Commentary

This transcript has been edited for clarity.

Much of my research focuses on what is known as clinical decision support — prompts and messages to providers to help them make good decisions for their patients. I know that these things can be annoying, which is exactly why I study them — to figure out which ones actually help.

When I got started on this about 10 years ago, we were learning a lot about how best to message providers about their patients. My team had developed a simple alert for acute kidney injury (AKI). We knew that providers often missed the diagnosis, so maybe letting them know would improve patient outcomes.

As we tested the alert, we got feedback, and I have kept an email from an ICU doctor from those early days. It read:

Dear Dr. Wilson: Thank you for the automated alert informing me that my patient had AKI. Regrettably, the alert fired about an hour after the patient had died. I feel that the information is less than actionable at this time.

Our early system had neglected to add a conditional flag ensuring that the patient was still alive at the time it sent the alert message. A small oversight, but one that had very large implications. Future studies would show that “false positive” alerts like this seriously degrade physician confidence in the system. And why wouldn’t they?

Knowing whether a patient is alive or dead seems like it should be trivial. But, as it turns out, in our modern balkanized health care system, it can be quite difficult. Not knowing the vital status of a patient can have major consequences.

Health systems send messages to their patients all the time: reminders of appointments, reminders for preventive care, reminders for vaccinations, and so on.

But what if the patient being reminded has died? It’s a waste of resources, of course, but more than that, it can be painful for their families and reflects poorly on the health care system. Of all the people who should know whether someone is alive or dead, shouldn’t their doctor be at the top of the list?

A new study in JAMA Internal Medicine quantifies this very phenomenon.

Researchers examined 11,658 primary care patients in their health system who met the criteria of being “seriously ill” and followed them for 2 years. During that period of time, 25% were recorded as deceased in the electronic health record. But 30.8% had died. That left 676 patients who had died, but were not known to have died, left in the system.

Courtesy Dr. F. Perry Wilson

Courtesy Dr. F. Perry Wilson

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com .

This transcript has been edited for clarity.

Much of my research focuses on what is known as clinical decision support — prompts and messages to providers to help them make good decisions for their patients. I know that these things can be annoying, which is exactly why I study them — to figure out which ones actually help.

When I got started on this about 10 years ago, we were learning a lot about how best to message providers about their patients. My team had developed a simple alert for acute kidney injury (AKI). We knew that providers often missed the diagnosis, so maybe letting them know would improve patient outcomes.

As we tested the alert, we got feedback, and I have kept an email from an ICU doctor from those early days. It read:

Dear Dr. Wilson: Thank you for the automated alert informing me that my patient had AKI. Regrettably, the alert fired about an hour after the patient had died. I feel that the information is less than actionable at this time.

Our early system had neglected to add a conditional flag ensuring that the patient was still alive at the time it sent the alert message. A small oversight, but one that had very large implications. Future studies would show that “false positive” alerts like this seriously degrade physician confidence in the system. And why wouldn’t they?

Knowing whether a patient is alive or dead seems like it should be trivial. But, as it turns out, in our modern balkanized health care system, it can be quite difficult. Not knowing the vital status of a patient can have major consequences.

Health systems send messages to their patients all the time: reminders of appointments, reminders for preventive care, reminders for vaccinations, and so on.

But what if the patient being reminded has died? It’s a waste of resources, of course, but more than that, it can be painful for their families and reflects poorly on the health care system. Of all the people who should know whether someone is alive or dead, shouldn’t their doctor be at the top of the list?

A new study in JAMA Internal Medicine quantifies this very phenomenon.

Researchers examined 11,658 primary care patients in their health system who met the criteria of being “seriously ill” and followed them for 2 years. During that period of time, 25% were recorded as deceased in the electronic health record. But 30.8% had died. That left 676 patients who had died, but were not known to have died, left in the system.

Courtesy Dr. F. Perry Wilson

Courtesy Dr. F. Perry Wilson

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com .

This transcript has been edited for clarity.

Much of my research focuses on what is known as clinical decision support — prompts and messages to providers to help them make good decisions for their patients. I know that these things can be annoying, which is exactly why I study them — to figure out which ones actually help.

When I got started on this about 10 years ago, we were learning a lot about how best to message providers about their patients. My team had developed a simple alert for acute kidney injury (AKI). We knew that providers often missed the diagnosis, so maybe letting them know would improve patient outcomes.

As we tested the alert, we got feedback, and I have kept an email from an ICU doctor from those early days. It read:

Dear Dr. Wilson: Thank you for the automated alert informing me that my patient had AKI. Regrettably, the alert fired about an hour after the patient had died. I feel that the information is less than actionable at this time.

Our early system had neglected to add a conditional flag ensuring that the patient was still alive at the time it sent the alert message. A small oversight, but one that had very large implications. Future studies would show that “false positive” alerts like this seriously degrade physician confidence in the system. And why wouldn’t they?

Knowing whether a patient is alive or dead seems like it should be trivial. But, as it turns out, in our modern balkanized health care system, it can be quite difficult. Not knowing the vital status of a patient can have major consequences.

Health systems send messages to their patients all the time: reminders of appointments, reminders for preventive care, reminders for vaccinations, and so on.

But what if the patient being reminded has died? It’s a waste of resources, of course, but more than that, it can be painful for their families and reflects poorly on the health care system. Of all the people who should know whether someone is alive or dead, shouldn’t their doctor be at the top of the list?

A new study in JAMA Internal Medicine quantifies this very phenomenon.

Researchers examined 11,658 primary care patients in their health system who met the criteria of being “seriously ill” and followed them for 2 years. During that period of time, 25% were recorded as deceased in the electronic health record. But 30.8% had died. That left 676 patients who had died, but were not known to have died, left in the system.

Courtesy Dr. F. Perry Wilson

Courtesy Dr. F. Perry Wilson

Dr. Wilson is associate professor of medicine and public health and director of the Clinical and Translational Research Accelerator at Yale University, New Haven, Connecticut. He has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com .

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

Dr. Cerfolio

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, there is a growing body of scientific research that indicates a strong association of untreated brain illness with those who commit mass shootings.^4,5,6 This research demonstrates that such untreated illness combined with access to firearms poses a lethal threat to society.

Stanford University

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

Dr. Cerfolio

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, there is a growing body of scientific research that indicates a strong association of untreated brain illness with those who commit mass shootings.^4,5,6 This research demonstrates that such untreated illness combined with access to firearms poses a lethal threat to society.

Stanford University

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

Dr. Cerfolio

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, there is a growing body of scientific research that indicates a strong association of untreated brain illness with those who commit mass shootings.^4,5,6 This research demonstrates that such untreated illness combined with access to firearms poses a lethal threat to society.

Stanford University

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.

Prurigo nodularis (PN), a condition that historically has been a challenge to treat, now has a US Food and Drug Administration (FDA)–approved therapy—dupilumab—with other agents in the pipeline. As clinicians, we recognize PN as typically symmetric, keratotic, papular and nodular lesions presenting in older adults with chronic pruritus; patients with atopic dermatitis make up roughly half of patients with PN, but a workup for pruritus is indicated in other settings.¹ In the United States, Black patients are 3.4-times more likely than White patients to have PN.² The differential diagnosis includes conditions such nodular scabies, pemphigoid nodularis, acquired perforating disorders, and hypertrophic lichen planus, which also should be considered, especially in cases that are refractory to first-line therapies. Recent breakthroughs in therapy have come from substantial progress in our understanding of the pathogenesis of PN as driven by disorders of cytokine expression and/or neurocutaneous aberrations. We review progress in the treatment of PN over the last 3 years.

Treatment Guidelines

In 2020, an expert panel published consensus treatment guidelines for PN.¹ The panel, which proposed a 4-tiered approach targeting both neural and immunologic mechanisms in the pathogenesis of PN, emphasized the importance of tailoring treatment to the individual patient. Topical therapies remained the mainstay of treatment, with agents such as topical capsaicin, ketamine, lidocaine, and amitriptyline targeting the neural component and topical corticosteroids, calcineurin inhibitors, and calcipotriol and intralesional corticosteroids targeting the immunologic component. Phototherapy, methotrexate, cyclosporine, antidepressants, and gabapentinoids used with varying degrees of success were noted to have acceptable tolerability.¹

FDA-Approved Therapy

In September 2022, the FDA approved dupilumab for the treatment of PN. An antagonist of the IL-4 receptor, dupilumab was found to reduce both pruritus and skin lesions over a 24-week period in 2 phase 3 clinical trials.³ Results also demonstrated progressive improvements in measures assessing quality of life and pruritus over the study period, suggesting that continued treatment could lead to even further improvements in these measures. Adverse events were minimal and similar between the dupilumab- and placebo-treated groups.³

The FDA approval of dupilumab is a promising step in decreasing the disease burden of widespread or refractory PN, both for patients and the health care system. The treatment of patients with PN has been more challenging due to comorbidities, including mental health conditions, endocrine disorders, cardiovascular conditions, renal conditions, malignancy, and HIV.^4,5 These comorbidities can complicate the use of traditional systemic and immunosuppressive agents. Dupilumab has virtually no contraindications and has demonstrated safety in almost all patient populations.⁶

Consistent insurance coverage for patients who respond to dupilumab remains to be determined. A review investigating the use of dupilumab in patients with atopic dermatitis at the University of Pittsburgh Medical Center (Pittsburgh, Pennsylvania) found that of 179 patients, 67 (37.4%) did not start dupilumab, mainly due to insurance denial (34/179 [19%]) or copay (20/179 [11%]). Medicare patients were less likely to receive treatment compared to those on private insurance or Medicaid.⁷ In a recent review of 701 patients with PN, the mean age was 64.8 years,⁵ highlighting the concern about obtaining insurance coverage for dupilumab in this population given the higher likelihood that these patients will be on Medicare. Prescribers should be aware that coverage denials are likely and should be prepared to advocate for their patients by citing recent studies to hopefully obtain coverage for dupilumab in the treatment of PN. Resources such as the Dupixent MyWay program (https://www.dupixent.com/support-savings/dupixent-my-way) can provide useful recommendations for pursuing insurance approval for this agent.

Investigation of Janus Kinase Inhibitors

Emerging data suggest that Janus kinase (JAK) inhibitors may be beneficial in the treatment of PN. Patients with refractory PN have been treated off label with the JAK inhibitor tofacitinib at a dosage of 5 mg twice daily with improvement in symptoms and minimal side effects.^8,9 Similarly, a case report showed that off-label use of the JAK inhibitor baricitinib resulted in marked improvement in pruritus and clearance of lesions at a dosage of 4 mg daily, with reduction in pruritus seen as early as 1 week after treatment initiation.¹⁰ Although most patients are able to tolerate JAK inhibitors, known side effects include acne, viral infections, gastrointestinal tract upset, and the potential increased risk for malignancy.¹¹ The use of topical JAK inhibitors such as ruxolitinib has not yet been studied in PN, though cost may limit use to localized disease.

Other New Therapies

Recent case reports and case series have found the vitamin A derivative alitretinoin to be an effective treatment for recalcitrant PN, typically at a dosage of 30 mg daily.^12,13 Sustained remission was noted even after discontinuation of the medication.¹² Alitretinoin, which has been demonstrated to be effective in treating dermatitis,¹⁴ was well tolerated. Similar to JAK inhibitors, there are minimal data investigating the use of topical retinoids in the treatment of localized PN.

Topical cannabinoids have shown benefit in the treatment of pruritus¹⁵ and may be beneficial for the treatment of PN, though there currently are limited data in the literature. With the use of both medical and legal recreational marijuana on the rise, there is an increased interest in cannabinoids, particularly as many patients consider these agents to be more “natural”—and therefore preferable—treatment options. As the use of cannabis derivatives become more commonplace in both traditional and complementary medicine, providers should be prepared to field questions from patients about their potential for PN.

Finally, the IL-31RA inhibitor nemolizumab also has shown promise in the treatment of PN. A recent study suggested that nemolizumab helps modulate inflammatory and neural signaling in PN.¹⁶ Nemolizumab has been granted breakthrough therapy designation for the treatment of pruritus in PN based on a phase 2 study that demonstrated improvement in pruritus and skin lesions in a group of 70 patients with moderate to severe PN.¹⁷ Nemolizumab, which is used to treat pruritus in atopic dermatitis, has minimal side effects including upper respiratory tract infections and peripheral edema.¹⁸

Final Thoughts

Prurigo nodularis historically has been considered difficult to treat, particularly in those with widespread lesions. Dupilumab—the first FDA-approved treatment of PN—is now an exciting option, not just for patients with underlying atopic dermatitis. Not all patients will respond to the medication, and the ease of obtaining insurance approval has yet to be established; therefore, having other treatment options will be imperative. In patients with recalcitrant disease, several other treatment options have shown promise in the treatment of PN; in particular, JAK inhibitors, alitretinoin, and nemolizumab should be considered in patients with widespread refractory PN who are willing to try alternative agents. Ongoing research should be focused on these medications as well as on the development of other novel treatments aimed at relieving affected patients.

Prurigo nodularis (PN), a condition that historically has been a challenge to treat, now has a US Food and Drug Administration (FDA)–approved therapy—dupilumab—with other agents in the pipeline. As clinicians, we recognize PN as typically symmetric, keratotic, papular and nodular lesions presenting in older adults with chronic pruritus; patients with atopic dermatitis make up roughly half of patients with PN, but a workup for pruritus is indicated in other settings.¹ In the United States, Black patients are 3.4-times more likely than White patients to have PN.² The differential diagnosis includes conditions such nodular scabies, pemphigoid nodularis, acquired perforating disorders, and hypertrophic lichen planus, which also should be considered, especially in cases that are refractory to first-line therapies. Recent breakthroughs in therapy have come from substantial progress in our understanding of the pathogenesis of PN as driven by disorders of cytokine expression and/or neurocutaneous aberrations. We review progress in the treatment of PN over the last 3 years.

Treatment Guidelines

In 2020, an expert panel published consensus treatment guidelines for PN.¹ The panel, which proposed a 4-tiered approach targeting both neural and immunologic mechanisms in the pathogenesis of PN, emphasized the importance of tailoring treatment to the individual patient. Topical therapies remained the mainstay of treatment, with agents such as topical capsaicin, ketamine, lidocaine, and amitriptyline targeting the neural component and topical corticosteroids, calcineurin inhibitors, and calcipotriol and intralesional corticosteroids targeting the immunologic component. Phototherapy, methotrexate, cyclosporine, antidepressants, and gabapentinoids used with varying degrees of success were noted to have acceptable tolerability.¹

FDA-Approved Therapy

In September 2022, the FDA approved dupilumab for the treatment of PN. An antagonist of the IL-4 receptor, dupilumab was found to reduce both pruritus and skin lesions over a 24-week period in 2 phase 3 clinical trials.³ Results also demonstrated progressive improvements in measures assessing quality of life and pruritus over the study period, suggesting that continued treatment could lead to even further improvements in these measures. Adverse events were minimal and similar between the dupilumab- and placebo-treated groups.³

The FDA approval of dupilumab is a promising step in decreasing the disease burden of widespread or refractory PN, both for patients and the health care system. The treatment of patients with PN has been more challenging due to comorbidities, including mental health conditions, endocrine disorders, cardiovascular conditions, renal conditions, malignancy, and HIV.^4,5 These comorbidities can complicate the use of traditional systemic and immunosuppressive agents. Dupilumab has virtually no contraindications and has demonstrated safety in almost all patient populations.⁶

Consistent insurance coverage for patients who respond to dupilumab remains to be determined. A review investigating the use of dupilumab in patients with atopic dermatitis at the University of Pittsburgh Medical Center (Pittsburgh, Pennsylvania) found that of 179 patients, 67 (37.4%) did not start dupilumab, mainly due to insurance denial (34/179 [19%]) or copay (20/179 [11%]). Medicare patients were less likely to receive treatment compared to those on private insurance or Medicaid.⁷ In a recent review of 701 patients with PN, the mean age was 64.8 years,⁵ highlighting the concern about obtaining insurance coverage for dupilumab in this population given the higher likelihood that these patients will be on Medicare. Prescribers should be aware that coverage denials are likely and should be prepared to advocate for their patients by citing recent studies to hopefully obtain coverage for dupilumab in the treatment of PN. Resources such as the Dupixent MyWay program (https://www.dupixent.com/support-savings/dupixent-my-way) can provide useful recommendations for pursuing insurance approval for this agent.

Investigation of Janus Kinase Inhibitors

Emerging data suggest that Janus kinase (JAK) inhibitors may be beneficial in the treatment of PN. Patients with refractory PN have been treated off label with the JAK inhibitor tofacitinib at a dosage of 5 mg twice daily with improvement in symptoms and minimal side effects.^8,9 Similarly, a case report showed that off-label use of the JAK inhibitor baricitinib resulted in marked improvement in pruritus and clearance of lesions at a dosage of 4 mg daily, with reduction in pruritus seen as early as 1 week after treatment initiation.¹⁰ Although most patients are able to tolerate JAK inhibitors, known side effects include acne, viral infections, gastrointestinal tract upset, and the potential increased risk for malignancy.¹¹ The use of topical JAK inhibitors such as ruxolitinib has not yet been studied in PN, though cost may limit use to localized disease.

Other New Therapies

Recent case reports and case series have found the vitamin A derivative alitretinoin to be an effective treatment for recalcitrant PN, typically at a dosage of 30 mg daily.^12,13 Sustained remission was noted even after discontinuation of the medication.¹² Alitretinoin, which has been demonstrated to be effective in treating dermatitis,¹⁴ was well tolerated. Similar to JAK inhibitors, there are minimal data investigating the use of topical retinoids in the treatment of localized PN.

Topical cannabinoids have shown benefit in the treatment of pruritus¹⁵ and may be beneficial for the treatment of PN, though there currently are limited data in the literature. With the use of both medical and legal recreational marijuana on the rise, there is an increased interest in cannabinoids, particularly as many patients consider these agents to be more “natural”—and therefore preferable—treatment options. As the use of cannabis derivatives become more commonplace in both traditional and complementary medicine, providers should be prepared to field questions from patients about their potential for PN.

Finally, the IL-31RA inhibitor nemolizumab also has shown promise in the treatment of PN. A recent study suggested that nemolizumab helps modulate inflammatory and neural signaling in PN.¹⁶ Nemolizumab has been granted breakthrough therapy designation for the treatment of pruritus in PN based on a phase 2 study that demonstrated improvement in pruritus and skin lesions in a group of 70 patients with moderate to severe PN.¹⁷ Nemolizumab, which is used to treat pruritus in atopic dermatitis, has minimal side effects including upper respiratory tract infections and peripheral edema.¹⁸

Final Thoughts

Prurigo nodularis historically has been considered difficult to treat, particularly in those with widespread lesions. Dupilumab—the first FDA-approved treatment of PN—is now an exciting option, not just for patients with underlying atopic dermatitis. Not all patients will respond to the medication, and the ease of obtaining insurance approval has yet to be established; therefore, having other treatment options will be imperative. In patients with recalcitrant disease, several other treatment options have shown promise in the treatment of PN; in particular, JAK inhibitors, alitretinoin, and nemolizumab should be considered in patients with widespread refractory PN who are willing to try alternative agents. Ongoing research should be focused on these medications as well as on the development of other novel treatments aimed at relieving affected patients.

Prurigo nodularis (PN), a condition that historically has been a challenge to treat, now has a US Food and Drug Administration (FDA)–approved therapy—dupilumab—with other agents in the pipeline. As clinicians, we recognize PN as typically symmetric, keratotic, papular and nodular lesions presenting in older adults with chronic pruritus; patients with atopic dermatitis make up roughly half of patients with PN, but a workup for pruritus is indicated in other settings.¹ In the United States, Black patients are 3.4-times more likely than White patients to have PN.² The differential diagnosis includes conditions such nodular scabies, pemphigoid nodularis, acquired perforating disorders, and hypertrophic lichen planus, which also should be considered, especially in cases that are refractory to first-line therapies. Recent breakthroughs in therapy have come from substantial progress in our understanding of the pathogenesis of PN as driven by disorders of cytokine expression and/or neurocutaneous aberrations. We review progress in the treatment of PN over the last 3 years.

Treatment Guidelines

In 2020, an expert panel published consensus treatment guidelines for PN.¹ The panel, which proposed a 4-tiered approach targeting both neural and immunologic mechanisms in the pathogenesis of PN, emphasized the importance of tailoring treatment to the individual patient. Topical therapies remained the mainstay of treatment, with agents such as topical capsaicin, ketamine, lidocaine, and amitriptyline targeting the neural component and topical corticosteroids, calcineurin inhibitors, and calcipotriol and intralesional corticosteroids targeting the immunologic component. Phototherapy, methotrexate, cyclosporine, antidepressants, and gabapentinoids used with varying degrees of success were noted to have acceptable tolerability.¹

FDA-Approved Therapy

In September 2022, the FDA approved dupilumab for the treatment of PN. An antagonist of the IL-4 receptor, dupilumab was found to reduce both pruritus and skin lesions over a 24-week period in 2 phase 3 clinical trials.³ Results also demonstrated progressive improvements in measures assessing quality of life and pruritus over the study period, suggesting that continued treatment could lead to even further improvements in these measures. Adverse events were minimal and similar between the dupilumab- and placebo-treated groups.³

The FDA approval of dupilumab is a promising step in decreasing the disease burden of widespread or refractory PN, both for patients and the health care system. The treatment of patients with PN has been more challenging due to comorbidities, including mental health conditions, endocrine disorders, cardiovascular conditions, renal conditions, malignancy, and HIV.^4,5 These comorbidities can complicate the use of traditional systemic and immunosuppressive agents. Dupilumab has virtually no contraindications and has demonstrated safety in almost all patient populations.⁶

Consistent insurance coverage for patients who respond to dupilumab remains to be determined. A review investigating the use of dupilumab in patients with atopic dermatitis at the University of Pittsburgh Medical Center (Pittsburgh, Pennsylvania) found that of 179 patients, 67 (37.4%) did not start dupilumab, mainly due to insurance denial (34/179 [19%]) or copay (20/179 [11%]). Medicare patients were less likely to receive treatment compared to those on private insurance or Medicaid.⁷ In a recent review of 701 patients with PN, the mean age was 64.8 years,⁵ highlighting the concern about obtaining insurance coverage for dupilumab in this population given the higher likelihood that these patients will be on Medicare. Prescribers should be aware that coverage denials are likely and should be prepared to advocate for their patients by citing recent studies to hopefully obtain coverage for dupilumab in the treatment of PN. Resources such as the Dupixent MyWay program (https://www.dupixent.com/support-savings/dupixent-my-way) can provide useful recommendations for pursuing insurance approval for this agent.

Investigation of Janus Kinase Inhibitors

Emerging data suggest that Janus kinase (JAK) inhibitors may be beneficial in the treatment of PN. Patients with refractory PN have been treated off label with the JAK inhibitor tofacitinib at a dosage of 5 mg twice daily with improvement in symptoms and minimal side effects.^8,9 Similarly, a case report showed that off-label use of the JAK inhibitor baricitinib resulted in marked improvement in pruritus and clearance of lesions at a dosage of 4 mg daily, with reduction in pruritus seen as early as 1 week after treatment initiation.¹⁰ Although most patients are able to tolerate JAK inhibitors, known side effects include acne, viral infections, gastrointestinal tract upset, and the potential increased risk for malignancy.¹¹ The use of topical JAK inhibitors such as ruxolitinib has not yet been studied in PN, though cost may limit use to localized disease.

Other New Therapies

Recent case reports and case series have found the vitamin A derivative alitretinoin to be an effective treatment for recalcitrant PN, typically at a dosage of 30 mg daily.^12,13 Sustained remission was noted even after discontinuation of the medication.¹² Alitretinoin, which has been demonstrated to be effective in treating dermatitis,¹⁴ was well tolerated. Similar to JAK inhibitors, there are minimal data investigating the use of topical retinoids in the treatment of localized PN.

Topical cannabinoids have shown benefit in the treatment of pruritus¹⁵ and may be beneficial for the treatment of PN, though there currently are limited data in the literature. With the use of both medical and legal recreational marijuana on the rise, there is an increased interest in cannabinoids, particularly as many patients consider these agents to be more “natural”—and therefore preferable—treatment options. As the use of cannabis derivatives become more commonplace in both traditional and complementary medicine, providers should be prepared to field questions from patients about their potential for PN.

Finally, the IL-31RA inhibitor nemolizumab also has shown promise in the treatment of PN. A recent study suggested that nemolizumab helps modulate inflammatory and neural signaling in PN.¹⁶ Nemolizumab has been granted breakthrough therapy designation for the treatment of pruritus in PN based on a phase 2 study that demonstrated improvement in pruritus and skin lesions in a group of 70 patients with moderate to severe PN.¹⁷ Nemolizumab, which is used to treat pruritus in atopic dermatitis, has minimal side effects including upper respiratory tract infections and peripheral edema.¹⁸

Final Thoughts

Prurigo nodularis historically has been considered difficult to treat, particularly in those with widespread lesions. Dupilumab—the first FDA-approved treatment of PN—is now an exciting option, not just for patients with underlying atopic dermatitis. Not all patients will respond to the medication, and the ease of obtaining insurance approval has yet to be established; therefore, having other treatment options will be imperative. In patients with recalcitrant disease, several other treatment options have shown promise in the treatment of PN; in particular, JAK inhibitors, alitretinoin, and nemolizumab should be considered in patients with widespread refractory PN who are willing to try alternative agents. Ongoing research should be focused on these medications as well as on the development of other novel treatments aimed at relieving affected patients.

A recent article hypothesized that fructose causes more metabolic disease than does sucrose when overfed in the human diet. Fructose intake as high-fructose corn syrup (HFCS) has risen since its use in soft drinks in the United States and parallels the increase in the prevalence of obesity.

The newest hypothesis regarding fructose invokes a genetic survival of the fittest rationale for how fructose-enhanced fat deposition exacerbates the increased caloric consumption from the Western diet to promote metabolic disease especially in our adolescent and young adult population. This theory suggests that fructose consumption causes low adenosine triphosphate, which stimulates energy intake causing an imbalance of energy regulation.

Ongoing interest in the association between the increased use of HFCS and the prevalence of obesity in the United States continues. The use of HFCS in sugary sweetened beverages (SSBs) has reduced the cost of these beverages because of technology in preparing HFCS from corn and the substitution of the cheaper HFCS for sugar in SSBs. Although SSBs haven’t been proven to cause obesity, there has been an increase in the risk for type 2 diabetes, cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and even cancer. Research in HFCS, weight gain, and metabolic disease continues despite little definitive evidence of causation.

The relationship between SSBs consumption and obesity has been attributed to the increase in overall total caloric intake of the diet. These liquid calories do not suppress the intake of other foods to equalize the total amount of calories ingested. This knowledge has been gleaned from work performed by R. Mattes and B. Rolls in the 1990s through the early 2000s.

This research and the current work on HFCS and metabolic disease is important because there are adolescents and young adults in the United States and globally that ingest a large amount of SSBs and therefore are at risk for metabolic disease, type 2 diabetes, NAFLD, and CVD at an early age.

The concern over fructose stems from the association between the advent of increasing HFCS in SSBs and the increase in prevalence of obesity occurring at similar time periods in the United States, around 1970-1980.

Researchers noted the association and began to focus on potential reasons to pinpoint HFCS or fructose itself so we have a mechanism of action specific to fructose. Therefore, the public could be warned about the risk of drinking SSBs due to the HFCS and fructose ingested and the possibility of metabolic disease. Perhaps, there is a method to remove harmful HFCS from the food supply much like what has happened with industrially produced trans fatty acids. In 2018, the World Health Organization called for a total ban on trans fats due to causation of 500 million early deaths per year globally.

Similar to the process of making HFCS, most trans fats are formed through an industrial process that alters vegetable oil and creates a shelf stable inexpensive partially hydrogenated oil. Trans fats have been shown to increase low-density lipoprotein (LDL) cholesterol and decrease high-density lipoprotein (HDL) increasing the risk for myocardial infarction and stroke.

The prevalence of obesity has increased worldwide, even in countries where SSBs do not contain HFCS.

Still, the proof that HFCS can override the satiety pathway and cause excess calorie intake is intriguing and may have teeth if we can pinpoint the increase in prevalence of obesity in children and adolescents on increased ingestion of HFCS in SSBs. There is no reason nutritionally to add sugar or HFCS to liquids. Plus, if HFCS has a metabolic disadvantage then all the more reason to ban it. Then, it becomes like trans fats: a toxin in the food supply.


Dr. Apovian is a Faculty Member, Department of Medicine; Co-Director, Center for Weight Management and Wellness, Section of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. She has disclosed financial relationships with Altimmune, Inc; Cowen and Company, LLC; Currax Pharmaceuticals, LLC; EPG Communication Holdings, Ltd; Gelesis, Srl; L-Nutra, Inc; NeuroBo Pharmaceuticals; and Novo Nordisk, Inc. She has received research grants from the National Institutes of Health; Patient-Centered Outcomes Research Institute; GI Dynamics, Inc.

A version of this article appeared on Medscape.com.

A recent article hypothesized that fructose causes more metabolic disease than does sucrose when overfed in the human diet. Fructose intake as high-fructose corn syrup (HFCS) has risen since its use in soft drinks in the United States and parallels the increase in the prevalence of obesity.

The newest hypothesis regarding fructose invokes a genetic survival of the fittest rationale for how fructose-enhanced fat deposition exacerbates the increased caloric consumption from the Western diet to promote metabolic disease especially in our adolescent and young adult population. This theory suggests that fructose consumption causes low adenosine triphosphate, which stimulates energy intake causing an imbalance of energy regulation.

Ongoing interest in the association between the increased use of HFCS and the prevalence of obesity in the United States continues. The use of HFCS in sugary sweetened beverages (SSBs) has reduced the cost of these beverages because of technology in preparing HFCS from corn and the substitution of the cheaper HFCS for sugar in SSBs. Although SSBs haven’t been proven to cause obesity, there has been an increase in the risk for type 2 diabetes, cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and even cancer. Research in HFCS, weight gain, and metabolic disease continues despite little definitive evidence of causation.

The relationship between SSBs consumption and obesity has been attributed to the increase in overall total caloric intake of the diet. These liquid calories do not suppress the intake of other foods to equalize the total amount of calories ingested. This knowledge has been gleaned from work performed by R. Mattes and B. Rolls in the 1990s through the early 2000s.

This research and the current work on HFCS and metabolic disease is important because there are adolescents and young adults in the United States and globally that ingest a large amount of SSBs and therefore are at risk for metabolic disease, type 2 diabetes, NAFLD, and CVD at an early age.

The concern over fructose stems from the association between the advent of increasing HFCS in SSBs and the increase in prevalence of obesity occurring at similar time periods in the United States, around 1970-1980.

Researchers noted the association and began to focus on potential reasons to pinpoint HFCS or fructose itself so we have a mechanism of action specific to fructose. Therefore, the public could be warned about the risk of drinking SSBs due to the HFCS and fructose ingested and the possibility of metabolic disease. Perhaps, there is a method to remove harmful HFCS from the food supply much like what has happened with industrially produced trans fatty acids. In 2018, the World Health Organization called for a total ban on trans fats due to causation of 500 million early deaths per year globally.

Similar to the process of making HFCS, most trans fats are formed through an industrial process that alters vegetable oil and creates a shelf stable inexpensive partially hydrogenated oil. Trans fats have been shown to increase low-density lipoprotein (LDL) cholesterol and decrease high-density lipoprotein (HDL) increasing the risk for myocardial infarction and stroke.

The prevalence of obesity has increased worldwide, even in countries where SSBs do not contain HFCS.

Still, the proof that HFCS can override the satiety pathway and cause excess calorie intake is intriguing and may have teeth if we can pinpoint the increase in prevalence of obesity in children and adolescents on increased ingestion of HFCS in SSBs. There is no reason nutritionally to add sugar or HFCS to liquids. Plus, if HFCS has a metabolic disadvantage then all the more reason to ban it. Then, it becomes like trans fats: a toxin in the food supply.


Dr. Apovian is a Faculty Member, Department of Medicine; Co-Director, Center for Weight Management and Wellness, Section of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. She has disclosed financial relationships with Altimmune, Inc; Cowen and Company, LLC; Currax Pharmaceuticals, LLC; EPG Communication Holdings, Ltd; Gelesis, Srl; L-Nutra, Inc; NeuroBo Pharmaceuticals; and Novo Nordisk, Inc. She has received research grants from the National Institutes of Health; Patient-Centered Outcomes Research Institute; GI Dynamics, Inc.

A version of this article appeared on Medscape.com.

A recent article hypothesized that fructose causes more metabolic disease than does sucrose when overfed in the human diet. Fructose intake as high-fructose corn syrup (HFCS) has risen since its use in soft drinks in the United States and parallels the increase in the prevalence of obesity.

The newest hypothesis regarding fructose invokes a genetic survival of the fittest rationale for how fructose-enhanced fat deposition exacerbates the increased caloric consumption from the Western diet to promote metabolic disease especially in our adolescent and young adult population. This theory suggests that fructose consumption causes low adenosine triphosphate, which stimulates energy intake causing an imbalance of energy regulation.

Ongoing interest in the association between the increased use of HFCS and the prevalence of obesity in the United States continues. The use of HFCS in sugary sweetened beverages (SSBs) has reduced the cost of these beverages because of technology in preparing HFCS from corn and the substitution of the cheaper HFCS for sugar in SSBs. Although SSBs haven’t been proven to cause obesity, there has been an increase in the risk for type 2 diabetes, cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and even cancer. Research in HFCS, weight gain, and metabolic disease continues despite little definitive evidence of causation.

The relationship between SSBs consumption and obesity has been attributed to the increase in overall total caloric intake of the diet. These liquid calories do not suppress the intake of other foods to equalize the total amount of calories ingested. This knowledge has been gleaned from work performed by R. Mattes and B. Rolls in the 1990s through the early 2000s.

This research and the current work on HFCS and metabolic disease is important because there are adolescents and young adults in the United States and globally that ingest a large amount of SSBs and therefore are at risk for metabolic disease, type 2 diabetes, NAFLD, and CVD at an early age.

The concern over fructose stems from the association between the advent of increasing HFCS in SSBs and the increase in prevalence of obesity occurring at similar time periods in the United States, around 1970-1980.

Researchers noted the association and began to focus on potential reasons to pinpoint HFCS or fructose itself so we have a mechanism of action specific to fructose. Therefore, the public could be warned about the risk of drinking SSBs due to the HFCS and fructose ingested and the possibility of metabolic disease. Perhaps, there is a method to remove harmful HFCS from the food supply much like what has happened with industrially produced trans fatty acids. In 2018, the World Health Organization called for a total ban on trans fats due to causation of 500 million early deaths per year globally.

Similar to the process of making HFCS, most trans fats are formed through an industrial process that alters vegetable oil and creates a shelf stable inexpensive partially hydrogenated oil. Trans fats have been shown to increase low-density lipoprotein (LDL) cholesterol and decrease high-density lipoprotein (HDL) increasing the risk for myocardial infarction and stroke.

The prevalence of obesity has increased worldwide, even in countries where SSBs do not contain HFCS.

Still, the proof that HFCS can override the satiety pathway and cause excess calorie intake is intriguing and may have teeth if we can pinpoint the increase in prevalence of obesity in children and adolescents on increased ingestion of HFCS in SSBs. There is no reason nutritionally to add sugar or HFCS to liquids. Plus, if HFCS has a metabolic disadvantage then all the more reason to ban it. Then, it becomes like trans fats: a toxin in the food supply.


Dr. Apovian is a Faculty Member, Department of Medicine; Co-Director, Center for Weight Management and Wellness, Section of Endocrinology, Diabetes, and Hypertension, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts. She has disclosed financial relationships with Altimmune, Inc; Cowen and Company, LLC; Currax Pharmaceuticals, LLC; EPG Communication Holdings, Ltd; Gelesis, Srl; L-Nutra, Inc; NeuroBo Pharmaceuticals; and Novo Nordisk, Inc. She has received research grants from the National Institutes of Health; Patient-Centered Outcomes Research Institute; GI Dynamics, Inc.

A version of this article appeared on Medscape.com.

The medical knowledge that William Shakespeare possessed has awed scholars for centuries. Theories about the provenance of his knowledge abound (such as his son-in-law being a physician), and the inclusion of medical terms and ailments throughout his plays suggests a broad knowledge of disease and sickness. Scholars have noted how he sprinkles references to dermatologic, neurologic, orthopedic, and metabolic ailments throughout his plays, mentioning carbuncles, fistulas, corpulence, rhinophyma, scurvy, ague, enuresis, kyphosis, epilepsy, and parkinsonism.¹ What seems to strike post-Enlightenment audiences—and what sets Shakespeare apart from many of his contemporaries—is his portrayal of “complex” characters, those with what we envision as rich interior worlds and with whom a modern audience can resonate. There is a reason psychiatrists such as Sigmund Freud have rushed back to Shakespeare and (sometimes anachronistically) found in his characters various psychiatric diagnoses such as depression, anxiety, paranoia, jealous delusions, and obsessive-compulsive disorder. Suicide and suicidal ideation are prevalent themes in some of Shakespeare’s most well-known characters.

A surprisingly common theme

The gravest outcome of a psychiatric illness is death by suicide, which occurs in 13 of Shakespeare’s characters.² There are additional characters who exhibit suicidal ideation without a completed act. Shakespearean characters whose lives end in suicide are variably portrayed, dying by various means and circumstances. Hamlet (who dies at the hand of his foe, Laertes), famously soliloquizes the theme of suicide and the afterlife. He ponders “tak[ing] arms against a sea of troubles.” Ophelia dies ambiguously. Immediately after, her mother and brother recount her death in a brook—having had “too much of water” when her garments “heavy with their drink, | pull’d the poor wretch from her melodious lay | To muddy death.” The 2 clowns/gravediggers then debate whether Ophelia deserves a Christian burial and if her death should be considered a suicide: did the water drown her, or did she drown herself?³

Lady Macbeth’s suicide is offstage, punctuated by a “night-shriek.” Romeo drinks poison and dies “with a kiss.” Juliet quickly follows, making her body the sword’s sheath which “there rust, and let [her] die.” Othello stabs himself after requesting that his peers will “speak of me as I am.” One of King Lear’s daughters poisons her sister “and after [slays] herself.” Timon dies by his cave, “entomb’d upon the very hem o’ the sea.” In Antony and Cleopatra, after being told that Cleopatra has killed herself with Antony’s name on her lips, Antony begs to be stabbed and then stabs himself; he is not defeated by Caesar, but rather conquered by himself: “none but Antony | Should conquer Antony.” Cleopatra and her lady-in-waiting, Charmian, kill themselves with an asp. In Julius Caesar, Brutus runs upon his sword. Cassius begs for his own death, asking that “this good sword, | That ran through Caesar’s bowels, search this bosom.” Portia, it is reported, “swallowed fire.”

Shakespeare uses specific stylized language to portray characters in psychological anguish and suicidal states. Scholars have discussed how he uses certain stylistic language to highlight the anguish that happens during solitary, solipsistic moments of contemplation.⁴ Moments of anguish and suicidal ideation are marked by verbal repetition. An example of this repetition comes in Hamlet’s speech after he returns to the kingdom where his uncle has usurped his father, when he laments that he cannot end his own life. He says:

O, that this too too sullied flesh would melt,
Thaw, and resolve itself into a dew!
Or that the Everlasting had not fix’d
His canon ’gainst self-slaughter! O God, God,
How weary, stale, flat, and unprofitable
Seem to me all the uses of this world.

In these 6 lines, there are 2 instances of verbal repetition: “too too” and “God, God.” In this moment of solitude and despair, Hamlet’s speech fractures; his fractured speech reflects his fractured psyche. While Hamlet speaks of staleness and stagnation in the world, his words represent a sterile excess. No meaning is elicited by their repetition; there is no forward momentum to his speech. The words reflect the extent to which Hamlet is stuck and divided in this moment. Something similar happens in Macbeth’s “Tomorrow and tomorrow and tomorrow” speech. The words march on, and with each repetition they become increasingly hollow and brittle.

Why does this discussion of suicide in Shakespeare hold value for a contemporary psychiatrist? First, there is no single prototypical suicidal character in Shakespeare. His characters who are suicidal vary in their demographics and incentives for ending their lives. In this way, he provides a rich framework, one with which many people can engage. Second, this discussion fits into an existing paradigm for using art therapy (specifically Shakespeare) as a treatment modality for trauma.⁵ Programs such as DE-CRUIT have used the recitation of Shakespearean verse as a means of processing trauma in veterans.⁵ While Shakespeare does not mention a remedy for suicide in his plays, perhaps the text can serve as medicine. Third, the repetitive speech that Shakespeare uses in times of anguish could be a fairly accurate reflection of speech patterns in patients who are suicidal. Research that completed a spoken language analysis of patients who were suicidal has found “mechanical and repetitive phrasing” as a quality of these patients’ speech.^6,7

For hundreds of years, critics have searched beyond the text for Shakespeare’s voice and opinion; what did he himself think of melancholy, despair, or suicide? We cannot know. We, as readers, are invited to explore a nuanced and multifaceted view of suicide, one that neither chides nor valorizes the act, and provides ambiguity rather than condemnation.

The medical knowledge that William Shakespeare possessed has awed scholars for centuries. Theories about the provenance of his knowledge abound (such as his son-in-law being a physician), and the inclusion of medical terms and ailments throughout his plays suggests a broad knowledge of disease and sickness. Scholars have noted how he sprinkles references to dermatologic, neurologic, orthopedic, and metabolic ailments throughout his plays, mentioning carbuncles, fistulas, corpulence, rhinophyma, scurvy, ague, enuresis, kyphosis, epilepsy, and parkinsonism.¹ What seems to strike post-Enlightenment audiences—and what sets Shakespeare apart from many of his contemporaries—is his portrayal of “complex” characters, those with what we envision as rich interior worlds and with whom a modern audience can resonate. There is a reason psychiatrists such as Sigmund Freud have rushed back to Shakespeare and (sometimes anachronistically) found in his characters various psychiatric diagnoses such as depression, anxiety, paranoia, jealous delusions, and obsessive-compulsive disorder. Suicide and suicidal ideation are prevalent themes in some of Shakespeare’s most well-known characters.

A surprisingly common theme

The gravest outcome of a psychiatric illness is death by suicide, which occurs in 13 of Shakespeare’s characters.² There are additional characters who exhibit suicidal ideation without a completed act. Shakespearean characters whose lives end in suicide are variably portrayed, dying by various means and circumstances. Hamlet (who dies at the hand of his foe, Laertes), famously soliloquizes the theme of suicide and the afterlife. He ponders “tak[ing] arms against a sea of troubles.” Ophelia dies ambiguously. Immediately after, her mother and brother recount her death in a brook—having had “too much of water” when her garments “heavy with their drink, | pull’d the poor wretch from her melodious lay | To muddy death.” The 2 clowns/gravediggers then debate whether Ophelia deserves a Christian burial and if her death should be considered a suicide: did the water drown her, or did she drown herself?³

Lady Macbeth’s suicide is offstage, punctuated by a “night-shriek.” Romeo drinks poison and dies “with a kiss.” Juliet quickly follows, making her body the sword’s sheath which “there rust, and let [her] die.” Othello stabs himself after requesting that his peers will “speak of me as I am.” One of King Lear’s daughters poisons her sister “and after [slays] herself.” Timon dies by his cave, “entomb’d upon the very hem o’ the sea.” In Antony and Cleopatra, after being told that Cleopatra has killed herself with Antony’s name on her lips, Antony begs to be stabbed and then stabs himself; he is not defeated by Caesar, but rather conquered by himself: “none but Antony | Should conquer Antony.” Cleopatra and her lady-in-waiting, Charmian, kill themselves with an asp. In Julius Caesar, Brutus runs upon his sword. Cassius begs for his own death, asking that “this good sword, | That ran through Caesar’s bowels, search this bosom.” Portia, it is reported, “swallowed fire.”

Shakespeare uses specific stylized language to portray characters in psychological anguish and suicidal states. Scholars have discussed how he uses certain stylistic language to highlight the anguish that happens during solitary, solipsistic moments of contemplation.⁴ Moments of anguish and suicidal ideation are marked by verbal repetition. An example of this repetition comes in Hamlet’s speech after he returns to the kingdom where his uncle has usurped his father, when he laments that he cannot end his own life. He says:

O, that this too too sullied flesh would melt,
Thaw, and resolve itself into a dew!
Or that the Everlasting had not fix’d
His canon ’gainst self-slaughter! O God, God,
How weary, stale, flat, and unprofitable
Seem to me all the uses of this world.

In these 6 lines, there are 2 instances of verbal repetition: “too too” and “God, God.” In this moment of solitude and despair, Hamlet’s speech fractures; his fractured speech reflects his fractured psyche. While Hamlet speaks of staleness and stagnation in the world, his words represent a sterile excess. No meaning is elicited by their repetition; there is no forward momentum to his speech. The words reflect the extent to which Hamlet is stuck and divided in this moment. Something similar happens in Macbeth’s “Tomorrow and tomorrow and tomorrow” speech. The words march on, and with each repetition they become increasingly hollow and brittle.

Why does this discussion of suicide in Shakespeare hold value for a contemporary psychiatrist? First, there is no single prototypical suicidal character in Shakespeare. His characters who are suicidal vary in their demographics and incentives for ending their lives. In this way, he provides a rich framework, one with which many people can engage. Second, this discussion fits into an existing paradigm for using art therapy (specifically Shakespeare) as a treatment modality for trauma.⁵ Programs such as DE-CRUIT have used the recitation of Shakespearean verse as a means of processing trauma in veterans.⁵ While Shakespeare does not mention a remedy for suicide in his plays, perhaps the text can serve as medicine. Third, the repetitive speech that Shakespeare uses in times of anguish could be a fairly accurate reflection of speech patterns in patients who are suicidal. Research that completed a spoken language analysis of patients who were suicidal has found “mechanical and repetitive phrasing” as a quality of these patients’ speech.^6,7

For hundreds of years, critics have searched beyond the text for Shakespeare’s voice and opinion; what did he himself think of melancholy, despair, or suicide? We cannot know. We, as readers, are invited to explore a nuanced and multifaceted view of suicide, one that neither chides nor valorizes the act, and provides ambiguity rather than condemnation.

The medical knowledge that William Shakespeare possessed has awed scholars for centuries. Theories about the provenance of his knowledge abound (such as his son-in-law being a physician), and the inclusion of medical terms and ailments throughout his plays suggests a broad knowledge of disease and sickness. Scholars have noted how he sprinkles references to dermatologic, neurologic, orthopedic, and metabolic ailments throughout his plays, mentioning carbuncles, fistulas, corpulence, rhinophyma, scurvy, ague, enuresis, kyphosis, epilepsy, and parkinsonism.¹ What seems to strike post-Enlightenment audiences—and what sets Shakespeare apart from many of his contemporaries—is his portrayal of “complex” characters, those with what we envision as rich interior worlds and with whom a modern audience can resonate. There is a reason psychiatrists such as Sigmund Freud have rushed back to Shakespeare and (sometimes anachronistically) found in his characters various psychiatric diagnoses such as depression, anxiety, paranoia, jealous delusions, and obsessive-compulsive disorder. Suicide and suicidal ideation are prevalent themes in some of Shakespeare’s most well-known characters.

A surprisingly common theme

The gravest outcome of a psychiatric illness is death by suicide, which occurs in 13 of Shakespeare’s characters.² There are additional characters who exhibit suicidal ideation without a completed act. Shakespearean characters whose lives end in suicide are variably portrayed, dying by various means and circumstances. Hamlet (who dies at the hand of his foe, Laertes), famously soliloquizes the theme of suicide and the afterlife. He ponders “tak[ing] arms against a sea of troubles.” Ophelia dies ambiguously. Immediately after, her mother and brother recount her death in a brook—having had “too much of water” when her garments “heavy with their drink, | pull’d the poor wretch from her melodious lay | To muddy death.” The 2 clowns/gravediggers then debate whether Ophelia deserves a Christian burial and if her death should be considered a suicide: did the water drown her, or did she drown herself?³

Lady Macbeth’s suicide is offstage, punctuated by a “night-shriek.” Romeo drinks poison and dies “with a kiss.” Juliet quickly follows, making her body the sword’s sheath which “there rust, and let [her] die.” Othello stabs himself after requesting that his peers will “speak of me as I am.” One of King Lear’s daughters poisons her sister “and after [slays] herself.” Timon dies by his cave, “entomb’d upon the very hem o’ the sea.” In Antony and Cleopatra, after being told that Cleopatra has killed herself with Antony’s name on her lips, Antony begs to be stabbed and then stabs himself; he is not defeated by Caesar, but rather conquered by himself: “none but Antony | Should conquer Antony.” Cleopatra and her lady-in-waiting, Charmian, kill themselves with an asp. In Julius Caesar, Brutus runs upon his sword. Cassius begs for his own death, asking that “this good sword, | That ran through Caesar’s bowels, search this bosom.” Portia, it is reported, “swallowed fire.”

Shakespeare uses specific stylized language to portray characters in psychological anguish and suicidal states. Scholars have discussed how he uses certain stylistic language to highlight the anguish that happens during solitary, solipsistic moments of contemplation.⁴ Moments of anguish and suicidal ideation are marked by verbal repetition. An example of this repetition comes in Hamlet’s speech after he returns to the kingdom where his uncle has usurped his father, when he laments that he cannot end his own life. He says:

O, that this too too sullied flesh would melt,
Thaw, and resolve itself into a dew!
Or that the Everlasting had not fix’d
His canon ’gainst self-slaughter! O God, God,
How weary, stale, flat, and unprofitable
Seem to me all the uses of this world.

In these 6 lines, there are 2 instances of verbal repetition: “too too” and “God, God.” In this moment of solitude and despair, Hamlet’s speech fractures; his fractured speech reflects his fractured psyche. While Hamlet speaks of staleness and stagnation in the world, his words represent a sterile excess. No meaning is elicited by their repetition; there is no forward momentum to his speech. The words reflect the extent to which Hamlet is stuck and divided in this moment. Something similar happens in Macbeth’s “Tomorrow and tomorrow and tomorrow” speech. The words march on, and with each repetition they become increasingly hollow and brittle.

Why does this discussion of suicide in Shakespeare hold value for a contemporary psychiatrist? First, there is no single prototypical suicidal character in Shakespeare. His characters who are suicidal vary in their demographics and incentives for ending their lives. In this way, he provides a rich framework, one with which many people can engage. Second, this discussion fits into an existing paradigm for using art therapy (specifically Shakespeare) as a treatment modality for trauma.⁵ Programs such as DE-CRUIT have used the recitation of Shakespearean verse as a means of processing trauma in veterans.⁵ While Shakespeare does not mention a remedy for suicide in his plays, perhaps the text can serve as medicine. Third, the repetitive speech that Shakespeare uses in times of anguish could be a fairly accurate reflection of speech patterns in patients who are suicidal. Research that completed a spoken language analysis of patients who were suicidal has found “mechanical and repetitive phrasing” as a quality of these patients’ speech.^6,7

For hundreds of years, critics have searched beyond the text for Shakespeare’s voice and opinion; what did he himself think of melancholy, despair, or suicide? We cannot know. We, as readers, are invited to explore a nuanced and multifaceted view of suicide, one that neither chides nor valorizes the act, and provides ambiguity rather than condemnation.

All that’s bright must fade,
The brightest still the fleetest;
All that’s sweet was made
But to be lost when sweetest.
Thomas Moore

I sometimes hold it half a sin
To put in words the grief I feel;
For words, like Nature, half reveal
And half conceal the Soul within.
Alfred, Lord Tennyson, In Memoriam

Dear Readers,

I have sad news to share with you. This is the last issue of Current Psychiatry.

During my travels around the country over the past 2 decades, countless psychiatrists have told me that Current Psychiatry is their favorite journal and they greatly appreciate it due to the practical, useful, and pithy clinical updates it provides them as busy clinicians.

Current Psychiatry was born on January 1, 2002, and will be 21 years old at its premature demise on December 31, 2023 (This reminds me of the Billy Joel song “Only the Good Die Young”). The first Editor-in-Chief was Randolph Hillard, MD, who at the time was the psychiatry chair at the University of Cincinnati. I succeeded him as Editor-in-Chief in 2006 and will have served in that role for 17 years when Current Psychiatry is sunset. I have established 2 other research journals, Schizophrenia Research and Biomarkers in Neuropsychiatry, both of which are thriving. However, editing Current Psychiatry has been one of the most gratifying roles I have had in my career because Current Psychiatry promotes sound, evidence-based clinical practice to its 45,000 psychiatric clinician readers, who provide care for millions of psychiatric patients of all ages and DSM-5-TR diagnostic categories every day.

As the saying goes: All good things eventually come to an end. I am so grateful to have had the opportunity to collaborate with a wonderful, highly competent editorial staff, as well as with outstanding colleagues who served on the editorial board all those years. A special shout-out to Jeff Bauer, the publishing staff editor, with whom I worked so closely. I very much appreciated all the authors and peer reviewers who contributed timely clinical articles month after month and made Current Psychiatry such a valuable, evidence-based educational medium.

This has been a unique journey for all of us who strived to transform Current Psychiatry into a prominent, must-read clinical journal. This valedictory is both a fond farewell and a warm appreciation to you, our loyal readers. I hope that in the future we will reconnect and interact again in another meaningful way, advocating for the health and welfare of our psychiatric patients.

All that’s bright must fade,
The brightest still the fleetest;
All that’s sweet was made
But to be lost when sweetest.
Thomas Moore

I sometimes hold it half a sin
To put in words the grief I feel;
For words, like Nature, half reveal
And half conceal the Soul within.
Alfred, Lord Tennyson, In Memoriam

Dear Readers,

I have sad news to share with you. This is the last issue of Current Psychiatry.

During my travels around the country over the past 2 decades, countless psychiatrists have told me that Current Psychiatry is their favorite journal and they greatly appreciate it due to the practical, useful, and pithy clinical updates it provides them as busy clinicians.

Current Psychiatry was born on January 1, 2002, and will be 21 years old at its premature demise on December 31, 2023 (This reminds me of the Billy Joel song “Only the Good Die Young”). The first Editor-in-Chief was Randolph Hillard, MD, who at the time was the psychiatry chair at the University of Cincinnati. I succeeded him as Editor-in-Chief in 2006 and will have served in that role for 17 years when Current Psychiatry is sunset. I have established 2 other research journals, Schizophrenia Research and Biomarkers in Neuropsychiatry, both of which are thriving. However, editing Current Psychiatry has been one of the most gratifying roles I have had in my career because Current Psychiatry promotes sound, evidence-based clinical practice to its 45,000 psychiatric clinician readers, who provide care for millions of psychiatric patients of all ages and DSM-5-TR diagnostic categories every day.

As the saying goes: All good things eventually come to an end. I am so grateful to have had the opportunity to collaborate with a wonderful, highly competent editorial staff, as well as with outstanding colleagues who served on the editorial board all those years. A special shout-out to Jeff Bauer, the publishing staff editor, with whom I worked so closely. I very much appreciated all the authors and peer reviewers who contributed timely clinical articles month after month and made Current Psychiatry such a valuable, evidence-based educational medium.

This has been a unique journey for all of us who strived to transform Current Psychiatry into a prominent, must-read clinical journal. This valedictory is both a fond farewell and a warm appreciation to you, our loyal readers. I hope that in the future we will reconnect and interact again in another meaningful way, advocating for the health and welfare of our psychiatric patients.

All that’s bright must fade,
The brightest still the fleetest;
All that’s sweet was made
But to be lost when sweetest.
Thomas Moore

I sometimes hold it half a sin
To put in words the grief I feel;
For words, like Nature, half reveal
And half conceal the Soul within.
Alfred, Lord Tennyson, In Memoriam

Dear Readers,

I have sad news to share with you. This is the last issue of Current Psychiatry.

During my travels around the country over the past 2 decades, countless psychiatrists have told me that Current Psychiatry is their favorite journal and they greatly appreciate it due to the practical, useful, and pithy clinical updates it provides them as busy clinicians.

Current Psychiatry was born on January 1, 2002, and will be 21 years old at its premature demise on December 31, 2023 (This reminds me of the Billy Joel song “Only the Good Die Young”). The first Editor-in-Chief was Randolph Hillard, MD, who at the time was the psychiatry chair at the University of Cincinnati. I succeeded him as Editor-in-Chief in 2006 and will have served in that role for 17 years when Current Psychiatry is sunset. I have established 2 other research journals, Schizophrenia Research and Biomarkers in Neuropsychiatry, both of which are thriving. However, editing Current Psychiatry has been one of the most gratifying roles I have had in my career because Current Psychiatry promotes sound, evidence-based clinical practice to its 45,000 psychiatric clinician readers, who provide care for millions of psychiatric patients of all ages and DSM-5-TR diagnostic categories every day.

As the saying goes: All good things eventually come to an end. I am so grateful to have had the opportunity to collaborate with a wonderful, highly competent editorial staff, as well as with outstanding colleagues who served on the editorial board all those years. A special shout-out to Jeff Bauer, the publishing staff editor, with whom I worked so closely. I very much appreciated all the authors and peer reviewers who contributed timely clinical articles month after month and made Current Psychiatry such a valuable, evidence-based educational medium.

This has been a unique journey for all of us who strived to transform Current Psychiatry into a prominent, must-read clinical journal. This valedictory is both a fond farewell and a warm appreciation to you, our loyal readers. I hope that in the future we will reconnect and interact again in another meaningful way, advocating for the health and welfare of our psychiatric patients.

In “Treating chronic insomnia: An alternating medication strategy” (Current Psychiatry, October 2023, p. 25-31, doi:10.12788/cp.0397), Dr. Kaplan correctly identified tolerance and tachyphylaxis as significant problems when prescribing traditional hypnotics, and proposed a solution of using 2 sleep medications, each having a different mechanism of action, on an alternating schedule. However, with the availability of the dual orexin receptor antagonists (DORAs) daridorexant, lemborexant, and suvorexant, this approach is unnecessary. Moreover, the mechanism of action of orexin receptor antagonism directly addresses extant hyperarousal by decreasing wake signaling, without any deleterious effect on sleep architecture.¹ Additionally, the DORAs are not associated with physiological dependence, withdrawal, or rebound. Their efficacy profile is as good as or better than other FDA-approved agents for insomnia disorder.¹ An obstacle to their use is that they are not yet available as generic products, but access is facilitated by the manufacturers’ patient assistance programs. Additional resources elaborate on indirect comparisons among agents using number needed to treat and number needed to harm, metrics that are helpful when clinically appraising new agents.^2-5

Leslie Citrome, MD, MPH
Valhalla, New York

In “Treating chronic insomnia: An alternating medication strategy” (Current Psychiatry, October 2023, p. 25-31, doi:10.12788/cp.0397), Dr. Kaplan correctly identified tolerance and tachyphylaxis as significant problems when prescribing traditional hypnotics, and proposed a solution of using 2 sleep medications, each having a different mechanism of action, on an alternating schedule. However, with the availability of the dual orexin receptor antagonists (DORAs) daridorexant, lemborexant, and suvorexant, this approach is unnecessary. Moreover, the mechanism of action of orexin receptor antagonism directly addresses extant hyperarousal by decreasing wake signaling, without any deleterious effect on sleep architecture.¹ Additionally, the DORAs are not associated with physiological dependence, withdrawal, or rebound. Their efficacy profile is as good as or better than other FDA-approved agents for insomnia disorder.¹ An obstacle to their use is that they are not yet available as generic products, but access is facilitated by the manufacturers’ patient assistance programs. Additional resources elaborate on indirect comparisons among agents using number needed to treat and number needed to harm, metrics that are helpful when clinically appraising new agents.^2-5

Leslie Citrome, MD, MPH
Valhalla, New York

In “Treating chronic insomnia: An alternating medication strategy” (Current Psychiatry, October 2023, p. 25-31, doi:10.12788/cp.0397), Dr. Kaplan correctly identified tolerance and tachyphylaxis as significant problems when prescribing traditional hypnotics, and proposed a solution of using 2 sleep medications, each having a different mechanism of action, on an alternating schedule. However, with the availability of the dual orexin receptor antagonists (DORAs) daridorexant, lemborexant, and suvorexant, this approach is unnecessary. Moreover, the mechanism of action of orexin receptor antagonism directly addresses extant hyperarousal by decreasing wake signaling, without any deleterious effect on sleep architecture.¹ Additionally, the DORAs are not associated with physiological dependence, withdrawal, or rebound. Their efficacy profile is as good as or better than other FDA-approved agents for insomnia disorder.¹ An obstacle to their use is that they are not yet available as generic products, but access is facilitated by the manufacturers’ patient assistance programs. Additional resources elaborate on indirect comparisons among agents using number needed to treat and number needed to harm, metrics that are helpful when clinically appraising new agents.^2-5

Leslie Citrome, MD, MPH
Valhalla, New York

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style.

The second-generation antipsychotic quetiapine is commonly used to treat several psychiatric disorders, including bipolar disorder (BD) and insomnia. In this case report, we discuss a patient with a history of unipolar depression and initial signs of mania who experienced an exacerbation of manic symptoms following administration of low-dose quetiapine. This case underscores the need for careful monitoring of patients receiving quetiapine, especially at lower doses, and the potential limitations of its efficacy in controlling manic symptoms.

Depressed with racing thoughts

Mr. X, age 58, is an Army veteran who lives with his wife of 29 years and works as a contractor. He has a history of depression and a suicide attempt 10 years ago by self-inflicted gunshot wound to the head, which left him with a bullet lodged in his sinus cavity and residual dysarthria after tongue surgery. After the suicide attempt, Mr. X was medically hospitalized, but not psychiatrically hospitalized. Shortly after, he self-discontinued all psychotropic medications and follow-up.

Mr. X has no other medical history and takes no other medications or supplements. His family history includes a mother with schizoaffective disorder, 1 brother with BD, and another brother with developmental delay.

Mr. X remained euthymic until his brother died. Soon after, he began to experience low mood, heightened anxiety, racing thoughts, tearfulness, and mild insomnia. He was prescribed quetiapine 25 mg/d at bedtime and instructed to titrate up to 50 mg/d.

Ten days later, Mr. X was brought to the hospital by his wife, who reported that after starting quetiapine, her husband began to act erratically. He had disorganized and racing thoughts, loose associations, labile affect, hyperactivity/restlessness, and was not sleeping. In the morning before presenting to the hospital, Mr. X had gone to work, laid down on the floor, began mumbling to himself, and would not respond to coworkers. Upon evaluation, Mr. X was noted to have pressured speech, disorganized speech, delusions, anxiety, and hallucinations. A CT scan of his head was normal, and a complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, B12, folate, and hemoglobin A1c were within normal limits. Mr. X’s vitamin D level was low at 22 ng/mL, and a syphilis screen was negative.

Mr. X was admitted to the hospital for his safety. The treatment team discontinued quetiapine and started risperidone 3 mg twice a day for psychotic symptoms and mood stabilization. At the time of discharge 7 days later, Mr. X was no longer experiencing any hallucinations or delusions, his thought process was linear and goal-directed, his mood was stable, and his insomnia had improved. Based on the temporal relationship between the initiation of quetiapine and the onset of Mr. X’s manic symptoms, along with an absence of organic causes, the treatment team suspected Mr. X had experienced a worsening of manic symptoms induced by quetiapine. Before starting quetiapine, he had presented with an initial manic symptom of racing thoughts.

At his next outpatient appointment, Mr. X exhibited significant akathisia. The treatment team initiated propranolol 20 mg twice a day but Mr. X did not experience much improvement. Risperidone was reduced to 1 mg twice a day and Mr. X was started on clonazepam 0.5 mg twice a day. The akathisia resolved. The treatment team decided to discontinue all medications and observe Mr. X for any recurrence of symptoms. One year after his manic episode. Mr. X remained euthymic. He was able to resume full-time work and began psychotherapy to process the grief over the loss of his brother.

Quetiapine’s unique profile

This case sheds light on the potential limitations of quetiapine, especially at lower doses, for managing manic symptoms. Quetiapine exhibits antidepressant effects, even at doses as low as 50 mg/d.¹ At higher doses, quetiapine acts as an antagonist at serotonin (5-HT1A and 5-HT2A), dopamine (D1 and D2), histamine H1, and adrenergic receptors.² At doses <300 mg/d, there is an absence of dopamine receptor blockade and a higher affinity for 5-HT2A receptors, which could explain why higher doses are generally necessary for treating mania and psychotic symptoms.^3-5 High 5-HT2A antagonism may disinhibit the dopaminergic system and paradoxically increase dopaminergic activity, which could be the mechanism responsible for lack of control of manic symptoms with low doses of quetiapine.² Another possible explanation is that the metabolite of quetiapine, N-desalkylquetiapine, acts as a norepine­phrine reuptake blocker and partial 5-HT1Aantagonist, which acts as an antidepressant, and antidepressants are known to induce mania in vulnerable patients.⁴

The antimanic property of most antipsychotics (except possibly clozapine) is attributed to their D2 antagonistic potency. Because quetiapine is among the weaker D2 antagonists, its inability to prevent the progression of mania, especially at 50 mg/d, is not unexpected. Mr. X’s subsequent need for a stronger D2 antagonist—risperidone—at a significant dose further supports this observation. A common misconception is that quetiapine’s sedating effects make it effective for treating mania, but that is not the case. Clinicians should be cautious when prescribing quetiapine, especially at lower doses, to patients who exhibit signs of mania. Given the potential risk, clinicians should consider alternative treatments before resorting to low-dose quetiapine for insomnia. Regular monitoring for manic symptoms is crucial for all patients receiving quetiapine. If patients present with signs of mania or hypomania, a therapeutic dose range of 600 to 800 mg/d is recommended.⁶

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style.

The second-generation antipsychotic quetiapine is commonly used to treat several psychiatric disorders, including bipolar disorder (BD) and insomnia. In this case report, we discuss a patient with a history of unipolar depression and initial signs of mania who experienced an exacerbation of manic symptoms following administration of low-dose quetiapine. This case underscores the need for careful monitoring of patients receiving quetiapine, especially at lower doses, and the potential limitations of its efficacy in controlling manic symptoms.

Depressed with racing thoughts

Mr. X, age 58, is an Army veteran who lives with his wife of 29 years and works as a contractor. He has a history of depression and a suicide attempt 10 years ago by self-inflicted gunshot wound to the head, which left him with a bullet lodged in his sinus cavity and residual dysarthria after tongue surgery. After the suicide attempt, Mr. X was medically hospitalized, but not psychiatrically hospitalized. Shortly after, he self-discontinued all psychotropic medications and follow-up.

Mr. X has no other medical history and takes no other medications or supplements. His family history includes a mother with schizoaffective disorder, 1 brother with BD, and another brother with developmental delay.

Mr. X remained euthymic until his brother died. Soon after, he began to experience low mood, heightened anxiety, racing thoughts, tearfulness, and mild insomnia. He was prescribed quetiapine 25 mg/d at bedtime and instructed to titrate up to 50 mg/d.

Ten days later, Mr. X was brought to the hospital by his wife, who reported that after starting quetiapine, her husband began to act erratically. He had disorganized and racing thoughts, loose associations, labile affect, hyperactivity/restlessness, and was not sleeping. In the morning before presenting to the hospital, Mr. X had gone to work, laid down on the floor, began mumbling to himself, and would not respond to coworkers. Upon evaluation, Mr. X was noted to have pressured speech, disorganized speech, delusions, anxiety, and hallucinations. A CT scan of his head was normal, and a complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, B12, folate, and hemoglobin A1c were within normal limits. Mr. X’s vitamin D level was low at 22 ng/mL, and a syphilis screen was negative.

Mr. X was admitted to the hospital for his safety. The treatment team discontinued quetiapine and started risperidone 3 mg twice a day for psychotic symptoms and mood stabilization. At the time of discharge 7 days later, Mr. X was no longer experiencing any hallucinations or delusions, his thought process was linear and goal-directed, his mood was stable, and his insomnia had improved. Based on the temporal relationship between the initiation of quetiapine and the onset of Mr. X’s manic symptoms, along with an absence of organic causes, the treatment team suspected Mr. X had experienced a worsening of manic symptoms induced by quetiapine. Before starting quetiapine, he had presented with an initial manic symptom of racing thoughts.

At his next outpatient appointment, Mr. X exhibited significant akathisia. The treatment team initiated propranolol 20 mg twice a day but Mr. X did not experience much improvement. Risperidone was reduced to 1 mg twice a day and Mr. X was started on clonazepam 0.5 mg twice a day. The akathisia resolved. The treatment team decided to discontinue all medications and observe Mr. X for any recurrence of symptoms. One year after his manic episode. Mr. X remained euthymic. He was able to resume full-time work and began psychotherapy to process the grief over the loss of his brother.

Quetiapine’s unique profile

This case sheds light on the potential limitations of quetiapine, especially at lower doses, for managing manic symptoms. Quetiapine exhibits antidepressant effects, even at doses as low as 50 mg/d.¹ At higher doses, quetiapine acts as an antagonist at serotonin (5-HT1A and 5-HT2A), dopamine (D1 and D2), histamine H1, and adrenergic receptors.² At doses <300 mg/d, there is an absence of dopamine receptor blockade and a higher affinity for 5-HT2A receptors, which could explain why higher doses are generally necessary for treating mania and psychotic symptoms.^3-5 High 5-HT2A antagonism may disinhibit the dopaminergic system and paradoxically increase dopaminergic activity, which could be the mechanism responsible for lack of control of manic symptoms with low doses of quetiapine.² Another possible explanation is that the metabolite of quetiapine, N-desalkylquetiapine, acts as a norepine­phrine reuptake blocker and partial 5-HT1Aantagonist, which acts as an antidepressant, and antidepressants are known to induce mania in vulnerable patients.⁴

The antimanic property of most antipsychotics (except possibly clozapine) is attributed to their D2 antagonistic potency. Because quetiapine is among the weaker D2 antagonists, its inability to prevent the progression of mania, especially at 50 mg/d, is not unexpected. Mr. X’s subsequent need for a stronger D2 antagonist—risperidone—at a significant dose further supports this observation. A common misconception is that quetiapine’s sedating effects make it effective for treating mania, but that is not the case. Clinicians should be cautious when prescribing quetiapine, especially at lower doses, to patients who exhibit signs of mania. Given the potential risk, clinicians should consider alternative treatments before resorting to low-dose quetiapine for insomnia. Regular monitoring for manic symptoms is crucial for all patients receiving quetiapine. If patients present with signs of mania or hypomania, a therapeutic dose range of 600 to 800 mg/d is recommended.⁶

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry. All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style.

The second-generation antipsychotic quetiapine is commonly used to treat several psychiatric disorders, including bipolar disorder (BD) and insomnia. In this case report, we discuss a patient with a history of unipolar depression and initial signs of mania who experienced an exacerbation of manic symptoms following administration of low-dose quetiapine. This case underscores the need for careful monitoring of patients receiving quetiapine, especially at lower doses, and the potential limitations of its efficacy in controlling manic symptoms.

Depressed with racing thoughts

Mr. X, age 58, is an Army veteran who lives with his wife of 29 years and works as a contractor. He has a history of depression and a suicide attempt 10 years ago by self-inflicted gunshot wound to the head, which left him with a bullet lodged in his sinus cavity and residual dysarthria after tongue surgery. After the suicide attempt, Mr. X was medically hospitalized, but not psychiatrically hospitalized. Shortly after, he self-discontinued all psychotropic medications and follow-up.

Mr. X has no other medical history and takes no other medications or supplements. His family history includes a mother with schizoaffective disorder, 1 brother with BD, and another brother with developmental delay.

Mr. X remained euthymic until his brother died. Soon after, he began to experience low mood, heightened anxiety, racing thoughts, tearfulness, and mild insomnia. He was prescribed quetiapine 25 mg/d at bedtime and instructed to titrate up to 50 mg/d.

Ten days later, Mr. X was brought to the hospital by his wife, who reported that after starting quetiapine, her husband began to act erratically. He had disorganized and racing thoughts, loose associations, labile affect, hyperactivity/restlessness, and was not sleeping. In the morning before presenting to the hospital, Mr. X had gone to work, laid down on the floor, began mumbling to himself, and would not respond to coworkers. Upon evaluation, Mr. X was noted to have pressured speech, disorganized speech, delusions, anxiety, and hallucinations. A CT scan of his head was normal, and a complete blood count, comprehensive metabolic panel, thyroid-stimulating hormone, B12, folate, and hemoglobin A1c were within normal limits. Mr. X’s vitamin D level was low at 22 ng/mL, and a syphilis screen was negative.

Mr. X was admitted to the hospital for his safety. The treatment team discontinued quetiapine and started risperidone 3 mg twice a day for psychotic symptoms and mood stabilization. At the time of discharge 7 days later, Mr. X was no longer experiencing any hallucinations or delusions, his thought process was linear and goal-directed, his mood was stable, and his insomnia had improved. Based on the temporal relationship between the initiation of quetiapine and the onset of Mr. X’s manic symptoms, along with an absence of organic causes, the treatment team suspected Mr. X had experienced a worsening of manic symptoms induced by quetiapine. Before starting quetiapine, he had presented with an initial manic symptom of racing thoughts.

At his next outpatient appointment, Mr. X exhibited significant akathisia. The treatment team initiated propranolol 20 mg twice a day but Mr. X did not experience much improvement. Risperidone was reduced to 1 mg twice a day and Mr. X was started on clonazepam 0.5 mg twice a day. The akathisia resolved. The treatment team decided to discontinue all medications and observe Mr. X for any recurrence of symptoms. One year after his manic episode. Mr. X remained euthymic. He was able to resume full-time work and began psychotherapy to process the grief over the loss of his brother.

Quetiapine’s unique profile

This case sheds light on the potential limitations of quetiapine, especially at lower doses, for managing manic symptoms. Quetiapine exhibits antidepressant effects, even at doses as low as 50 mg/d.¹ At higher doses, quetiapine acts as an antagonist at serotonin (5-HT1A and 5-HT2A), dopamine (D1 and D2), histamine H1, and adrenergic receptors.² At doses <300 mg/d, there is an absence of dopamine receptor blockade and a higher affinity for 5-HT2A receptors, which could explain why higher doses are generally necessary for treating mania and psychotic symptoms.^3-5 High 5-HT2A antagonism may disinhibit the dopaminergic system and paradoxically increase dopaminergic activity, which could be the mechanism responsible for lack of control of manic symptoms with low doses of quetiapine.² Another possible explanation is that the metabolite of quetiapine, N-desalkylquetiapine, acts as a norepine­phrine reuptake blocker and partial 5-HT1Aantagonist, which acts as an antidepressant, and antidepressants are known to induce mania in vulnerable patients.⁴

The antimanic property of most antipsychotics (except possibly clozapine) is attributed to their D2 antagonistic potency. Because quetiapine is among the weaker D2 antagonists, its inability to prevent the progression of mania, especially at 50 mg/d, is not unexpected. Mr. X’s subsequent need for a stronger D2 antagonist—risperidone—at a significant dose further supports this observation. A common misconception is that quetiapine’s sedating effects make it effective for treating mania, but that is not the case. Clinicians should be cautious when prescribing quetiapine, especially at lower doses, to patients who exhibit signs of mania. Given the potential risk, clinicians should consider alternative treatments before resorting to low-dose quetiapine for insomnia. Regular monitoring for manic symptoms is crucial for all patients receiving quetiapine. If patients present with signs of mania or hypomania, a therapeutic dose range of 600 to 800 mg/d is recommended.⁶

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style.

Working closely with individuals with substance use disorders (SUDs), we’ve observed a worrisome trend of patients leaving the hospital against medical advice (AMA). This issue is not only prevalent in psychiatric settings, but also in emergency departments, medical and surgical floors, and even intensive care units.¹

Compared to individuals without such disorders, individuals with SUDs—particularly those with opioid use disorders—are up to 3 times more likely to leave the hospital AMA.^1,2 Leaving AMA can lead to multiple complications, including an increased risk of readmission, suboptimal treatment outcomes, and an increased use of health care resources.^1-3

It is critical to understand why patients elect to leave a hospital AMA. In a qualitative study, Simon et al¹ found that individuals with SUDs often leave AMA due to uncontrolled withdrawal symptoms and pain, perceived stigma and discrimination, and dissatisfaction with care. Predictors of patients leaving the hospital AMA include the severity of their drug dependence and previous negative treatment experiences.⁴ A systematic review found housing instability and a lack of social support influence an individual’s decision to leave AMA.⁵

Recommendations for managing patients who leave AMA

Enhancing your understanding of withdrawal symptoms may allow you to offer patients more effective symptom control, possibly with methadone or buprenorphine.² Injectable opioid agonist treatment may also help to retain a patient in care. In a case report, a 47-year-old man with a severe opioid use disorder who had left the hospital AMA due to uncontrolled opioid withdrawal was readmitted, treated with IV hydromorphone, and enrolled in ongoing community injectable opioid agonist treatment.⁶

Clinicians must address the stigma and discrimination patients with SUDs often face in health care institutions. Additional training for clinicians to improve their understanding of these disorders and foster a more compassionate and nonjudgmental approach to care may be beneficial.

Like most medicolegal conflicts, leaving AMA is often a clinical and interpersonal problem disguised as a legal one. When assessing these patients’ decision-making capacity, we often find they are angry and dissatisfied with the care they have (or have not) received. The most useful intervention may be to restore communication between the patient and their treatment team.

Even after a patient leaves AMA, the treatment team may experience countertransference issues, such as heightened emotional reactions or biases, that could compromise their clinical judgment. Addressing these dynamics may require team debriefings, supervision, or further training in managing transference and countertransference, particularly since patients who leave AMA may return for subsequent care.⁷

Integrated care models, which feature close collaboration between clinicians from different specialties, can help ensure that a patient’s diverse health needs are met and reduce the likelihood of them leaving AMA. Integrated care models may be particularly effective for patients with co-occurring conditions such as HIV and SUDs.⁸

Implementing these recommendations can be challenging. Barriers to addressing AMA departures span several domains, including patient-specific barriers (eg, stigma and discrimination), clinical barriers (eg, lack of resources and training for clinicians), institutional hurdles (eg, systemic inefficiencies), and broader social barriers (eg, housing instability and inadequate social support). Overcoming these barriers requires a multifaceted approach involving clinicians, policymakers, and the community that considers medical, psychological, and social factors.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style.

Working closely with individuals with substance use disorders (SUDs), we’ve observed a worrisome trend of patients leaving the hospital against medical advice (AMA). This issue is not only prevalent in psychiatric settings, but also in emergency departments, medical and surgical floors, and even intensive care units.¹

Compared to individuals without such disorders, individuals with SUDs—particularly those with opioid use disorders—are up to 3 times more likely to leave the hospital AMA.^1,2 Leaving AMA can lead to multiple complications, including an increased risk of readmission, suboptimal treatment outcomes, and an increased use of health care resources.^1-3

It is critical to understand why patients elect to leave a hospital AMA. In a qualitative study, Simon et al¹ found that individuals with SUDs often leave AMA due to uncontrolled withdrawal symptoms and pain, perceived stigma and discrimination, and dissatisfaction with care. Predictors of patients leaving the hospital AMA include the severity of their drug dependence and previous negative treatment experiences.⁴ A systematic review found housing instability and a lack of social support influence an individual’s decision to leave AMA.⁵

Recommendations for managing patients who leave AMA

Enhancing your understanding of withdrawal symptoms may allow you to offer patients more effective symptom control, possibly with methadone or buprenorphine.² Injectable opioid agonist treatment may also help to retain a patient in care. In a case report, a 47-year-old man with a severe opioid use disorder who had left the hospital AMA due to uncontrolled opioid withdrawal was readmitted, treated with IV hydromorphone, and enrolled in ongoing community injectable opioid agonist treatment.⁶

Clinicians must address the stigma and discrimination patients with SUDs often face in health care institutions. Additional training for clinicians to improve their understanding of these disorders and foster a more compassionate and nonjudgmental approach to care may be beneficial.

Like most medicolegal conflicts, leaving AMA is often a clinical and interpersonal problem disguised as a legal one. When assessing these patients’ decision-making capacity, we often find they are angry and dissatisfied with the care they have (or have not) received. The most useful intervention may be to restore communication between the patient and their treatment team.

Even after a patient leaves AMA, the treatment team may experience countertransference issues, such as heightened emotional reactions or biases, that could compromise their clinical judgment. Addressing these dynamics may require team debriefings, supervision, or further training in managing transference and countertransference, particularly since patients who leave AMA may return for subsequent care.⁷

Integrated care models, which feature close collaboration between clinicians from different specialties, can help ensure that a patient’s diverse health needs are met and reduce the likelihood of them leaving AMA. Integrated care models may be particularly effective for patients with co-occurring conditions such as HIV and SUDs.⁸

Implementing these recommendations can be challenging. Barriers to addressing AMA departures span several domains, including patient-specific barriers (eg, stigma and discrimination), clinical barriers (eg, lack of resources and training for clinicians), institutional hurdles (eg, systemic inefficiencies), and broader social barriers (eg, housing instability and inadequate social support). Overcoming these barriers requires a multifaceted approach involving clinicians, policymakers, and the community that considers medical, psychological, and social factors.

Editor’s note: Readers’ Forum is a department for correspondence from readers that is not in response to articles published in Current Psychiatry . All submissions to Readers’ Forum undergo peer review and are subject to editing for length and style.

Working closely with individuals with substance use disorders (SUDs), we’ve observed a worrisome trend of patients leaving the hospital against medical advice (AMA). This issue is not only prevalent in psychiatric settings, but also in emergency departments, medical and surgical floors, and even intensive care units.¹

Compared to individuals without such disorders, individuals with SUDs—particularly those with opioid use disorders—are up to 3 times more likely to leave the hospital AMA.^1,2 Leaving AMA can lead to multiple complications, including an increased risk of readmission, suboptimal treatment outcomes, and an increased use of health care resources.^1-3

It is critical to understand why patients elect to leave a hospital AMA. In a qualitative study, Simon et al¹ found that individuals with SUDs often leave AMA due to uncontrolled withdrawal symptoms and pain, perceived stigma and discrimination, and dissatisfaction with care. Predictors of patients leaving the hospital AMA include the severity of their drug dependence and previous negative treatment experiences.⁴ A systematic review found housing instability and a lack of social support influence an individual’s decision to leave AMA.⁵

Recommendations for managing patients who leave AMA

Enhancing your understanding of withdrawal symptoms may allow you to offer patients more effective symptom control, possibly with methadone or buprenorphine.² Injectable opioid agonist treatment may also help to retain a patient in care. In a case report, a 47-year-old man with a severe opioid use disorder who had left the hospital AMA due to uncontrolled opioid withdrawal was readmitted, treated with IV hydromorphone, and enrolled in ongoing community injectable opioid agonist treatment.⁶

Clinicians must address the stigma and discrimination patients with SUDs often face in health care institutions. Additional training for clinicians to improve their understanding of these disorders and foster a more compassionate and nonjudgmental approach to care may be beneficial.

Like most medicolegal conflicts, leaving AMA is often a clinical and interpersonal problem disguised as a legal one. When assessing these patients’ decision-making capacity, we often find they are angry and dissatisfied with the care they have (or have not) received. The most useful intervention may be to restore communication between the patient and their treatment team.

Even after a patient leaves AMA, the treatment team may experience countertransference issues, such as heightened emotional reactions or biases, that could compromise their clinical judgment. Addressing these dynamics may require team debriefings, supervision, or further training in managing transference and countertransference, particularly since patients who leave AMA may return for subsequent care.⁷

Integrated care models, which feature close collaboration between clinicians from different specialties, can help ensure that a patient’s diverse health needs are met and reduce the likelihood of them leaving AMA. Integrated care models may be particularly effective for patients with co-occurring conditions such as HIV and SUDs.⁸

Implementing these recommendations can be challenging. Barriers to addressing AMA departures span several domains, including patient-specific barriers (eg, stigma and discrimination), clinical barriers (eg, lack of resources and training for clinicians), institutional hurdles (eg, systemic inefficiencies), and broader social barriers (eg, housing instability and inadequate social support). Overcoming these barriers requires a multifaceted approach involving clinicians, policymakers, and the community that considers medical, psychological, and social factors.