New Drug Combination Shows Promise for Schizophrenia in Phase 2 Trials

A new drug combination appears to significantly reduce symptoms of schizophrenia compared with placebo, according to the results of a phase 2 trial published this week in the New England Journal of Medicine.

The drugs are xanomeline, which has shown promise for Alzheimer’s disease, and trospium chloride, which is approved for overactive bladder and has been shown to reduce some of the gastrointestinal side effects of xanomeline.

Steven K. Brennan, M.D., chief medical officer of Karuna Pharmaceuticals, and colleagues randomly assigned 90 adults aged 18 to 60 with schizophrenia to receive twice-daily xanomeline-trospium and 92 patients to receive placebo for five weeks. For inclusion in the trial, patients were required to have a baseline Positive and Negative Syndrome Scale (PANSS) total score of 80 or more, with a score of at least 5 on one positive symptom item or at least 4 on two positive symptom items. (Positive symptoms refer to delusions, hallucinations, and other acute symptoms of psychosis; negative symptoms refer to symptoms such as social and emotional withdrawal.)

The study was funded and sponsored by Karuna Pharmaceuticals, which is investigating the drug combination.

The primary end point was the change from baseline to week 5 in the total score on the PANSS. Secondary endpoints included specific scores on the PANSS and scores on the Clinical Global Impression–Severity (CGI-S) scale.

The change in the PANSS total score from baseline to week 5 was significantly better in the xanomeline-trospium group: Scores dropped 17.4 points in the group receiving the drug combination versus 5.9 points in the placebo group. The results for the secondary end points, including PANSS positive and negative symptom subscores as well as CGI-S scores, were also significantly better in the xanomeline-trospium group than in the placebo group.

The most common adverse events associated with the drug combination were constipation, nausea, dry mouth, dyspepsia, and vomiting. None of these adverse events resulted in the participants’ discontinuation of xanomeline-trospium, and all of the adverse events were rated by site investigators as mild or moderate in severity.

William Carpenter, M.D., editor of Schizophrenia Bulletin and chair of the DSM-5 Task Force on Psychotic Disorders, told Psychiatric News that the results are potentially important because xanomeline-trospium targets different brain receptors than most other schizophrenia medications. Xanomeline acts on the cholinergic system, which regulates involuntary actions of the body such as muscle contraction and the dilation of blood vessels, but also influences memory and attention.

Carpenter said future research needs to determine whether more adverse events and more serious side effects are seen in larger samples over a longer period and whether the pattern of beneficial effects seen in the trial will also be seen when the drug combination is compared with other antipsychotics. Researchers also need to better pinpoint how xanomeline works in the brain to treat schizophrenia.

“What is exciting at this point is that it is not another ‘me-too’ drug,” Carpenter said.

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Only Days Left to Register for Annual Meeting at Lowest Fees

Register today through March 1 for the best rates available for APA’s online 2021 Annual Meeting. The meeting, which will be held Saturday to Monday, May 1 to 3, will include 135 scientific sessions led by experts with live Q&As, poster sessions, Virtual Exhibit Gallery, Product Theaters, opportunities for member engagement, and more. Pulitzer Prize–winner Isabel Wilkerson, author of The New York Times bestsellers The Warmth of Other Suns and Caste: The Origins of Our Discontents, will be the keynote speaker at the 2021 Annual Meeting Opening Session on Saturday, May 1. National Institute of Allergy and Infectious Diseases Director Anthony Fauci, M.D., will deliver the William C. Menninger Memorial Convocation Lecture on Sunday, May 2.

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Youth With ADHD May Have Increased Risk for Psychotic Disorders

Children and adolescents with attention-deficit/hyperactivity disorder (ADHD) may be at increased risk for subsequent psychotic disorders, according to a report published Wednesday in JAMA Psychiatry.

Given that psychotic disorders have a major effect on functioning, “early detection and appropriate management are essential to improve the prognosis of children diagnosed with ADHD,” wrote Mikaïl Nourredine, M.D., M.Sc., of the Centre Hospitalier Le Vinatier in Bron, France, and colleagues. The findings suggest that patients with ADHD need follow-up even after 18 years of age, the authors noted.

Nourredine and colleagues searched the MEDLINE, Scopus, PsycInfo, and Web of Science databases for original, peer-reviewed studies that included children and adolescents younger than 18 with ADHD, as well as a control group with no ADHD. For the purposes of this meta-analysis, a study had to include data on diagnoses of psychotic disorders (including schizophrenia, schizophreniform disorder, schizotypal personality disorder, schizoaffective disorder, delusional disorder, or brief psychotic disorder) that occurred after the ADHD diagnosis.

The authors identified 12 studies in which a diagnosis of ADHD was present and psychotic disorder was the outcome of interest, representing 124,095 children/adolescents with ADHD and 1.7 million controls. The prevalence of psychotic disorders among the ADHD population ranged from 0.7% to 12.5%, while the prevalence among the control population ranged from 0% to 4.2%. Altogether, the studies suggested that children and adolescents with ADHD were nearly five times as likely to be subsequently diagnosed with a psychotic disorder as those without ADHD.

“Many potential mechanisms could underlie the association between ADHD and subsequent psychosis,” the authors wrote, including shared genetic susceptibility, social or environmental factors, or prenatal factors such as diabetes during pregnancy or neonatal complications. The authors also noted the possible association between psychostimulant treatment and later risk of psychotic disorders, as well as the possibility that children and adolescents with early signs of a psychotic disorder may be misdiagnosed with ADHD.

More research is needed, the authors concluded, particularly studies with long follow-up periods to determine when psychotic disorders are most likely to develop, and studies that consider what may be linking psychotic disorders and ADHD.

For related information, see the Psychiatric News article “Study Finds Higher Risk of Psychosis With Amphetamines for ADHD.”

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Mental Illness, Substance Use Disorders Found Common Among Individuals Who Die Suddenly

More than half of individuals living in a large metropolitan county in North Carolina who died suddenly outside the hospital had at least one diagnosed mental illness or substance use disorder in the previous five years, and more than one-third had two or more, according to a report in Psychiatric Services in Advance.

Among those with mental and/or substance use disorders, cardiovascular, respiratory, and metabolic conditions were common, wrote Jessica Ford, Ph.D., of the Department of Veterans Affairs in Greenville, N.D., and colleagues.

Ford and colleagues screened for sudden deaths attended by emergency medical services in Wake County, N.C., from March 1, 2013, to February 28, 2015. Deaths were considered sudden if the circumstances before death suggested an “abrupt pulseless condition” in the absence of any terminal disease (such as cancer or liver disease), drug overdoses, death from trauma, or other nonnatural cause.

Of 1,592 deaths that the researchers identified, there were 399 cases of sudden death. Of these, 270 had available medical records. The average age at death was 53. Chronic comorbid conditions, including hypertension, diabetes, coronary disease, and respiratory disease, were common among those with and without mental illness who died suddenly.

More than half (59%) of the individuals who died suddenly had at least one documented mental disorder or substance use disorder in their medical record, and 39% had more than one mental disorder or substance use disorder. Yet only 41% of the individuals had a documented referral to a mental health professional, and 33% had a documented visit with a mental health professional.

Although referrals to and treatment by mental health professionals were uncommon, almost one-half (46%) of individuals who died suddenly had prescriptions for psychotropic medications. Among those with mental illness, more than 75% of individuals had received prescriptions for psychotropic medications.

“The observed combination of mental disorders and medical conditions in sudden-death victims implies the need for collaborative care involving mental health and clinical professionals to help prevent sudden death among working-age adults,” Ford and colleagues concluded.

For related information, see the Psychiatric News article “Patients With Serious Mental Illness Need Better Primary Care Integration, Health Advocacy.”

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Connecting With Older Adults by Phone May Reduce Loneliness, Depression, Anxiety During Pandemic

Older adults who received regular phone calls from a young adult a few months into the COVID-19 pandemic experienced greater improvements in loneliness, depression, and anxiety after four weeks compared with older adults who did not receive these calls. The findings were published today in JAMA Psychiatry.

“The use of lay callers, deliberate but brief approach on training, and the use of ubiquitous telephones made the approach easily deployable and scalable,” wrote Maninder K. Kahlon, Ph.D., of the University of Texas at Austin and colleagues.

The study included 240 participants aged 27 to 101 who were homebound, had at least one chronic condition, and were receiving services for food through Meals on Wheels Central Texas. More than 60% of the participants were at least 65 years, 56% were living alone, 79% were women, 39% identified as Black or African American, and 22% identified as Hispanic or Latino. The participants were randomly assigned to receive phone calls from the same volunteer for a four-week period (intervention group) or no calls until after the four-week follow-up (control group).

The volunteers, aged 17 to 23, attended one hour of training by videoconference on how to engage participants in conversation on topics of their choice and were asked to watch less than one hour of videotaped instructions on the program. For the first five days of the program, the volunteers called all participants every day at the time they requested. After the first week, the participants also chose the frequency of calls, with a minimum of two and maximum of five a week. According to the researchers, most participants chose to be called five times a week.

Kahlon and colleagues evaluated the participants on measures of loneliness (including the UCLA Loneliness Scale), depression (eight-item Patient Health Questionnaire for Depression, or PHQ-8), anxiety (Generalized Anxiety Disorder scale, or GAD-7), and more at the beginning of the study as well as four weeks later.

Participants in the intervention group improved from a mean of 6.5 to 5.2 on the UCLA Loneliness Scale and in the control group, from 6.5 to 6.3. Depression decreased from a mean of 6.3 to 4.8 on the PHQ-8, and in the control arm, increased from a mean of 6.2 to 6.3. For participants in the intervention group, anxiety decreased from a mean of 5.9 to 4.1 on the GAD-7, and in the control arm, increased from a mean of 5.8 to 6.0.

Kahlon and colleagues noted that additional studies are needed to assess whether the participants continued to experience benefits after the program ended and/or if a longer program would lead to greater improvements. “Additionally, future research might explore the effect of this program when participants are screened for mental health conditions or stratified based on age,” they added. “It may be particularly interesting to assess whether the program can play a protective role for those at risk of clinical anxiety or depression.”

For related information, see the Psychiatric News article “COVID-19 Guidance to Help Our Patients and Ourselves.”

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Education, Outreach, and Firearm Restrictions Offer Effective and Scalable Suicide Prevention

Educating primary care physicians on depression management, increasing awareness about mental illness and suicide among high school students, and reaching out to previously hospitalized psychiatric patients after discharge represent several of the most effective and scalable approaches to suicide prevention, according to a review in AJP in Advance.

J. John Mann, M.D., and colleagues at Columbia University reviewed 97 clinical trials and 30 population-level studies published between 2005 and 2019 that explored interventions aimed at reducing suicides or suicidal behavior such as self-harm. “We focused on suicidal behavior as an outcome and not suicidal ideation, because there is a closer relationship between nonfatal suicide attempts and suicide deaths than there is between suicidal ideation and suicide deaths,” they wrote.

The authors focused on a variety of suicide prevention strategies, including education campaigns, screening tools, medication, psychotherapy, follow-up contact with people who had attempted suicide, and restricting access to firearms. The authors evaluated each strategy on the following two criteria: evidence that the method prevented suicide attempts and the reliability with which it could be scaled up to city, county, state, and/or national levels.

Most studies found the interventions examined were superior to control at preventing suicide attempts. Among interventions that could be easily scaled up, four showed strong evidence of effect:

• Educating youth about suicidal behaviors (100% of studies included in this review found this approach to be an effective intervention)
• Firearm restrictions (98% of studies)
• General practitioner education (83% of studies)
• Outreach to recently discharged patients (70% of studies)

“Doctors in primary care and other nonpsychiatric care settings see 45% of future suicide decedents in the 30 days prior to suicide, and 77% within 12 months of suicide, about double the rate of mental health professionals,” Mann and colleagues wrote. “Therefore, educating nonpsychiatrist physicians may prevent more suicides than further training for psychiatrists.”

They added, “Further suicide rate reduction requires evaluating newer approaches, such as electronic health record–derived algorithms, internet-based screening methods, ketamine’s potential benefit for preventing attempts, and passive monitoring of acute suicide risk change.”

To read more on this topic, see the Psychiatric News article “Innovative Suicide Prevention Program Using Psychotherapy Shows Early Success.”

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Gastrointestinal Symptoms Common in Major Depressive Disorder, Study Shows

Gastrointestinal symptoms are common in people who have major depressive disorder (MDD), a study in the Journal of Affective Disorders has found.

Yiru Fang, M.D., Ph.D., of Shanghai Jiao Tong University School of Medicine in China and colleagues analyzed data from 3,256 MDD patients aged 18 years and older from the National Survey on Symptomatology of Depression. As part of the survey, patients were asked how often over the last two weeks they experienced depressive symptoms and gastrointestinal symptoms. Fang and colleagues compared the occurrence of gastrointestinal symptoms with the occurrence of depressive episodes in these patients.

The researchers found that more than 70% of patients experienced gastrointestinal symptoms during depressive episodes. Thirty-eight percent had a frequency of gastrointestinal symptoms “several days,” 23% had a frequency of symptoms “more than half of all days,” and nearly 10% had a frequency of symptoms “nearly every day” during their depressive episodes.

The researchers also found that a higher frequency of gastrointestinal symptoms was associated with an increased risk of psychological symptoms such as suicidal ideation, suicide attempts, anxious mood, depressed mood, insomnia, and feeling like a failure.

“[T]hese results suggest that [gastrointestinal] symptoms might be consistently associated with the onset and clinical severity of depression, which could be used as a useful auxiliary indicator in the clinical management of [major depressive disorder],” they wrote.

For related information, see Chapter 19 on Gastrointestinal Disorders in The American Psychiatric Association Publishing Textbook of Psychosomatic Medicine and Consultation-Liaison Psychiatry, Third Edition.

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APA Calls on Public Health Officials to Ensure Vaccine Access to People With SMI, SUDs

State public health officials should ensure that people with serious mental illness (SMI) and/or substance use disorders (SUDs) are prioritized along with individuals with other high-risk medical conditions in receiving the COVID-19 vaccine, APA urged today in a news release.

People with SMIs and/or SUDs often have comorbid conditions, which can increase the risk of severe complications from COVID-19, stated an APA guidance document titled “The Role of the Psychiatrist in the Equitable Distribution of the COVID-19 Vaccine.” Additionally, these individuals may live in overcrowded conditions, increasing their risk of infection.

“Historically these populations have had limited access to preventative care and vaccinations, foreshadowing inequitable distribution of COVID-19 vaccines,” continued the guidance document. The document was created by APA’s Committee on Psychiatric Dimensions of Disaster, Committee on Integrated Care, Council on Communications, Council on Minority Mental Health and Health Disparities, and Council on Healthcare Systems and Financing.

In the news release, APA urged public health authorities to include people with mental illness in the equivalent of the Centers for Disease Control and Prevention’s Phase 1c, which refers to people with high-risk medical conditions, as well as those who are aged 65 to 74 and essential workers.

“It’s all too common that people with serious mental illness and/or substance use disorders don’t have access to health care; are of low socioeconomic status; or, based on history, harbor mistrust toward the medical establishment,” said APA President Jeffrey Geller, M.D., M.P.H., in the news release. “States should treat psychiatric illnesses like other high-risk conditions and prioritize this population’s access to the vaccine.”

According to the guidance document, while the CDC provides guidance on which conditions are considered high risk, every state has its own plan for prioritizing eligible populations and disseminating vaccines. Many patients with mental illness “fall into high priority groups due to medical comorbidity or social risk factors such as homelessness,” the guidance document stated. “Psychiatrists should help patients to identify locations where they can receive vaccines; these may include community mental health centers, inpatient or residential facilities, primary care clinics, public health clinics, or local pharmacies.”

“APA and its member psychiatrists have worked throughout this pandemic, many on the frontlines,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A., in the news release. “We will continue to promote policies that keep our patients safe and particularly in getting vaccines that require two doses over time.”

For related information, see the Psychiatric News articles “Vaccination Conversations: Influencing Critical Health Behaviors in COVID-19” and “Hope and the Hesitancy for the Vaccine: How Can We Help Our Minority Patients?”

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History of Mental Illness Associated With Earlier Signs of Aging

Individuals with a history mental illness are more likely to show signs of aging by age 45—including cognitive decline and loss of motor coordination—than are people without such a history, according to a report published today in JAMA Psychiatry.

This remained true even after controlling for a host of other factors that might explain early aging, such as poor health in childhood; being overweight; smoking; or a history of cancer, diabetes, or heart attack.

“In this cohort study, a history of psychopathology was associated with accelerated aging at midlife, years before the typical onset of age-related diseases,” wrote lead author Jasmin Wertz, Ph.D., of Duke University and colleagues.

Wertz and colleagues analyzed data from the Dunedin Multidisciplinary Health and Development Study, a study of 1,037 individuals (93% White) born between April 1, 1972, and March 31, 1973, in Dunedin, New Zealand. Participants were followed up to age 45. Of the original cohort, 997 were still alive at age 45 years, and 938 participated in the assessment at age 45 years.

Interviews were conducted by health professionals using the Diagnostic Interview Schedule at ages 18, 21, 26, 32, 38, and 45 years to assess for symptoms of mental disorders, including attention-deficit/hyperactivity disorder, substance use disorder, generalized anxiety disorder, depression, obsessive-compulsive disorder, and schizophrenia. Based on these assessments, the researchers developed an overall score for psychopathology.

They also measured the pace of aging among participants using laboratory biomarkers of cardiovascular, metabolic, pulmonary, kidney, immune, and dental systems. Additionally, the researchers tested hearing and vision, balance, motor functioning, and cognitive functioning. The participants were also asked questions about vision, balance, and hearing difficulties as well as how old they felt at age 45 (for example, “Many people feel younger or older than they really are. What age do you feel most of the time?”).

At age 45, participants with higher scores of psychopathology were aging faster across all signs of aging, including more problems with hearing, vision, balance, and gait speed. They also experienced more cognitive difficulties at age 45.

“[I]ndividuals with mental disorders are a high-priority group to monitor for signs of accelerated aging,” the researchers wrote. “Such monitoring will require greater integration of mental and physical health services to reduce health inequalities and lengthen healthy lives.”

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Switching to Aripiprazole or Ziprasidone May Reduce Weight Gain in Patients Taking Antipsychotics

It is well established that a common side effect of second-generation antipsychotics is weight gain, which can influence a patient’s attitude toward the treatment and reduce adherence, worsening symptoms and quality of life. A meta-analysis in Schizophrenia Bulletin suggests that switching patients with serious mental illness who are taking one or more antipsychotics to aripiprazole or ziprasidone may lead to weight loss and other cardiometabolic improvements.

Dan Siskind, M.B.B.S., M.P.H., Ph.D., of Metro South Addiction and Mental Health Service in Brisbane, Australia, and colleagues combed through the scientific literature for studies of people with serious mental illness that investigated a switch from any single or combination of antipsychotics to a different antipsychotic monotherapy for ≥4 weeks. Only studies that reported an endpoint and/or mean change for cardiometabolic parameters, including weight, body mass index (BMI), waist circumference, cholesterol, and blood glucose levels, were included in the meta-analysis.

In total, the authors analyzed 61 articles, which described studies of 8,554 people (mean age, 39 years)—the majority of whom had been diagnosed with schizophrenia or schizoaffective disorder, bipolar disorder, or comorbid mental disorders. Most of the studies provided observational data on the outcomes of interest before and after a switch to a specific antipsychotic. Ten studies, however, had data on switching to a new antipsychotic versus staying on the previous agent. The mean duration of the studies included in the meta-analysis was 26 weeks.

Siskind and colleagues noted that meta-analyses of switch-versus-stay were possible only for aripiprazole and olanzapine. In contrast, before-to-after meta-analyses were conducted for the following antipsychotics: aripiprazole, amisulpride, clozapine, lurasidone, olanzapine, paliperidone/risperidone, quetiapine, and ziprasidone.

In the switch-versus-stay meta-analyses, only aripiprazole significantly reduced weight (−5.52 kg), while olanzapine significantly increased weight (2.46 kg). Switching to aripiprazole also significantly improved fasting glucose (−3.99 mg/dl) and triglycerides (−31.03 mg/dl). Dropout and psychosis ratings did not differ between switch and stay groups for aripiprazole and olanzapine.

In before-to-after switch meta-analyses, aripiprazole (−1.96 kg) and ziprasidone (−2.22 kg) were associated with weight loss, whereas olanzapine (2.71 kg) and clozapine (2.80 kg) were associated with weight gain. No significant weight or other cardiometabolic changes were observed when switching to amisulpride, paliperidone/risperidone, quetiapine, or lurasidone.

“Although switching to a different antipsychotic, notably aripiprazole and ziprasidone, may lead to weight loss, these benefits must be weighed against any potential risks of adverse drug reactions or deterioration in psychotic symptoms,” Siskind and colleagues cautioned. “[S]witching antipsychotics in psychiatrically stable patients may risk relapse and detrimental consequences for at least some patients.” They added that antipsychotic switching is only one of several interventions that might help reduce weight and improve cardiometabolic parameters in patients with serious mental illness. Other interventions include lifestyle counseling and exercise.

For related information, see the American Journal of Psychiatry article “How Much of an Advance Is the Addition of Samidorphan to Olanzapine?”

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APA Announces Results of 2021 Election

At its meeting on February 11th, APA’s Committee of Tellers approved the following results for the 2021 APA National Election. Please note that these results are considered public but not official until approved by the Board of Trustees at its meeting on March 12 and 13.

President-Elect
Rebecca W. Brendel, M.D., J.D.

Secretary
Sandra M. DeJong, M.D., M.Sc.

Early Career Psychiatrist Trustee
Elie G. Aoun, M.D., M.R.O.

Minority/Underrepresented Representative Trustee
Felix Torres, M.D., M.B.A.

Area 1 Trustee
Eric M. Plakun, M.D.

Area 4 Trustee
Cheryl D. Wills, M.D.

Area 7 Trustee
Mary Hasbah Roessel, M.D.

Resident-Fellow Member Trustee-Elect
Urooj Yazdani, M.D.

“Congratulations to Dr. Brendel and the other candidates on their election,” said APA President Jeffrey Geller, M.D., M.P.H. “Dr. Brendel has been involved with APA in so many different capacities over the years, and I look forward to working with her and all the newly elected APA leaders in the coming years to advance psychiatry and APA.”

Brendel’s term as APA president-elect will begin at the conclusion of APA’s virtual Annual Meeting in May, when current President-elect Vivian Pender, M.D., begins her one-year term as president.

“Dr. Brendel’s dedication and passion for psychiatry will greatly benefit APA during her tenure,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A. “APA members and the profession of psychiatry will be well served by her leadership.”

Complete results of the election will be reported in the March issue of Psychiatric News.

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For Patients With Schizophrenia, Five Variables Associated With Everyday Functioning

Assessments targeting neurocognition, social cognition, positive symptoms, motivation, and access to resources may help to predict everyday functioning in patients with schizophrenia, suggests a study published in JAMA Psychiatry.

“Schizophrenia is no longer conceptualized as a progressive deteriorating illness,” wrote Armida Mucci, M.D., of the University of Campania Luigi Vanvitelli in Naples, Italy, and colleagues. “However, although a clinical stability with persistent symptomatic remission is now considered a realistic outcome for affected people, the level of social, vocational, and everyday life functioning attained by the majority of individuals with schizophrenia is still poor.”

Mucci and colleagues analyzed data from 618 clinically stable individuals with schizophrenia living in the community. They were recruited from 24 Italian university psychiatric clinics or mental health departments from March 2016 to December 2017. At both baseline and follow-up after four years, the participants were assessed for numerous illness-related factors (including negative symptoms, depression, neurocognition, social cognition, and psychiatric comorbidities), personal resources (including resilience and engagement with mental health services), context-related factors (including internalized stigma and available incentives such as access to family support or a disability pension), and real-life functioning. Each patient’s key caregiver was invited to join in the interview. The mean age at follow-up was 45 years.

Five baseline variables were directly associated with real-life functioning at follow-up, including the following:

• Higher neurocognitive abilities were associated with a positive change in everyday life skills, work skills, and interpersonal functioning.
• Higher baseline social cognition was associated with positive change in interpersonal functioning and work skills.
• Fewer problems with motivation were associated with positive change in interpersonal relationships.
• Positive symptoms were negatively but weakly associated with work skills.
• The greater the number of incentives available to participants was positively associated with everyday life skills.

Neurocognition, the authors noted, was by far the variable with the strongest association with functioning in everyday life at follow-up, “which is crucial for independent living and for reducing the burden on families and society.”

“People with schizophrenia, even in advanced stages of the disorder, require a detailed assessment of their psychopathological and functional characteristics,” Mucci and colleagues wrote. “If data relevant to the individual characteristics in all mentioned domains are available, then personalized and integrated management programs can be implemented, their impact can be constantly monitored, and changes to ongoing programs can be introduced to meet new or still unmet needs.”

For related information, see the Psychiatric News article “Milestones in the History of Schizophrenia. A Comprehensive Chronology of Schizophrenia Research: What Do We Know and When Did We Know It.”

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Psychiatric Diagnoses Prior to Colorectal Cancer Surgery Associated With Worse Outcomes

Patients with psychiatric diagnoses who undergo colorectal cancer surgery may be at increased risk for postoperative complications and readmission within 90 days, but psychiatric treatment prior to surgery may help to reduce these risks, according to a study published Tuesday in Psychiatric Services.

“Mental health problems among surgical patients remain understudied, but data suggest that they may represent an underappreciated risk factor for poor preoperative outcomes and that they may be responsive to preoperative treatment,” wrote Chelsea G. Ratcliff, Ph.D., and Nader N. Massarweh, M.D., of Baylor College of Medicine in Houston and colleagues.

The researchers used data from the Veterans Health Administration’s Patient Care Services database, which captures health care encounters, and the U.S. Department of Veterans Affairs Surgical Quality Improvement Program, which measures and provides feedback on the quality of surgical care before and after surgery. From 2000 to 2014, 58,961 patients underwent colon or rectal surgery for colon or rectal cancer.

In total, 15.3% of the patients had a psychiatric diagnosis before surgery, the most common of which were substance use disorders, depression, posttraumatic stress disorder, and anxiety. Of those patients, 49% received no psychiatric treatment in the 30 days before surgery.

Findings include the following:

• Patients with psychiatric diagnoses who received no psychiatric treatment or only medication treatment had a 7% to 17% increased risk for postoperative complications compared with patients with no psychiatric diagnosis.
• Patients who were treated with medication only had a 4% increase in length of stay relative to patients with no psychiatric diagnosis. Length of stay did not differ between patients with psychiatric diagnoses who received psychotherapy only, both medication and psychotherapy, or no treatment and patients with no psychiatric diagnosis.
• Patients with a psychiatric diagnosis who received only psychotherapy treatment or both medication and psychotherapy did not significantly differ from patients with no psychiatric diagnosis in terms of complications.
• Substance use disorders were associated with an increased risk for postoperative complications; depression and psychotic disorders were associated with longer length of stay; and depressive, posttraumatic stress, and substance use disorders were associated with an increased risk for 90-day readmission.

“[T]he findings of this study suggest that the risk associated with a psychiatric diagnosis may partially depend on preoperative mental health treatment,” the authors wrote. “Careful screening for mental health concerns during preoperative appointments may help identify patients at risk for postoperative complications and readmissions.”

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Impact of ‘Minority Tax,’ Need for Diversity in Academic Psychiatry Discussed at APA Town Hall

Structural racism has led to a lack of diversity in the psychiatric academic workforce and needs to be addressed, said panelists last night in the fourth online town hall meeting hosted by APA’s Presidential Task Force to Address Structural Racism Throughout Psychiatry. The panelists also described the impact of the “minority tax,” defined as extra, financially uncompensated duties and responsibilities that minorities are asked to perform to increase diversity at their institutions, such as serving on a search committee that would otherwise be all White.

“[The minority tax] is a major source of inequity in academic medicine. … It is one of the major factors in delaying promotion for us in academia,” said Sheritta Strong, M.D., director of inclusion and an assistant professor of psychiatry at the University of Nebraska Medical Center. She added that when there is a lack of mentorship by minority psychiatrists, residents and psychiatrists who are members of ethnic and racial minorities may fall prey to accepting roles that may be “tokenized” and incorporate activities that are not recognized for promotion.

Nhi-Ha Trinh, M.D., M.P.H., director of the Psychiatry Center for Diversity in the Department of Psychiatry at Massachusetts General Hospital, emphasized the necessity of tailoring mentorship.

“[It] is very important [to] focus on the individual trainee and junior faculty member regarding their academic pursuits, the time they can devote to those pursuits, and also what their individual career path might be, which may be different from what the mentor or sponsor might envision,” Trinh said.

Crystal Clark, M.D., M.Sc., an associate professor of psychiatry and behavioral sciences and obstetrics and gynecology at the Northwestern University Feinberg School of Medicine, said that the pipeline for bringing more trainees from minority and underrepresented populations into psychiatry as a career does not begin in medical school. “We have to get down to primary education, really. To achieve that [comes down to] finding a way to be more present in the community, finding a way to reach out to young students in high school and even elementary school … so that [mental illness] is not seen as a horror that can happen to you but is seen as just one of the many health conditions that someone might suffer from.”

Michael Mensah, M.D., M.P.H., APA’s resident-fellow member trustee and co-chief resident in the University of California, Los Angeles Department of Psychiatry, emphasized the need for residents and faculty in minority and underrepresented populations to ensure their own well-being as a counterbalance to the minority tax.

“You’re a valuable member of your community. You need to preserve yourself and make sure you are feeling healthy enough to take care of your patients and yourself,” Mensah said. “Don’t overwhelm yourself with this responsibility. If you burn out as a result of anti-racist work, that is a loss to your community that really can’t be replaced.”

The panelists were joined by Gabriel Felix, M.D., an APA/APAF Public Psychiatry Fellow and adult psychiatry resident at Cambridge Health Alliance/Harvard Medical School; Anthony Kulukulualani, M.D., an APA/APAF Jeanne Spurlock Congressional Fellow and a psychiatry resident at the Brody School of Medicine at East Carolina University; and Nicole Pacheco, M.D., an APA/APAF SAMHSA Minority Fellow, chair of the Minority Fellowship Program, and a psychiatry resident at Columbia-New York State Psychiatric Institute. A question-and-answer session after the panel discussion was moderated by task force member and APA Trustee-at-Large Michele Reid, M.D., a clinical assistant professor in the Department of Psychiatry and Behavioral Neurosciences at Wayne State University in Detroit and the chief medical officer of CNS Healthcare. An article in the March issue of Psychiatric News will provide more details on this productive discussion.

The next town hall will take place on May 1 from 4 p.m. to 5:30 p.m. ET as part of APA’s virtual 2021 Annual Meeting.

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Antidepressants May Reduce Risk of Intubation or Death in Hospitalized COVID-19 Patients

Antidepressants may reduce the risk of intubation or death in patients hospitalized with COVID-19, according to a large observational study published in Molecular Psychiatry.

“[A]ntidepressant use, at a mean dosage of 21.6 fluoxetine-equivalent milligrams, was significantly and substantially associated with reduced risk of intubation or death, independently of patient characteristics, clinical and biological markers of disease severity, and other psychotropic medications,” wrote Nicolas Hoertel, M.D., Ph.D., M.P.H., of the University of Paris and colleagues. “These findings should be interpreted with caution due to the observational design of the study. However, our findings provide support for conducting controlled randomized clinical trials of antidepressant medications for COVID-19.”

Hoertel and colleagues looked at health data from 7,230 adults aged 18 and older who were admitted to one of the 39 Assistance Publique-Hôpitaux de Paris for COVID-19 between January 24 and April 1, 2020 (Assistance Publique-Hôpitaux de Paris is the largest hospital system in Europe). Of this group, 345 patients received an antidepressant within 48 hours of admission; this included 195 patients receiving a selective serotonin reuptake inhibitor (SSRI) and 150 patients receiving antidepressants in other classes. The patients who received antidepressants were older and sicker than the patients who did not receive antidepressants.

Overall, about 24% of COVID-19 patients who received an antidepressant and 17% who did not receive an antidepressant died or required intubation while hospitalized. After adjusting for other health factors, however, the patients taking antidepressants had a 44% reduced risk of intubation or death; SSRIs reduced the risk by 49%, while non-SSRIs reduced the risk by 35%. When the researchers conducted a smaller analysis comparing the 345 antidepressant-receiving patients with a matched group of 345 control patients, they obtained similar results. They also obtained similar results when comparing patients who received an antidepressant with those who received the sedative diazepam.

The researchers did not observe any reduced risk of death among patients who had a history of antidepressant use but did not receive an antidepressant during their hospitalization. This suggests that the reduced risk is related to acute effects of the medications.

Hoertel and colleagues noted that several antidepressants are known to have anti-inflammatory properties, which could partially explain their association with reduced death or intubation. Studies have also shown that many antidepressants can reduce the ability of viruses to invade certain cells, while some—including fluoxetine—may even have direct antiviral properties.

For more information, see the Psychiatric News article “Patients With MH Disorders Found More Susceptible to COVID-19, Death.”

(Image: iStock/gorodenkoff)

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Join Us Tonight for APA’s Town Hall on How Racism Impacts Workforce Diversity

Please plan to attend the APA town hall “Structural Racism & Psychiatric Residency Training: Recruitment, Retention, and Development,” tonight at 8 p.m. ET. Panelists will address the disproportionate number of minority psychiatrists, their experiences in different practice settings, and why having diversity in the psychiatric workforce psychiatry is important for everyone.

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Pandemic Prompts Increase in Emergency Department Visits for Mental Illness, Suicide, Overdose

Emergency department (ED) visits for mental health conditions, suicide attempts, and drug overdoses were higher in mid-March through October 2020, during the COVID-19 pandemic, compared with the same period in 2019, a study in JAMA Psychiatry has found. These increases ran counter to an overall decline in ED visits for all causes that began soon after the nation implemented COVID-19 mitigation measures in mid-March 2020.

Kristin M. Holland, Ph.D., M.P.H., of the National Center for Injury Prevention and Control and colleagues analyzed data from the Centers for Disease Control and Prevention’s National Syndromic Surveillance Program to examine national changes in ED visits for mental health conditions, suicide attempts, drug overdose, opioid overdose, intimate partner violence, and suspected child abuse and neglect from December 30, 2018, to October 10, 2020. The program captures roughly 70% of ED visits from more than 3,500 EDs in 48 states and the District of Columbia.

When the researchers compared median weekly ED visit counts between March 15 and October 2020 with the same period in 2019, they found the following increases per 100,000 visits:

• Visits for mental health conditions rose from 40,257 to 42,610.
• Visits for suicide attempts rose from 4,656 to 4,940.
• Visits for all drug overdoses rose from 13,371 to 15,604.
• Visits for opioid overdoses rose from 4,168 to 5,502.

“[T]he findings suggest that visits for these outcomes were likely of sufficient severity that treatment at an ED was a necessary risk during the pandemic, despite stay-at-home orders advising people to avoid public spaces,” Holland and colleagues wrote. They added that the visits for all drug and opioid overdoses were especially compelling.

“This finding might reflect changes in the illicit drug supply during the pandemic and that persons using opioids used them alone or in higher-risk ways, increasing the likelihood of [overdose], or that they lacked access to naloxone or other risk-reduction services—all potential effects of COVID-19 mitigation measures,” they continued.

The researchers noted that their results likely underestimate the number of visits associated with these measures because many patients who experience mental health conditions, suicide attempts, and overdoses do not visit an ED.

“These findings suggest that ED use and priorities for care seeking shifted during the COVID-19 pandemic, underscoring mental health, substance use, and violence risk screening and prevention needs during public health crises,” they wrote.

For related information, see the Psychiatric News article “Expect a ‘Long Trail’ of Mental Health Effects From COVID-19.”

(Image: iStock/Jobalou)

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APA’s Town Hall on How Racism Impacts Workforce Diversity Is Next Monday

Register now for the town hall “Structural Racism & Psychiatric Residency Training: Recruitment, Retention, and Development,” to be held Monday, February 8, at 8 p.m. ET. Panelists will address the disproportionate number of minority psychiatrists, their experiences in different practice settings, and why having diversity in the psychiatric workforce psychiatry is important for everyone.

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Mental Illness Found to Be Significant Contributor to Maternal Deaths After Giving Birth

Suicide, drug overdose, and mental illness in the perinatal period are significant and preventable contributors to maternal deaths, said psychiatrists at a workshop on perinatal maternal mortality during the virtual annual meeting of the Academy of Consultation-Liaison Psychiatry.

“Overall, mental health conditions are on a par with hypertensive crisis and postpartum hemorrhage as causes of maternal mortality,” said James Levenson, M.D., a professor of psychiatry at the Virginia Commonwealth University.

During the workshop, perinatal psychiatrists presented data from the Centers for Disease Control and Prevention (CDC) and state-level data from Maternal Mortality Review Committees (MMRCs) in Massachusetts and Washington. MMRCs are multidisciplinary committees charged with reviewing cases of maternal death, determining causes and contributing factors, and developing recommendations to prevent deaths.

Analyzing data from 14 state MMRCs, the CDC Maternal Mortality Team determined that of 453 pregnancy-related deaths between 2008 and 2017, 46 were related to mental illness, including deaths by suicide (63%), nonsuicidal overdoses (24%), or other mental illness–related causes or injury of unknown intent (13%). Of these deaths, 65% occurred between 42 days and one year after giving birth. Analyses of perinatal maternal mortality data from Massachusetts and Washington State mirrored those results.

The data have resulted in recommendations from the American College of Obstetrics and Gynecology for a “new paradigm” of postpartum care: shifting from a single encounter at six weeks to care that is an ongoing, individualized, and woman-centered process. Likewise, the American Academy of Pediatrics recommends that primary care pediatricians screen mothers for depression at children’s one- , two- , four- , and six-month well visits.

Speakers at the meeting encouraged psychiatrists to participate in state MMRCs. “We know that the perinatal period is often associated with the first onset of mental illness, and psychiatric illness is under- or misdiagnosed in this period,” said Christina Wichman, D.O., a professor of psychiatry and behavioral medicine and obstetrics and gynecology at Medical College of Wisconsin. “Involvement of mental health professionals on these committees is really important.

For related information, see the Psychiatric News article “Study Finds Alarming Increase in Suicidality During Pregnancy.”

(Image: iStock/fotostorm)

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APA’s Next Town Hall to Examine How Racism Affects Diversity in Psychiatric Workforce

Register now for the town hall “Structural Racism & Psychiatric Residency Training: Recruitment, Retention, and Development,” to be held Monday, February 8, at 8 p.m. ET. Panelists will address the disproportionate number of minority psychiatrists, their experiences in different practice settings, and why having diversity in the psychiatric workforce psychiatry is important for everyone.

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APA Condemns Pepper-Spraying, Handcuffing of 9-Year-Old Girl by Rochester Police

APA today denounced the treatment by Rochester, N.Y., police officers of a 9-year-old girl who was pepper-sprayed, pushed into the snow, and handcuffed when they responded to a family disturbance. The girl is believed to have been experiencing a mental health crisis at the time.

In a body-cam video released Sunday by the Rochester police department, the girl was calling for her father. According to a New York Times report, an officer told her, “You’re acting like a child.”

She responded, “I am a child.” When she refused to sit inside a police car, an officer pepper-sprayed her.

“Children should never be treated like this,” said APA President Jeffrey Geller, M.D., M.P.H. “People in psychiatric distress should never be treated like this. We condemn the appalling actions of the police on this video. The girl and her family have experienced this violence and are now dealing with trauma, and watching this video is distressing for many others.”

According to the Times report, Rochester Mayor Lovely Warren said the officers involved in the spraying would be suspended until the conclusion of an internal investigation. She said state laws and union rules prevented her from taking more serious action, according to the Times.

“It is sad and deeply disturbing to see yet another example of police violence in this country, this time directly involving a young child,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A. “APA supports policies that train law enforcement to recognize and appropriately respond to a mental health crisis. The actions in that video underscore the need for that training as well as partnerships among local law enforcement and behavioral health systems.”

For more information, see APA’s “Position Statement on Police Interactions With Persons With Mental Illness.”

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APA’s Next Town Hall to Examine How Racism Affects Diversity in Psychiatric Workforce

Register now for the town hall “Structural Racism & Psychiatric Residency Training: Recruitment, Retention, and Development,” to be held Monday, February 8, at 8 p.m. ET. Panelists will address the disproportionate number of minority psychiatrists, their experiences in different practice settings, and why having diversity in the psychiatric workforce psychiatry is important for everyone.

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Study Highlights Importance of Targeting Emotion Regulation to Reduce Self-Harm in Youth

Youth at high risk of suicide may be less likely to engage in self-harm following dialectical behavior therapy (DBT) compared with individual and group supportive therapy (IGST) due to improvements in their ability to regulate emotions, suggests a report published yesterday in the Journal of the American Academy of Child & Adolescent Psychiatry. The findings expand on previously reported results indicating the efficacy of DBT for reducing self-harm and suicide attempts in highly suicidal self-harming adolescents.

“These data suggest that DBT may be particularly beneficial for changing behavior to a point where youth refrain from self-harm,” wrote Joan Rosenbaum Asarnow, Ph.D., of the University of California, Los Angeles, and colleagues.

The authors analyzed data from a previous trial of 173 youth aged 12 to 18 years who had elevated past-month suicidal ideation and a history of prior suicide attempts and repeated self-harm episodes. They received either six months of weekly and individual DBT or IGST. Whereas DBT aims to strengthen skills that lead to improved emotion regulation (including sensitivity to emotional stimuli and the ability to regulate negative affective responses), IGST emphasizes acceptance, validation, and feelings of connectedness and belonging, the authors noted.

Participants in the DBT group received weekly individual psychotherapy, multifamily group skills training, youth and parent telephone coaching, and weekly therapist team consultation. Parents were also seen in the first session, and families were offered up to seven additional family sessions. Participants in the IGST group received individual sessions and adolescent supportive group therapy, as-needed parent sessions (up to seven sessions), and weekly therapist team consultation.

The participants were evaluated at baseline, three months, 6 months, 9 months, and 12 months using several measures, including the Suicide Attempt Self-Injury Interview (SASII) and Difficulties in Emotion Regulation Scale (DERS). A total of 84 participants in the DBT group and 80 in the IGST group completed the six-month treatment, and 77 in the DBT group and 69 in the IGST group completed 12-month follow-up.

As previously reported, participants in the DBT group were significantly less likely to self-harm during the treatment and follow-up period. Youth in the DBT group showed greater improvements in emotion regulation during the active treatment and follow-up. The “improvements in emotion regulation at post-treatment significantly predicted greater self-harm remission at 12 months … and mediated the effect of DBT on self-harm remission at 12 months,” the authors added.

“Our results … suggest that improvements in emotion regulation contributed to the DBT effect on self-harm remission, perhaps due to increased DBT-skill use—a healthy safe way to manage painful emotions,” they continued. “These findings support the significance of emotion regulation as a therapeutic target in treatments for self-harming youth and improvements in emotion regulation as a therapeutic change mechanism in DBT.”

For related information, see the American Journal of Psychiatry article “Suicide Attempt Prevention: A Technology-Enhanced Intervention for Treating Suicidal Adolescents After Hospitalization.”

(Image: iStock/fizkes)

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APA’s Next Town Hall to Examine How Racism Affects Diversity in Psychiatric Workforce

Register now for the town hall “Structural Racism & Psychiatric Residency Training: Recruitment, Retention, and Development,” to be held Monday, February 8, at 8 p.m. ET. Panelists will address the disproportionate number of minority psychiatrists, their experiences in different practice settings, and why having diversity in the psychiatric workforce psychiatry is important for everyone.

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APA, Pa. Psychiatric Society Announce Support for Rachel Levine, M.D., as Assistant Secretary of Health

APA and the Pennsylvania Psychiatric Society today urged the Senate to move swiftly to confirm the appointment of Rachel Levine, M.D., as assistant secretary of health in the U.S. Department of Health and Human Services (HHS).

Since 2017, Levine served as the secretary of health for the Commonwealth of Pennsylvania. In this role, she signed a standing order for naloxone, enabling pharmacies in Pennsylvania to dispense this life-saving treatment to thousands, and headed efforts to establish opioid-prescribing guidelines and prescribing education for medical students. She also led COVID-19 response efforts in the state.

“Dr. Rachel Levine’s work fighting the opioid epidemic in Pennsylvania [has been] tremendous,” said APA President Jeffrey Geller, M.D., M.P.H., in a press statement. “The United States will be well served by her leadership as we navigate COVID-19 and its impacts on mental health.”

Levine is also a professor of pediatrics and psychiatry at the Penn State College of Medicine and serves as president of the Association of State and Territorial Health Officials. She has been a leader at promoting the interconnection between physical and mental health as well as a staunch advocate for the LGBTQ community. In 2018, APA awarded Levine the Jacob J. Javits Award, given to a public servant who has made significant contributions to the field of mental health and worked to better the lives of people with mental illness and underserved populations.

“Dr. Rachel Levine’s credentials as a leader in medicine are impeccable,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A., in a press statement. She will be an important voice in the Biden administration for everyone in the country, including members of the LGBTQ community and those with mental health and substance use disorders, he continued. “We urge the Senate to confirm her appointment as soon as it has the opportunity.”

“Working closely with our society, [Dr. Levine] has made it her mission to reduce stigma and advance the availability of evidenced-based, holistic, and affordable mental health treatment and services for all individuals seeking assistance,” added Pennsylvania Psychiatric Society President Richard R. Silbert, M.D.

If confirmed, Levine would be the first transgender person confirmed by the Senate as a federal official.

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Today Is Last Day to Vote in APA’s 2021 Election

You have until 11:59 p.m. ET today to vote in APA’s 2021 election. Review the individuals running for office, watch candidate videos, and learn more about the election process at psychiatry.org/elections. If you are a voting member of APA, just go to APA’s website at psychiatry.org/election and click on “Vote Today.”

VOTE NOW

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