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Depression, constipation, UTIs early signs of MS?
However, these prodromal symptoms are also more likely to occur in people with two other autoimmune diseases — lupus and Crohn’s disease — and therefore, will not help earlier diagnosis, study investigator, Céline Louapre, professor of neurology, Sorbonne University and Paris Brain Institute, Paris, France, said in an interview.
“On the other hand, in certain patients who may be at particular risk of developing MS, such as in certain familial forms or in patients with incidental inflammatory lesions discovered on MRI, the presence of these symptoms could suggest an already active process, prior to the first typical symptoms of the disease,” she noted.
Retracing MS Origins
The case-control study, published online in Neurology, included 20,174 people with newly diagnosed MS who were matched to 54,790 without MS, as well as 30,477 with Crohn’s disease and 7337 with lupus.
Using International Classification of Diseases, 10th revision (ICD-10) codes in electronic health records, the researchers assessed the associations between 113 diseases and symptoms in the 5 years before and after an MS diagnosis.
Twelve ICD-10 codes were significantly positively associated with the risk for MS compared with controls without MS.
After considering ICD-10 codes suggestive of neurologic symptoms as the first diagnosis of MS, the following five ICD-10 codes remained significantly associated with MS:
- Depression (odds ratio [OR], 1.22; 95% CI, 1.11-1.34)
- Sexual dysfunction (OR, 1.47; 95% CI, 1.11-1.95)
- Constipation (OR, 1.5; 95% CI, 1.27-1.78)
- Cystitis (OR, 1.21; 95% CI, 1.05-1.39)
- UTIs of unspecified site (OR, 1.38; 95% CI, 1.18-1.61)
However, none of these conditions was selectively associated with MS in comparison with both lupus and Crohn’s disease. All five ICD-10 codes identified were still associated with MS during the 5 years after diagnosis.
“The importance of investigating prodromal signs in MS is that it allows us to retrace the origins of the disease,” said Dr. Louapre.
“The main contribution of the data on prodromes in MS is to clarify that the disease and its mechanisms are frequently underway well before the first typical neurological symptoms, and that the causes of MS are probably present many years before diagnosis,” she added.
A limitation of the study was that data were not available for other factors that could influence people’s risk of developing MS, such as education level, ethnicity, body mass index, socioeconomic status, or genetic information.
It also remains unclear whether the conditions linked to MS are risk factors for the disease or nonspecific early MS symptoms.
Preventing Disease Evolution
In a linked editorial, Ruth Ann Marrie, MD, PhD, with the University of Manitoba, Manitoba, Canada, and Raffaele Palladino, MD, PhD, with the University of Naples Federico II, Naples, Italy, note these findings highlight the challenges of accurately identifying the prodromal stage of a specific disease.
“Commonalities of prodromal features are recognized across neurodegenerative diseases; this is also true for immune-mediated diseases, and it is not surprising, given shared etiologic factors and pathobiological mechanisms,” they point out.
“This suggests that we should be trying to link prodromal features to specific underlying pathobiological changes rather than specific diseases. This approach would require use of different study designs, including broad, deeply phenotyped cohorts, but would allow us to develop and test interventions targeted at those mechanisms, and could ultimately achieve the goal of preventing disease evolution,” they add.
The study was supported by the French National Research Agency. Dr. Louapre has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono, unrelated to this study. Dr. Marrie is a coinvestigator on studies receiving funding from Biogen Idec and Roche Canada; receives research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense; and serves on the editorial board of Neurology. Dr. Palladino has taken part in advisory boards/consultancy for MSD and Sanofi and has received support from the UK MS Society.
A version of this article appeared on Medscape.com.
However, these prodromal symptoms are also more likely to occur in people with two other autoimmune diseases — lupus and Crohn’s disease — and therefore, will not help earlier diagnosis, study investigator, Céline Louapre, professor of neurology, Sorbonne University and Paris Brain Institute, Paris, France, said in an interview.
“On the other hand, in certain patients who may be at particular risk of developing MS, such as in certain familial forms or in patients with incidental inflammatory lesions discovered on MRI, the presence of these symptoms could suggest an already active process, prior to the first typical symptoms of the disease,” she noted.
Retracing MS Origins
The case-control study, published online in Neurology, included 20,174 people with newly diagnosed MS who were matched to 54,790 without MS, as well as 30,477 with Crohn’s disease and 7337 with lupus.
Using International Classification of Diseases, 10th revision (ICD-10) codes in electronic health records, the researchers assessed the associations between 113 diseases and symptoms in the 5 years before and after an MS diagnosis.
Twelve ICD-10 codes were significantly positively associated with the risk for MS compared with controls without MS.
After considering ICD-10 codes suggestive of neurologic symptoms as the first diagnosis of MS, the following five ICD-10 codes remained significantly associated with MS:
- Depression (odds ratio [OR], 1.22; 95% CI, 1.11-1.34)
- Sexual dysfunction (OR, 1.47; 95% CI, 1.11-1.95)
- Constipation (OR, 1.5; 95% CI, 1.27-1.78)
- Cystitis (OR, 1.21; 95% CI, 1.05-1.39)
- UTIs of unspecified site (OR, 1.38; 95% CI, 1.18-1.61)
However, none of these conditions was selectively associated with MS in comparison with both lupus and Crohn’s disease. All five ICD-10 codes identified were still associated with MS during the 5 years after diagnosis.
“The importance of investigating prodromal signs in MS is that it allows us to retrace the origins of the disease,” said Dr. Louapre.
“The main contribution of the data on prodromes in MS is to clarify that the disease and its mechanisms are frequently underway well before the first typical neurological symptoms, and that the causes of MS are probably present many years before diagnosis,” she added.
A limitation of the study was that data were not available for other factors that could influence people’s risk of developing MS, such as education level, ethnicity, body mass index, socioeconomic status, or genetic information.
It also remains unclear whether the conditions linked to MS are risk factors for the disease or nonspecific early MS symptoms.
Preventing Disease Evolution
In a linked editorial, Ruth Ann Marrie, MD, PhD, with the University of Manitoba, Manitoba, Canada, and Raffaele Palladino, MD, PhD, with the University of Naples Federico II, Naples, Italy, note these findings highlight the challenges of accurately identifying the prodromal stage of a specific disease.
“Commonalities of prodromal features are recognized across neurodegenerative diseases; this is also true for immune-mediated diseases, and it is not surprising, given shared etiologic factors and pathobiological mechanisms,” they point out.
“This suggests that we should be trying to link prodromal features to specific underlying pathobiological changes rather than specific diseases. This approach would require use of different study designs, including broad, deeply phenotyped cohorts, but would allow us to develop and test interventions targeted at those mechanisms, and could ultimately achieve the goal of preventing disease evolution,” they add.
The study was supported by the French National Research Agency. Dr. Louapre has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono, unrelated to this study. Dr. Marrie is a coinvestigator on studies receiving funding from Biogen Idec and Roche Canada; receives research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense; and serves on the editorial board of Neurology. Dr. Palladino has taken part in advisory boards/consultancy for MSD and Sanofi and has received support from the UK MS Society.
A version of this article appeared on Medscape.com.
However, these prodromal symptoms are also more likely to occur in people with two other autoimmune diseases — lupus and Crohn’s disease — and therefore, will not help earlier diagnosis, study investigator, Céline Louapre, professor of neurology, Sorbonne University and Paris Brain Institute, Paris, France, said in an interview.
“On the other hand, in certain patients who may be at particular risk of developing MS, such as in certain familial forms or in patients with incidental inflammatory lesions discovered on MRI, the presence of these symptoms could suggest an already active process, prior to the first typical symptoms of the disease,” she noted.
Retracing MS Origins
The case-control study, published online in Neurology, included 20,174 people with newly diagnosed MS who were matched to 54,790 without MS, as well as 30,477 with Crohn’s disease and 7337 with lupus.
Using International Classification of Diseases, 10th revision (ICD-10) codes in electronic health records, the researchers assessed the associations between 113 diseases and symptoms in the 5 years before and after an MS diagnosis.
Twelve ICD-10 codes were significantly positively associated with the risk for MS compared with controls without MS.
After considering ICD-10 codes suggestive of neurologic symptoms as the first diagnosis of MS, the following five ICD-10 codes remained significantly associated with MS:
- Depression (odds ratio [OR], 1.22; 95% CI, 1.11-1.34)
- Sexual dysfunction (OR, 1.47; 95% CI, 1.11-1.95)
- Constipation (OR, 1.5; 95% CI, 1.27-1.78)
- Cystitis (OR, 1.21; 95% CI, 1.05-1.39)
- UTIs of unspecified site (OR, 1.38; 95% CI, 1.18-1.61)
However, none of these conditions was selectively associated with MS in comparison with both lupus and Crohn’s disease. All five ICD-10 codes identified were still associated with MS during the 5 years after diagnosis.
“The importance of investigating prodromal signs in MS is that it allows us to retrace the origins of the disease,” said Dr. Louapre.
“The main contribution of the data on prodromes in MS is to clarify that the disease and its mechanisms are frequently underway well before the first typical neurological symptoms, and that the causes of MS are probably present many years before diagnosis,” she added.
A limitation of the study was that data were not available for other factors that could influence people’s risk of developing MS, such as education level, ethnicity, body mass index, socioeconomic status, or genetic information.
It also remains unclear whether the conditions linked to MS are risk factors for the disease or nonspecific early MS symptoms.
Preventing Disease Evolution
In a linked editorial, Ruth Ann Marrie, MD, PhD, with the University of Manitoba, Manitoba, Canada, and Raffaele Palladino, MD, PhD, with the University of Naples Federico II, Naples, Italy, note these findings highlight the challenges of accurately identifying the prodromal stage of a specific disease.
“Commonalities of prodromal features are recognized across neurodegenerative diseases; this is also true for immune-mediated diseases, and it is not surprising, given shared etiologic factors and pathobiological mechanisms,” they point out.
“This suggests that we should be trying to link prodromal features to specific underlying pathobiological changes rather than specific diseases. This approach would require use of different study designs, including broad, deeply phenotyped cohorts, but would allow us to develop and test interventions targeted at those mechanisms, and could ultimately achieve the goal of preventing disease evolution,” they add.
The study was supported by the French National Research Agency. Dr. Louapre has received consulting or travel fees from Biogen, Novartis, Roche, Sanofi, Teva, and Merck Serono, unrelated to this study. Dr. Marrie is a coinvestigator on studies receiving funding from Biogen Idec and Roche Canada; receives research funding from CIHR, Research Manitoba, Multiple Sclerosis Society of Canada, Multiple Sclerosis Scientific Foundation, Crohn’s and Colitis Canada, National Multiple Sclerosis Society, CMSC, the Arthritis Society and the US Department of Defense; and serves on the editorial board of Neurology. Dr. Palladino has taken part in advisory boards/consultancy for MSD and Sanofi and has received support from the UK MS Society.
A version of this article appeared on Medscape.com.
FROM NEUROLOGY
Toward a better framework for postmarketing reproductive safety surveillance of medications
For the last 30 years, the Center for Women’s Mental Health at Massachusetts General Hospital (MGH) has had as part of its mission, the conveying of accurate information about the reproductive safety of psychiatric medications. There has been a spectrum of medicines developed across psychiatric indications over the last several decades, and many studies over those decades have attempted to delineate the reproductive safety of these agents.
With the development of new antidepressants and second-generation antipsychotics has come an appreciation of the utility of these agents across a wide range of psychiatric disease states and psychiatric symptoms. More and more data demonstrate the efficacy of these medicines for mood and anxiety disorders; these agents are also used for a broad array of symptoms from insomnia, irritability, and symptoms of posttraumatic stress disorder (PTSD) just as examples — even absent formal approval by the US Food and Drug Administration (FDA) for these specific indications. With the growing use of medicines, including new antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors, and second-generation atypical antipsychotics, there has been a greater interest and appreciation of the need to provide women with the best information about reproductive safety of these medicines as well.
When I began working in reproductive psychiatry, the FDA was using the pregnancy labeling categories introduced in 1979. The categories were simple, but also oversimplified in terms of incompletely conveying information about reproductive safety. For instance, category labels of B and C under the old labeling system could be nebulous, containing sparse information (in the case of category B) or animal data and some conflicting human data (in the case of category C) that may not have translated into relevant or easily interpretable safety information for patients and clinicians.
It was on that basis the current Pregnancy and Lactation Labeling (PLLR) Final Rule was published in 2014, which was a shift from categorical labeling to more descriptive labeling, including updated actual information on the package insert about available reproductive safety data, animal data, and data on lactation.
Even following the publication of the PLLR, there has still been an acknowledgment in the field that our assessment tools for postmarketing reproductive safety surveillance are incomplete. A recent 2-day FDA workshop hosted by the Duke-Margolis Center for Health Policy on optimizing the use of postapproval pregnancy safety studies sought to discuss the many questions that still surround this issue. Based on presentations at this workshop, a framework emerged for the future of assessing the reproductive safety of medications, which included an effort to develop the most effective model using tools such as pregnancy registries and harnessing “big data,” whether through electronic health records or large administrative databases from public and private insurers. Together, these various sources of information can provide signals of potential concern, prompting the need for a more rigorous look at the reproductive safety of a medication, or provide reassurance if data fail to indicate the absence of a signal of risk.
FDA’s new commitments under the latest reauthorization of the Prescription Drug User Fee Act (PDUFA VII) include pregnancy-specific postmarketing safety requirements as well as the creation of a framework for how data from pregnancy-specific postmarketing studies can be used. The agency is also conducting demonstration projects, including one for assessing the performance of pregnancy registries for the potential to detect safety signals for medications early in pregnancy. FDA is expanding its Sentinel Initiative to help accomplish these aims, and is implementing an Active Risk Identification and Analysis (ARIA) system to conduct active safety surveillance of medications used during pregnancy.
Pregnancy registries have now been available for decades, and some have been more successful than others across different classes of medicines, with the most rigorous registries including prospective follow-up of women across pregnancies and careful documentation of malformations (at best with original source data and with a blinded dysmorphologist). Still, with all of its rigor, even the best-intentioned efforts with respect to pregnancy registries have limitations. As I mentioned in my testimony during the public comment portion of the workshop, the sheer volume of pregnancy data from administrative databases we now have access to is attractive, but the quality of these data needs to be good enough to ascertain a signal of risk if they are to be used as a basis for reproductive safety determination.
The flip side of using data from large administrative databases is using carefully collected data from pregnancy registries. With a pregnancy registry, accrual of a substantial number of participants can also take a considerable period of time, and initial risk estimates of outcomes can have typically large confidence intervals, which can make it difficult to discern whether a drug is safe for women of reproductive age.
Another key issue is a lack of participation from manufacturers with respect to commitment to collection of high-quality reproductive safety data. History has shown that many medication manufacturers, unless required to have a dedicated registry as part of a postmarketing requirement or commitment, will invest sparse resources to track data on safety of fetal drug exposure. Participation is typically voluntary and varies from company to company unless, as noted previously, there is a postmarketing requirement or commitment tied to the approval of a medication. Just as a recent concrete example, the manufacturer of a new medication recently approved by the FDA for the treatment of postpartum depression (which will include presumably sexually active women well into the first postpartum year) has no plan to support the collection of reproductive safety data on this new medication because it is not required to, based on current FDA guidelines and the absence of a postmarketing requirement to do so.
Looking ahead
While the PLLR was a huge step forward in the field from the old pregnancy category system that could misinform women contemplating pregnancy, it also sets the stage for the next iteration of a system that allows us to generate information more quickly about the reproductive safety of medications. In psychiatry, as many as 10% of women use SSRIs during pregnancy. With drugs like atypical antipsychotics being used across disease states — in schizophrenia, bipolar disorder, depression, anxiety, insomnia, and PTSD — and where new classes of medicine are becoming available, like with ketamine or steroids, we need to have a system by which we can more quickly ascertain reproductive safety information. This information informs treatment decisions during a critical life event of deciding to try to become pregnant or during an actual pregnancy.
In my mind, it is reassuring when a registry has even as few as 50-60 cases of fetal exposure without an increase in the risk for malformation, because it can mean we are not seeing a repeat of the past with medications like thalidomide and sodium valproate. However, patients and clinicians are starved for better data. Risk assessment is also different from clinician to clinician and patient to patient. We want to empower patients to make decisions that work for them based on more rapidly accumulating information and help inform their decisions.
To come out on the “other side” of the PLLR, , which can be confusing when study results frequently conflict. I believe we have an obligation today to do this better, because the areas of reproductive toxicology and pharmacovigilance are growing incredibly quickly, and clinicians and patients are seeing these volumes of data being published without the ability to integrate that information in a systematic way.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.
For the last 30 years, the Center for Women’s Mental Health at Massachusetts General Hospital (MGH) has had as part of its mission, the conveying of accurate information about the reproductive safety of psychiatric medications. There has been a spectrum of medicines developed across psychiatric indications over the last several decades, and many studies over those decades have attempted to delineate the reproductive safety of these agents.
With the development of new antidepressants and second-generation antipsychotics has come an appreciation of the utility of these agents across a wide range of psychiatric disease states and psychiatric symptoms. More and more data demonstrate the efficacy of these medicines for mood and anxiety disorders; these agents are also used for a broad array of symptoms from insomnia, irritability, and symptoms of posttraumatic stress disorder (PTSD) just as examples — even absent formal approval by the US Food and Drug Administration (FDA) for these specific indications. With the growing use of medicines, including new antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors, and second-generation atypical antipsychotics, there has been a greater interest and appreciation of the need to provide women with the best information about reproductive safety of these medicines as well.
When I began working in reproductive psychiatry, the FDA was using the pregnancy labeling categories introduced in 1979. The categories were simple, but also oversimplified in terms of incompletely conveying information about reproductive safety. For instance, category labels of B and C under the old labeling system could be nebulous, containing sparse information (in the case of category B) or animal data and some conflicting human data (in the case of category C) that may not have translated into relevant or easily interpretable safety information for patients and clinicians.
It was on that basis the current Pregnancy and Lactation Labeling (PLLR) Final Rule was published in 2014, which was a shift from categorical labeling to more descriptive labeling, including updated actual information on the package insert about available reproductive safety data, animal data, and data on lactation.
Even following the publication of the PLLR, there has still been an acknowledgment in the field that our assessment tools for postmarketing reproductive safety surveillance are incomplete. A recent 2-day FDA workshop hosted by the Duke-Margolis Center for Health Policy on optimizing the use of postapproval pregnancy safety studies sought to discuss the many questions that still surround this issue. Based on presentations at this workshop, a framework emerged for the future of assessing the reproductive safety of medications, which included an effort to develop the most effective model using tools such as pregnancy registries and harnessing “big data,” whether through electronic health records or large administrative databases from public and private insurers. Together, these various sources of information can provide signals of potential concern, prompting the need for a more rigorous look at the reproductive safety of a medication, or provide reassurance if data fail to indicate the absence of a signal of risk.
FDA’s new commitments under the latest reauthorization of the Prescription Drug User Fee Act (PDUFA VII) include pregnancy-specific postmarketing safety requirements as well as the creation of a framework for how data from pregnancy-specific postmarketing studies can be used. The agency is also conducting demonstration projects, including one for assessing the performance of pregnancy registries for the potential to detect safety signals for medications early in pregnancy. FDA is expanding its Sentinel Initiative to help accomplish these aims, and is implementing an Active Risk Identification and Analysis (ARIA) system to conduct active safety surveillance of medications used during pregnancy.
Pregnancy registries have now been available for decades, and some have been more successful than others across different classes of medicines, with the most rigorous registries including prospective follow-up of women across pregnancies and careful documentation of malformations (at best with original source data and with a blinded dysmorphologist). Still, with all of its rigor, even the best-intentioned efforts with respect to pregnancy registries have limitations. As I mentioned in my testimony during the public comment portion of the workshop, the sheer volume of pregnancy data from administrative databases we now have access to is attractive, but the quality of these data needs to be good enough to ascertain a signal of risk if they are to be used as a basis for reproductive safety determination.
The flip side of using data from large administrative databases is using carefully collected data from pregnancy registries. With a pregnancy registry, accrual of a substantial number of participants can also take a considerable period of time, and initial risk estimates of outcomes can have typically large confidence intervals, which can make it difficult to discern whether a drug is safe for women of reproductive age.
Another key issue is a lack of participation from manufacturers with respect to commitment to collection of high-quality reproductive safety data. History has shown that many medication manufacturers, unless required to have a dedicated registry as part of a postmarketing requirement or commitment, will invest sparse resources to track data on safety of fetal drug exposure. Participation is typically voluntary and varies from company to company unless, as noted previously, there is a postmarketing requirement or commitment tied to the approval of a medication. Just as a recent concrete example, the manufacturer of a new medication recently approved by the FDA for the treatment of postpartum depression (which will include presumably sexually active women well into the first postpartum year) has no plan to support the collection of reproductive safety data on this new medication because it is not required to, based on current FDA guidelines and the absence of a postmarketing requirement to do so.
Looking ahead
While the PLLR was a huge step forward in the field from the old pregnancy category system that could misinform women contemplating pregnancy, it also sets the stage for the next iteration of a system that allows us to generate information more quickly about the reproductive safety of medications. In psychiatry, as many as 10% of women use SSRIs during pregnancy. With drugs like atypical antipsychotics being used across disease states — in schizophrenia, bipolar disorder, depression, anxiety, insomnia, and PTSD — and where new classes of medicine are becoming available, like with ketamine or steroids, we need to have a system by which we can more quickly ascertain reproductive safety information. This information informs treatment decisions during a critical life event of deciding to try to become pregnant or during an actual pregnancy.
In my mind, it is reassuring when a registry has even as few as 50-60 cases of fetal exposure without an increase in the risk for malformation, because it can mean we are not seeing a repeat of the past with medications like thalidomide and sodium valproate. However, patients and clinicians are starved for better data. Risk assessment is also different from clinician to clinician and patient to patient. We want to empower patients to make decisions that work for them based on more rapidly accumulating information and help inform their decisions.
To come out on the “other side” of the PLLR, , which can be confusing when study results frequently conflict. I believe we have an obligation today to do this better, because the areas of reproductive toxicology and pharmacovigilance are growing incredibly quickly, and clinicians and patients are seeing these volumes of data being published without the ability to integrate that information in a systematic way.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.
For the last 30 years, the Center for Women’s Mental Health at Massachusetts General Hospital (MGH) has had as part of its mission, the conveying of accurate information about the reproductive safety of psychiatric medications. There has been a spectrum of medicines developed across psychiatric indications over the last several decades, and many studies over those decades have attempted to delineate the reproductive safety of these agents.
With the development of new antidepressants and second-generation antipsychotics has come an appreciation of the utility of these agents across a wide range of psychiatric disease states and psychiatric symptoms. More and more data demonstrate the efficacy of these medicines for mood and anxiety disorders; these agents are also used for a broad array of symptoms from insomnia, irritability, and symptoms of posttraumatic stress disorder (PTSD) just as examples — even absent formal approval by the US Food and Drug Administration (FDA) for these specific indications. With the growing use of medicines, including new antidepressants like selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors, and second-generation atypical antipsychotics, there has been a greater interest and appreciation of the need to provide women with the best information about reproductive safety of these medicines as well.
When I began working in reproductive psychiatry, the FDA was using the pregnancy labeling categories introduced in 1979. The categories were simple, but also oversimplified in terms of incompletely conveying information about reproductive safety. For instance, category labels of B and C under the old labeling system could be nebulous, containing sparse information (in the case of category B) or animal data and some conflicting human data (in the case of category C) that may not have translated into relevant or easily interpretable safety information for patients and clinicians.
It was on that basis the current Pregnancy and Lactation Labeling (PLLR) Final Rule was published in 2014, which was a shift from categorical labeling to more descriptive labeling, including updated actual information on the package insert about available reproductive safety data, animal data, and data on lactation.
Even following the publication of the PLLR, there has still been an acknowledgment in the field that our assessment tools for postmarketing reproductive safety surveillance are incomplete. A recent 2-day FDA workshop hosted by the Duke-Margolis Center for Health Policy on optimizing the use of postapproval pregnancy safety studies sought to discuss the many questions that still surround this issue. Based on presentations at this workshop, a framework emerged for the future of assessing the reproductive safety of medications, which included an effort to develop the most effective model using tools such as pregnancy registries and harnessing “big data,” whether through electronic health records or large administrative databases from public and private insurers. Together, these various sources of information can provide signals of potential concern, prompting the need for a more rigorous look at the reproductive safety of a medication, or provide reassurance if data fail to indicate the absence of a signal of risk.
FDA’s new commitments under the latest reauthorization of the Prescription Drug User Fee Act (PDUFA VII) include pregnancy-specific postmarketing safety requirements as well as the creation of a framework for how data from pregnancy-specific postmarketing studies can be used. The agency is also conducting demonstration projects, including one for assessing the performance of pregnancy registries for the potential to detect safety signals for medications early in pregnancy. FDA is expanding its Sentinel Initiative to help accomplish these aims, and is implementing an Active Risk Identification and Analysis (ARIA) system to conduct active safety surveillance of medications used during pregnancy.
Pregnancy registries have now been available for decades, and some have been more successful than others across different classes of medicines, with the most rigorous registries including prospective follow-up of women across pregnancies and careful documentation of malformations (at best with original source data and with a blinded dysmorphologist). Still, with all of its rigor, even the best-intentioned efforts with respect to pregnancy registries have limitations. As I mentioned in my testimony during the public comment portion of the workshop, the sheer volume of pregnancy data from administrative databases we now have access to is attractive, but the quality of these data needs to be good enough to ascertain a signal of risk if they are to be used as a basis for reproductive safety determination.
The flip side of using data from large administrative databases is using carefully collected data from pregnancy registries. With a pregnancy registry, accrual of a substantial number of participants can also take a considerable period of time, and initial risk estimates of outcomes can have typically large confidence intervals, which can make it difficult to discern whether a drug is safe for women of reproductive age.
Another key issue is a lack of participation from manufacturers with respect to commitment to collection of high-quality reproductive safety data. History has shown that many medication manufacturers, unless required to have a dedicated registry as part of a postmarketing requirement or commitment, will invest sparse resources to track data on safety of fetal drug exposure. Participation is typically voluntary and varies from company to company unless, as noted previously, there is a postmarketing requirement or commitment tied to the approval of a medication. Just as a recent concrete example, the manufacturer of a new medication recently approved by the FDA for the treatment of postpartum depression (which will include presumably sexually active women well into the first postpartum year) has no plan to support the collection of reproductive safety data on this new medication because it is not required to, based on current FDA guidelines and the absence of a postmarketing requirement to do so.
Looking ahead
While the PLLR was a huge step forward in the field from the old pregnancy category system that could misinform women contemplating pregnancy, it also sets the stage for the next iteration of a system that allows us to generate information more quickly about the reproductive safety of medications. In psychiatry, as many as 10% of women use SSRIs during pregnancy. With drugs like atypical antipsychotics being used across disease states — in schizophrenia, bipolar disorder, depression, anxiety, insomnia, and PTSD — and where new classes of medicine are becoming available, like with ketamine or steroids, we need to have a system by which we can more quickly ascertain reproductive safety information. This information informs treatment decisions during a critical life event of deciding to try to become pregnant or during an actual pregnancy.
In my mind, it is reassuring when a registry has even as few as 50-60 cases of fetal exposure without an increase in the risk for malformation, because it can mean we are not seeing a repeat of the past with medications like thalidomide and sodium valproate. However, patients and clinicians are starved for better data. Risk assessment is also different from clinician to clinician and patient to patient. We want to empower patients to make decisions that work for them based on more rapidly accumulating information and help inform their decisions.
To come out on the “other side” of the PLLR, , which can be confusing when study results frequently conflict. I believe we have an obligation today to do this better, because the areas of reproductive toxicology and pharmacovigilance are growing incredibly quickly, and clinicians and patients are seeing these volumes of data being published without the ability to integrate that information in a systematic way.
Dr. Cohen is the director of the Ammon-Pinizzotto Center for Women’s Mental Health at Massachusetts General Hospital (MGH) in Boston, which provides information resources and conducts clinical care and research in reproductive mental health. He has been a consultant to manufacturers of psychiatric medications. Full disclosure information for Dr. Cohen is available at womensmentalhealth.org. Email Dr. Cohen at obnews@mdedge.com.
1 in 3 women have lasting health problems after giving birth: Study
Those problems include pain during sexual intercourse (35%), low back pain (32%), urinary incontinence (8% to 31%), anxiety (9% to 24%), anal incontinence (19%), depression (11% to 17%), fear of childbirth (6% to 15%), perineal pain (11%), and secondary infertility (11%).
Other problems included pelvic organ prolapse, posttraumatic stress disorder, thyroid dysfunction, mastitis, HIV seroconversion (when the body begins to produce detectable levels of HIV antibodies), nerve injury, and psychosis.
The study says most women see a doctor 6 to 12 weeks after birth and then rarely talk to doctors about these nagging health problems. Many of the problems don’t show up until 6 or more weeks after birth.
“To comprehensively address these conditions, broader and more comprehensive health service opportunities are needed, which should extend beyond 6 weeks postpartum and embrace multidisciplinary models of care,” the study says. “This approach can ensure that these conditions are promptly identified and given the attention that they deserve.”
The study is part of a series organized by the United Nation’s Special Program on Human Reproduction, the World Health Organization, and the U.S. Agency for International Development. The authors said most of the data came from high-income nations. There was little data from low-income and middle-income countries except for postpartum depression, anxiety, and psychosis.
“Many postpartum conditions cause considerable suffering in women’s daily life long after birth, both emotionally and physically, and yet they are largely underappreciated, underrecognized, and underreported,” Pascale Allotey, MD, director of Sexual and Reproductive Health and Research at WHO, said in a statement.
“Throughout their lives, and beyond motherhood, women need access to a range of services from health-care providers who listen to their concerns and meet their needs — so they not only survive childbirth but can enjoy good health and quality of life.”
A version of this article appeared on WebMD.com.
Those problems include pain during sexual intercourse (35%), low back pain (32%), urinary incontinence (8% to 31%), anxiety (9% to 24%), anal incontinence (19%), depression (11% to 17%), fear of childbirth (6% to 15%), perineal pain (11%), and secondary infertility (11%).
Other problems included pelvic organ prolapse, posttraumatic stress disorder, thyroid dysfunction, mastitis, HIV seroconversion (when the body begins to produce detectable levels of HIV antibodies), nerve injury, and psychosis.
The study says most women see a doctor 6 to 12 weeks after birth and then rarely talk to doctors about these nagging health problems. Many of the problems don’t show up until 6 or more weeks after birth.
“To comprehensively address these conditions, broader and more comprehensive health service opportunities are needed, which should extend beyond 6 weeks postpartum and embrace multidisciplinary models of care,” the study says. “This approach can ensure that these conditions are promptly identified and given the attention that they deserve.”
The study is part of a series organized by the United Nation’s Special Program on Human Reproduction, the World Health Organization, and the U.S. Agency for International Development. The authors said most of the data came from high-income nations. There was little data from low-income and middle-income countries except for postpartum depression, anxiety, and psychosis.
“Many postpartum conditions cause considerable suffering in women’s daily life long after birth, both emotionally and physically, and yet they are largely underappreciated, underrecognized, and underreported,” Pascale Allotey, MD, director of Sexual and Reproductive Health and Research at WHO, said in a statement.
“Throughout their lives, and beyond motherhood, women need access to a range of services from health-care providers who listen to their concerns and meet their needs — so they not only survive childbirth but can enjoy good health and quality of life.”
A version of this article appeared on WebMD.com.
Those problems include pain during sexual intercourse (35%), low back pain (32%), urinary incontinence (8% to 31%), anxiety (9% to 24%), anal incontinence (19%), depression (11% to 17%), fear of childbirth (6% to 15%), perineal pain (11%), and secondary infertility (11%).
Other problems included pelvic organ prolapse, posttraumatic stress disorder, thyroid dysfunction, mastitis, HIV seroconversion (when the body begins to produce detectable levels of HIV antibodies), nerve injury, and psychosis.
The study says most women see a doctor 6 to 12 weeks after birth and then rarely talk to doctors about these nagging health problems. Many of the problems don’t show up until 6 or more weeks after birth.
“To comprehensively address these conditions, broader and more comprehensive health service opportunities are needed, which should extend beyond 6 weeks postpartum and embrace multidisciplinary models of care,” the study says. “This approach can ensure that these conditions are promptly identified and given the attention that they deserve.”
The study is part of a series organized by the United Nation’s Special Program on Human Reproduction, the World Health Organization, and the U.S. Agency for International Development. The authors said most of the data came from high-income nations. There was little data from low-income and middle-income countries except for postpartum depression, anxiety, and psychosis.
“Many postpartum conditions cause considerable suffering in women’s daily life long after birth, both emotionally and physically, and yet they are largely underappreciated, underrecognized, and underreported,” Pascale Allotey, MD, director of Sexual and Reproductive Health and Research at WHO, said in a statement.
“Throughout their lives, and beyond motherhood, women need access to a range of services from health-care providers who listen to their concerns and meet their needs — so they not only survive childbirth but can enjoy good health and quality of life.”
A version of this article appeared on WebMD.com.
FROM THE LANCET GLOBAL HEALTH
Adverse events in childhood alter brain function
In a meta-analysis of 83 functional magnetic resonance imaging (fMRI) studies that included more than 5000 patients, exposure to adversity was associated with higher amygdala reactivity and lower prefrontal cortical reactivity across a range of task domains.
The altered responses were only observed in studies including adult participants and were clearest in participants who had been exposed to severe threat and trauma. Children and adolescents did not show significant adversity-related differences in brain function.
“By integrating the results from 83 previous brain imaging studies, we were able to provide what is arguably the clearest evidence to date that adults who have been exposed to early life trauma have different brain responses to psychological challenges,” senior author Marco Leyton, PhD, professor of psychiatry and director of the Temperament Adversity Biology Lab at McGill University in Montreal, Quebec, Canada, said in a press release. “This includes exaggerated responses in a region that processes emotionally intense information (the amygdala) and reduced responses in a region that helps people regulate emotions and associated behaviors (the frontal cortex).”
The findings were published in JAMA Network Open.
Changes in Reactivity
“One big issue we have in psychology, and especially in neuroscience, is that single-study results are often not reproducible,” lead author Niki Hosseini-Kamkar, PhD, neuroimaging research associate at Atlas Institute for Veterans and Families at Royal Ottawa Hospital, said in an interview.
“It was very important to me to use a meta-analysis to get an overall picture of what brain regions are consistently reported across all these different studies. That is what we did here,” she added. Dr. Hosseini-Kamkar conducted this analysis while she was a postdoctoral research fellow at McGill University in Montreal.
She and her group examined adversity exposure and brain function in the following four domains of task-based fMRI: emotion processing, memory processing, inhibitory control, and reward processing. Their study included 5242 participants. The researchers used multilevel kernel density analyses (MKDA) to analyze the data more accurately.
Adversity exposure was associated with higher amygdala reactivity (P < .001) and lower prefrontal cortical reactivity (P < .001), compared with controls with no adversity exposure.
Threat types of adversity were associated with greater blood-oxygen-level-dependent (BOLD) responses in the superior temporal gyrus and lower prefrontal cortex activity in participants exposed to threat, compared with controls.
Analysis of studies of inhibitory control tasks found greater activity in the claustrum, anterior cingulate cortex, and insula in the adversity-exposed participants, compared with controls.
In addition, studies that administered emotion processing tasks showed greater amygdala reactivity and lower prefrontal cortex (superior frontal gyrus) reactivity in the adversity exposure group, compared with controls.
“The main takeaway is that there’s an exaggerated activity in the amygdala, and diminished prefrontal cortex activity, and together, this might point to a mechanism for how a history of adversity diminishes the ability to cope with later stressors and can therefore heighten susceptibility to mental illness,” said Dr. Hosseini-Kamkar.
‘Important Next Step’
“Overall, the meta-analysis by Dr. Hosseini-Kamkar and colleagues represents an important next step in understanding associations of adversity exposure with brain function while highlighting the importance of considering the role of development,” wrote Dylan G. Gee, PhD, associate professor of psychology at Yale University in New Haven, Connecticut, and Alexis Brieant, PhD, assistant professor of research or creative works at the University of Vermont in Burlington, in an accompanying commentary.
They also applauded the authors for their use of MKDA. They noted that the technique “allows inferences about the consistency and specificity of brain activation across studies and is thought to be more robust to small sample sizes than activation likelihood estimation (ALE) meta-analysis.”
Dr. Gee and Dr. Brieant also observed that a recent ALE meta-analysis failed to find a link between adversity and brain function. “Although it is important to note that the file drawer problem — by which researchers are less likely to publish null results — presents challenges to the inferences that can be drawn in the current work, the current study may provide complementary information to prior ALE meta-analyses.”
Epigenetic Changes?
Commenting on the findings for this article, Victor Fornari, MD, director of child and adolescent psychiatry at Northwell Health in Glen Oaks, New York, said, “Historically, when someone went through a traumatic event, they were told to just get over it, because somehow trauma doesn’t have a lasting impact on the brain.” Dr. Fornari was not involved in the research.
“We have certainly learned so much more over the past decade about early adversity and that it does have a profound impact on the brain and probably even epigenetic changes in our genes,” Dr. Fornari said.
“This is a very important avenue of investigation. People are really trying to understand if there are biological markers that we can actually measure in the brain that will offer us a window to better understand the consequence of adversity, as well as possible avenues of treatment.”
No funding source for this study was reported. Dr. Leyton, Dr. Hosseini-Kamkar, and Dr. Fornari report no relevant financial relationships. Gee reports receiving grants from the National Science Foundation and National Institutes of Health outside the submitted work. Dr. Brieant reports receiving grants from the National Institute of Mental Health outside the submitted work.
A version of this article appeared on Medscape.com.
In a meta-analysis of 83 functional magnetic resonance imaging (fMRI) studies that included more than 5000 patients, exposure to adversity was associated with higher amygdala reactivity and lower prefrontal cortical reactivity across a range of task domains.
The altered responses were only observed in studies including adult participants and were clearest in participants who had been exposed to severe threat and trauma. Children and adolescents did not show significant adversity-related differences in brain function.
“By integrating the results from 83 previous brain imaging studies, we were able to provide what is arguably the clearest evidence to date that adults who have been exposed to early life trauma have different brain responses to psychological challenges,” senior author Marco Leyton, PhD, professor of psychiatry and director of the Temperament Adversity Biology Lab at McGill University in Montreal, Quebec, Canada, said in a press release. “This includes exaggerated responses in a region that processes emotionally intense information (the amygdala) and reduced responses in a region that helps people regulate emotions and associated behaviors (the frontal cortex).”
The findings were published in JAMA Network Open.
Changes in Reactivity
“One big issue we have in psychology, and especially in neuroscience, is that single-study results are often not reproducible,” lead author Niki Hosseini-Kamkar, PhD, neuroimaging research associate at Atlas Institute for Veterans and Families at Royal Ottawa Hospital, said in an interview.
“It was very important to me to use a meta-analysis to get an overall picture of what brain regions are consistently reported across all these different studies. That is what we did here,” she added. Dr. Hosseini-Kamkar conducted this analysis while she was a postdoctoral research fellow at McGill University in Montreal.
She and her group examined adversity exposure and brain function in the following four domains of task-based fMRI: emotion processing, memory processing, inhibitory control, and reward processing. Their study included 5242 participants. The researchers used multilevel kernel density analyses (MKDA) to analyze the data more accurately.
Adversity exposure was associated with higher amygdala reactivity (P < .001) and lower prefrontal cortical reactivity (P < .001), compared with controls with no adversity exposure.
Threat types of adversity were associated with greater blood-oxygen-level-dependent (BOLD) responses in the superior temporal gyrus and lower prefrontal cortex activity in participants exposed to threat, compared with controls.
Analysis of studies of inhibitory control tasks found greater activity in the claustrum, anterior cingulate cortex, and insula in the adversity-exposed participants, compared with controls.
In addition, studies that administered emotion processing tasks showed greater amygdala reactivity and lower prefrontal cortex (superior frontal gyrus) reactivity in the adversity exposure group, compared with controls.
“The main takeaway is that there’s an exaggerated activity in the amygdala, and diminished prefrontal cortex activity, and together, this might point to a mechanism for how a history of adversity diminishes the ability to cope with later stressors and can therefore heighten susceptibility to mental illness,” said Dr. Hosseini-Kamkar.
‘Important Next Step’
“Overall, the meta-analysis by Dr. Hosseini-Kamkar and colleagues represents an important next step in understanding associations of adversity exposure with brain function while highlighting the importance of considering the role of development,” wrote Dylan G. Gee, PhD, associate professor of psychology at Yale University in New Haven, Connecticut, and Alexis Brieant, PhD, assistant professor of research or creative works at the University of Vermont in Burlington, in an accompanying commentary.
They also applauded the authors for their use of MKDA. They noted that the technique “allows inferences about the consistency and specificity of brain activation across studies and is thought to be more robust to small sample sizes than activation likelihood estimation (ALE) meta-analysis.”
Dr. Gee and Dr. Brieant also observed that a recent ALE meta-analysis failed to find a link between adversity and brain function. “Although it is important to note that the file drawer problem — by which researchers are less likely to publish null results — presents challenges to the inferences that can be drawn in the current work, the current study may provide complementary information to prior ALE meta-analyses.”
Epigenetic Changes?
Commenting on the findings for this article, Victor Fornari, MD, director of child and adolescent psychiatry at Northwell Health in Glen Oaks, New York, said, “Historically, when someone went through a traumatic event, they were told to just get over it, because somehow trauma doesn’t have a lasting impact on the brain.” Dr. Fornari was not involved in the research.
“We have certainly learned so much more over the past decade about early adversity and that it does have a profound impact on the brain and probably even epigenetic changes in our genes,” Dr. Fornari said.
“This is a very important avenue of investigation. People are really trying to understand if there are biological markers that we can actually measure in the brain that will offer us a window to better understand the consequence of adversity, as well as possible avenues of treatment.”
No funding source for this study was reported. Dr. Leyton, Dr. Hosseini-Kamkar, and Dr. Fornari report no relevant financial relationships. Gee reports receiving grants from the National Science Foundation and National Institutes of Health outside the submitted work. Dr. Brieant reports receiving grants from the National Institute of Mental Health outside the submitted work.
A version of this article appeared on Medscape.com.
In a meta-analysis of 83 functional magnetic resonance imaging (fMRI) studies that included more than 5000 patients, exposure to adversity was associated with higher amygdala reactivity and lower prefrontal cortical reactivity across a range of task domains.
The altered responses were only observed in studies including adult participants and were clearest in participants who had been exposed to severe threat and trauma. Children and adolescents did not show significant adversity-related differences in brain function.
“By integrating the results from 83 previous brain imaging studies, we were able to provide what is arguably the clearest evidence to date that adults who have been exposed to early life trauma have different brain responses to psychological challenges,” senior author Marco Leyton, PhD, professor of psychiatry and director of the Temperament Adversity Biology Lab at McGill University in Montreal, Quebec, Canada, said in a press release. “This includes exaggerated responses in a region that processes emotionally intense information (the amygdala) and reduced responses in a region that helps people regulate emotions and associated behaviors (the frontal cortex).”
The findings were published in JAMA Network Open.
Changes in Reactivity
“One big issue we have in psychology, and especially in neuroscience, is that single-study results are often not reproducible,” lead author Niki Hosseini-Kamkar, PhD, neuroimaging research associate at Atlas Institute for Veterans and Families at Royal Ottawa Hospital, said in an interview.
“It was very important to me to use a meta-analysis to get an overall picture of what brain regions are consistently reported across all these different studies. That is what we did here,” she added. Dr. Hosseini-Kamkar conducted this analysis while she was a postdoctoral research fellow at McGill University in Montreal.
She and her group examined adversity exposure and brain function in the following four domains of task-based fMRI: emotion processing, memory processing, inhibitory control, and reward processing. Their study included 5242 participants. The researchers used multilevel kernel density analyses (MKDA) to analyze the data more accurately.
Adversity exposure was associated with higher amygdala reactivity (P < .001) and lower prefrontal cortical reactivity (P < .001), compared with controls with no adversity exposure.
Threat types of adversity were associated with greater blood-oxygen-level-dependent (BOLD) responses in the superior temporal gyrus and lower prefrontal cortex activity in participants exposed to threat, compared with controls.
Analysis of studies of inhibitory control tasks found greater activity in the claustrum, anterior cingulate cortex, and insula in the adversity-exposed participants, compared with controls.
In addition, studies that administered emotion processing tasks showed greater amygdala reactivity and lower prefrontal cortex (superior frontal gyrus) reactivity in the adversity exposure group, compared with controls.
“The main takeaway is that there’s an exaggerated activity in the amygdala, and diminished prefrontal cortex activity, and together, this might point to a mechanism for how a history of adversity diminishes the ability to cope with later stressors and can therefore heighten susceptibility to mental illness,” said Dr. Hosseini-Kamkar.
‘Important Next Step’
“Overall, the meta-analysis by Dr. Hosseini-Kamkar and colleagues represents an important next step in understanding associations of adversity exposure with brain function while highlighting the importance of considering the role of development,” wrote Dylan G. Gee, PhD, associate professor of psychology at Yale University in New Haven, Connecticut, and Alexis Brieant, PhD, assistant professor of research or creative works at the University of Vermont in Burlington, in an accompanying commentary.
They also applauded the authors for their use of MKDA. They noted that the technique “allows inferences about the consistency and specificity of brain activation across studies and is thought to be more robust to small sample sizes than activation likelihood estimation (ALE) meta-analysis.”
Dr. Gee and Dr. Brieant also observed that a recent ALE meta-analysis failed to find a link between adversity and brain function. “Although it is important to note that the file drawer problem — by which researchers are less likely to publish null results — presents challenges to the inferences that can be drawn in the current work, the current study may provide complementary information to prior ALE meta-analyses.”
Epigenetic Changes?
Commenting on the findings for this article, Victor Fornari, MD, director of child and adolescent psychiatry at Northwell Health in Glen Oaks, New York, said, “Historically, when someone went through a traumatic event, they were told to just get over it, because somehow trauma doesn’t have a lasting impact on the brain.” Dr. Fornari was not involved in the research.
“We have certainly learned so much more over the past decade about early adversity and that it does have a profound impact on the brain and probably even epigenetic changes in our genes,” Dr. Fornari said.
“This is a very important avenue of investigation. People are really trying to understand if there are biological markers that we can actually measure in the brain that will offer us a window to better understand the consequence of adversity, as well as possible avenues of treatment.”
No funding source for this study was reported. Dr. Leyton, Dr. Hosseini-Kamkar, and Dr. Fornari report no relevant financial relationships. Gee reports receiving grants from the National Science Foundation and National Institutes of Health outside the submitted work. Dr. Brieant reports receiving grants from the National Institute of Mental Health outside the submitted work.
A version of this article appeared on Medscape.com.
FROM JAMA NETWORK OPEN
VA’s Annual Report on Suicide: Reasons for Despair—and Hope
When COVID-19 hit, the number of suicides among veterans had been going down. Before 2021, veteran suicide declined 2 years in a row—from 6718 in 2018 to 6278 in 2020. But in 2021, the trend began to reverse: 6392 veterans died by suicide, according to the US Department of Veterans Affairs (VA) recently released National Veteran Suicide Prevention Annual Report, which includes the first full year of information since March 2020.
The pandemic took a toll in uncountable ways: increasing social and financial insecurity, anxiety, depression, and barriers to health care—all factors associated with a higher risk of suicide. Nonveteran suicides also increased, to 40,020 deaths in 2021, 2000 more than in 2020. But the age- and sex-adjusted suicide rate among veterans increased by 11.6%, compared with an increase of 4.5% among nonveteran adults.
In 2021, the unadjusted suicide rate was highest among American Indian or Alaska Natives (46.3 per 100,000), followed by 36.3 per 100,000 for White veterans; 31.6 per 100,000 for Asian, Native Hawaiian or Pacific Islander veterans; 19.7 per 100,000 for veterans with Hispanic ethnicity; 17.4 per 100,000 for Black or African American veterans; and 6.7 per 100,000 for veterans of multiple races.
The report demonstrates a deep dive into the data but the findings on risk factors may come as no surprise. A documented factor in the rise in suicide among veterans was distress, which increased from fall 2019 to fall and winter 2020, with evidence of the highest increases in distress among veterans aged 18 to 44 years and among women veterans. The rise in distress was associated with increasing socioeconomic concerns, greater problematic alcohol use, and less community integration. Moreover, during the pandemic, veterans were found to experience more mental health concerns than nonveterans.
A review of 23 studies found a greater prevalence of alcohol use, anxiety, depression, posttraumatic stress disorder, stress, loneliness, and suicidal ideation. Key risk factors included pandemic-related stress, family relationship strain, lack of social support, financial concerns, and preexisting mental health disorders.
VA Behavioral Health Autopsy Program data indicated that the most frequently identified risk factors for suicide deaths in 2019 to 2021 were pain (55.9%), sleep problems (51.7%), increased health problems (40.7%), relationship problems (33.7%), recent declines in physical ability (33.0%), hopelessness (30.6%) and unsecured firearms in the home (28.8%).
Meanwhile, more people were buying guns: A study published in the Annals of Internal Medicine found that, as of April 2021, approximately 10% of gun owners in the US had become new gun owners over the previous 28 months. Firearm availability is known to increase the risk of suicide and the risk of dying during a suicide attempt. According to 2021 VA data, nearly 7 of every 10 veteran deaths by suicide are the result of firearm injuries.
Among US adults who died from suicide in 2021, firearms were more commonly involved among veteran deaths (72.2%) than among nonveteran deaths (52.2%). In each year studied, firearm suicide mortality rates were greater for men than for women; however, the firearm suicide rate among veteran women was 281.1% higher than that of nonveteran women, while the firearm suicide rate among veteran men was 62.4% higher than for nonveteran men.
But there were some bright spots. “Hope is essential to life,” the report says, “and hope serves an important role within suicide prevention efforts.” It points to areas where things improved, even amid the pandemic. Suicide rates fell by 8.1% for veteran men aged 75 years and older. Among recent VA users between ages 55 and 74 years, the suicide rate fell by 2.2% overall (-0.6% for men, -24.9% for women). Among male recent VA users, suicide rates fell by 1.9% for those aged 18 to 34 years. From 2001 to 2021, the suicide rate among recent VA users with mental health or substance use disorder diagnoses fell from 77.8 per 100,000 to 58.2 per 100,000.
Nonetheless, the data show veterans “remain at elevated risk for suicide.” “We will do everything in our power to learn from this report and use its findings to help us save lives,” said VA Under Secretary for Health Shereef Elnahal, MD. “It will take all of us—working together—to end veteran suicide, and we will not rest until that goal becomes a reality.”
“Suicide is a complex problem,” Dr. Carolyn Clancy, Executive in Charge, Office of the Under Secretary for Health, writes in the VA publication National Strategy for Preventing Veteran Suicide, 2018–2028. “[I]t requires coordinated, evidence-based solutions that reach beyond the traditional medical model of prevention.” She notes that the VA has “embraced a comprehensive public health approach to reduce veteran suicide rates, one that looks beyond the individual to involve peers, family members, and the community.”
“Yet we know we cannot do it alone, as roughly half of all veterans in the US do not receive services or benefits from VA. This means we must collaborate with partners and communities nationwide to use the best available information and practices to support all veterans, whether or not they’re engaging with VA.”
The VA calls ending veteran suicide its top clinical priority and supports the Biden Administration’s goal of reducing the annual suicide rate in the US by 20% by 2025. Since 2021, the VA has bolstered and broadened resources for at-risk veterans, such as no-cost health care at VA or non-VA facilities for those in crisis; the 988 (then press 1) Veterans Crisis Line; partnerships with community-based suicide prevention organizations; and expanded firearm suicide prevention efforts.
The VA says these efforts, plus a national veteran suicide prevention awareness campaign, have led to more than 33,000 veterans getting free emergency health care, a 12.1% increase in use of the Veterans Crisis Line, and more than 3.5 million visits to the VA’s support website. Moving forward, the VA says, it will continue to work “urgently” alongside the Biden-Harris Administration to end veteran suicide through a public health approach that combines both community-based and clinically based strategies to save lives.
“There is nothing more important to VA than preventing veteran suicide —nothing,” said Secretary of VA Denis McDonough. “One veteran suicide will always be too many, and we at VA will use every tool to our disposal to prevent these tragedies and save veterans’ lives.”
If you or someone you know is having thoughts of suicide, call or text 988 to reach the National Suicide Prevention Lifeline or contact the Veterans Crisis Line: www.veteranscrisisline.net.
Related resources:
- The National Suicide Prevention Lifeline is a hotline for individuals in crisis or for those looking to help someone else. To speak with a certified listener, call 1-800-273-8255.
- Crisis Text Line is a texting service for emotional crisis support. To speak with a trained listener, text HELLO to 741741. It is free, available 24/7, and confidential.
- American Foundation for Suicide Prevention. https://afsp.org/
When COVID-19 hit, the number of suicides among veterans had been going down. Before 2021, veteran suicide declined 2 years in a row—from 6718 in 2018 to 6278 in 2020. But in 2021, the trend began to reverse: 6392 veterans died by suicide, according to the US Department of Veterans Affairs (VA) recently released National Veteran Suicide Prevention Annual Report, which includes the first full year of information since March 2020.
The pandemic took a toll in uncountable ways: increasing social and financial insecurity, anxiety, depression, and barriers to health care—all factors associated with a higher risk of suicide. Nonveteran suicides also increased, to 40,020 deaths in 2021, 2000 more than in 2020. But the age- and sex-adjusted suicide rate among veterans increased by 11.6%, compared with an increase of 4.5% among nonveteran adults.
In 2021, the unadjusted suicide rate was highest among American Indian or Alaska Natives (46.3 per 100,000), followed by 36.3 per 100,000 for White veterans; 31.6 per 100,000 for Asian, Native Hawaiian or Pacific Islander veterans; 19.7 per 100,000 for veterans with Hispanic ethnicity; 17.4 per 100,000 for Black or African American veterans; and 6.7 per 100,000 for veterans of multiple races.
The report demonstrates a deep dive into the data but the findings on risk factors may come as no surprise. A documented factor in the rise in suicide among veterans was distress, which increased from fall 2019 to fall and winter 2020, with evidence of the highest increases in distress among veterans aged 18 to 44 years and among women veterans. The rise in distress was associated with increasing socioeconomic concerns, greater problematic alcohol use, and less community integration. Moreover, during the pandemic, veterans were found to experience more mental health concerns than nonveterans.
A review of 23 studies found a greater prevalence of alcohol use, anxiety, depression, posttraumatic stress disorder, stress, loneliness, and suicidal ideation. Key risk factors included pandemic-related stress, family relationship strain, lack of social support, financial concerns, and preexisting mental health disorders.
VA Behavioral Health Autopsy Program data indicated that the most frequently identified risk factors for suicide deaths in 2019 to 2021 were pain (55.9%), sleep problems (51.7%), increased health problems (40.7%), relationship problems (33.7%), recent declines in physical ability (33.0%), hopelessness (30.6%) and unsecured firearms in the home (28.8%).
Meanwhile, more people were buying guns: A study published in the Annals of Internal Medicine found that, as of April 2021, approximately 10% of gun owners in the US had become new gun owners over the previous 28 months. Firearm availability is known to increase the risk of suicide and the risk of dying during a suicide attempt. According to 2021 VA data, nearly 7 of every 10 veteran deaths by suicide are the result of firearm injuries.
Among US adults who died from suicide in 2021, firearms were more commonly involved among veteran deaths (72.2%) than among nonveteran deaths (52.2%). In each year studied, firearm suicide mortality rates were greater for men than for women; however, the firearm suicide rate among veteran women was 281.1% higher than that of nonveteran women, while the firearm suicide rate among veteran men was 62.4% higher than for nonveteran men.
But there were some bright spots. “Hope is essential to life,” the report says, “and hope serves an important role within suicide prevention efforts.” It points to areas where things improved, even amid the pandemic. Suicide rates fell by 8.1% for veteran men aged 75 years and older. Among recent VA users between ages 55 and 74 years, the suicide rate fell by 2.2% overall (-0.6% for men, -24.9% for women). Among male recent VA users, suicide rates fell by 1.9% for those aged 18 to 34 years. From 2001 to 2021, the suicide rate among recent VA users with mental health or substance use disorder diagnoses fell from 77.8 per 100,000 to 58.2 per 100,000.
Nonetheless, the data show veterans “remain at elevated risk for suicide.” “We will do everything in our power to learn from this report and use its findings to help us save lives,” said VA Under Secretary for Health Shereef Elnahal, MD. “It will take all of us—working together—to end veteran suicide, and we will not rest until that goal becomes a reality.”
“Suicide is a complex problem,” Dr. Carolyn Clancy, Executive in Charge, Office of the Under Secretary for Health, writes in the VA publication National Strategy for Preventing Veteran Suicide, 2018–2028. “[I]t requires coordinated, evidence-based solutions that reach beyond the traditional medical model of prevention.” She notes that the VA has “embraced a comprehensive public health approach to reduce veteran suicide rates, one that looks beyond the individual to involve peers, family members, and the community.”
“Yet we know we cannot do it alone, as roughly half of all veterans in the US do not receive services or benefits from VA. This means we must collaborate with partners and communities nationwide to use the best available information and practices to support all veterans, whether or not they’re engaging with VA.”
The VA calls ending veteran suicide its top clinical priority and supports the Biden Administration’s goal of reducing the annual suicide rate in the US by 20% by 2025. Since 2021, the VA has bolstered and broadened resources for at-risk veterans, such as no-cost health care at VA or non-VA facilities for those in crisis; the 988 (then press 1) Veterans Crisis Line; partnerships with community-based suicide prevention organizations; and expanded firearm suicide prevention efforts.
The VA says these efforts, plus a national veteran suicide prevention awareness campaign, have led to more than 33,000 veterans getting free emergency health care, a 12.1% increase in use of the Veterans Crisis Line, and more than 3.5 million visits to the VA’s support website. Moving forward, the VA says, it will continue to work “urgently” alongside the Biden-Harris Administration to end veteran suicide through a public health approach that combines both community-based and clinically based strategies to save lives.
“There is nothing more important to VA than preventing veteran suicide —nothing,” said Secretary of VA Denis McDonough. “One veteran suicide will always be too many, and we at VA will use every tool to our disposal to prevent these tragedies and save veterans’ lives.”
If you or someone you know is having thoughts of suicide, call or text 988 to reach the National Suicide Prevention Lifeline or contact the Veterans Crisis Line: www.veteranscrisisline.net.
Related resources:
- The National Suicide Prevention Lifeline is a hotline for individuals in crisis or for those looking to help someone else. To speak with a certified listener, call 1-800-273-8255.
- Crisis Text Line is a texting service for emotional crisis support. To speak with a trained listener, text HELLO to 741741. It is free, available 24/7, and confidential.
- American Foundation for Suicide Prevention. https://afsp.org/
When COVID-19 hit, the number of suicides among veterans had been going down. Before 2021, veteran suicide declined 2 years in a row—from 6718 in 2018 to 6278 in 2020. But in 2021, the trend began to reverse: 6392 veterans died by suicide, according to the US Department of Veterans Affairs (VA) recently released National Veteran Suicide Prevention Annual Report, which includes the first full year of information since March 2020.
The pandemic took a toll in uncountable ways: increasing social and financial insecurity, anxiety, depression, and barriers to health care—all factors associated with a higher risk of suicide. Nonveteran suicides also increased, to 40,020 deaths in 2021, 2000 more than in 2020. But the age- and sex-adjusted suicide rate among veterans increased by 11.6%, compared with an increase of 4.5% among nonveteran adults.
In 2021, the unadjusted suicide rate was highest among American Indian or Alaska Natives (46.3 per 100,000), followed by 36.3 per 100,000 for White veterans; 31.6 per 100,000 for Asian, Native Hawaiian or Pacific Islander veterans; 19.7 per 100,000 for veterans with Hispanic ethnicity; 17.4 per 100,000 for Black or African American veterans; and 6.7 per 100,000 for veterans of multiple races.
The report demonstrates a deep dive into the data but the findings on risk factors may come as no surprise. A documented factor in the rise in suicide among veterans was distress, which increased from fall 2019 to fall and winter 2020, with evidence of the highest increases in distress among veterans aged 18 to 44 years and among women veterans. The rise in distress was associated with increasing socioeconomic concerns, greater problematic alcohol use, and less community integration. Moreover, during the pandemic, veterans were found to experience more mental health concerns than nonveterans.
A review of 23 studies found a greater prevalence of alcohol use, anxiety, depression, posttraumatic stress disorder, stress, loneliness, and suicidal ideation. Key risk factors included pandemic-related stress, family relationship strain, lack of social support, financial concerns, and preexisting mental health disorders.
VA Behavioral Health Autopsy Program data indicated that the most frequently identified risk factors for suicide deaths in 2019 to 2021 were pain (55.9%), sleep problems (51.7%), increased health problems (40.7%), relationship problems (33.7%), recent declines in physical ability (33.0%), hopelessness (30.6%) and unsecured firearms in the home (28.8%).
Meanwhile, more people were buying guns: A study published in the Annals of Internal Medicine found that, as of April 2021, approximately 10% of gun owners in the US had become new gun owners over the previous 28 months. Firearm availability is known to increase the risk of suicide and the risk of dying during a suicide attempt. According to 2021 VA data, nearly 7 of every 10 veteran deaths by suicide are the result of firearm injuries.
Among US adults who died from suicide in 2021, firearms were more commonly involved among veteran deaths (72.2%) than among nonveteran deaths (52.2%). In each year studied, firearm suicide mortality rates were greater for men than for women; however, the firearm suicide rate among veteran women was 281.1% higher than that of nonveteran women, while the firearm suicide rate among veteran men was 62.4% higher than for nonveteran men.
But there were some bright spots. “Hope is essential to life,” the report says, “and hope serves an important role within suicide prevention efforts.” It points to areas where things improved, even amid the pandemic. Suicide rates fell by 8.1% for veteran men aged 75 years and older. Among recent VA users between ages 55 and 74 years, the suicide rate fell by 2.2% overall (-0.6% for men, -24.9% for women). Among male recent VA users, suicide rates fell by 1.9% for those aged 18 to 34 years. From 2001 to 2021, the suicide rate among recent VA users with mental health or substance use disorder diagnoses fell from 77.8 per 100,000 to 58.2 per 100,000.
Nonetheless, the data show veterans “remain at elevated risk for suicide.” “We will do everything in our power to learn from this report and use its findings to help us save lives,” said VA Under Secretary for Health Shereef Elnahal, MD. “It will take all of us—working together—to end veteran suicide, and we will not rest until that goal becomes a reality.”
“Suicide is a complex problem,” Dr. Carolyn Clancy, Executive in Charge, Office of the Under Secretary for Health, writes in the VA publication National Strategy for Preventing Veteran Suicide, 2018–2028. “[I]t requires coordinated, evidence-based solutions that reach beyond the traditional medical model of prevention.” She notes that the VA has “embraced a comprehensive public health approach to reduce veteran suicide rates, one that looks beyond the individual to involve peers, family members, and the community.”
“Yet we know we cannot do it alone, as roughly half of all veterans in the US do not receive services or benefits from VA. This means we must collaborate with partners and communities nationwide to use the best available information and practices to support all veterans, whether or not they’re engaging with VA.”
The VA calls ending veteran suicide its top clinical priority and supports the Biden Administration’s goal of reducing the annual suicide rate in the US by 20% by 2025. Since 2021, the VA has bolstered and broadened resources for at-risk veterans, such as no-cost health care at VA or non-VA facilities for those in crisis; the 988 (then press 1) Veterans Crisis Line; partnerships with community-based suicide prevention organizations; and expanded firearm suicide prevention efforts.
The VA says these efforts, plus a national veteran suicide prevention awareness campaign, have led to more than 33,000 veterans getting free emergency health care, a 12.1% increase in use of the Veterans Crisis Line, and more than 3.5 million visits to the VA’s support website. Moving forward, the VA says, it will continue to work “urgently” alongside the Biden-Harris Administration to end veteran suicide through a public health approach that combines both community-based and clinically based strategies to save lives.
“There is nothing more important to VA than preventing veteran suicide —nothing,” said Secretary of VA Denis McDonough. “One veteran suicide will always be too many, and we at VA will use every tool to our disposal to prevent these tragedies and save veterans’ lives.”
If you or someone you know is having thoughts of suicide, call or text 988 to reach the National Suicide Prevention Lifeline or contact the Veterans Crisis Line: www.veteranscrisisline.net.
Related resources:
- The National Suicide Prevention Lifeline is a hotline for individuals in crisis or for those looking to help someone else. To speak with a certified listener, call 1-800-273-8255.
- Crisis Text Line is a texting service for emotional crisis support. To speak with a trained listener, text HELLO to 741741. It is free, available 24/7, and confidential.
- American Foundation for Suicide Prevention. https://afsp.org/
Higher blood levels of oleic acid tied to depression
TOPLINE:
National survey data reveal an association between higher serum oleic acid levels and depression in adults, new research shows.
METHODOLOGY:
Oleic acid is the most abundant fatty acid in plasma and has been associated with multiple neurologic diseases. However, the relationship between oleic acid and depression is unclear.
This cross-sectional analyzed data on 4459 adults from the 2011-2014 National Health and Nutrition Examination Survey (NHANES).
Multivariable logistic regression models adjusting for demographics, health and lifestyle factors quantified the association between oleic acid levels and depression. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) with depression defined as a score ≥ 10.
TAKEAWAY:
Serum oleic acid levels were positively associated with depression before and after multivariable adjustment.
After adjusting for all covariates, for every 1 mmol/L increase in serum oleic acid levels, the prevalence of depression increased by 40% (adjusted odds ratio [aOR], 1.40; 95% CI, 1.03-1.90).
Adults in the top quartile of oleic acid (≥ 2.51 mmol/L) had a greater than twofold higher likelihood of depression (aOR, 2.22; 95% CI, 1.04-4.73) compared with peers in the lowest quartile (≤ 1.54 mmol/L).
IN PRACTICE:
“A better understanding of the role of oleic acid in depression may lead to new preventive and therapeutic methods. Thus, carefully designed prospective studies are necessary to explore the positive effects of changing serum oleic acid levels through diet, medicine, or other measures on depression,” the authors write.
SOURCE:
The study, with first author Jiahui Yin of Shandong University of Traditional Chinese Medicine in Jinan, China, was published online on November 16, 2023 in BMC Psychiatry .
LIMITATIONS:
The cross-sectional study can’t prove causality. The findings may not apply to clinically diagnosed major depressive disorder.
DISCLOSURES:
The study had no specific funding. The authors report no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
National survey data reveal an association between higher serum oleic acid levels and depression in adults, new research shows.
METHODOLOGY:
Oleic acid is the most abundant fatty acid in plasma and has been associated with multiple neurologic diseases. However, the relationship between oleic acid and depression is unclear.
This cross-sectional analyzed data on 4459 adults from the 2011-2014 National Health and Nutrition Examination Survey (NHANES).
Multivariable logistic regression models adjusting for demographics, health and lifestyle factors quantified the association between oleic acid levels and depression. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) with depression defined as a score ≥ 10.
TAKEAWAY:
Serum oleic acid levels were positively associated with depression before and after multivariable adjustment.
After adjusting for all covariates, for every 1 mmol/L increase in serum oleic acid levels, the prevalence of depression increased by 40% (adjusted odds ratio [aOR], 1.40; 95% CI, 1.03-1.90).
Adults in the top quartile of oleic acid (≥ 2.51 mmol/L) had a greater than twofold higher likelihood of depression (aOR, 2.22; 95% CI, 1.04-4.73) compared with peers in the lowest quartile (≤ 1.54 mmol/L).
IN PRACTICE:
“A better understanding of the role of oleic acid in depression may lead to new preventive and therapeutic methods. Thus, carefully designed prospective studies are necessary to explore the positive effects of changing serum oleic acid levels through diet, medicine, or other measures on depression,” the authors write.
SOURCE:
The study, with first author Jiahui Yin of Shandong University of Traditional Chinese Medicine in Jinan, China, was published online on November 16, 2023 in BMC Psychiatry .
LIMITATIONS:
The cross-sectional study can’t prove causality. The findings may not apply to clinically diagnosed major depressive disorder.
DISCLOSURES:
The study had no specific funding. The authors report no conflicts of interest.
A version of this article first appeared on Medscape.com.
TOPLINE:
National survey data reveal an association between higher serum oleic acid levels and depression in adults, new research shows.
METHODOLOGY:
Oleic acid is the most abundant fatty acid in plasma and has been associated with multiple neurologic diseases. However, the relationship between oleic acid and depression is unclear.
This cross-sectional analyzed data on 4459 adults from the 2011-2014 National Health and Nutrition Examination Survey (NHANES).
Multivariable logistic regression models adjusting for demographics, health and lifestyle factors quantified the association between oleic acid levels and depression. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) with depression defined as a score ≥ 10.
TAKEAWAY:
Serum oleic acid levels were positively associated with depression before and after multivariable adjustment.
After adjusting for all covariates, for every 1 mmol/L increase in serum oleic acid levels, the prevalence of depression increased by 40% (adjusted odds ratio [aOR], 1.40; 95% CI, 1.03-1.90).
Adults in the top quartile of oleic acid (≥ 2.51 mmol/L) had a greater than twofold higher likelihood of depression (aOR, 2.22; 95% CI, 1.04-4.73) compared with peers in the lowest quartile (≤ 1.54 mmol/L).
IN PRACTICE:
“A better understanding of the role of oleic acid in depression may lead to new preventive and therapeutic methods. Thus, carefully designed prospective studies are necessary to explore the positive effects of changing serum oleic acid levels through diet, medicine, or other measures on depression,” the authors write.
SOURCE:
The study, with first author Jiahui Yin of Shandong University of Traditional Chinese Medicine in Jinan, China, was published online on November 16, 2023 in BMC Psychiatry .
LIMITATIONS:
The cross-sectional study can’t prove causality. The findings may not apply to clinically diagnosed major depressive disorder.
DISCLOSURES:
The study had no specific funding. The authors report no conflicts of interest.
A version of this article first appeared on Medscape.com.
Mass shooters and mental illness: Reexamining the connection
Our psychiatric research, which found a high incidence of undiagnosed mental illness in mass shooters, was recently awarded the esteemed Psychodynamic Psychiatry Journal Prize for best paper published in the last 2 years (2022-2023). The editors noted our integrity in using quantitative data to argue against the common, careless assumption that mass shooters are not mentally ill.
Some of the mass shooters we studied were motivated by religious or political ideologies that were considered forms of terrorism. Given the current tragically violent landscape both at home and in Israel/Palestine, the “desire for destruction” is vital to understand.
Although there have been a limited number of psychiatric studies of perpetrators of mass shootings, our team took the first step to lay the groundwork by conducting a systematic, quantitative study. Our psychiatric research team’s research findings were published in the Journal of Clinical Psychopharmacology and then in greater detail in Psychodynamic Psychiatry,1,2 which provided important context to the complicated backgrounds of these mass shooters who suffer from abuse, marginalization, and severe undiagnosed brain illness.3
The Mother Jones database of 115 mass shootings from 1982 to 2019 was used to study retrospectively 55 shooters in the United States. We developed a uniform, comprehensive, 62-item questionnaire to compile the data collection from multiple sources and record our psychiatric assessments of the assailants, using DSM-5 criteria. After developing this detailed psychiatric assessment questionnaire, psychiatric researchers evaluated the weight and quality of clinical evidence by (1) interviewing forensic psychiatrists who had assessed the assailant following the crime, and/or (2) reviewing court records of psychiatric evaluations conducted during the postcrime judicial proceedings to determine the prevalence of psychiatric illness. Rather than accepting diagnoses from forensic psychiatrists and/or court records, our team independently reviewed the clinical data gathered from multiple sources to apply the DSM-5 criteria to diagnose mental illness.
In most incidents in the database, the perpetrator died either during or shortly after the crime. We examined every case (n=35) in which the assailant survived, and criminal proceedings were instituted.
Of the 35 cases in which the assailant survived and criminal proceedings were instituted, there was insufficient information to make a diagnosis in 3 cases. Of the remaining 32 cases in which we had sufficient information, we determined that 87.5% had the following psychiatric diagnosis: 18 assailants (56%) had schizophrenia, while 10 assailants (31%) had other psychiatric diagnoses: 3 had bipolar I disorder, 2 had delusional disorders (persecutory), 2 had personality disorders (1 paranoid, 1 borderline), 2 had substance-related disorders without other psychiatric diagnosis, and 1 had post-traumatic stress disorder (PTSD).
Out of the 32 surviving assailants for whom we have sufficient evidence, 87.5% of perpetrators of mass shootings were diagnosed with major psychiatric illness, and none were treated appropriately with medication at the time of the crime. Four assailants (12.5%) had no psychiatric diagnosis that we could discern. Of the 18 surviving assailants with schizophrenia, no assailant was on antipsychotic medication for the treatment of schizophrenia prior to the crime. Of the 10 surviving assailants with other psychiatric illnesses, no assailant was on antipsychotic and/or appropriate medication.
In addition, we found that the clinical misdiagnosis of early-onset schizophrenia was associated with the worsening of many of these assailants’ psychotic symptoms. Many of our adolescent shooters prior to the massacre had been misdiagnosed with attention-deficit disorder (ADD), major depression disorder (MDD), or autism spectrum disorder.
Though the vast majority of those suffering from psychiatric illnesses who are appropriately treated are not violent, .4,5,6 This research demonstrates that such untreated illness combined with access to firearms poses a lethal threat to society.
Most of the assailants also experienced profound estrangement, not only from families and friends, but most importantly from themselves. Being marginalized rendered them more vulnerable to their untreated psychiatric illness and to radicalization online, which fostered their violence. While there are complex reasons that a person is not diagnosed, there remains a vital need to decrease the stigma of mental illness to enable those with psychiatric illness to be more respected, less marginalized, and encouraged to receive effective psychiatric treatments.
Dr. Cerfolio is author of “Psychoanalytic and Spiritual Perspectives on Terrorism: Desire for Destruction.” She is clinical assistant professor at the Icahn School of Medicine at Mount Sinai, New York. Dr. Glick is Professor Emeritus, Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, Stanford, Calif.
References
1. Glick ID, et al. Domestic Mass Shooters: The Association With Unmedicated and Untreated Psychiatric Illness. J Clin Psychopharmacol. 2021 Jul-Aug;41(4):366-369. doi: 10.1097/JCP.0000000000001417.
2. Cerfolio NE, et al. A Retrospective Observational Study of Psychosocial Determinants and Psychiatric Diagnoses of Mass Shooters in the United States. Psychodyn Psychiatry. 2022 Fall;50(3):1-16. doi: 10.1521/pdps.2022.50.5.001.
3. Cerfolio NE. The Parkland gunman, a horrific crime, and mental illness. The New York Times. 2022 Oct 14. www.nytimes.com/2022/10/14/opinion/letters/jan-6-panel-trump.html#link-5e2ccc1.
4. Corner E, et al. Mental Health Disorders and the Terrorist: A Research Note Probing Selection Effects and Disorder Prevalence. Stud Confl Terror. 2016 Jan;39(6):560–568. doi: 10.1080/1057610X.2015.1120099.
5. Gruenewald J, et al. Distinguishing “Loner” Attacks from Other Domestic Extremist Violence. Criminol Public Policy. 2013 Feb;12(1):65–91. doi: 10.1111/1745-9133.12008.
6. Lankford A. Detecting mental health problems and suicidal motives among terrorists and mass shooters. Crim Behav Ment Health. 2016 Dec;26(5):315-321. doi: 10.1002/cbm.2020.
Our psychiatric research, which found a high incidence of undiagnosed mental illness in mass shooters, was recently awarded the esteemed Psychodynamic Psychiatry Journal Prize for best paper published in the last 2 years (2022-2023). The editors noted our integrity in using quantitative data to argue against the common, careless assumption that mass shooters are not mentally ill.
Some of the mass shooters we studied were motivated by religious or political ideologies that were considered forms of terrorism. Given the current tragically violent landscape both at home and in Israel/Palestine, the “desire for destruction” is vital to understand.
Although there have been a limited number of psychiatric studies of perpetrators of mass shootings, our team took the first step to lay the groundwork by conducting a systematic, quantitative study. Our psychiatric research team’s research findings were published in the Journal of Clinical Psychopharmacology and then in greater detail in Psychodynamic Psychiatry,1,2 which provided important context to the complicated backgrounds of these mass shooters who suffer from abuse, marginalization, and severe undiagnosed brain illness.3
The Mother Jones database of 115 mass shootings from 1982 to 2019 was used to study retrospectively 55 shooters in the United States. We developed a uniform, comprehensive, 62-item questionnaire to compile the data collection from multiple sources and record our psychiatric assessments of the assailants, using DSM-5 criteria. After developing this detailed psychiatric assessment questionnaire, psychiatric researchers evaluated the weight and quality of clinical evidence by (1) interviewing forensic psychiatrists who had assessed the assailant following the crime, and/or (2) reviewing court records of psychiatric evaluations conducted during the postcrime judicial proceedings to determine the prevalence of psychiatric illness. Rather than accepting diagnoses from forensic psychiatrists and/or court records, our team independently reviewed the clinical data gathered from multiple sources to apply the DSM-5 criteria to diagnose mental illness.
In most incidents in the database, the perpetrator died either during or shortly after the crime. We examined every case (n=35) in which the assailant survived, and criminal proceedings were instituted.
Of the 35 cases in which the assailant survived and criminal proceedings were instituted, there was insufficient information to make a diagnosis in 3 cases. Of the remaining 32 cases in which we had sufficient information, we determined that 87.5% had the following psychiatric diagnosis: 18 assailants (56%) had schizophrenia, while 10 assailants (31%) had other psychiatric diagnoses: 3 had bipolar I disorder, 2 had delusional disorders (persecutory), 2 had personality disorders (1 paranoid, 1 borderline), 2 had substance-related disorders without other psychiatric diagnosis, and 1 had post-traumatic stress disorder (PTSD).
Out of the 32 surviving assailants for whom we have sufficient evidence, 87.5% of perpetrators of mass shootings were diagnosed with major psychiatric illness, and none were treated appropriately with medication at the time of the crime. Four assailants (12.5%) had no psychiatric diagnosis that we could discern. Of the 18 surviving assailants with schizophrenia, no assailant was on antipsychotic medication for the treatment of schizophrenia prior to the crime. Of the 10 surviving assailants with other psychiatric illnesses, no assailant was on antipsychotic and/or appropriate medication.
In addition, we found that the clinical misdiagnosis of early-onset schizophrenia was associated with the worsening of many of these assailants’ psychotic symptoms. Many of our adolescent shooters prior to the massacre had been misdiagnosed with attention-deficit disorder (ADD), major depression disorder (MDD), or autism spectrum disorder.
Though the vast majority of those suffering from psychiatric illnesses who are appropriately treated are not violent, .4,5,6 This research demonstrates that such untreated illness combined with access to firearms poses a lethal threat to society.
Most of the assailants also experienced profound estrangement, not only from families and friends, but most importantly from themselves. Being marginalized rendered them more vulnerable to their untreated psychiatric illness and to radicalization online, which fostered their violence. While there are complex reasons that a person is not diagnosed, there remains a vital need to decrease the stigma of mental illness to enable those with psychiatric illness to be more respected, less marginalized, and encouraged to receive effective psychiatric treatments.
Dr. Cerfolio is author of “Psychoanalytic and Spiritual Perspectives on Terrorism: Desire for Destruction.” She is clinical assistant professor at the Icahn School of Medicine at Mount Sinai, New York. Dr. Glick is Professor Emeritus, Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, Stanford, Calif.
References
1. Glick ID, et al. Domestic Mass Shooters: The Association With Unmedicated and Untreated Psychiatric Illness. J Clin Psychopharmacol. 2021 Jul-Aug;41(4):366-369. doi: 10.1097/JCP.0000000000001417.
2. Cerfolio NE, et al. A Retrospective Observational Study of Psychosocial Determinants and Psychiatric Diagnoses of Mass Shooters in the United States. Psychodyn Psychiatry. 2022 Fall;50(3):1-16. doi: 10.1521/pdps.2022.50.5.001.
3. Cerfolio NE. The Parkland gunman, a horrific crime, and mental illness. The New York Times. 2022 Oct 14. www.nytimes.com/2022/10/14/opinion/letters/jan-6-panel-trump.html#link-5e2ccc1.
4. Corner E, et al. Mental Health Disorders and the Terrorist: A Research Note Probing Selection Effects and Disorder Prevalence. Stud Confl Terror. 2016 Jan;39(6):560–568. doi: 10.1080/1057610X.2015.1120099.
5. Gruenewald J, et al. Distinguishing “Loner” Attacks from Other Domestic Extremist Violence. Criminol Public Policy. 2013 Feb;12(1):65–91. doi: 10.1111/1745-9133.12008.
6. Lankford A. Detecting mental health problems and suicidal motives among terrorists and mass shooters. Crim Behav Ment Health. 2016 Dec;26(5):315-321. doi: 10.1002/cbm.2020.
Our psychiatric research, which found a high incidence of undiagnosed mental illness in mass shooters, was recently awarded the esteemed Psychodynamic Psychiatry Journal Prize for best paper published in the last 2 years (2022-2023). The editors noted our integrity in using quantitative data to argue against the common, careless assumption that mass shooters are not mentally ill.
Some of the mass shooters we studied were motivated by religious or political ideologies that were considered forms of terrorism. Given the current tragically violent landscape both at home and in Israel/Palestine, the “desire for destruction” is vital to understand.
Although there have been a limited number of psychiatric studies of perpetrators of mass shootings, our team took the first step to lay the groundwork by conducting a systematic, quantitative study. Our psychiatric research team’s research findings were published in the Journal of Clinical Psychopharmacology and then in greater detail in Psychodynamic Psychiatry,1,2 which provided important context to the complicated backgrounds of these mass shooters who suffer from abuse, marginalization, and severe undiagnosed brain illness.3
The Mother Jones database of 115 mass shootings from 1982 to 2019 was used to study retrospectively 55 shooters in the United States. We developed a uniform, comprehensive, 62-item questionnaire to compile the data collection from multiple sources and record our psychiatric assessments of the assailants, using DSM-5 criteria. After developing this detailed psychiatric assessment questionnaire, psychiatric researchers evaluated the weight and quality of clinical evidence by (1) interviewing forensic psychiatrists who had assessed the assailant following the crime, and/or (2) reviewing court records of psychiatric evaluations conducted during the postcrime judicial proceedings to determine the prevalence of psychiatric illness. Rather than accepting diagnoses from forensic psychiatrists and/or court records, our team independently reviewed the clinical data gathered from multiple sources to apply the DSM-5 criteria to diagnose mental illness.
In most incidents in the database, the perpetrator died either during or shortly after the crime. We examined every case (n=35) in which the assailant survived, and criminal proceedings were instituted.
Of the 35 cases in which the assailant survived and criminal proceedings were instituted, there was insufficient information to make a diagnosis in 3 cases. Of the remaining 32 cases in which we had sufficient information, we determined that 87.5% had the following psychiatric diagnosis: 18 assailants (56%) had schizophrenia, while 10 assailants (31%) had other psychiatric diagnoses: 3 had bipolar I disorder, 2 had delusional disorders (persecutory), 2 had personality disorders (1 paranoid, 1 borderline), 2 had substance-related disorders without other psychiatric diagnosis, and 1 had post-traumatic stress disorder (PTSD).
Out of the 32 surviving assailants for whom we have sufficient evidence, 87.5% of perpetrators of mass shootings were diagnosed with major psychiatric illness, and none were treated appropriately with medication at the time of the crime. Four assailants (12.5%) had no psychiatric diagnosis that we could discern. Of the 18 surviving assailants with schizophrenia, no assailant was on antipsychotic medication for the treatment of schizophrenia prior to the crime. Of the 10 surviving assailants with other psychiatric illnesses, no assailant was on antipsychotic and/or appropriate medication.
In addition, we found that the clinical misdiagnosis of early-onset schizophrenia was associated with the worsening of many of these assailants’ psychotic symptoms. Many of our adolescent shooters prior to the massacre had been misdiagnosed with attention-deficit disorder (ADD), major depression disorder (MDD), or autism spectrum disorder.
Though the vast majority of those suffering from psychiatric illnesses who are appropriately treated are not violent, .4,5,6 This research demonstrates that such untreated illness combined with access to firearms poses a lethal threat to society.
Most of the assailants also experienced profound estrangement, not only from families and friends, but most importantly from themselves. Being marginalized rendered them more vulnerable to their untreated psychiatric illness and to radicalization online, which fostered their violence. While there are complex reasons that a person is not diagnosed, there remains a vital need to decrease the stigma of mental illness to enable those with psychiatric illness to be more respected, less marginalized, and encouraged to receive effective psychiatric treatments.
Dr. Cerfolio is author of “Psychoanalytic and Spiritual Perspectives on Terrorism: Desire for Destruction.” She is clinical assistant professor at the Icahn School of Medicine at Mount Sinai, New York. Dr. Glick is Professor Emeritus, Department of Psychiatry and Behavioral Sciences at Stanford University School of Medicine, Stanford, Calif.
References
1. Glick ID, et al. Domestic Mass Shooters: The Association With Unmedicated and Untreated Psychiatric Illness. J Clin Psychopharmacol. 2021 Jul-Aug;41(4):366-369. doi: 10.1097/JCP.0000000000001417.
2. Cerfolio NE, et al. A Retrospective Observational Study of Psychosocial Determinants and Psychiatric Diagnoses of Mass Shooters in the United States. Psychodyn Psychiatry. 2022 Fall;50(3):1-16. doi: 10.1521/pdps.2022.50.5.001.
3. Cerfolio NE. The Parkland gunman, a horrific crime, and mental illness. The New York Times. 2022 Oct 14. www.nytimes.com/2022/10/14/opinion/letters/jan-6-panel-trump.html#link-5e2ccc1.
4. Corner E, et al. Mental Health Disorders and the Terrorist: A Research Note Probing Selection Effects and Disorder Prevalence. Stud Confl Terror. 2016 Jan;39(6):560–568. doi: 10.1080/1057610X.2015.1120099.
5. Gruenewald J, et al. Distinguishing “Loner” Attacks from Other Domestic Extremist Violence. Criminol Public Policy. 2013 Feb;12(1):65–91. doi: 10.1111/1745-9133.12008.
6. Lankford A. Detecting mental health problems and suicidal motives among terrorists and mass shooters. Crim Behav Ment Health. 2016 Dec;26(5):315-321. doi: 10.1002/cbm.2020.
Mobile mental health apps linked with ‘significantly reduced’ depressive symptoms
TOPLINE:
A meta-analysis supports the use of mobile mental health apps, both as a standalone and added to conventional treatment, for adults with moderate to severe depression.
METHODOLOGY:
Mobile mental health apps have proliferated but data on their effectiveness in different patient populations is lacking.
To investigate, researchers conducted a systematic review and meta-analysis of 13 randomized clinical trials assessing treatment efficacy of mobile mental health apps in 1470 adults with moderate to severe depression.
The primary outcome was change in depression symptoms from pre- to post-treatment; secondary outcomes included patient-level factors associated with app efficacy.
TAKEAWAY:
Mobile app interventions were associated with significantly reduced depressive symptoms vs both active and inactive control groups, with a medium effect size (standardized mean difference [SMD] 0.50).
App interventions delivered for < 8 weeks had a significantly greater effect size than those delivered for 8+ weeks (SMD 0.77 vs 0.43). Apps were more effective in patients not on medication or in therapy. Apps offering rewards or incentives also appeared to be more effective.
Interventions with in-app notifications were associated with significantly lower treatment outcomes (SMD 0.45) than interventions without (SMD 0.45 vs 0.71).
IN PRACTICE:
“The significant treatment efficacy of app-based interventions compared with active and inactive controls suggests the potential of mobile app interventions as an alternative to conventional psychotherapy, with further merits in accessibility, financial affordability, and safety from stigma,” the authors write.
SOURCE:
The study, with first author Hayoung Bae, BA, with Korea University School of Psychology, Seoul, South Korea, was published online November 20 in JAMA Network Open .
LIMITATIONS:
The findings are based on a small number of trials, with significant heterogeneity among the included trials. The analysis included only English-language publications. Using summary data for the subgroup analyses might have prevented a detailed understanding of the moderating associations of individual participant characteristics.
DISCLOSURES:
The study was supported by a grant from the National Research Foundation funded by the Korean government. The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com .
TOPLINE:
A meta-analysis supports the use of mobile mental health apps, both as a standalone and added to conventional treatment, for adults with moderate to severe depression.
METHODOLOGY:
Mobile mental health apps have proliferated but data on their effectiveness in different patient populations is lacking.
To investigate, researchers conducted a systematic review and meta-analysis of 13 randomized clinical trials assessing treatment efficacy of mobile mental health apps in 1470 adults with moderate to severe depression.
The primary outcome was change in depression symptoms from pre- to post-treatment; secondary outcomes included patient-level factors associated with app efficacy.
TAKEAWAY:
Mobile app interventions were associated with significantly reduced depressive symptoms vs both active and inactive control groups, with a medium effect size (standardized mean difference [SMD] 0.50).
App interventions delivered for < 8 weeks had a significantly greater effect size than those delivered for 8+ weeks (SMD 0.77 vs 0.43). Apps were more effective in patients not on medication or in therapy. Apps offering rewards or incentives also appeared to be more effective.
Interventions with in-app notifications were associated with significantly lower treatment outcomes (SMD 0.45) than interventions without (SMD 0.45 vs 0.71).
IN PRACTICE:
“The significant treatment efficacy of app-based interventions compared with active and inactive controls suggests the potential of mobile app interventions as an alternative to conventional psychotherapy, with further merits in accessibility, financial affordability, and safety from stigma,” the authors write.
SOURCE:
The study, with first author Hayoung Bae, BA, with Korea University School of Psychology, Seoul, South Korea, was published online November 20 in JAMA Network Open .
LIMITATIONS:
The findings are based on a small number of trials, with significant heterogeneity among the included trials. The analysis included only English-language publications. Using summary data for the subgroup analyses might have prevented a detailed understanding of the moderating associations of individual participant characteristics.
DISCLOSURES:
The study was supported by a grant from the National Research Foundation funded by the Korean government. The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com .
TOPLINE:
A meta-analysis supports the use of mobile mental health apps, both as a standalone and added to conventional treatment, for adults with moderate to severe depression.
METHODOLOGY:
Mobile mental health apps have proliferated but data on their effectiveness in different patient populations is lacking.
To investigate, researchers conducted a systematic review and meta-analysis of 13 randomized clinical trials assessing treatment efficacy of mobile mental health apps in 1470 adults with moderate to severe depression.
The primary outcome was change in depression symptoms from pre- to post-treatment; secondary outcomes included patient-level factors associated with app efficacy.
TAKEAWAY:
Mobile app interventions were associated with significantly reduced depressive symptoms vs both active and inactive control groups, with a medium effect size (standardized mean difference [SMD] 0.50).
App interventions delivered for < 8 weeks had a significantly greater effect size than those delivered for 8+ weeks (SMD 0.77 vs 0.43). Apps were more effective in patients not on medication or in therapy. Apps offering rewards or incentives also appeared to be more effective.
Interventions with in-app notifications were associated with significantly lower treatment outcomes (SMD 0.45) than interventions without (SMD 0.45 vs 0.71).
IN PRACTICE:
“The significant treatment efficacy of app-based interventions compared with active and inactive controls suggests the potential of mobile app interventions as an alternative to conventional psychotherapy, with further merits in accessibility, financial affordability, and safety from stigma,” the authors write.
SOURCE:
The study, with first author Hayoung Bae, BA, with Korea University School of Psychology, Seoul, South Korea, was published online November 20 in JAMA Network Open .
LIMITATIONS:
The findings are based on a small number of trials, with significant heterogeneity among the included trials. The analysis included only English-language publications. Using summary data for the subgroup analyses might have prevented a detailed understanding of the moderating associations of individual participant characteristics.
DISCLOSURES:
The study was supported by a grant from the National Research Foundation funded by the Korean government. The authors report no relevant financial relationships.
A version of this article first appeared on Medscape.com .
Rx for resilience: Five prescriptions for physician burnout
Physician burnout persists even as the height of the COVID-19 crisis fades farther into the rear-view mirror. The causes for the sadness, stress, and frustration among doctors vary, but the effects are universal and often debilitating: exhaustion, emotional detachment, lethargy, feeling useless, and lacking purpose.
When surveyed, physicians pointed to many systemic solutions for burnout in Medscape’s Physician Burnout & Depression Report 2023, such as a need for greater compensation, more manageable workloads and schedules, and more support staff. But for many doctors, these fixes may be years if not decades away. Equally important are strategies for relieving burnout symptoms now, especially as we head into a busy holiday season.
Because not every stress-relief practice works for everyone, it’s crucial to try various methods until you find something that makes a difference for you, said Christine Gibson, MD, a family physician and trauma therapist in Calgary, Alta., and author of The Modern Trauma Toolkit.
“Every person should have a toolkit of the things that bring them out of the psychological and physical distress that dysregulates their nervous system,” said Dr. Gibson.
Once you learn the personal ways to alleviate your specific brand of burnout, you can start working on systemic changes that might help the culture of medicine overall.
Symptoms speak louder than words
It seems obvious, but if you aren’t aware that what you’re feeling is burnout, you probably aren’t going to find effective steps to relieve it. Jessi Gold, MD, assistant professor and director of wellness, engagement, and outreach in the department of psychiatry, Washington University in St. Louis, is a psychiatrist who treats health care professionals, including frontline workers during the height of the pandemic. But even as a burnout expert, she admits that she misses the signs in herself.
“I was fighting constant fatigue, falling asleep the minute I got home from work every day, but I thought a B12 shot would solve all my problems. I didn’t realize I was having symptoms of burnout until my own therapist told me,” said Dr. Gold. “As doctors, we spend so much time focusing on other people that we don’t necessarily notice very much in ourselves – usually once it starts to impact our job.”
Practices like meditation and mindfulness can help you delve into your feelings and emotions and notice how you’re doing. But you may also need to ask spouses, partners, and friends and family – or better yet, a mental health professional – if they notice that you seem burnt out.
Practice ‘in the moment’ relief
Sometimes, walking away at the moment of stress helps like when stepping away from a heated argument. “Step out of a frustrating staff meeting to go to the bathroom and splash your face,” said Eran Magan, PhD, a psychologist at the University of Pennsylvania, Philadelphia, and founder and CEO of the suicide prevention system EarlyAlert.me. “Tell a patient you need to check something in the next room, so you have time to take a breath.”
Dr. Magan recommended finding techniques that help lower acute stress while it’s actually happening. First, find a way to escape or excuse yourself from the event, and when possible, stop situations that are actively upsetting or triggering in their tracks.
Next, recharge by doing something that helps you feel better, like looking at a cute video of your child or grandchild or closing your eyes and taking a deep breath. You can also try to “catch” good feelings from someone else, said Dr. Magan. Ask someone about a trip, vacation, holiday, or pleasant event. “Ask a colleague about something that makes [them] happy,” he said. “Happiness can be infectious too.”
Burnout is also in the body
“Body psychotherapy” or somatic therapy is a treatment that focuses on how emotions appear within your body. Dr. Gibson said it’s a valuable tool for addressing trauma and a mainstay in many a medical career; it’s useful to help physicians learn to “befriend” their nervous system.
Somatic therapy exercises involve things like body scanning, scanning for physical sensations; conscious breathing, connecting to each inhale and exhale; grounding your weight by releasing tension through your feet, doing a total body stretch; or releasing shoulder and neck tension by consciously relaxing each of these muscle groups.
“We spend our whole day in sympathetic tone; our amygdala’s are firing, telling us that we’re in danger,” said Dr. Gibson. “We actually have to practice getting into and spending time in our parasympathetic nervous system to restore the balance in our autonomic nervous system.”
Somatic therapy includes a wide array of exercises that help reconnect you to your body through calming or activation. The movements release tension, ground you, and restore balance.
Bite-sized tools for well-being
Because of the prevalence of physician burnout, there’s been a groundswell of researchers and organizations who have turned their focus toward improving the well-being in the health care workforce.
One such effort comes from the Duke Center for the Advancement of Well-being Science, which “camouflages” well-being tools as continuing education credits to make them accessible for busy, stressed, and overworked physicians.
“They’re called bite-sized tools for well-being, and they have actual evidence behind them,” said Dr. Gold. For example, she said, one tools is a text program called Three Good Things that encourages physicians to send a text listing three positive things that happened during the day. The exercise lasts 15 days, and texters have access to others’ answers as well. After 3 months, participants’ baseline depression, gratitude, and life satisfaction had all “significantly improved.”
“It feels almost ridiculous that that could work, but it does,” said Dr. Gold. “I’ve had patients push back and say: ‘Well, isn’t that toxic positivity?’ But really what it is is dialectics. It’s not saying there’s only positive; it’s just making you realize there is more than just the negative.”
These and other short interventions focus on concepts such as joy, humor, awe, engagement, and self-kindness to build resilience and help physicians recover from burnout symptoms.
Cognitive restructuring could work
Cognitive restructuring is a therapeutic process of learning new ways of interpreting and responding to people and situations. It helps you change the “filter” through which you interact with your environment. Dr. Gibson said it’s a tool to use with care after other modes of therapy that help you understand your patterns and how they developed because of how you view and understand the world.
“The message of [cognitive-behavioral therapy] or cognitive restructuring is there’s something wrong with the way you’re thinking, and we need to change it or fix it, but in a traumatic system [like health care], you’re thinking has been an adaptive process related to the harm in the environment you’re in,” said Dr. Gibson.
“So, if you [jump straight to cognitive restructuring before other types of therapy], then we just gaslight ourselves into believing that there’s something wrong with us, that we haven’t adapted sufficiently to an environment that’s actually harmful.”
Strive for a few systemic changes
Systemic changes can be small ones within your own sphere. For example, Dr. Magan said, work toward making little tweaks to the flow of your day that will increase calm and reduce frustration.
“Make a ‘bug list,’ little, regular demands that drain your energy, and discuss them with your colleagues and supervisors to see if they can be improved,” he said. Examples include everyday frustrations like having unsolicited visitors popping into your office, scheduling complex patients too late in the day, or having a computer freeze whenever you access patient charts.
Though not always financially feasible, affecting real change and finding relief from all these insidious bugs can improve your mental health and burnout symptoms.
“Physicians tend to work extremely hard in order to keep holding together a system that is often not inherently sustainable, like the fascia of a body under tremendous strain,” said Dr. Magan. “Sometimes the brave thing to do is to refuse to continue being the lynchpin and let things break, so the system will have to start improving itself, rather than demanding more and more of the people in it.”
A version of this article first appeared on Medscape.com.
Physician burnout persists even as the height of the COVID-19 crisis fades farther into the rear-view mirror. The causes for the sadness, stress, and frustration among doctors vary, but the effects are universal and often debilitating: exhaustion, emotional detachment, lethargy, feeling useless, and lacking purpose.
When surveyed, physicians pointed to many systemic solutions for burnout in Medscape’s Physician Burnout & Depression Report 2023, such as a need for greater compensation, more manageable workloads and schedules, and more support staff. But for many doctors, these fixes may be years if not decades away. Equally important are strategies for relieving burnout symptoms now, especially as we head into a busy holiday season.
Because not every stress-relief practice works for everyone, it’s crucial to try various methods until you find something that makes a difference for you, said Christine Gibson, MD, a family physician and trauma therapist in Calgary, Alta., and author of The Modern Trauma Toolkit.
“Every person should have a toolkit of the things that bring them out of the psychological and physical distress that dysregulates their nervous system,” said Dr. Gibson.
Once you learn the personal ways to alleviate your specific brand of burnout, you can start working on systemic changes that might help the culture of medicine overall.
Symptoms speak louder than words
It seems obvious, but if you aren’t aware that what you’re feeling is burnout, you probably aren’t going to find effective steps to relieve it. Jessi Gold, MD, assistant professor and director of wellness, engagement, and outreach in the department of psychiatry, Washington University in St. Louis, is a psychiatrist who treats health care professionals, including frontline workers during the height of the pandemic. But even as a burnout expert, she admits that she misses the signs in herself.
“I was fighting constant fatigue, falling asleep the minute I got home from work every day, but I thought a B12 shot would solve all my problems. I didn’t realize I was having symptoms of burnout until my own therapist told me,” said Dr. Gold. “As doctors, we spend so much time focusing on other people that we don’t necessarily notice very much in ourselves – usually once it starts to impact our job.”
Practices like meditation and mindfulness can help you delve into your feelings and emotions and notice how you’re doing. But you may also need to ask spouses, partners, and friends and family – or better yet, a mental health professional – if they notice that you seem burnt out.
Practice ‘in the moment’ relief
Sometimes, walking away at the moment of stress helps like when stepping away from a heated argument. “Step out of a frustrating staff meeting to go to the bathroom and splash your face,” said Eran Magan, PhD, a psychologist at the University of Pennsylvania, Philadelphia, and founder and CEO of the suicide prevention system EarlyAlert.me. “Tell a patient you need to check something in the next room, so you have time to take a breath.”
Dr. Magan recommended finding techniques that help lower acute stress while it’s actually happening. First, find a way to escape or excuse yourself from the event, and when possible, stop situations that are actively upsetting or triggering in their tracks.
Next, recharge by doing something that helps you feel better, like looking at a cute video of your child or grandchild or closing your eyes and taking a deep breath. You can also try to “catch” good feelings from someone else, said Dr. Magan. Ask someone about a trip, vacation, holiday, or pleasant event. “Ask a colleague about something that makes [them] happy,” he said. “Happiness can be infectious too.”
Burnout is also in the body
“Body psychotherapy” or somatic therapy is a treatment that focuses on how emotions appear within your body. Dr. Gibson said it’s a valuable tool for addressing trauma and a mainstay in many a medical career; it’s useful to help physicians learn to “befriend” their nervous system.
Somatic therapy exercises involve things like body scanning, scanning for physical sensations; conscious breathing, connecting to each inhale and exhale; grounding your weight by releasing tension through your feet, doing a total body stretch; or releasing shoulder and neck tension by consciously relaxing each of these muscle groups.
“We spend our whole day in sympathetic tone; our amygdala’s are firing, telling us that we’re in danger,” said Dr. Gibson. “We actually have to practice getting into and spending time in our parasympathetic nervous system to restore the balance in our autonomic nervous system.”
Somatic therapy includes a wide array of exercises that help reconnect you to your body through calming or activation. The movements release tension, ground you, and restore balance.
Bite-sized tools for well-being
Because of the prevalence of physician burnout, there’s been a groundswell of researchers and organizations who have turned their focus toward improving the well-being in the health care workforce.
One such effort comes from the Duke Center for the Advancement of Well-being Science, which “camouflages” well-being tools as continuing education credits to make them accessible for busy, stressed, and overworked physicians.
“They’re called bite-sized tools for well-being, and they have actual evidence behind them,” said Dr. Gold. For example, she said, one tools is a text program called Three Good Things that encourages physicians to send a text listing three positive things that happened during the day. The exercise lasts 15 days, and texters have access to others’ answers as well. After 3 months, participants’ baseline depression, gratitude, and life satisfaction had all “significantly improved.”
“It feels almost ridiculous that that could work, but it does,” said Dr. Gold. “I’ve had patients push back and say: ‘Well, isn’t that toxic positivity?’ But really what it is is dialectics. It’s not saying there’s only positive; it’s just making you realize there is more than just the negative.”
These and other short interventions focus on concepts such as joy, humor, awe, engagement, and self-kindness to build resilience and help physicians recover from burnout symptoms.
Cognitive restructuring could work
Cognitive restructuring is a therapeutic process of learning new ways of interpreting and responding to people and situations. It helps you change the “filter” through which you interact with your environment. Dr. Gibson said it’s a tool to use with care after other modes of therapy that help you understand your patterns and how they developed because of how you view and understand the world.
“The message of [cognitive-behavioral therapy] or cognitive restructuring is there’s something wrong with the way you’re thinking, and we need to change it or fix it, but in a traumatic system [like health care], you’re thinking has been an adaptive process related to the harm in the environment you’re in,” said Dr. Gibson.
“So, if you [jump straight to cognitive restructuring before other types of therapy], then we just gaslight ourselves into believing that there’s something wrong with us, that we haven’t adapted sufficiently to an environment that’s actually harmful.”
Strive for a few systemic changes
Systemic changes can be small ones within your own sphere. For example, Dr. Magan said, work toward making little tweaks to the flow of your day that will increase calm and reduce frustration.
“Make a ‘bug list,’ little, regular demands that drain your energy, and discuss them with your colleagues and supervisors to see if they can be improved,” he said. Examples include everyday frustrations like having unsolicited visitors popping into your office, scheduling complex patients too late in the day, or having a computer freeze whenever you access patient charts.
Though not always financially feasible, affecting real change and finding relief from all these insidious bugs can improve your mental health and burnout symptoms.
“Physicians tend to work extremely hard in order to keep holding together a system that is often not inherently sustainable, like the fascia of a body under tremendous strain,” said Dr. Magan. “Sometimes the brave thing to do is to refuse to continue being the lynchpin and let things break, so the system will have to start improving itself, rather than demanding more and more of the people in it.”
A version of this article first appeared on Medscape.com.
Physician burnout persists even as the height of the COVID-19 crisis fades farther into the rear-view mirror. The causes for the sadness, stress, and frustration among doctors vary, but the effects are universal and often debilitating: exhaustion, emotional detachment, lethargy, feeling useless, and lacking purpose.
When surveyed, physicians pointed to many systemic solutions for burnout in Medscape’s Physician Burnout & Depression Report 2023, such as a need for greater compensation, more manageable workloads and schedules, and more support staff. But for many doctors, these fixes may be years if not decades away. Equally important are strategies for relieving burnout symptoms now, especially as we head into a busy holiday season.
Because not every stress-relief practice works for everyone, it’s crucial to try various methods until you find something that makes a difference for you, said Christine Gibson, MD, a family physician and trauma therapist in Calgary, Alta., and author of The Modern Trauma Toolkit.
“Every person should have a toolkit of the things that bring them out of the psychological and physical distress that dysregulates their nervous system,” said Dr. Gibson.
Once you learn the personal ways to alleviate your specific brand of burnout, you can start working on systemic changes that might help the culture of medicine overall.
Symptoms speak louder than words
It seems obvious, but if you aren’t aware that what you’re feeling is burnout, you probably aren’t going to find effective steps to relieve it. Jessi Gold, MD, assistant professor and director of wellness, engagement, and outreach in the department of psychiatry, Washington University in St. Louis, is a psychiatrist who treats health care professionals, including frontline workers during the height of the pandemic. But even as a burnout expert, she admits that she misses the signs in herself.
“I was fighting constant fatigue, falling asleep the minute I got home from work every day, but I thought a B12 shot would solve all my problems. I didn’t realize I was having symptoms of burnout until my own therapist told me,” said Dr. Gold. “As doctors, we spend so much time focusing on other people that we don’t necessarily notice very much in ourselves – usually once it starts to impact our job.”
Practices like meditation and mindfulness can help you delve into your feelings and emotions and notice how you’re doing. But you may also need to ask spouses, partners, and friends and family – or better yet, a mental health professional – if they notice that you seem burnt out.
Practice ‘in the moment’ relief
Sometimes, walking away at the moment of stress helps like when stepping away from a heated argument. “Step out of a frustrating staff meeting to go to the bathroom and splash your face,” said Eran Magan, PhD, a psychologist at the University of Pennsylvania, Philadelphia, and founder and CEO of the suicide prevention system EarlyAlert.me. “Tell a patient you need to check something in the next room, so you have time to take a breath.”
Dr. Magan recommended finding techniques that help lower acute stress while it’s actually happening. First, find a way to escape or excuse yourself from the event, and when possible, stop situations that are actively upsetting or triggering in their tracks.
Next, recharge by doing something that helps you feel better, like looking at a cute video of your child or grandchild or closing your eyes and taking a deep breath. You can also try to “catch” good feelings from someone else, said Dr. Magan. Ask someone about a trip, vacation, holiday, or pleasant event. “Ask a colleague about something that makes [them] happy,” he said. “Happiness can be infectious too.”
Burnout is also in the body
“Body psychotherapy” or somatic therapy is a treatment that focuses on how emotions appear within your body. Dr. Gibson said it’s a valuable tool for addressing trauma and a mainstay in many a medical career; it’s useful to help physicians learn to “befriend” their nervous system.
Somatic therapy exercises involve things like body scanning, scanning for physical sensations; conscious breathing, connecting to each inhale and exhale; grounding your weight by releasing tension through your feet, doing a total body stretch; or releasing shoulder and neck tension by consciously relaxing each of these muscle groups.
“We spend our whole day in sympathetic tone; our amygdala’s are firing, telling us that we’re in danger,” said Dr. Gibson. “We actually have to practice getting into and spending time in our parasympathetic nervous system to restore the balance in our autonomic nervous system.”
Somatic therapy includes a wide array of exercises that help reconnect you to your body through calming or activation. The movements release tension, ground you, and restore balance.
Bite-sized tools for well-being
Because of the prevalence of physician burnout, there’s been a groundswell of researchers and organizations who have turned their focus toward improving the well-being in the health care workforce.
One such effort comes from the Duke Center for the Advancement of Well-being Science, which “camouflages” well-being tools as continuing education credits to make them accessible for busy, stressed, and overworked physicians.
“They’re called bite-sized tools for well-being, and they have actual evidence behind them,” said Dr. Gold. For example, she said, one tools is a text program called Three Good Things that encourages physicians to send a text listing three positive things that happened during the day. The exercise lasts 15 days, and texters have access to others’ answers as well. After 3 months, participants’ baseline depression, gratitude, and life satisfaction had all “significantly improved.”
“It feels almost ridiculous that that could work, but it does,” said Dr. Gold. “I’ve had patients push back and say: ‘Well, isn’t that toxic positivity?’ But really what it is is dialectics. It’s not saying there’s only positive; it’s just making you realize there is more than just the negative.”
These and other short interventions focus on concepts such as joy, humor, awe, engagement, and self-kindness to build resilience and help physicians recover from burnout symptoms.
Cognitive restructuring could work
Cognitive restructuring is a therapeutic process of learning new ways of interpreting and responding to people and situations. It helps you change the “filter” through which you interact with your environment. Dr. Gibson said it’s a tool to use with care after other modes of therapy that help you understand your patterns and how they developed because of how you view and understand the world.
“The message of [cognitive-behavioral therapy] or cognitive restructuring is there’s something wrong with the way you’re thinking, and we need to change it or fix it, but in a traumatic system [like health care], you’re thinking has been an adaptive process related to the harm in the environment you’re in,” said Dr. Gibson.
“So, if you [jump straight to cognitive restructuring before other types of therapy], then we just gaslight ourselves into believing that there’s something wrong with us, that we haven’t adapted sufficiently to an environment that’s actually harmful.”
Strive for a few systemic changes
Systemic changes can be small ones within your own sphere. For example, Dr. Magan said, work toward making little tweaks to the flow of your day that will increase calm and reduce frustration.
“Make a ‘bug list,’ little, regular demands that drain your energy, and discuss them with your colleagues and supervisors to see if they can be improved,” he said. Examples include everyday frustrations like having unsolicited visitors popping into your office, scheduling complex patients too late in the day, or having a computer freeze whenever you access patient charts.
Though not always financially feasible, affecting real change and finding relief from all these insidious bugs can improve your mental health and burnout symptoms.
“Physicians tend to work extremely hard in order to keep holding together a system that is often not inherently sustainable, like the fascia of a body under tremendous strain,” said Dr. Magan. “Sometimes the brave thing to do is to refuse to continue being the lynchpin and let things break, so the system will have to start improving itself, rather than demanding more and more of the people in it.”
A version of this article first appeared on Medscape.com.
Isotretinoin users do not have higher suicide risk: meta-analysis
.
Instead, those who are treated with the drug for severe acne may have a lower risk of suicide attempts 2-4 years after treatment, wrote the authors, led by Nicole Kye Wen Tan, MBBS, of Yong Loo Lin School of Medicine at the National University of Singapore. The results were published online in JAMA Dermatology.
The analysis showed that the 1-year absolute risk from between two and eight studies of suicide attempts, suicidal ideation, completed suicides, and self-harm were each less than 0.5%. For comparison, the absolute risk of depression was 3.83% (95% confidence interval [CI], 2.45-5.93; I2 [measuring heterogeneity] = 77%) in 11 studies.
Less likely to attempt suicide
Isotretinoin users were less likely than were nonusers to attempt suicide at 2 years (relative risk [RR], 0.92; 95% CI, 0.84-1.00; I2 = 0%); 3 years (RR, 0.86; 95% CI, 0.77-0.95; I2 = 0%); and 4 years (RR, 0.85; 95% CI, 0.72-1.00; I2 = 23%) following treatment.
Additionally, isotretinoin was not linked with the risk of “all psychiatric disorders” (RR, 1.08; 95% CI, 0.99-1.19; I2 = 0%).
Among the study limitations, the authors noted that because of the widespread claims that isotretinoin can affect mental health, it is plausible that patients at high risk of psychiatric illness were less likely to be treated with isotretinoin in the first place, which could have resulted in underestimating psychiatric risks in the observational studies.
“Two things can be true”
John S. Barbieri, MD, MBA, assistant professor at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at the Brigham and Women’s Hospital in Boston, who was not involved with this research, said the study helps confirm what he and many others have long thought.
The results of the meta-analysis show that “two things can be true, which often gets lost with isotretinoin,” he said. At a population level, isotretinoin improves mental health but on the individual level, it may cause rare side effects that harm mental health, he added.
In making decisions on the use of isotretinoin, he continued, “we should feel reassured that the likely outcome is improved mental health compared to other alternatives that we have, but at the same time we should be vigilant about monitoring a patient’s mental health while they are being treated with isotretinoin.”
He said that this topic draws extreme views on social media, with people who want the drug off the market and those who discount concerns altogether.
“I think the real answer is a little more in the middle,” he said. “We still have to be thoughtful when we use it.”
Because outcomes such as suicide in patients on isotretinoin are not common, Dr. Barbieri said, smaller studies individually have lacked precision on effect. The size of this meta-analysis helps add confidence in the results, he said.
In addition, this study can help clinicians point to numbers when they talk with their patients about benefits and risks, he said.
What a meta-analysis might miss
In an accompanying editorial, Parker Magin, PhD, of the School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia, and Shaun Prentice, PhD, of the School of Psychology, Faculty of Health and Medical Sciences at the University of Adelaide, South Australia, wrote that though the work by Tan et al. is “broadly reassuring,” they have concerns about the patients a meta-analysis might miss.
They wrote that other studies have shown evidence both of biological plausibility that isotretinoin may be linked with psychiatric effects and that it may cause these side effects. “One could conclude that it is plausible that isotretinoin has markedly adverse, idiosyncratic psychiatric effects in a small minority of individual patients,” they wrote. “It is also plausible that these presumably rare occurrences are not detectable in studies where the majority of patients experience no adverse psychiatric outcomes or even positive outcomes.”
Far from the “final word”
Dr. Magin and Dr. Prentice pointed out that while the study adds to the literature on his topic, the relationship between acne, psychiatric conditions, and isotretinoin is complex and thus these findings “are far from the final word.”
Randomized, controlled trials have limited use in this area and observational studies are always susceptible to bias, they noted. “Clinicians, though, can take some degree of further reassurance from this extension of the literature around the psychiatric sequelae of isotretinoin,” they wrote.
Senior author Hazel Oon, MD, of the National Skin Centre, Singapore, disclosed ties with AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, and Pfizer. No other author disclosures were reported. Dr. Barbieri is an associate editor at JAMA Dermatology and is cochair of the American Academy of Dermatology Acne Guidelines Work Group.
.
Instead, those who are treated with the drug for severe acne may have a lower risk of suicide attempts 2-4 years after treatment, wrote the authors, led by Nicole Kye Wen Tan, MBBS, of Yong Loo Lin School of Medicine at the National University of Singapore. The results were published online in JAMA Dermatology.
The analysis showed that the 1-year absolute risk from between two and eight studies of suicide attempts, suicidal ideation, completed suicides, and self-harm were each less than 0.5%. For comparison, the absolute risk of depression was 3.83% (95% confidence interval [CI], 2.45-5.93; I2 [measuring heterogeneity] = 77%) in 11 studies.
Less likely to attempt suicide
Isotretinoin users were less likely than were nonusers to attempt suicide at 2 years (relative risk [RR], 0.92; 95% CI, 0.84-1.00; I2 = 0%); 3 years (RR, 0.86; 95% CI, 0.77-0.95; I2 = 0%); and 4 years (RR, 0.85; 95% CI, 0.72-1.00; I2 = 23%) following treatment.
Additionally, isotretinoin was not linked with the risk of “all psychiatric disorders” (RR, 1.08; 95% CI, 0.99-1.19; I2 = 0%).
Among the study limitations, the authors noted that because of the widespread claims that isotretinoin can affect mental health, it is plausible that patients at high risk of psychiatric illness were less likely to be treated with isotretinoin in the first place, which could have resulted in underestimating psychiatric risks in the observational studies.
“Two things can be true”
John S. Barbieri, MD, MBA, assistant professor at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at the Brigham and Women’s Hospital in Boston, who was not involved with this research, said the study helps confirm what he and many others have long thought.
The results of the meta-analysis show that “two things can be true, which often gets lost with isotretinoin,” he said. At a population level, isotretinoin improves mental health but on the individual level, it may cause rare side effects that harm mental health, he added.
In making decisions on the use of isotretinoin, he continued, “we should feel reassured that the likely outcome is improved mental health compared to other alternatives that we have, but at the same time we should be vigilant about monitoring a patient’s mental health while they are being treated with isotretinoin.”
He said that this topic draws extreme views on social media, with people who want the drug off the market and those who discount concerns altogether.
“I think the real answer is a little more in the middle,” he said. “We still have to be thoughtful when we use it.”
Because outcomes such as suicide in patients on isotretinoin are not common, Dr. Barbieri said, smaller studies individually have lacked precision on effect. The size of this meta-analysis helps add confidence in the results, he said.
In addition, this study can help clinicians point to numbers when they talk with their patients about benefits and risks, he said.
What a meta-analysis might miss
In an accompanying editorial, Parker Magin, PhD, of the School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia, and Shaun Prentice, PhD, of the School of Psychology, Faculty of Health and Medical Sciences at the University of Adelaide, South Australia, wrote that though the work by Tan et al. is “broadly reassuring,” they have concerns about the patients a meta-analysis might miss.
They wrote that other studies have shown evidence both of biological plausibility that isotretinoin may be linked with psychiatric effects and that it may cause these side effects. “One could conclude that it is plausible that isotretinoin has markedly adverse, idiosyncratic psychiatric effects in a small minority of individual patients,” they wrote. “It is also plausible that these presumably rare occurrences are not detectable in studies where the majority of patients experience no adverse psychiatric outcomes or even positive outcomes.”
Far from the “final word”
Dr. Magin and Dr. Prentice pointed out that while the study adds to the literature on his topic, the relationship between acne, psychiatric conditions, and isotretinoin is complex and thus these findings “are far from the final word.”
Randomized, controlled trials have limited use in this area and observational studies are always susceptible to bias, they noted. “Clinicians, though, can take some degree of further reassurance from this extension of the literature around the psychiatric sequelae of isotretinoin,” they wrote.
Senior author Hazel Oon, MD, of the National Skin Centre, Singapore, disclosed ties with AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, and Pfizer. No other author disclosures were reported. Dr. Barbieri is an associate editor at JAMA Dermatology and is cochair of the American Academy of Dermatology Acne Guidelines Work Group.
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Instead, those who are treated with the drug for severe acne may have a lower risk of suicide attempts 2-4 years after treatment, wrote the authors, led by Nicole Kye Wen Tan, MBBS, of Yong Loo Lin School of Medicine at the National University of Singapore. The results were published online in JAMA Dermatology.
The analysis showed that the 1-year absolute risk from between two and eight studies of suicide attempts, suicidal ideation, completed suicides, and self-harm were each less than 0.5%. For comparison, the absolute risk of depression was 3.83% (95% confidence interval [CI], 2.45-5.93; I2 [measuring heterogeneity] = 77%) in 11 studies.
Less likely to attempt suicide
Isotretinoin users were less likely than were nonusers to attempt suicide at 2 years (relative risk [RR], 0.92; 95% CI, 0.84-1.00; I2 = 0%); 3 years (RR, 0.86; 95% CI, 0.77-0.95; I2 = 0%); and 4 years (RR, 0.85; 95% CI, 0.72-1.00; I2 = 23%) following treatment.
Additionally, isotretinoin was not linked with the risk of “all psychiatric disorders” (RR, 1.08; 95% CI, 0.99-1.19; I2 = 0%).
Among the study limitations, the authors noted that because of the widespread claims that isotretinoin can affect mental health, it is plausible that patients at high risk of psychiatric illness were less likely to be treated with isotretinoin in the first place, which could have resulted in underestimating psychiatric risks in the observational studies.
“Two things can be true”
John S. Barbieri, MD, MBA, assistant professor at Harvard Medical School and director of the Advanced Acne Therapeutics Clinic at the Brigham and Women’s Hospital in Boston, who was not involved with this research, said the study helps confirm what he and many others have long thought.
The results of the meta-analysis show that “two things can be true, which often gets lost with isotretinoin,” he said. At a population level, isotretinoin improves mental health but on the individual level, it may cause rare side effects that harm mental health, he added.
In making decisions on the use of isotretinoin, he continued, “we should feel reassured that the likely outcome is improved mental health compared to other alternatives that we have, but at the same time we should be vigilant about monitoring a patient’s mental health while they are being treated with isotretinoin.”
He said that this topic draws extreme views on social media, with people who want the drug off the market and those who discount concerns altogether.
“I think the real answer is a little more in the middle,” he said. “We still have to be thoughtful when we use it.”
Because outcomes such as suicide in patients on isotretinoin are not common, Dr. Barbieri said, smaller studies individually have lacked precision on effect. The size of this meta-analysis helps add confidence in the results, he said.
In addition, this study can help clinicians point to numbers when they talk with their patients about benefits and risks, he said.
What a meta-analysis might miss
In an accompanying editorial, Parker Magin, PhD, of the School of Medicine and Public Health, University of Newcastle, Callaghan, New South Wales, Australia, and Shaun Prentice, PhD, of the School of Psychology, Faculty of Health and Medical Sciences at the University of Adelaide, South Australia, wrote that though the work by Tan et al. is “broadly reassuring,” they have concerns about the patients a meta-analysis might miss.
They wrote that other studies have shown evidence both of biological plausibility that isotretinoin may be linked with psychiatric effects and that it may cause these side effects. “One could conclude that it is plausible that isotretinoin has markedly adverse, idiosyncratic psychiatric effects in a small minority of individual patients,” they wrote. “It is also plausible that these presumably rare occurrences are not detectable in studies where the majority of patients experience no adverse psychiatric outcomes or even positive outcomes.”
Far from the “final word”
Dr. Magin and Dr. Prentice pointed out that while the study adds to the literature on his topic, the relationship between acne, psychiatric conditions, and isotretinoin is complex and thus these findings “are far from the final word.”
Randomized, controlled trials have limited use in this area and observational studies are always susceptible to bias, they noted. “Clinicians, though, can take some degree of further reassurance from this extension of the literature around the psychiatric sequelae of isotretinoin,” they wrote.
Senior author Hazel Oon, MD, of the National Skin Centre, Singapore, disclosed ties with AbbVie, Amgen, Boehringer Ingelheim, Eli Lilly, Galderma, Janssen, LEO Pharma, Novartis, and Pfizer. No other author disclosures were reported. Dr. Barbieri is an associate editor at JAMA Dermatology and is cochair of the American Academy of Dermatology Acne Guidelines Work Group.
FROM JAMA DERMATOLOGY