Anger, Aggression Reactivity in Depression May Signal Risk for Converting to Bipolar Disorder

Patients who have depression and frequently experience bouts of anger may have an increased risk of developing bipolar disorder, a study in Depression & Anxiety has found. The study also found a link between aggression reactivity—aggressive behavior in response to feeling threatened, provoked, or frustrated—and conversion to bipolar disorder.

Rahele Mesbah, M.Sc., of Leiden University Medical Center in Leiden, The Netherlands, and colleagues analyzed data from 1,585 people with depression who participated in the Netherlands Study of Depression and Anxiety (NSDA), a longitudinal study of adults aged 18 to 65 years. Four years into their participation, people in the NSDA completed questionnaires about trait anger (tendency toward anger as a personality trait), aggression reactivity, anger attacks, and personality traits associated with greater amounts of anger. NSDA participants were also evaluated using the Composite International Diagnostic Interview at two, four, six, and nine years of follow-up.

At the end of four years, 77 people converted to bipolar disorder, 349 had current depressive disorder, and 1,159 had remitted depressive disorder. Those who converted to bipolar disorder had the highest levels of trait anger and aggression reactivity. They also had the greatest prevalence of anger attacks, antisocial personality traits, and borderline personality traits.

In a separate analysis, this time including 1,744 people with depression in the NSDA who had nine years of follow-up, the researchers found that aggression reactivity predicted incident hypomania and thus conversion to bipolar disorder.

“Feelings of anger might be an important target for early recognition of illness and intervention in BD [bipolar disorder],” Mesbah and colleagues wrote. “Increased feelings of anger in unipolar patients in combination with some other known clinical characteristics, such as multiple brief depressed episodes, a lack of response to antidepressants, [or] a family history of [bipolar disorder] might help to signal an upcoming conversion to [bipolar disorder].”

For related information, see the American Journal of Psychiatry article “Early Intervention in Bipolar Disorder.”

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High Psychological Distress Found Among Chinese Students During Early Weeks of Pandemic

Students in China reported high rates of psychological distress during the early weeks of the COVID-19 pandemic, but wearing a face mask frequently and exercising had some protective benefits, according to a study published this week in JAMA Network Open.

“The COVID-19 pandemic may worsen existing mental health problems and be associated with more mental health problems among children and adolescents because of the unique combination of the public health crisis and social isolation,” wrote Lei Shi, M.D., of Southern Medical University in Guangzhou, China, and colleagues. 

Shi and colleagues analyzed data from nearly 1.2 million school-aged children and adolescents living in the Guangdong province in China. The students completed online questionnaires from March 8 to 30, 2020, which assessed mental health status using the Chinese version of the 12-item General Heath Questionnaire. Students were considered to be experiencing psychological distress if they scored 3 or greater on the questionnaire. The researchers asked questions specifically related to the pandemic, including how many sources they used to obtain COVID-19 information and how often they wore face masks (always, most of the time, sometimes, few, or never).

In total, 10.5% of the respondents—whose mean age was 12 years—reported psychological distress. Older students reported higher levels of psychological distress compared with younger students, especially those in their final year of high school. Students from areas with a high risk for COVID-19 transmission had higher odds of psychological distress compared with students from areas with a lower risk of transmission.

The study also revealed the following behaviors that seemed to lower risk of psychological distress: 

• Students who knew of more than five sources for COVID-19 information had lower odds of psychological distress compared with students who knew of only one source.
• Students who reported always wearing face masks were less likely  to report psychological distress than students who reported rarely wearing face masks. 
• Students who spent more than one hour exercising a week had lower odds of psychological distress than students who spent less than 30 minutes exercising a week. 

“Based on these findings, it is necessary for governments, schools, and families to pay attention to the mental health of school-aged children and adolescents during the COVID-19 pandemic and take appropriate countermeasures to reduce the impact of the COVID-19 pandemic on mental health for children and adolescents,” the authors concluded.

For related information, see the Psychiatric News article “Long-Term Impact of COVID-19 on Children, Adolescents Constitutes Public Health Emergency.”

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Patients With Schizophrenia Have More Than Twice the Risk of Death Related to COVID-19

Individuals with schizophrenia spectrum disorders appear to have more than twice the risk of dying from illness related to COVID-19 than do those without schizophrenia, according to a study published today in JAMA Psychiatry. The study further found that people with mood and anxiety disorders were not at a greater risk of mortality from COVID-19 compared with people without these disorders.

“The results of this analysis suggest that the risk of severe or fatal illness may differ by diagnosis,” wrote Katlyn Nemani, M.D., of New York University Langone Medical Center and colleagues. “In a population that may be more susceptible to infection, determining which patients may be at highest risk for adverse outcomes is necessary to guide clinical decision making, including the need for enhanced monitoring and targeted interventions.”

Nemani and colleagues analyzed data from the electronic health records of 7,348 adults, aged 18 years or older, who tested positive for coronavirus 2 (SARS-CoV-2) between March 3 and May 31, 2020, in the NYU Langone Health System. The system includes more than 260 outpatient office sites and four acute care hospitals in Manhattan, Brooklyn, and Long Island, N.Y.

The authors classified these patients into one of three groups: those with schizophrenia spectrum disorders (n=75), mood disorders (n=564), and anxiety disorders (n=360). Patients in each category were compared with 6,349 patients who did not have psychiatric diagnoses documented before March 3, 2020.

Overall, 864 patients (11.8%) died or were discharged to hospice within 45 days of a positive test result. The researchers found that after adjusting for demographic factors (age, sex, and race), patients with schizophrenia spectrum disorders were 2.87 times more likely to die from COVID-19 within 45 days of testing positive than individuals with no mental illness; after adjusting for medical risk factors, patients with schizophrenia spectrum disorders were 2.67 times more likely to die from COVID-19 within 45 days of testing positive than individuals with no mental illness. After adjusting for similar factors, the researchers found that patients with mood disorders and anxiety disorders were not more likely to die from COVID-19 compared with individuals with no mental illness.

“The most notable finding from this study is the high risk of mortality associated with schizophrenia spectrum diagnoses, ranking second behind age in strength of an association among all demographic and medical risk factors examined in this sample,” Nemani and colleagues wrote. “Targeted interventions may be needed for patients with severe mental illness to prevent worsening health disparities.”

For more information, see the Psychiatric News article “COVID-19 and People With SMI—New Notes From the Field.”

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Edinburgh Postnatal Depression Scale May Detect More Than Depression in Early Pregnancy

Screening women in early pregnancy with the Edinburgh Postnatal Depression Scale (EPDS) may help to detect women experiencing more than depression symptoms alone, suggests a study Acta Obstetricia et Gynecologica Scandinavica.

Caroline Lilliecreutz, M.D., Ph.D., of the University Hospital Linköping in Sweden and colleagues analyzed data collected from more than 2,200 Swedish-speaking women receiving prenatal care in Linköping during their first trimester of pregnancy. The women, aged 18 and older, were screened using the EPDS (a 10‐item self‐report scale designed to screen for postnatal depression) before their 14th week of pregnancy. A woman was considered to have screened positive for depression if she had an EPDS score of ≥13 or any indication of thoughts of harming herself (scoring one to three points on item 10 on the EPDS while having a total score <13). The women who screened positive on the EPDS were then evaluated using a structured diagnostic interview known as the Primary Care Evaluation of Mental Disorders. They were also asked questions about substance misuse, partner abuse, financial problems, serious life events (such as a death of a close relative or life-threatening trauma), sleep disturbances, and more. The researchers then compared the medical records of women who screened positive on the EPDS with a group of 150 women who had EPDS scores of 12 or lower.

Of the 149 pregnant women who scored 13 or higher on the EPDS, 126 (85%) were diagnosed during the face‐to‐face interview with a current mental disorder or risk factor for mental disorders, Lilliecreutz and colleagues reported. Among these women, 36% were diagnosed with depression, nearly 15% were diagnosed with an anxiety disorder, 48% had a history of depression, and nearly 21% reported a severe fear of childbirth. Among the women who screened negative, only three (2%) presented with symptoms of depression during pregnancy. Compared with women who screened negative on the EPDS, those who screened positive were more often smokers (16% vs 1%), unemployed (20% vs 1%), or on sick leave (25% vs 14%) during pregnancy.

“The EPDS is constructed for the detection of depressive symptoms, but in this study, we have also shown that the presumption that EPDS scores >12 only indicate probable depression is an oversimplification,” Lilliecreutz and colleagues wrote. “This study shows that the EPDS might be a helpful tool for ... identifying women in early pregnancy who are suffering from different types of mental disorders or risk factors for mental disorders.”

For related information, see the Psychiatric News article “Suicide, Overdose Are Significant Contributors to Pregnancy-Related Maternal Deaths.”

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Clozapine Found Most Effective to Reduce Aggression in Patients With Schizophrenia and Conduct Disorder

Clozapine is more effective than olanzapine or haloperidol at reducing aggression in patients with schizophrenia and conduct disorder, according to a study appearing in AJP in Advance.

The study by Menahem Krakowski, M.D., Ph.D., of the Nathan Kline Institute for Psychiatric Research in Orangeburg, N.Y., and colleagues examined data from 99 hospitalized schizophrenia patients aged 18 to 60. For the 12-week, double-blind clinical trial, the patients were randomly assigned to receive clozapine, olanzapine, or haloperidol to see which drug was associated with the greatest reduction in aggression. All participants had at least one clearly documented instance of verbal or physical aggression.

Based on clinical interviews and a review of the patients’ medical charts, the investigators diagnosed 53 of these patients with conduct disorder. The patients with or without conduct disorder were similar in many demographic and clinical factors, but those with conduct disorder had a longer duration of schizophrenia, were more likely to have a substance use disorder, and had fewer negative symptoms.

During the 12-week study, the patients with conduct disorder were more likely to exhibit aggression than those without, as assessed by the Modified Overt Aggression Scale (MOAS). This scale quantifies the number and severity of incidents involving verbal aggression, physical aggression against other people, and physical aggression against objects. Average MOAS scores at the end of the study were 42.6 for patients with conduct disorder and 22.1 for patients without. There were significant differences in medication groups, however: Among patients with conduct disorder, average MOAS scores were 71.6 in the haloperidol group, 40.7 in the olanzapine group, and 26.6 in the clozapine group. The average MOAS scores for patients with no conduct disorder who received haloperidol, olanzapine, and clozapine were 28.7, 24.9, and 15.0.

Krakowski and colleagues found that patients with schizophrenia and conduct disorder taking clozapine were three times as likely to exhibit less overall aggression and four times as likely to exhibit less physical aggression than those taking haloperidol. They noted that changes in both positive and negative schizophrenia symptom scores were similar among the patients during the study; thus, the improvements in aggression were likely not related to overall antipsychotic effects.

“The findings point to the superiority of clozapine, and to a lesser extent olanzapine, for these patients and have important implications for treatment,” the researchers wrote. “It is imperative to obtain a good history of conduct disorder, for if it is present, clinicians should consider clozapine as the primary drug for treatment.”

For related information, see the Psychiatric News article “Study Provides More Insight Into Association Between Schizophrenia, Violence.”

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Specialized Form of CBT May Be Effective for Treating Prolonged Grief in Children, Adolescents

A specialized form of cognitive-behavioral therapy (CBT) may reduce symptoms of prolonged grief disorder in children and adolescents, an effect that continues up to a year after treatment, a study in AJP in Advance has found.

Paul A. Boelen, Ph.D., of Utrecht University, in Utrecht, the Netherlands, and colleagues compared the effectiveness of CBT Grief-Help with supportive counseling for 134 bereaved children and adolescents between 8 and 18 years old who had prolonged grief disorder as determined by a score of greater than 40 on the Inventory of Prolonged Grief for Children (IPG-C). 

All patients received nine counseling sessions. Seventy-four of the patients received CBT Grief-Help, which includes exposure interventions such as imaginary exposure (telling the story of the loss), direct exposure (visiting the scene of the death), and writing (writing a letter to the lost person about what the patient misses most). Patients who receive CBT Grief-Help are also taught specific skills to replace maladaptive ways of coping with healthy ones. The remaining patients were assigned to the supportive counseling group. They received nondirective treatments for grief wherein therapists were unconditionally supportive of issues that the patients raised in their sessions as well as their attempts at solving problems without using exposure techniques or addressing patients’ thought processes.

Patients were assessed again immediately after treatment ended, and IPG-C scores suggested improvement in prolonged grief symptoms in 76.1% of those in the CBT group versus 57.4% in the supportive counseling group. These results remained consistent at three months and six months. At 12 months, IPG-C scores suggested improvement in 78.6% of those in the CBT group versus 60.0% in the supportive counseling group.

“Although mechanisms of change are still to be researched, it is conceivable that CBT Grief-Help more effectively alleviates prolonged grief disorder by yielding positive changes in negative thinking patterns, decreasing maladaptive coping, increasing pleasant activities, and strengthening social problem-solving skills,” the researchers wrote. “In addition, whereas supportive counseling leaves room to avoid the reality of the loss and associated feelings, CBT Grief-Help encourages emotional processing of this reality.”

For related information, see the American Journal of Psychiatry article “Persistent Impairment: Life After Losing a Parent.” 

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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 Points to Methamphetamine Crisis Among American Indians, Alaska Natives

There was a fivefold increase in methamphetamine overdose deaths from 2011 to 2018 among U.S. adults aged 25 to 54, with American Indians and Alaska Natives experiencing the highest death rates, according to a report published Wednesday in JAMA Psychiatry.

“While much attention is focused on the opioid crisis, a methamphetamine crisis has been quietly, but actively, gaining steam—particularly among American Indians and Alaska Natives, who are disproportionately affected by a number of health conditions,” said Nora D. Volkow, M.D., director of the National Institute on Drug Abuse and a senior author of the report, in a news release. “American Indian and Alaska Native populations experience structural disadvantages but have cultural strengths that can be leveraged to prevent methamphetamine use and improve health outcomes for those living with addiction.”

Volkow and colleagues collected deidentified public health surveillance data on methamphetamine-related deaths from 2011 to 2018 from the National Vital Statistics System. The authors limited their analysis to individuals between 25 and 54 years old, as national data show that four-fifths of people who use methamphetamines are within this age group.

The report revealed the following:

• Overall, deaths involving methamphetamines rose from 1.8 to 10.1 per 100,000 among men and 0.8 to 4.5 per 100,000 among women from 2011 to 2018.
• Methamphetamine-related deaths were higher among men across all racial/ethnic groups included in the study.
• For both men and women, non-Hispanic American Indian and Alaska Native individuals had the highest death rates by far, rising from 5.6 to 26.4 per 100,000 among men and 3.6 to 15.6 per 100,000 among women. Non-Hispanic Whites had the second-highest rates, increasing from 2.2 to 12.6 per 100,000 among men and from 1.1 to 6.2 per 100,000 among women.
• American Indian and Alaska Native women had higher rates than non-Hispanic Black, Asian, and Hispanic men from 2012 to 2018.

The authors also noted that methamphetamine death rates may be underestimated because some overdose death certificates did not report the specific drugs involved.

“Identifying populations that have a higher rate of methamphetamine overdose is a crucial step toward curbing the underlying methamphetamine crisis,” said the study’s lead author, Beth Han, M.D., Ph.D., M.P.H., in the news release. “By focusing on the unique needs of individuals and developing culturally tailored interventions, we can begin to move away from one-size-fits-all approaches and toward more effective, tailored interventions.”

For related information, see the Psychiatric News Alert “Naltrexone-Bupropion Combination May Help People With Methamphetamine Use Disorder.”

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Free Webinar for Members: How You Can Help Protect Patient Safety

APA members are invited to register for a free webinar on Tuesday, January 26, to examine ways to increase access to care during the pandemic and discuss advocacy strategies to combat dangerous legislation and solutions to safely increase access to care.

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HHS Takes Steps to Encourage More Physicians to Prescribe Buprenorphine

Physicians with a Drug Enforcement Administration (DEA) registration number may no longer be required to apply for a separate waiver to prescribe buprenorphine to patients with opioid use disorder (OUD), according to new practice guidelines by the Department of Health and Human Services (HHS). This waiver is referred to as X-waiver of the Controlled Substances Act (CSA).

Physicians who dispense narcotic drugs to individuals for maintenance treatment or detoxification treatment have been required to complete additional certifications under Title 21 of the CSA.

“The Office of the Assistant Secretary for Health in HHS has determined that the need for physicians to make all of the certifications under 21 U.S.C. 823(g)(2)(b) represents a significant perceived barrier to prescribing buprenorphine in the United States, and removing the certification requirements would dramatically improve access to buprenorphine and save lives,” according to the guidelines.

The Practice Guidelines for the Administration of Buprenorphine for Treating Opioid Use Disorder outlines the following changes:

• A physician who is licensed under state law and possesses a DEA registration under 21 U.S.C. 823(f) is exempt from the certification requirements under 21 U.S.C. 823(g)(2)(b) when prescribing such medications as buprenorphine. (Physicians utilizing this exemption may treat only those patients who are located in states where those physicians are authorized to practice medicine.)
• The exemption applies only to the prescription of drugs or formulations covered under the X-waiver of the CSA, such as buprenorphine, and does not apply to the prescription, dispensation, or use of methadone for the treatment of OUD.
• Physicians utilizing this exemption will be limited to treating no more than 30 patients with buprenorphine for OUD at any one time. (This cap does not apply to hospital-based physicians, such as emergency department physicians).
• Physicians utilizing this exemption must place an "X" on the prescription and clearly identify that the prescription is being written for OUD.
• An interagency working group will be established to monitor the implementation and results of these practice guidelines, as well as the impact on diversion.

“With this change,” said psychiatrist and immediate past AMA President Patrice Harris, M.D., M.A., in a statement, “office-based physicians and physician-led teams working with patients to manage their other medical conditions can also treat them for their opioid use disorder without being subjected to a separate and burdensome regulatory regime. Ensuring physician-led teams for treating patients with opioid use disorder is critical to ending the opioid epidemic. Removing the waiver requirement can also help lessen the stigma associated with this treatment and the persistent health disparities in treating substance use disorders.”

For related information, see the Psychiatric News article “Patients and Psychiatrists Alike Face Hurdles in Buprenorphine Prescribing.”

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APA Issues Apology for History of Racism Contributing to Discrimination, MH Care Inequities

The APA Board of Trustees today issued an apology for APA’s history of racism and for “enabling discriminatory and prejudicial actions within APA and racist practices in psychiatric treatment for Black, Indigenous, and People of Color (BIPOC).” The statement of apology—addressed to members, patients, their families, and the public—is accompanied by a document outlining specific practices and policies (including failures to speak out and protest racist practices) that have damaged BIPOC patients and their families dating to the time of the founding of APA.

“The Board is issuing this document on Martin Luther King Jr. Day because we hope that it honors his life’s work of reconciliation and equality,” said APA President Jeffrey Geller, M.D., M.P.H., in a press statement. “We do not take that legacy or his call to action lightly.”

In the statement, APA’s trustees acknowledged that early psychiatric practices laid the groundwork for the inequities in clinical treatment that have historically limited access to quality psychiatric care for BIPOC.

“These actions sadly connect with larger social issues, such as race-based discrimination and racial injustice, that have furthered poverty along with other adverse outcomes,” according to the statement. “Since APA’s inception, practitioners have at times subjected persons of African descent and Indigenous people who suffered from mental illness to abusive treatment, experimentation, victimization in the name of ‘scientific evidence,’ along with racialized theories that attempted to confirm their deficit status. Similar race-based discrepancies in care also exist in medical practice today as evidenced by the variations in schizophrenia diagnosis between white and BIPOC patients, for instance.”

The statement continues, “Unfortunately, APA has historically remained silent on these issues. As the leading American organization in psychiatric care, APA recognizes that this inaction has contributed to perpetuation of structural racism that has adversely impacted not just its own BIPOC members, but also psychiatric patients across America. … We hope this apology will be a turning point as we strive to make the future of psychiatry more equitable for all.”

The apology is part of an initiative begun by Geller soon after he became president last April to address structural racism in psychiatry and eradicate it. Carrying out this work is a task force whose goals are to provide education and resources on APA’s and psychiatry’s history regarding structural racism, explain the current impact of structural racism on the mental health of patients and colleagues, develop achievable recommendations for change to eliminate structural racism in APA and psychiatry now and in the future, and provide reports with specific recommendations for achievable actions to the APA Board of Trustees at each of its meetings through May. This work will continue beyond Geller’s one-year presidency.

“Many will argue this apology should have come sooner,” said Geller. “That said, the events of 2020—the killings of Black people by police, the health inequities laid bare by the pandemic—were an eye-opener for many among our membership and a clarion call that it was past time to take action.”

Said APA CEO and Medical Director Saul Levin, M.D., M.P.A., “The Board of Trustees of APA has taken an important step in issuing this apology. The APA administration is committed to working toward achieving inclusion, health equity, and fairness that everyone deserves.”

For more information on the task force, see the Psychiatric News article “APA Task Force Charged With Examining Structural Racism Throughout Psychiatry.” 

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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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Insulin Levels, BMI in Youth May Be Linked to Psychosis, Depression Risk in Adulthood

Disrupted insulin sensitivity in childhood and adolescence may be a shared risk factor for cardiometabolic disorders and psychosis in adulthood, a study in JAMA Psychiatry has found. The study also found that a major increase in BMI around puberty may indicate a greater risk for adult depression.

Benjamin I. Perry, M.R.C.Psych., of the University of Cambridge School of Clinical Medicine in Cambridge, United Kingdom, and colleagues examined data from people aged 1 to 24 years in the Avon Longitudinal Study of Parents and Children, a prospective study of approximately 15,000 British people. They obtained data on fasting insulin levels for 5,790 people measured at ages 9, 15, 18, and 24 years, and BMI for 10,463 people measured at 1, 2, 3, 4, 7, 9, 10, 11, 12, 15, 18, and 24 years.

Those with persistently high fasting insulin levels from age 9 years had five times the odds of psychosis and 3.22 times the odds of having a psychotic disorder at age 24. However, fasting insulin levels were not associated with depression.

“Our findings complement meta-analyses reporting altered glucose-insulin homeostasis in first-episode psychosis. Moreover, our results suggest that disruptions to glucose-insulin homeostasis detectable at first-episode psychosis in adults may begin in childhood,” Perry and colleagues wrote. Altered glucose-insulin homeostasis could be a shared mechanism for psychosis and type 2 diabetes, they added.

People who experienced a major increase in BMI as they entered puberty had 4.46 times the odds of having a depressive episode at age 24. BMI was not associated with an increased risk of psychosis.

“[O]ur results suggest that these cardiometabolic markers could be among shared risk factors and indicators for adult cardiometabolic and psychiatric disorders and may represent novel targets for prevention and treatment of cardiometabolic disorders in people with psychosis and depression,” the researchers wrote.

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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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Naltrexone-Bupropion Combination May Help People With Methamphetamine Use Disorder

A combination of naltrexone plus bupropion can reduce methamphetamine use in people with moderate to severe methamphetamine use disorder, reports a study in the New England Journal of Medicine. In a randomized clinical trial of over 400 adults, 13.6% of participants who took extended-release naltrexone/bupropion significantly reduced or stopped their methamphetamine use compared with 2.5% of those who took placebo.

“Methamphetamine use disorder is a serious illness and is associated with medical conditions and mental health issues, marked functional impairment, and frequent relapses,” wrote Madhukar Trivedi, M.D., of the University of Texas Southwestern Medical Center in Dallas and colleagues. “There is no medication approved by the Food and Drug Administration for the treatment of methamphetamine use disorder, and effective treatment has been identified as an essential public health goal.”

Trivedi and colleagues enrolled 403 adults aged 18 to 65 who met the DSM-5 criteria for moderate or severe stimulant use disorder (methamphetamine type) and reported using methamphetamine on at least 18 of the 30 previous days. Adults were excluded from the trial if they were undergoing concurrent treatment for substance use disorder, were taking opioids, and/or expected a need for opioid medications during the trial (for example, for a planned surgery). The participants were then assigned to receive either 380 mg of injectable naltrexone every three weeks combined with 450 mg oral bupropion once daily or matching placebo injections and pills.

The trial was divided into two six-week stages. In the first stage, 109 participants were given naltrexone/bupropion, and 294 were given placebo. After six weeks, the 225 participants in the placebo group who remained in the trial after showing no response to placebo were randomly assigned to one of two groups: 114 received naltrexone/bupropion, and 111 continued to take placebo. Medication response was defined as having at least three out of four urine samples provided during the last two weeks of each study stage test negative for methamphetamine.

After the first stage, 16.5% of participants in the naltrexone/bupropion group and 3.4% in the placebo group had a response. In the second stage, 11.4% of participants in the naltrexone/bupropion group and 1.8% in the placebo group had a response. Participants taking naltrexone/bupropion also reported lower drug cravings than those taking placebo.

Most of the participants in either group reported at least one adverse event during the trial, but most of these events were mild to moderate in severity. Adverse events that were more common in people taking naltrexone/bupropion included nausea, vomiting, tremors, malaise, and loss of appetite.

To read more on this topic, see the Psychiatric News article “Why Aren’t There More Medications for Substance Use Disorders?”

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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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Suicide and Suicide Attempts Higher Among People With Autism Spectrum Disorder

People with autism spectrum disorder (ASD) have higher rates of suicide and suicide attempts than people without ASD, a study published today in JAMA Network Open has found.

Kairi Kõlves, Ph.D., of Griffith University in Mt. Gravatt, Queensland, Australia, and colleagues analyzed data collected by the Danish Civil Registration System between January 1995 and December 2016 for more than 6.5 million people in Denmark aged 10 years or older. Among those individuals, 35,020 had received a diagnosis of ASD. There were 64,109 suicide attempts among all registered individuals, 587 of them by people with ASD, and there were 14,197 suicides, 53 of them by people with ASD.

The researchers found that people with ASD had 3.19 times the rate of attempted suicide and 3.75 times the rate of suicide of those without ASD. Compared with people who did not have any psychiatric disorders, people diagnosed with only ASD had 1.33 times the rate of attempted suicide, and people who had comorbid psychiatric disorders in addition to ASD had 9.27 times the rate of attempted suicide. More than 90% of people with ASD who attempted suicide or died by suicide had at least one other psychiatric condition.

“A possible causal mechanism linking ASD to suicidality, particularly in adults, may be a combination of social isolation and poor access to health care,” the researchers wrote. “[I]t is essential to expand support and services for adults with ASD, especially those with psychiatric comorbidity, considering the higher risk of suicide attempt throughout the life span.”

Females with ASD had 4.41 times the rate of suicide attempts compared with males with the disorder, a finding that points to a need to improve diagnostic tools to avoid delays in treating ASD in females, the researchers wrote.

For related information, see the Psychiatric Services article “Self-Injurious Behavior Among Adults With ASD: Hospitalizations, Length of Stay, and Costs of Resources to Deliver Care.”

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Exposure to Valproate in the Womb May Increase Risk of Autism, ADHD

Valproate, which is used to treat epilepsy, migraines, and bipolar disorder, has previously been linked to neural tube birth defects if taken during pregnancy. An article appearing in the January issue of Psychiatric News reports new findings that children exposed to valproate in the womb had an elevated risk of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) compared with those who were not exposed to the medication in the womb.

The research was conducted by a team at Indiana University along with colleagues at Sweden’s Karolinska Institutet. The team used Swedish birth and medical registers to identify 14,614 children born between 1996 and 2011 to mothers with epilepsy. About 23% of the mothers used an anticonvulsant during the first trimester of pregnancy, with carbamazepine (9.7%), lamotrigine (6.8%), and valproate (4.8%) being the three most common.

After factoring in other variables that contribute to ASD or ADHD risk—including demographic characteristics, other medications used by the mothers, parental psychiatric history, and seizure severity—the investigators found that children who were exposed to valproate in the womb were 2.3 times as likely to be diagnosed with ASD and 1.74 times as likely to be diagnosed with ADHD as children who were not exposed to anticonvulsants. They also identified a small risk of ASD for carbamazepine exposure, but only in mothers who took this medication in combination with another anticonvulsant. There were no observable ASD or ADHD risks to children exposed to lamotrigine in the womb.

“While it’s important to identify evidence of risk, we should not overlook when we find evidence of relative safety,” lead author Kelsey Wiggs, a Ph.D. student at Indiana University’s Developmental Psychopathology Lab, told Psychiatric News. “And our data add to a growing body of evidence that lamotrigine is a good option for women with epilepsy who may become pregnant.”

Veerle Bergink, M.D., the director of Mount Sinai Hospital’s Women’s Mental Health Program, noted that while lamotrigine appears safer than other anticonvulsants, the medication may not always be the answer for women of reproductive age who have bipolar disorder due to its limited efficacy on mania symptoms.

The best guidance [for psychiatrists] we can give is to try and aim for monotherapy in pregnant women ... and keep them on the lowest dose possible during pregnancy,” Bergink said. “Importantly, ramp the dose back up after delivery, since the first few weeks after childbirth pose the greatest risk of symptom relapse in women with bipolar disorder.”

The study by Wiggs and colleagues was published in Neurology.

For related information on pregnancy and psychiatric illness, see the American Journal of Psychiatry article “Antidepressants, Pregnancy, and Autism: Setting the Record(s) Straight”.

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Study Confirms Well-Known Suicide Risk Factors, Identifies New Risks

Financial distress, feeling downhearted, and doing activities less carefully were identified through machine learning as risk factors for suicide, according to a study published in JAMA Psychiatry.

“[M]ost of the published literature on nonfatal suicide attempt prediction has focused on high-risk patients who have received mental health treatment,” wrote Ángel García de la Garza, B.A., of Columbia University, Carlos Blanco, M.D., Ph.D., of the National Institute on Drug Abuse, and colleagues. “These findings underscore the importance of extending suicide attempt prediction models beyond high-risk populations to the general adult population.”

The authors drew on data from the National Epidemiologic Survey on Alcohol and Related Conditions, which is conducted with a nationally representative sample of U.S. adults 18 years and older. The first wave of the survey took place from 2001 to 2002, during which participants were interviewed using the Alcohol Use Disorder and Associated Disabilities Interview Schedule. This interview assesses alcohol use, drug use, and mental illness according to DSM-IV criteria. During the second survey wave—from 2004 to 2005—the participants were assessed using a similar face-to-face structured interview and were asked whether they had attempted suicide in the three years prior. A total of 34,653 participants completed the second wave of the survey.

Attempted suicide during the three years between the wave 1 and wave 2 interviews was reported by 222 study participants. The researchers then used an algorithmic approach using machine learning to develop a suicide attempt risk model. The first wave revealed 2,978 potential risk factors, which were used to classify suicide attempts in the second wave.

According to the model, the three top risk factors in determining whether participants had made a nonfatal suicide attempt were whether individuals felt at any point as though they wanted to die, whether they thought about attempting suicide, and whether they’d made a previous suicide attempt. Additionally, feeling downhearted or depressed in the past four weeks, doing activities less carefully as a result of emotional problems, and accomplishing less than usual due to emotional problems were strong risk factors of future suicide attempts.

Younger age, lower educational achievement, and experiencing a financial crisis in the last year were also important variables for suicide risk. The authors noted the emotional effects of financial crises are of particular relevance due to the economic stress caused by the COVID-19 pandemic.

“We hope that these results deepen our understanding of the etiology of suicide attempts in adults and improve suicidal behavior prediction by identifying new risk variables to guide clinical assessment and development of suicide risk scales,” the authors concluded.

For additional information, see the Psychiatric News article “Four R’s Believed to Be Protective Against Suicide.”

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APA Condemns Violent Attack on U.S. Capitol, Warns of Long-Term Effects of Recurring Trauma

APA today condemned the violent action of a pro-Trump mob who on Wednesday stormed the halls of Capitol, forcing the evacuation of both chambers of Congress during the ceremonial reading of the electoral college votes for President-elect Joe Biden.

“Yesterday’s violence and the rhetoric that incited it are seditious,” said APA President Jeffrey Geller, M.D., M.P.H., in a statement that called attention to the stark contrast between the government’s strongarm response to Black Lives Matter protesters this summer and fall and the response yesterday as predominantly white rioters broke down barricades, smashed windows, and clashed with police.

“Americans are hurting in the pandemic, and this makes the pain, fear, and stress that many of us are feeling much worse. Those who have been subject to the impacts of systemic racism are dealing with the brunt of it.”

The recurring trauma of violence, racism, and reports that thousands of Americans continue to die from COVID-19 each day can lead to heightened anxiety and long-term health effects. If you or a family member or friend needs immediate assistance, help is available:

• Crisis Textline: Text HOME to 741741
• National Suicide Prevention Lifeline: Call 1-800-273-8255 or chat with Lifeline
• Veterans Crisis Line: Call 1-800-273-8255 or text 838255
• Physician Support Line: Call 1-888-409-0141
• NAMI Helpline: Call 1-800-950-6264 (available Monday thru Friday, 10 a.m. to 6 p.m. ET)

“We, as psychiatrists, are deeply concerned and angered by the violence that has occurred and that may continue in our communities,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A. “If you are feeling anxious or unsafe, talk with your family and friends. If your feelings continue and it is impacting your daily life, do not hesitate to seek help through your primary care provider, a psychiatrist or other mental health professional, or other resources in your community.”

For related information and additional resources on supporting adults and children following traumatic events, see the APA page “Coping After Disaster.”

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Initial Effects of Liking, Wanting Alcohol Linked to Later Development of Alcohol Use Disorder

Young adults who are particularly sensitive to the pleasurable effects of alcohol appear more likely to develop alcohol use disorder (AUD) within a decade than those who do not experience these feelings as young adults, according to a study in AJP in Advance. The study also found that people who developed AUD over the 10-year period reported increases in wanting alcohol over time.

“[M]arked stimulant-like, pleasurable, and appetitive effects after consuming alcohol are risk factors for the development and maintenance of addiction,” wrote lead author Andrea King, Ph.D., of the University of Chicago and colleagues.

King and colleagues analyzed follow-up data on 184 adults aged 21 to 35 years old enrolled in the Chicago Social Drinking Project—a study with repeated laboratory assessments of acute responses to alcohol compared with placebo over a 10-year period. For inclusion in the study, the participants had to weigh between 110 and 210 pounds, have good general health, and have no current or past major medical or psychiatric disorders.

For the initial evaluation as well as five and 10 years later, participants attended two individual four- to five-hour laboratory sessions, where they were asked to drink a beverage containing alcohol or placebo (placebo was masked to taste like alcohol). After consuming the beverage during these sessions, the participants were evaluated using the Biphasic Alcohol Effects Scale (assessed stimulation and sedation) and repeatedly asked such questions as “Do you like the effect you are feeling now?” and “Would you like more of what you consumed right now?”

Participants were evaluated for AUD using the structured Clinical Interview for DSM-IV at 1, 2, 4, 5, 6, 8, and 10 years following the initial assessment.

A total of 39 participants met criteria for AUD at year 10. At the initial assessment, the AUD group showed increased stimulation, feelings of “liking” the effect of alcohol, and feelings of “wanting” more alcohol compared with the non-AUD group. Moreover, the feeling of wanting more alcohol increased at the five- and 10-year follow-up in the AUD group; liking alcohol remained high but stable. In comparison, the non-AUD group showed low initial levels on measures of both liking and wanting more alcohol, with little or no change at later testing phases.

The findings are consistent with the “incentive-sensitization theory” of addiction: People increasingly want the substance to which they are addicted, King and colleagues noted.

The researchers said that the study points to preventive interventions designed to reduce the pleasurable effects associated with early drinking.

“Pharmacological and behavioral interventions focused on reducing positive rewarding effects and motivational salience during acute alcohol consumption may be crucial in future medication development and treatment of AUD,” they wrote.

For related information, see the Psychiatric News article “Underage Drinking Declines but Extreme Binge Drinking Rises.”

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Repeated Ketamine Infusions May Rapidly Reduce Chronic PTSD Symptoms

Repeated ketamine infusions may lead to rapid symptom improvement in people with chronic posttraumatic stress disorder (PTSD), suggests a study in AJP in Advance. Participants who received six ketamine infusions over a two-week period experienced greater drops in PTSD symptoms and comorbid depressive symptoms compared with participants who received the sedative midazolam.

The findings are “an important next step in our quest to develop novel pharmacologic interventions for this chronic and disabling disorder, as a large number of individuals are not sufficiently helped by currently available treatments,” said lead author Adriana Feder, M.D., of the Icahn School of Medicine at Mount Sinai in a press release.

The study involved patients aged 18 to 70 with a primary diagnosis of PTSD who had been experiencing symptoms for at least three months and had a score of ≥30 on the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), indicating symptoms of at least moderate severity. In total, 30 patients were randomly assigned to receive six infusions of either IV ketamine or midazolam (psychoactive placebo control) approximately three times a week for two weeks.

The researchers evaluated the study participants using several measures, including the CAPS-5 and the Montgomery-Åsberg Depression Rating Scale (MADRS), before the first infusion and following the first and second week of infusions. On infusion days, the researchers also evaluated the study participants for potential side effects (including dissociative and manic symptoms) before and following the infusion.

The ketamine group showed a significantly greater improvement in CAPS-5 and MADRS total scores than the midazolam group from baseline to week 2, Feder and colleagues reported. Additionally, significantly more participants in the ketamine group (67%) experienced a ≥30% reduction in symptoms from baseline compared with those in the midazolam group (20%).

“Ketamine infusions were associated with marked improvements across three of the four PTSD symptom clusters: intrusions, avoidance, and negative alterations in cognitions and mood,” the authors wrote. “In the subsample of ketamine responders, improvement in PTSD symptoms was rapid, observed 24 hours after the first infusion, and maintained for a median of 27.5 days after the primary outcome assessment day.”

The most frequently reported side effects by the ketamine group included blurred vision, dizziness, fatigue, and headache. Although some dissociative symptoms emerged during ketamine infusions, these symptoms tended to resolve within two hours.

“The study findings suggest the overall safety and tolerability of repeated ketamine infusions in this patient population. Further research is needed to evaluate the efficacy of novel interventions to prevent PTSD symptom relapse over time, including clinical trials to evaluate the safety, tolerability, and efficacy of periodic intravenous ketamine (or intranasal esketamine) administration as maintenance over several months … and studies examining whether combining repeated ketamine administration with evidence-based psychotherapy for PTSD can help reduce the likelihood of relapse after cessation of ketamine infusions,” the authors concluded.

For related information, see the American Journal of Psychiatry article “Psychedelics and Psychedelic-Assisted Psychotherapy.”

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Youth With Congenital Heart Disease at Elevated Risk of Depression, Anxiety, ADHD, Study Finds

Children and adolescents with a congenital heart disease are at greater risk than those without of developing depression, anxiety, or attention-deficit/hyperactivity disorder (ADHD), according to a report in Pediatrics.

“Our data support the notion that the population of patients with [congenital heart disease], regardless of disease severity, would likely benefit from mental health screening and evidence-based therapy earlier in childhood,” wrote Vincent Gonzalez, M.D., of Baylor College of Medicine and colleagues.

Gonzalez and colleagues compiled electronic health record data from 118,785 youth aged 4 to 17 years who were hospitalized or seen in the emergency department at Texas Children’s Hospital between 2011 and 2016. They compared the rates of depression, anxiety, and ADHD among children with or without congenital heart disease, based on receiving a diagnosis and/or medication for one of these disorders. (Since anxiety and depression are treated with similar medications, the authors condensed these disorders into one category.)

Of the 118,785 youth in the sample, 1,164 had congenital heart disease, split roughly equally between simple and complex defects, as defined by the American Heart Association/American College of Cardiology guidelines. Overall, 18.2% and 5.1% of youth with congenital heart disease had a diagnosis or medication for anxiety/depression and ADHD, respectively, compared with 5.2% and 2.1%, respectively, of youth with no congenital heart disease. The prevalence of anxiety/depression or ADHD was statistically higher in children with congenital heart disease across all age groups studied: 4 to 9 years, 10 to 13 years, and 14 to 17 years. The odds of depression/anxiety or ADHD was about the same in children with simple or complex congenital heart disease.

Gonzalez and colleagues also found that minority and uninsured youth were significantly less likely to be diagnosed or treated for anxiety/depression or ADHD compared with white and insured youth, respectively, regardless of congenital heart disease severity. “[T]hese data underscore the importance of recognizing potential racial or ethnic bias in diagnosing mental health in children with [congenital heart disease], as well as enabling insurance coverage for treating these disorders,” they wrote.

For related information, see the Psychiatric News article “Acquired Mutations Link Congenital Heart Disease, Neurodevelopmental Disorders.”

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