news organization.
How Does Rescheduling Work? What’s the Timeline?
The DEA will submit a formal rule proposing that marijuana be moved from Schedule I to Schedule III to the White House Office of Management and Budget. The timing of the submission is unclear.
Once the proposed rule is posted to the Federal Register, there will be a public comment period, which usually lasts 30-60 days.
“This will likely generate a lot of public comment,” Robert Mikos, JD, LaRoche Family Chair in Law at Vanderbilt University Law School in Nashville, Tennessee, told this news organization. “Then the agency has to go back and wade through those comments and decide if they want to proceed with the rule as proposed or modify it.”
A final rule will probably be posted before the end of the current presidential term in January, Mr. Mikos said. While a lawsuit blocking its implementation is possible, there is a “low chance that a court would block this,” he added.
How Will Rescheduling Affect Medical Marijuana?
For medical marijuana, changing the drug to a Schedule III means that it can legally be prescribed but only in states that have legalized medical cannabis, Mr. Mikos said.
“If you’re a patient in a state with a medical marijuana law and your physician gives you a prescription for medical marijuana and you possess it, you will no longer be guilty of a federal crime,” he said.
Rescheduling could also benefit patients who receive care through the Veterans Administration (VA), Mr. Mikos said. For several years, the VA has had a policy that blocked clinicians from prescribing medical marijuana because as a Schedule I drug, it was determined to have no accepted medical use.
“It’s possible the VA may drop that policy once the drug gets rescheduled. If you’re in a medical marijuana state, if you’re a VA patient, and you don’t want to spend the extra money to go outside that system, this will have meaningful impact on their lives,” Mr. Mikos said.
But what about patients living in states that have not legalized medical cannabis?
“You still wouldn’t be committing a federal crime, but you could be violating state law,” Mr. Mikos said. “That’s a much more salient consideration because if you look at who goes after individuals who possess small amounts of drugs, the state handles 99% of those cases.”
The manufacture, distribution, and possession of recreational marijuana would remain illegal under federal law.
What Does It Mean for Medical Marijuana Dispensaries?
Though rescheduling makes it legal for clinicians to prescribe medical marijuana and for patients to use it, the actual sale of the drug will remain illegal under federal law because rescheduling only changes prescribing under the CSA, Mr. Mikos said.
“If you’re a dispensary and you sell it, even if it’s to somebody who’s got a prescription, you’re still probably violating the Food, Drug and Cosmetics Act. Rescheduling doesn’t change that,” he said.
“Even assuming the DEA follows through with this and it doesn’t come undone at some future date, the industry is still going struggle to comply with the Controlled Substances Act post rescheduling because that statute is going to continue to impose a number of regulations on the industry,” Mr. Mikos added.
However, rescheduling would change the tax status of the estimated 12,000-15,000 state-licensed cannabis dispensaries in the United States, allowing access to certain tax deductions that are unavailable to sales involving Schedule I controlled substances, James Daily, JD, MS, with Center for Empirical Research in the Law at Washington University School of Law in St. Louis, told this news organization.
“Many cannabis businesses do in fact pay federal taxes, but the inability to take any federal tax credits or deductions means that their effective tax rate is much higher than it would otherwise be,” Mr. Daily said.
Although new federal tax deductions would likely available to cannabis businesses if marijuana were rescheduled to Schedule III, “their business would still be in violation of federal law,” he said.
“This creates a further tension between state and federal law, which could be resolved by further legalization or it could be resolved by extending the prohibition on tax deductions to include cannabis and not just Schedule I and II drugs,” he added.
Will Rescheduling Make It Easier to Conduct Cannabis-Related Research?
Research on medical cannabis has been stymied by FDA and DEA regulations regarding the study of Schedule I controlled substances. Although rescheduling could lift that barrier, other challenges would remain.
“Schedule III drugs can be more easily researched, but it’s unclear if, for example, a clinical trial could lawfully obtain the cannabis from a dispensary or if they would still have to go through the one legal federal supplier of cannabis,” Daily said.
The FDA reports having received more than 800 investigational new drug applications for and pre-investigational new drug applications related to cannabis and cannabis-derived products since the 1970s, the agency reports. To date, the FDA has not approved any marketing drug applications for cannabis for the treatment of any disease or condition.
In January 2023, the agency published updated guidelines for researchers and sponsors interested in developing drugs containing cannabis or cannabis-derived compounds.
It’s unclear whether those guidelines would be updated if the rescheduling moves forward.
Does Rescheduling Marijuana Pose Any Risk?
In its report to the DEA that marijuana be rescheduled, the FDA was careful to note that the agency’s recommendation is “not meant to imply that safety and effectiveness have been established for marijuana that would support FDA approval of a marijuana drug product for a particular indication.”
That’s a notation that clinicians and patients should take to heart, Dr. Strakowski said.
“It’s important to remind people that Schedule III drugs, by definition, have addiction and other side effect risks,” he said. “The celebrity marketing that sits behind a lot of this is incompletely informed. It’s portrayed as fun and harmless in almost every movie and conversation you see, and we know that’s not true.”
Previous studies have linked cannabis to increased risk for mania, anxiety disorders, and schizophrenia.
“It is increasingly clear that marijuana use is linked to poor outcomes in people who struggle with mental illness,” Dr. Strakowski said. “We have no evidence that it can help you but there is evidence that it can harm you.”
Dr. Strakowski likens cannabis use to alcohol, which is a known depressant that is associated with worse outcomes in people with mental illness.
“I think with cannabis, we don’t know enough about it yet, but we do know that it does have some anxiety risks,” he said. “The risks in people with mental illness are simply different than in people who don’t have mental illness.”
Dr. Strakowski, Mr. Mikos, and Mr. Daily report no relevant disclosures.
A version of this article appeared on Medscape.com.
The US Drug Enforcement Agency (DEA) is moving forward with plans to move marijuana from a Schedule I to a Schedule III controlled substance under the Controlled Substance Act (CSA), the US Department of Justice officials announced this week.
First reported by the Associated Press and since confirmed by this news organization through a US Department of Justice spokesperson, the news made international headlines. Despite the media splash, the final rule is still months away.
How did we get here? What happens next? What impact might rescheduling have on clinicians, patients, researchers, and the medical cannabis industry?
Why Reschedule? Why Now?
The DEA’s decision is based on a 2023 determination from the US Food and Drug Administration (FDA) that marijuana has a legitimate medical use and should be moved to Schedule III.
This class includes ketamine, acetaminophen with codeine, and buprenorphine.
Even though the manufacturing, distribution, sale, and use of marijuana has long violated federal law, 38 states and Washington, DC, have legalized medical cannabis, and 24 states and DC have legalized its recreational use.
Congress has allowed states leeway for the distribution and use of medical marijuana, and current and previous presidential administrations have chosen not to aggressively pursue prosecution of state-allowed marijuana use, the Congressional Research Service (CRS) reports.
Pressure to address the conflict between federal and state laws and an increasing interest in drug development of cannabis and cannabis-derived products probably contributed to the DEA’s decision, said Stephen Strakowski, MD, professor, and vice chair of psychiatry at Indiana University in Indianapolis, and professor and associate vice president at University of Texas in Austin.
“The trend toward legalization is everywhere and even though nationally the feds in this instance are lagging the states, the pressure to legalize has been intense for 50 years and it’s not surprising that the DEA is finally following that lead,” Dr. Strakowski told this news organization.
How Does Rescheduling Work? What’s the Timeline?
The DEA will submit a formal rule proposing that marijuana be moved from Schedule I to Schedule III to the White House Office of Management and Budget. The timing of the submission is unclear.
Once the proposed rule is posted to the Federal Register, there will be a public comment period, which usually lasts 30-60 days.
“This will likely generate a lot of public comment,” Robert Mikos, JD, LaRoche Family Chair in Law at Vanderbilt University Law School in Nashville, Tennessee, told this news organization. “Then the agency has to go back and wade through those comments and decide if they want to proceed with the rule as proposed or modify it.”
A final rule will probably be posted before the end of the current presidential term in January, Mr. Mikos said. While a lawsuit blocking its implementation is possible, there is a “low chance that a court would block this,” he added.
How Will Rescheduling Affect Medical Marijuana?
For medical marijuana, changing the drug to a Schedule III means that it can legally be prescribed but only in states that have legalized medical cannabis, Mr. Mikos said.
“If you’re a patient in a state with a medical marijuana law and your physician gives you a prescription for medical marijuana and you possess it, you will no longer be guilty of a federal crime,” he said.
Rescheduling could also benefit patients who receive care through the Veterans Administration (VA), Mr. Mikos said. For several years, the VA has had a policy that blocked clinicians from prescribing medical marijuana because as a Schedule I drug, it was determined to have no accepted medical use.
“It’s possible the VA may drop that policy once the drug gets rescheduled. If you’re in a medical marijuana state, if you’re a VA patient, and you don’t want to spend the extra money to go outside that system, this will have meaningful impact on their lives,” Mr. Mikos said.
But what about patients living in states that have not legalized medical cannabis?
“You still wouldn’t be committing a federal crime, but you could be violating state law,” Mr. Mikos said. “That’s a much more salient consideration because if you look at who goes after individuals who possess small amounts of drugs, the state handles 99% of those cases.”
The manufacture, distribution, and possession of recreational marijuana would remain illegal under federal law.
What Does It Mean for Medical Marijuana Dispensaries?
Though rescheduling makes it legal for clinicians to prescribe medical marijuana and for patients to use it, the actual sale of the drug will remain illegal under federal law because rescheduling only changes prescribing under the CSA, Mr. Mikos said.
“If you’re a dispensary and you sell it, even if it’s to somebody who’s got a prescription, you’re still probably violating the Food, Drug and Cosmetics Act. Rescheduling doesn’t change that,” he said.
“Even assuming the DEA follows through with this and it doesn’t come undone at some future date, the industry is still going struggle to comply with the Controlled Substances Act post rescheduling because that statute is going to continue to impose a number of regulations on the industry,” Mr. Mikos added.
However, rescheduling would change the tax status of the estimated 12,000-15,000 state-licensed cannabis dispensaries in the United States, allowing access to certain tax deductions that are unavailable to sales involving Schedule I controlled substances, James Daily, JD, MS, with Center for Empirical Research in the Law at Washington University School of Law in St. Louis, told this news organization.
“Many cannabis businesses do in fact pay federal taxes, but the inability to take any federal tax credits or deductions means that their effective tax rate is much higher than it would otherwise be,” Mr. Daily said.
Although new federal tax deductions would likely available to cannabis businesses if marijuana were rescheduled to Schedule III, “their business would still be in violation of federal law,” he said.
“This creates a further tension between state and federal law, which could be resolved by further legalization or it could be resolved by extending the prohibition on tax deductions to include cannabis and not just Schedule I and II drugs,” he added.
Will Rescheduling Make It Easier to Conduct Cannabis-Related Research?
Research on medical cannabis has been stymied by FDA and DEA regulations regarding the study of Schedule I controlled substances. Although rescheduling could lift that barrier, other challenges would remain.
“Schedule III drugs can be more easily researched, but it’s unclear if, for example, a clinical trial could lawfully obtain the cannabis from a dispensary or if they would still have to go through the one legal federal supplier of cannabis,” Daily said.
The FDA reports having received more than 800 investigational new drug applications for and pre-investigational new drug applications related to cannabis and cannabis-derived products since the 1970s, the agency reports. To date, the FDA has not approved any marketing drug applications for cannabis for the treatment of any disease or condition.
In January 2023, the agency published updated guidelines for researchers and sponsors interested in developing drugs containing cannabis or cannabis-derived compounds.
It’s unclear whether those guidelines would be updated if the rescheduling moves forward.
Does Rescheduling Marijuana Pose Any Risk?
In its report to the DEA that marijuana be rescheduled, the FDA was careful to note that the agency’s recommendation is “not meant to imply that safety and effectiveness have been established for marijuana that would support FDA approval of a marijuana drug product for a particular indication.”
That’s a notation that clinicians and patients should take to heart, Dr. Strakowski said.
“It’s important to remind people that Schedule III drugs, by definition, have addiction and other side effect risks,” he said. “The celebrity marketing that sits behind a lot of this is incompletely informed. It’s portrayed as fun and harmless in almost every movie and conversation you see, and we know that’s not true.”
Previous studies have linked cannabis to increased risk for mania, anxiety disorders, and schizophrenia.
“It is increasingly clear that marijuana use is linked to poor outcomes in people who struggle with mental illness,” Dr. Strakowski said. “We have no evidence that it can help you but there is evidence that it can harm you.”
Dr. Strakowski likens cannabis use to alcohol, which is a known depressant that is associated with worse outcomes in people with mental illness.
“I think with cannabis, we don’t know enough about it yet, but we do know that it does have some anxiety risks,” he said. “The risks in people with mental illness are simply different than in people who don’t have mental illness.”
Dr. Strakowski, Mr. Mikos, and Mr. Daily report no relevant disclosures.
A version of this article appeared on Medscape.com.
Most Homeless People Have Mental Health Disorders
Most people experiencing homelessness have mental health disorders, according to a systematic review and meta-analysis.
In an examination of studies that included nearly 50,000 participants, the current prevalence of mental health disorders among people experiencing homelessness was 67% and the lifetime prevalence was 77%.
“The relationship is likely bidirectional, where experiencing homelessness may exacerbate mental health symptoms or where having a mental health disorder may increase an individual’s risk for experiencing homelessness,” lead author Rebecca Barry, PhD, a postdoctoral fellow at the University of Calgary in Calgary, Alberta, Canada, told this news organization.
“There are also likely stressors that increase both risk for homelessness and risk for developing mental health disorders. This study examines prevalence but does not examine causal relationships,” she said.
The findings were published in JAMA Psychiatry.
A Growing Problem
To determine the current and lifetime prevalence of mental health disorders among the homeless population, the researchers analyzed 85 studies that examined this question in participants aged ≥ 18 years. The review included 48,414 participants, including 11,154 (23%) women and 37,260 (77%) men.
The lifetime prevalence of mental health disorders was significantly higher in men experiencing homelessness (86%) than in women (69%). The most common mental health disorder was substance use disorder (44%), followed by antisocial personality disorder (26%), major depression (19%), bipolar disorder (8%), and schizophrenia (7%).
The prevalence of current and lifetime mental health disorders among the homeless population was higher than that that observed in the general population (13%-15% and 12%-47%, respectively).
The results resembled those of a previous review that estimated that 76% of people experiencing homelessness living in high-income countries have mental health disorders.
“Even though our results are not surprising, they still are drawing attention to this issue because it is a big problem in Canada, the United States, Europe, and other places,” senior author Dallas Seitz, MD, PhD, professor of psychiatry at the University of Calgary’s Cumming School of Medicine, told this news organization. “The problem is concerning, and it’s not getting better. Addiction and mental health problems are becoming more common among people who are homeless.”
The bottom line is that people need affordable housing and mental health support, said Dr. Seitz. “It’s a housing problem and a health problem, and we need adequate resources to find better ways for those two systems to collaborate. There are public safety concerns, and we have to try and bring services to people experiencing homelessness. You have to come and meet people where they’re at. You have to try and establish a trusting relationship so that we can get people on the path to recovery.”
‘It’s Really About Income’
Commenting on the findings for this news organization, Stephen Hwang, MD, professor of medicine at the University of Toronto, Toronto, Ontario, Canada, said, “There have been previous studies of this type, but it is good to have an updated one.” Dr. Hwang, who is also chair in Homelessness, Housing, and Health at St. Michael’s Hospital, did not participate in the research.
The findings must be understood in the proper context, he added. For one thing, grouping together all mental health disorders and giving a single prevalence figure can be misleading. “They are including in that category a diverse group of conditions. Substance use disorder, personality disorder, schizophrenia, and depression are all lumped together. The 67% prevalence seems very high, but it is a combination of many different conditions. I just don’t want people to look at that number and think that this means that everyone is a substance user or everyone has schizophrenia,” said Dr. Hwang.
Also, some readers might interpret the findings to mean that mental problems are the reason people are homeless, he added. “That would be an incorrect interpretation because what this study is showing is that people with mental health disorders have a higher risk for becoming homeless. It doesn’t mean that it caused their homelessness. What really causes homelessness is a lack of affordable housing,” said Dr. Hwang.
“In a city or community where housing is very expensive, there’s not enough for everyone to be housed, there is a lot of competition for housing, and there’s not enough affordable housing for a number of reasons, we know that people with mental health conditions and substance use disorders will be among the first to lose their housing,” he said.
“It’s really about income. There are many reasons why a person cannot afford housing. So, not being able to earn enough money to afford it because you have a mental health disorder or substance use disorder is a common underlying reason for homelessness.”
Dr. Hwang also pointed out that people with mental illness who can access support, either through family members or through mental health care, and who also have the income to afford such services do not become homeless.
“Schizophrenia is seen in every population of the world at a rate of 1%. But you travel to certain cities and you see people who appear to have schizophrenia wandering the streets, and you go to other cities in the world and you don’t see anyone who looks like they’re homeless and have schizophrenia,” he said.
“It’s not because there are fewer people with schizophrenia in those cities or countries; it’s because people with schizophrenia are treated differently. The rate of homelessness is determined not by how many people have that condition [eg, schizophrenia] but by how we treat those people and how we set up our society to either support or not support people who have disabilities.”
The study was funded by the Precision Care With Information, Science and Experience – Mental Health grant funded by the Calgary Health Foundation. Dr. Barry is supported by the Harley Hotchkiss Samuel Weiss Postdoctoral Fellowship awarded by the Hotchkiss Brain Institute at the University of Calgary. Dr. Barry reported having no relevant financial relationships. Dr. Seitz reported grants from Calgary Health Foundation during the conduct of the study as well as grants from University Health Foundation, the Canadian Institutes of Health Research, the Public Health Agency of Canada, the Alzheimer’s Association, and the Hotchkiss Brain Institute. He received honoraria for guideline development from the Canadian Coalition for Seniors Mental Health outside the submitted work. Dr. Hwang reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Most people experiencing homelessness have mental health disorders, according to a systematic review and meta-analysis.
In an examination of studies that included nearly 50,000 participants, the current prevalence of mental health disorders among people experiencing homelessness was 67% and the lifetime prevalence was 77%.
“The relationship is likely bidirectional, where experiencing homelessness may exacerbate mental health symptoms or where having a mental health disorder may increase an individual’s risk for experiencing homelessness,” lead author Rebecca Barry, PhD, a postdoctoral fellow at the University of Calgary in Calgary, Alberta, Canada, told this news organization.
“There are also likely stressors that increase both risk for homelessness and risk for developing mental health disorders. This study examines prevalence but does not examine causal relationships,” she said.
The findings were published in JAMA Psychiatry.
A Growing Problem
To determine the current and lifetime prevalence of mental health disorders among the homeless population, the researchers analyzed 85 studies that examined this question in participants aged ≥ 18 years. The review included 48,414 participants, including 11,154 (23%) women and 37,260 (77%) men.
The lifetime prevalence of mental health disorders was significantly higher in men experiencing homelessness (86%) than in women (69%). The most common mental health disorder was substance use disorder (44%), followed by antisocial personality disorder (26%), major depression (19%), bipolar disorder (8%), and schizophrenia (7%).
The prevalence of current and lifetime mental health disorders among the homeless population was higher than that that observed in the general population (13%-15% and 12%-47%, respectively).
The results resembled those of a previous review that estimated that 76% of people experiencing homelessness living in high-income countries have mental health disorders.
“Even though our results are not surprising, they still are drawing attention to this issue because it is a big problem in Canada, the United States, Europe, and other places,” senior author Dallas Seitz, MD, PhD, professor of psychiatry at the University of Calgary’s Cumming School of Medicine, told this news organization. “The problem is concerning, and it’s not getting better. Addiction and mental health problems are becoming more common among people who are homeless.”
The bottom line is that people need affordable housing and mental health support, said Dr. Seitz. “It’s a housing problem and a health problem, and we need adequate resources to find better ways for those two systems to collaborate. There are public safety concerns, and we have to try and bring services to people experiencing homelessness. You have to come and meet people where they’re at. You have to try and establish a trusting relationship so that we can get people on the path to recovery.”
‘It’s Really About Income’
Commenting on the findings for this news organization, Stephen Hwang, MD, professor of medicine at the University of Toronto, Toronto, Ontario, Canada, said, “There have been previous studies of this type, but it is good to have an updated one.” Dr. Hwang, who is also chair in Homelessness, Housing, and Health at St. Michael’s Hospital, did not participate in the research.
The findings must be understood in the proper context, he added. For one thing, grouping together all mental health disorders and giving a single prevalence figure can be misleading. “They are including in that category a diverse group of conditions. Substance use disorder, personality disorder, schizophrenia, and depression are all lumped together. The 67% prevalence seems very high, but it is a combination of many different conditions. I just don’t want people to look at that number and think that this means that everyone is a substance user or everyone has schizophrenia,” said Dr. Hwang.
Also, some readers might interpret the findings to mean that mental problems are the reason people are homeless, he added. “That would be an incorrect interpretation because what this study is showing is that people with mental health disorders have a higher risk for becoming homeless. It doesn’t mean that it caused their homelessness. What really causes homelessness is a lack of affordable housing,” said Dr. Hwang.
“In a city or community where housing is very expensive, there’s not enough for everyone to be housed, there is a lot of competition for housing, and there’s not enough affordable housing for a number of reasons, we know that people with mental health conditions and substance use disorders will be among the first to lose their housing,” he said.
“It’s really about income. There are many reasons why a person cannot afford housing. So, not being able to earn enough money to afford it because you have a mental health disorder or substance use disorder is a common underlying reason for homelessness.”
Dr. Hwang also pointed out that people with mental illness who can access support, either through family members or through mental health care, and who also have the income to afford such services do not become homeless.
“Schizophrenia is seen in every population of the world at a rate of 1%. But you travel to certain cities and you see people who appear to have schizophrenia wandering the streets, and you go to other cities in the world and you don’t see anyone who looks like they’re homeless and have schizophrenia,” he said.
“It’s not because there are fewer people with schizophrenia in those cities or countries; it’s because people with schizophrenia are treated differently. The rate of homelessness is determined not by how many people have that condition [eg, schizophrenia] but by how we treat those people and how we set up our society to either support or not support people who have disabilities.”
The study was funded by the Precision Care With Information, Science and Experience – Mental Health grant funded by the Calgary Health Foundation. Dr. Barry is supported by the Harley Hotchkiss Samuel Weiss Postdoctoral Fellowship awarded by the Hotchkiss Brain Institute at the University of Calgary. Dr. Barry reported having no relevant financial relationships. Dr. Seitz reported grants from Calgary Health Foundation during the conduct of the study as well as grants from University Health Foundation, the Canadian Institutes of Health Research, the Public Health Agency of Canada, the Alzheimer’s Association, and the Hotchkiss Brain Institute. He received honoraria for guideline development from the Canadian Coalition for Seniors Mental Health outside the submitted work. Dr. Hwang reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Most people experiencing homelessness have mental health disorders, according to a systematic review and meta-analysis.
In an examination of studies that included nearly 50,000 participants, the current prevalence of mental health disorders among people experiencing homelessness was 67% and the lifetime prevalence was 77%.
“The relationship is likely bidirectional, where experiencing homelessness may exacerbate mental health symptoms or where having a mental health disorder may increase an individual’s risk for experiencing homelessness,” lead author Rebecca Barry, PhD, a postdoctoral fellow at the University of Calgary in Calgary, Alberta, Canada, told this news organization.
“There are also likely stressors that increase both risk for homelessness and risk for developing mental health disorders. This study examines prevalence but does not examine causal relationships,” she said.
The findings were published in JAMA Psychiatry.
A Growing Problem
To determine the current and lifetime prevalence of mental health disorders among the homeless population, the researchers analyzed 85 studies that examined this question in participants aged ≥ 18 years. The review included 48,414 participants, including 11,154 (23%) women and 37,260 (77%) men.
The lifetime prevalence of mental health disorders was significantly higher in men experiencing homelessness (86%) than in women (69%). The most common mental health disorder was substance use disorder (44%), followed by antisocial personality disorder (26%), major depression (19%), bipolar disorder (8%), and schizophrenia (7%).
The prevalence of current and lifetime mental health disorders among the homeless population was higher than that that observed in the general population (13%-15% and 12%-47%, respectively).
The results resembled those of a previous review that estimated that 76% of people experiencing homelessness living in high-income countries have mental health disorders.
“Even though our results are not surprising, they still are drawing attention to this issue because it is a big problem in Canada, the United States, Europe, and other places,” senior author Dallas Seitz, MD, PhD, professor of psychiatry at the University of Calgary’s Cumming School of Medicine, told this news organization. “The problem is concerning, and it’s not getting better. Addiction and mental health problems are becoming more common among people who are homeless.”
The bottom line is that people need affordable housing and mental health support, said Dr. Seitz. “It’s a housing problem and a health problem, and we need adequate resources to find better ways for those two systems to collaborate. There are public safety concerns, and we have to try and bring services to people experiencing homelessness. You have to come and meet people where they’re at. You have to try and establish a trusting relationship so that we can get people on the path to recovery.”
‘It’s Really About Income’
Commenting on the findings for this news organization, Stephen Hwang, MD, professor of medicine at the University of Toronto, Toronto, Ontario, Canada, said, “There have been previous studies of this type, but it is good to have an updated one.” Dr. Hwang, who is also chair in Homelessness, Housing, and Health at St. Michael’s Hospital, did not participate in the research.
The findings must be understood in the proper context, he added. For one thing, grouping together all mental health disorders and giving a single prevalence figure can be misleading. “They are including in that category a diverse group of conditions. Substance use disorder, personality disorder, schizophrenia, and depression are all lumped together. The 67% prevalence seems very high, but it is a combination of many different conditions. I just don’t want people to look at that number and think that this means that everyone is a substance user or everyone has schizophrenia,” said Dr. Hwang.
Also, some readers might interpret the findings to mean that mental problems are the reason people are homeless, he added. “That would be an incorrect interpretation because what this study is showing is that people with mental health disorders have a higher risk for becoming homeless. It doesn’t mean that it caused their homelessness. What really causes homelessness is a lack of affordable housing,” said Dr. Hwang.
“In a city or community where housing is very expensive, there’s not enough for everyone to be housed, there is a lot of competition for housing, and there’s not enough affordable housing for a number of reasons, we know that people with mental health conditions and substance use disorders will be among the first to lose their housing,” he said.
“It’s really about income. There are many reasons why a person cannot afford housing. So, not being able to earn enough money to afford it because you have a mental health disorder or substance use disorder is a common underlying reason for homelessness.”
Dr. Hwang also pointed out that people with mental illness who can access support, either through family members or through mental health care, and who also have the income to afford such services do not become homeless.
“Schizophrenia is seen in every population of the world at a rate of 1%. But you travel to certain cities and you see people who appear to have schizophrenia wandering the streets, and you go to other cities in the world and you don’t see anyone who looks like they’re homeless and have schizophrenia,” he said.
“It’s not because there are fewer people with schizophrenia in those cities or countries; it’s because people with schizophrenia are treated differently. The rate of homelessness is determined not by how many people have that condition [eg, schizophrenia] but by how we treat those people and how we set up our society to either support or not support people who have disabilities.”
The study was funded by the Precision Care With Information, Science and Experience – Mental Health grant funded by the Calgary Health Foundation. Dr. Barry is supported by the Harley Hotchkiss Samuel Weiss Postdoctoral Fellowship awarded by the Hotchkiss Brain Institute at the University of Calgary. Dr. Barry reported having no relevant financial relationships. Dr. Seitz reported grants from Calgary Health Foundation during the conduct of the study as well as grants from University Health Foundation, the Canadian Institutes of Health Research, the Public Health Agency of Canada, the Alzheimer’s Association, and the Hotchkiss Brain Institute. He received honoraria for guideline development from the Canadian Coalition for Seniors Mental Health outside the submitted work. Dr. Hwang reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
Childhood Loneliness Predictive of Subsequent Psychosis?
BUDAPEST, HUNGARY — Self-perceived loneliness during childhood is linked to a more than twofold increased risk for subsequent first-episode psychosis (FEP) — new findings that may point to a novel marker for the disorder.
The association between loneliness and FEP “appears to extend beyond the effects of objective social isolation,” said study presenter Covadonga M. Díaz-Caneja, MD, PhD, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, and “is particularly pronounced in females.”
“These findings suggest the potential of childhood loneliness as an early risk marker for psychosis that could help guide targeted interventions,” she added.
The results were presented at the European Psychiatric Association 2024 Congress.
Isolation a Major Risk Factor
There are two components to isolation, both of which are “major risk factors” for morbidity, mortality, and the onset of mental disorders, said Dr. Díaz-Caneja.
The first is “objective social isolation,” which consists of a demonstrable lack of social connections, including social interactions, contacts, and relationships, while the other is a perceived sense of isolation, or “loneliness,” defined as a “subjective feeling of distress associated with a lack of meaningful relationships,” regardless of the amount of actual social contact an individual experiences.
Childhood loneliness occurs before age 12 and is becoming increasingly prevalent, said Dr. Díaz-Caneja. A recent survey shows that approximately one third of children report they often feel lonely.
Genetic and observational research has shown there is a bidirectional relationship between loneliness and psychosis and that patients with schizophrenia are more likely to report loneliness than is the general population.
Dr. Díaz-Caneja noted that there is no previous research that has assessed the potential association between childhood loneliness and subsequent psychosis.
To investigate, the researchers conducted an observational, case-control study in seven university hospitals in Madrid. It included individuals aged 7-40 years, including FEP patients with a psychosis duration of less than 2 years, and healthy controls from the same geographic areas.
They assessed childhood objective social isolation using the Premorbid Adjustment Scale and examined childhood loneliness with the single item: “Have you ever felt lonely for more than 6 months before the age of 12?”
A range of measures and questionnaires were also administered to assess participants’ symptom scores, alongside the Global Assessment of Functioning (GAF).
Alone vs Lonely
Two hundred eighty-five patients with FEP participated in the study. They had a mean age of 24.5 years, and 32.6% were female. The study also included 261 healthy controls (average age, 25.9 years; 48.7% female).
After the researchers adjusted for age, gender, ethnicity, and socioeconomic status, loneliness during childhood was associated with a significantly increased risk for FEP (odds ratio [OR], 2.17; 95% CI, 1.40-3.51), which increased (OR, 2.70; 95% CI, 1.58-4.62) after further adjustment for objective social isolation.
Further analysis revealed that in those who did not have objective social isolation in childhood, loneliness was associated with a significantly increased risk for FEP (OR, 2.68; 95% CI, 1.56-4.60).
However, the relationship between loneliness and FEP was not significant in participants who were objectively socially isolated during childhood (OR, 0.33; 95% CI, 0.08-1.45).
Compared with males, females reporting loneliness had a markedly increased risk for FEP (OR, 4.74; 95% CI, 2.23-10.05 vs OR, 1.17; 95% CI, 0.63-2.19).
However, females had a reduced risk of receiving a diagnosis of schizophrenia spectrum disorder (OR, 0.155; 95% CI, 0.048-0.506), indicating that loneliness influenced the type of diagnosis, she noted.
There was a significant positive relationship between loneliness in childhood and symptom scores in men, and a negative association with GAF scores in men.
Dr. Díaz-Caneja noted that the study is preliminary and a “work in progress.” The investigators plan to increase the sample size and will conduct more complex analyses, she said.
“We also of course have to bear in mind that it is a cross-sectional study and that there may be some kind of recall biases [because] we are asking patients now about what happened in the past.”
She noted that it’s unclear whether the results can be extrapolated to individuals who are currently experiencing loneliness because “the determinants of loneliness 10 years ago or 15 years ago may be different.”
How, When to Intervene
Session chair Judit Lazáry, MD, PhD, Department of Clinical and Theoretical Mental Health, Kútvölgyi Clinical Center, Semmelweis University, Budapest, Hungary, told this news organization that the association between loneliness and FEP was “not surprising.”
She explained there are a lot of data indicating that premorbid symptoms in childhood are “predictive signs for the later onset of psychosis,” and loneliness may be “a part of that.”
Individuals experiencing loneliness are more anxious and have difficulties in cultivating and maintaining relationships. In addition, they tend to socially isolate, she said.
The key question, said Dr. Lazáry, is: “How can we intervene to prevent the onset of psychosis? What is the point at which we can support the young person?”
This is challenging, she added, because while “you can detect that a kid is always alone, you cannot detect the feeling of loneliness,” and children can’t always easily express themselves.
Another potential confounder is that in adults with current psychosis, the self-perception that they were lonely during childhood may be a consequence of the disorder.
In addition, she said, individuals with psychosis often experience cognitive impairment, which could affect memory reliability.
Nevertheless, said Dr. Lazáry, the study’s findings suggest that a young person reporting loneliness in childhood may be “another symptom that we have to investigate.”
No funding was declared.
Dr. Díaz-Caneja declared a relationship with Angelini, Janssen, and Viatris and grant support from Instituto de Salud Carlos III, the Spanish Ministry of Science and Innovation, and the European Commission.
A version of this article appeared on Medscape.com.
BUDAPEST, HUNGARY — Self-perceived loneliness during childhood is linked to a more than twofold increased risk for subsequent first-episode psychosis (FEP) — new findings that may point to a novel marker for the disorder.
The association between loneliness and FEP “appears to extend beyond the effects of objective social isolation,” said study presenter Covadonga M. Díaz-Caneja, MD, PhD, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, and “is particularly pronounced in females.”
“These findings suggest the potential of childhood loneliness as an early risk marker for psychosis that could help guide targeted interventions,” she added.
The results were presented at the European Psychiatric Association 2024 Congress.
Isolation a Major Risk Factor
There are two components to isolation, both of which are “major risk factors” for morbidity, mortality, and the onset of mental disorders, said Dr. Díaz-Caneja.
The first is “objective social isolation,” which consists of a demonstrable lack of social connections, including social interactions, contacts, and relationships, while the other is a perceived sense of isolation, or “loneliness,” defined as a “subjective feeling of distress associated with a lack of meaningful relationships,” regardless of the amount of actual social contact an individual experiences.
Childhood loneliness occurs before age 12 and is becoming increasingly prevalent, said Dr. Díaz-Caneja. A recent survey shows that approximately one third of children report they often feel lonely.
Genetic and observational research has shown there is a bidirectional relationship between loneliness and psychosis and that patients with schizophrenia are more likely to report loneliness than is the general population.
Dr. Díaz-Caneja noted that there is no previous research that has assessed the potential association between childhood loneliness and subsequent psychosis.
To investigate, the researchers conducted an observational, case-control study in seven university hospitals in Madrid. It included individuals aged 7-40 years, including FEP patients with a psychosis duration of less than 2 years, and healthy controls from the same geographic areas.
They assessed childhood objective social isolation using the Premorbid Adjustment Scale and examined childhood loneliness with the single item: “Have you ever felt lonely for more than 6 months before the age of 12?”
A range of measures and questionnaires were also administered to assess participants’ symptom scores, alongside the Global Assessment of Functioning (GAF).
Alone vs Lonely
Two hundred eighty-five patients with FEP participated in the study. They had a mean age of 24.5 years, and 32.6% were female. The study also included 261 healthy controls (average age, 25.9 years; 48.7% female).
After the researchers adjusted for age, gender, ethnicity, and socioeconomic status, loneliness during childhood was associated with a significantly increased risk for FEP (odds ratio [OR], 2.17; 95% CI, 1.40-3.51), which increased (OR, 2.70; 95% CI, 1.58-4.62) after further adjustment for objective social isolation.
Further analysis revealed that in those who did not have objective social isolation in childhood, loneliness was associated with a significantly increased risk for FEP (OR, 2.68; 95% CI, 1.56-4.60).
However, the relationship between loneliness and FEP was not significant in participants who were objectively socially isolated during childhood (OR, 0.33; 95% CI, 0.08-1.45).
Compared with males, females reporting loneliness had a markedly increased risk for FEP (OR, 4.74; 95% CI, 2.23-10.05 vs OR, 1.17; 95% CI, 0.63-2.19).
However, females had a reduced risk of receiving a diagnosis of schizophrenia spectrum disorder (OR, 0.155; 95% CI, 0.048-0.506), indicating that loneliness influenced the type of diagnosis, she noted.
There was a significant positive relationship between loneliness in childhood and symptom scores in men, and a negative association with GAF scores in men.
Dr. Díaz-Caneja noted that the study is preliminary and a “work in progress.” The investigators plan to increase the sample size and will conduct more complex analyses, she said.
“We also of course have to bear in mind that it is a cross-sectional study and that there may be some kind of recall biases [because] we are asking patients now about what happened in the past.”
She noted that it’s unclear whether the results can be extrapolated to individuals who are currently experiencing loneliness because “the determinants of loneliness 10 years ago or 15 years ago may be different.”
How, When to Intervene
Session chair Judit Lazáry, MD, PhD, Department of Clinical and Theoretical Mental Health, Kútvölgyi Clinical Center, Semmelweis University, Budapest, Hungary, told this news organization that the association between loneliness and FEP was “not surprising.”
She explained there are a lot of data indicating that premorbid symptoms in childhood are “predictive signs for the later onset of psychosis,” and loneliness may be “a part of that.”
Individuals experiencing loneliness are more anxious and have difficulties in cultivating and maintaining relationships. In addition, they tend to socially isolate, she said.
The key question, said Dr. Lazáry, is: “How can we intervene to prevent the onset of psychosis? What is the point at which we can support the young person?”
This is challenging, she added, because while “you can detect that a kid is always alone, you cannot detect the feeling of loneliness,” and children can’t always easily express themselves.
Another potential confounder is that in adults with current psychosis, the self-perception that they were lonely during childhood may be a consequence of the disorder.
In addition, she said, individuals with psychosis often experience cognitive impairment, which could affect memory reliability.
Nevertheless, said Dr. Lazáry, the study’s findings suggest that a young person reporting loneliness in childhood may be “another symptom that we have to investigate.”
No funding was declared.
Dr. Díaz-Caneja declared a relationship with Angelini, Janssen, and Viatris and grant support from Instituto de Salud Carlos III, the Spanish Ministry of Science and Innovation, and the European Commission.
A version of this article appeared on Medscape.com.
BUDAPEST, HUNGARY — Self-perceived loneliness during childhood is linked to a more than twofold increased risk for subsequent first-episode psychosis (FEP) — new findings that may point to a novel marker for the disorder.
The association between loneliness and FEP “appears to extend beyond the effects of objective social isolation,” said study presenter Covadonga M. Díaz-Caneja, MD, PhD, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, Madrid, and “is particularly pronounced in females.”
“These findings suggest the potential of childhood loneliness as an early risk marker for psychosis that could help guide targeted interventions,” she added.
The results were presented at the European Psychiatric Association 2024 Congress.
Isolation a Major Risk Factor
There are two components to isolation, both of which are “major risk factors” for morbidity, mortality, and the onset of mental disorders, said Dr. Díaz-Caneja.
The first is “objective social isolation,” which consists of a demonstrable lack of social connections, including social interactions, contacts, and relationships, while the other is a perceived sense of isolation, or “loneliness,” defined as a “subjective feeling of distress associated with a lack of meaningful relationships,” regardless of the amount of actual social contact an individual experiences.
Childhood loneliness occurs before age 12 and is becoming increasingly prevalent, said Dr. Díaz-Caneja. A recent survey shows that approximately one third of children report they often feel lonely.
Genetic and observational research has shown there is a bidirectional relationship between loneliness and psychosis and that patients with schizophrenia are more likely to report loneliness than is the general population.
Dr. Díaz-Caneja noted that there is no previous research that has assessed the potential association between childhood loneliness and subsequent psychosis.
To investigate, the researchers conducted an observational, case-control study in seven university hospitals in Madrid. It included individuals aged 7-40 years, including FEP patients with a psychosis duration of less than 2 years, and healthy controls from the same geographic areas.
They assessed childhood objective social isolation using the Premorbid Adjustment Scale and examined childhood loneliness with the single item: “Have you ever felt lonely for more than 6 months before the age of 12?”
A range of measures and questionnaires were also administered to assess participants’ symptom scores, alongside the Global Assessment of Functioning (GAF).
Alone vs Lonely
Two hundred eighty-five patients with FEP participated in the study. They had a mean age of 24.5 years, and 32.6% were female. The study also included 261 healthy controls (average age, 25.9 years; 48.7% female).
After the researchers adjusted for age, gender, ethnicity, and socioeconomic status, loneliness during childhood was associated with a significantly increased risk for FEP (odds ratio [OR], 2.17; 95% CI, 1.40-3.51), which increased (OR, 2.70; 95% CI, 1.58-4.62) after further adjustment for objective social isolation.
Further analysis revealed that in those who did not have objective social isolation in childhood, loneliness was associated with a significantly increased risk for FEP (OR, 2.68; 95% CI, 1.56-4.60).
However, the relationship between loneliness and FEP was not significant in participants who were objectively socially isolated during childhood (OR, 0.33; 95% CI, 0.08-1.45).
Compared with males, females reporting loneliness had a markedly increased risk for FEP (OR, 4.74; 95% CI, 2.23-10.05 vs OR, 1.17; 95% CI, 0.63-2.19).
However, females had a reduced risk of receiving a diagnosis of schizophrenia spectrum disorder (OR, 0.155; 95% CI, 0.048-0.506), indicating that loneliness influenced the type of diagnosis, she noted.
There was a significant positive relationship between loneliness in childhood and symptom scores in men, and a negative association with GAF scores in men.
Dr. Díaz-Caneja noted that the study is preliminary and a “work in progress.” The investigators plan to increase the sample size and will conduct more complex analyses, she said.
“We also of course have to bear in mind that it is a cross-sectional study and that there may be some kind of recall biases [because] we are asking patients now about what happened in the past.”
She noted that it’s unclear whether the results can be extrapolated to individuals who are currently experiencing loneliness because “the determinants of loneliness 10 years ago or 15 years ago may be different.”
How, When to Intervene
Session chair Judit Lazáry, MD, PhD, Department of Clinical and Theoretical Mental Health, Kútvölgyi Clinical Center, Semmelweis University, Budapest, Hungary, told this news organization that the association between loneliness and FEP was “not surprising.”
She explained there are a lot of data indicating that premorbid symptoms in childhood are “predictive signs for the later onset of psychosis,” and loneliness may be “a part of that.”
Individuals experiencing loneliness are more anxious and have difficulties in cultivating and maintaining relationships. In addition, they tend to socially isolate, she said.
The key question, said Dr. Lazáry, is: “How can we intervene to prevent the onset of psychosis? What is the point at which we can support the young person?”
This is challenging, she added, because while “you can detect that a kid is always alone, you cannot detect the feeling of loneliness,” and children can’t always easily express themselves.
Another potential confounder is that in adults with current psychosis, the self-perception that they were lonely during childhood may be a consequence of the disorder.
In addition, she said, individuals with psychosis often experience cognitive impairment, which could affect memory reliability.
Nevertheless, said Dr. Lazáry, the study’s findings suggest that a young person reporting loneliness in childhood may be “another symptom that we have to investigate.”
No funding was declared.
Dr. Díaz-Caneja declared a relationship with Angelini, Janssen, and Viatris and grant support from Instituto de Salud Carlos III, the Spanish Ministry of Science and Innovation, and the European Commission.
A version of this article appeared on Medscape.com.