FDA Approves Deutetrabenazine for Treatment of Tardive Dyskinesia

Teva Pharmaceuticals Ltd. on Wednesday announced that the Food and Drug Administration has approved Austedo (deutetrabenazine) tablets for the treatment of adults with tardive dyskinesia (TD). Deutetrabenazine is a small molecule vesicular monoamine 2 transporter (VMAT2) inhibitor that has FDA approval for the treatment of chorea associated with Huntington’s disease.

The approval was based in part on the results of two 12-week, randomized, double-blind, placebo-controlled, multicenter trials, which compared changes in involuntary movements in 335 patients with TD who took deutetrabenazine or placebo. A total of 62% of the patients had concurrent diagnoses of schizophrenia/schizoaffective disorder, and 33% had a mood disorder; 86% were receiving concomitant antipsychotics.  

For the first trial, 222 patients aged 21 to 81 were randomly assigned to deutetrabenazine (12 mg/day, 24 mg/day, 36 mg/day) or placebo. Two dosage levels—24 mg/day and 36 mg/day—were associated with statistically significant improvement in patients’ Abnormal Involuntary Movement Scale (AIMS) score, from baseline to week 12, compared with placebo.

For the second trial, 113 patients aged 25 to 75 received daily doses of placebo or deutetrabenazine, starting at 12 mg/day, with titration up to 48 mg/day over a six-week period. This was followed by a six-week maintenance period at an average dose of 38.3 mg/day. From baseline to week 12, the AIMS total score decreased significantly in patients receiving deutetrabenazine compared with those receiving placebo. 

“We are pleased to bring forward this second indication for Austedo to treat the underserved tardive dyskinesia population,” Michael Hayden, M.D., Ph.D., president of Global R&D and chief scientific officer at Teva, said in a Teva press release. “We believe physicians treating tardive dyskinesia will appreciate the therapy’s dosing flexibility and the ability to focus on directly treating the movement disorder and not disrupt the ongoing treatment for the underlying condition.”

According to Teva, the most common adverse effects reported by patients taking Austedo were nasopharyngitis and insomnia. 

For more information, see the Psychiatric News PsychoPharm article “New Hope for Patients With Tardive Dyskinesia” by Stanley N. Caroff, M.D.

Psychotic Experiences Increase Risk of Suicidal Thoughts, Behaviors

Regardless of age, psychotic experiences can increase the likelihood that a person will think about, plan, and/or attempt suicide, according to a study published today in JAMA Psychiatry. The report also suggests that the association between psychotic episodes and suicidal thoughts and behaviors was most prominent in children aged 12 years and younger and remained statistically significant after adjusting for antecedent mental disorders and demographic factors.

“This is an important finding from a clinical point of view because it suggests that PEs [psychotic experiences] may be a predictor of subsequent STBs [suicidal thoughts and behaviors] even in individuals who do not meet criteria for mental disorders,” wrote Evelyn J. Bromet, Ph.D., of the Department of Psychiatry at Stony Brook University School of Medicine and colleagues. 

The findings were based on data derived from World Health Organization World Mental Health Surveys. Survey participants were specifically asked about hallucinatory and delusional experiences, their age when the experiences began, and the number of psychotic episodes per year. Survey participants were also asked about lifetime occurrence of suicidal ideation, suicide plans, and suicide attempts, and their age when these thoughts and/or actions first occurred. The researchers controlled for demographic factors, including the respondent’s age at time of interview, sex, and country.

Of the 33,370 adults from 19 countries surveyed, 2,488 reported psychotic experiences. Respondents with one or more psychotic episodes had twofold increased odds of subsequent suicidal thoughts and behaviors after adjusting for antecedent or intervening mental disorders (suicidal ideation: odds ratio [OR], 2.2; suicide plans: OR, 2.1; and suicide attempts: OR, 1.9). There was also a threefold to fourfold increased odds of various suicidal thoughts and behaviors in those with more frequent annualized psychotic episodes (more than 0.3 episodes per year) compared with those with less frequent annualized psychotic episodes (0.3 episodes or less per year), with ORs ranging from 3.0 for attempts to 3.8 for plans.

“From a public health perspective, we speculate that the inclusion of PE items in routine screening tools could improve the prediction of suicide risk. Our study lends additional weight to the call for the routine inclusion of PE items when assessing STBs in both research and clinical settings,” the authors concluded.

For related information, see the Psychiatric News article “Hallucinations Can Be Marker for Variety of Psychiatric Disorders in Youth.”

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Collaborative Care Increases Access, Abstinence in Patients With Opioid, Alcohol Use Disorder

A collaborative care intervention implemented at two large clinics in a Federally Qualified Health Center (FQHC) appears to have expanded access to evidence-based treatment for patients with opioid and/or alcohol use disorder (OAUD) while also increasing the number of patients achieving abstinence, according to a report in JAMA Internal Medicine.

Katherine Watson, M.D., and colleagues at RAND randomized 377 primary care patients with OAUD to either a collaborative care intervention (187) or usual care (190). The collaborative care intervention was designed to increase the delivery of either a six-session brief psychotherapy treatment and/or medication-assisted treatment with either sublingual buprenorphine/naloxone for opioid use disorders or long-acting injectable naltrexone for alcohol use disorders. (Patients with both alcohol and opioid use disorders received one or the other of the medications, based on the clinical judgment of the physician.)

Following randomization, patients in the collaborative care group met with care coordinators, who encouraged the patients to meet with a therapist for evaluation and treatment planning. These patients were entered into a registry that tracked treatment progress and prompted care coordinators to reach out to patients following missed visits. Care coordinators conducted regular assessments of substance use; results were entered into the registry and reviewed during team meetings. In contrast, patients in the usual care group were told by the research team that the clinic provided OAUD treatment and given a phone number for appointment scheduling and a list of community referrals. They did not receive any additional outreach or contact.

At six months, the proportion of participants who had received any evidence-based OAUD treatment (brief psychotherapy treatment and/or medication-assisted treatment) was higher in the collaborative care group compared with the usual care group (39% vs. 16.8%). Also at six months, a higher proportion of patients in the collaborative care group reported abstinence from opioids or alcohol (32.8% vs. 22.3%).

“These findings suggest that treatment for OAUDs can be integrated into primary care, and that primary care-based treatment is effective for OAUDs,” the researchers wrote.

APA offers training in collaborative care through a federal grant. For more information about collaborative care, see the Psychiatric News article “Reflections on Implementation of Collaborative Care” and the Psychiatric Services article “A Research Agenda to Advance the Coordination of Care for General Medical and Substance Use Disorders.”

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ADHD Symptoms May Lead Adolescent Girls to Start Smoking Early

Adolescents with more severe symptoms of attention-deficit/hyperactivity disorder (ADHD)—particularly high levels of inattention—may be more likely to start smoking cigarettes before they reach 18, according to a study published Friday in AJP in Advance. This risk of smoking was especially apparent for adolescent girls with ADHD.

“This study confirms that specific relationships between inattention and smoking observed in previous research may arise partially from causal effects, which has implications for intervention,” wrote Irene Elkins, Ph.D., of the University of Minnesota and colleagues. “Preventing nicotine exposure among females with ADHD is critical, as adolescent females may be more susceptible to nicotine’s neurotoxic effects.”

Elkins and colleagues analyzed data from three study cohorts of same-sex twins that included 3,762 individuals (52% female). They found that regardless of gender, adolescents with high inattentive symptoms were more likely to start smoking (and to do so earlier). However, unlike with adolescent boys, these symptoms were also associated with a faster progression to daily smoking, more cigarettes smoked per day, and more symptoms of nicotine dependence. 

Further, within identical twin pairs of girls, the twin with greater inattention problems was significantly more likely to smoke more, smoke daily, and develop nicotine dependence. This finding points to a possible causal influence of inattention on smoking, as identical twins have similar genetic and familial traits. This difference between identical twin pairs was not seen in boys.

Elkins and colleagues noted that the evidence of causality bolsters the idea that teenage girls with ADHD use nicotine to self-medicate their attention problems, but cautioned that even if inattention is causal, other factors may be involved. “The increased vulnerability of females to peer and academic consequences of inattention may contribute to greater depression and anxiety among inattentive females relative to inattentive males, increasing their receptivity to nicotine’s effects on attention and mood.”

For related information, see the Psychiatric News article “ADHD Diagnoses Climb Across Racial/Ethnic Groups.” 

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Many Women Do Not Disclose Postpartum Mood Symptoms, Survey Finds

About 20% of women failed to disclose symptoms of postpartum mood disorder (PPMD) to their health care providers, while 46% said that barriers such as stigma and negative perception of therapy made it difficult or impossible to report such symptoms, according to the results of a survey published in this month’s Maternal and Child Health Journal.

Betty-Shannon Prevatt, M.A., L.P.A., and Sarah Desmarais, Ph.D. of North Carolina State University conducted an online survey of 211 predominantly white, middle-class women who had given birth within the past three years on their perceived barriers to psychological treatment (PBPT). The PBPT questionnaire included items in eight broad categories: stigma, lack of motivation, emotional concerns, negative evaluation of therapy, misfit of therapy to needs, time constraints, participation restrictions, and availability of services.

The participants also filled out self-reports on their socioeconomic status, depression and anxiety symptoms, stress levels, support network, and to whom they had disclosed possible PPMD symptoms.

Over half (107) of the respondents reported experiencing disrupted mood during the postpartum period, but only 52 received a mental health diagnosis from a physician. Stigma, time constraints, and lack of motivation were the most frequently reported barriers. Unemployment, history of mental illness, current depression/anxiety/stress symptoms, and self-identification of postpartum symptoms were associated with reporting more barriers.

“These findings suggest that those women most in need of treatment are also the ones who perceive the most barriers to receiving care,” the authors wrote. “Because the current sample was fairly well educated and affluent, we would expect even greater endorsement of barriers among women of more modest education and means, who are at heightened risk of PPMD.”

In contrast, higher levels of social support were associated with greater odds of symptom disclosure. “The social support networks of expectant women are underutilized resources for improving maternal mental health,” the authors wrote. “To that end, interventions should encourage women to fortify their social support network while pregnant and provide strategies for mobilizing this support during the postpartum period.”

For related information, see the Psychiatric News article “Early Postpartum Depression Screenings Not Enough to Identify High-Risk Women.”

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Reduced Nicotine Content in Cigarettes May Decrease Addiction Potential in Vulnerable Populations

A national regulatory policy that cuts the nicotine content of cigarettes may decrease the addiction potential of cigarettes—and those effects would extend to populations highly vulnerable to tobacco addiction, according to a study published Wednesday in JAMA Psychiatry.

In late July, the Food and Drug Administration proposed reducing nicotine levels in tobacco products to decrease the chances of people becoming addicted and help currently addicted smokers to quit.

“Evidence in relatively healthy and socially stable smokers indicates that reducing the nicotine content of cigarettes reduces their addictiveness,” lead author Stephen T. Higgins, Ph.D., a professor and vice chair of psychiatry at the University of Vermont in Burlington, said in a press release. “Whether that same effect would be seen in populations highly vulnerable to tobacco addiction was unknown.”

The study consisted of a double-blind, within-participant assessment of acute response to “research cigarettes” with nicotine content ranging from levels below a hypothesized addiction threshold to those representative of commercial cigarettes (0.4 mg/g, 2.3 mg/g, 5.2 mg/g, and 15.8 mg/g of tobacco) at three academic sites. A total of 169 daily smokers (120 women, 49 men) from three vulnerable populations—people with affective disorders (n=56), people with opioid dependence (n=60), and socioeconomically disadvantaged women (n=53)—completed 14 experimental sessions lasting two to four hours each.

After smoking their usual-brand cigarette in the first session, participants smoked one research cigarette of varying doses of nicotine under double-blind conditions for sessions 2 to 5. Participants were required to use a plastic cigarette holder when smoking research cigarettes, to measure smoking topography—the number of puffs, length, and speed of each puff. A Cigarette Purchase Task was completed after each smoking session to measure the effects of cost on the participant’s rate of smoking. Additional questionnaires assessed nicotine withdrawal, smoking urges, and nicotine dependence.

For sessions 6 to 11, participants were asked to select the cigarette they preferred of two options (six different dose combinations were offered over this phase of trial). A computer program recorded which of the two cigarettes participants preferred for each session and whether or not they wanted to continue to smoke that selection after two puffs or abstain. The final phase of the trial (sessions 12-14) followed the same protocol, but measured only the highest and lowest doses of nicotine.

While participants tended to prefer the higher nicotine dose cigarettes, the researchers found that the low-nicotine dose cigarettes could serve as economic substitutes for higher-dose commercial-level nicotine cigarettes when the cost of the latter was greater.

“Reductions in reinforcing effects were achieved in the present study without causing untoward withdrawal, craving, or compensatory smoking,” Higgins and colleagues noted.

For related information, see the Psychiatric News article “Tobacco Addiction, Treatment Need More Attention by Clinicians.”

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Physical Comorbidities, Poor Adherence Appear Linked to Delayed Remission, Nonremission in Depression

Physical comorbidities and poor treatment adherence appear to be associated with both a failure to remit and a longer time to remission of depression, according to a report using data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. The findings, which were reported in Depression and Anxiety, point to the importance of interventions aimed at improving treatment adherence and addressing both the physical and mental health needs of the patient.

STAR*D, a multisite, multistep, prospective, randomized trial, compared the effectiveness of several medications or combinations of medications in adults aged 18 to 75 with major depressive disorder. Those who did not become symptom-free during one level of treatment could move the next level of treatment. Relying on data from 3,606 patients in STAR*D, Ramin Mojtabai, M.D., Ph.D., M.P.H., of Johns Hopkins University used statistical modeling to distinguish patients whose depression symptoms did not remit during the trial from those whose symptoms did remit and to characterize risk factors for each. 

According to this analysis, 14.7% of the STAR*D participants were estimated to be nonremitters. Over the course of the 12-month trial, time to remission varied considerably among remitters.

“This finding is consistent with the past research on the treatment of chronic depression and is an important consideration when deciding on the length of a new medication treatment trial for patients who have not responded to prior trials,” Mojtabai wrote. “These patients may need a longer period than the 4-8 weeks recommended in the current practice guidelines to fully respond to a treatment regimen.”

Failure to remit was significantly associated with not having a college education, current unemployment, and longer duration of depressive episode. Longer time to remission was significantly associated with seeking care at a specialty treatment setting, poorer mental health functioning assessed by the 12-item Short-Form Health Survey, and impairment in role functioning assessed by the Work and Social Adjustment Scale.

“Treatment resistance is often clinically defined by nonremission after two adequate antidepressant medication treatment trials. Yet, treatment-resistant cases are likely heterogeneous, [composed] of those who would remit in response to treatment more slowly and those who would not remit and would have a chronic course,” Mojtabai wrote. “Being able to distinguish nonremission from a longer time to remission among the remitters has important implications for understanding the causes of treatment resistance and for treatment planning.”

For related information, see the Psychiatric News article “Self-Reported Health Status May Predict Response to Depression Treatment” and the Psychiatric Services article “Systematic Review of Integrated General Medical and Psychiatric Self-Management Interventions for Adults With Serious Mental Illness.”

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"Purpose in Life" Linked to Better Physical Functioning in Older Individuals

A sense of purpose in life appears to be associated with objective measures of physical function in individuals over 50 years of age, according to a report in JAMA Psychiatry.

The study adds to a growing literature supporting “positive psychiatry”—a focus on psychological strengths such as resilience and purpose—and supports the idea that clinicians should discuss purpose of life with their older patients.  

Eric Kim, Ph.D., of the Harvard T.H. Chan School of Public Health and colleagues analyzed data from the Health and Retirement Study, an ongoing nationally representative panel study of U.S. adults older than 50 years, at two points—2006 and 2010. Purpose in life was assessed in 2006 using the seven-item Purpose in Life subscale of the Ryff Psychological Well-being Scales, in which respondents rate the degree to which they agree with a statement (for example, “Some people wander aimlessly through life, but I am not one of them”) on a six-point Likert Scale.

At both time points (2006 and 2010) hand grip strength and walking speed were assessed using standard protocols and measurement tools.

The researchers found higher baseline purpose in life was associated with decreased risk of developing slow walking speed during four years of follow-up and small increases in walking speed among people with high purpose. Higher purpose was also associated with increases in grip strength but was less robustly associated with decreased risk of developing weak grip strength.

“Although mechanisms that explain the potential health effects of purpose have not yet been clearly defined, there are likely indirect (such as, other health-related behaviors) and/or direct effects (such as, altered biological function),” Kim and colleagues wrote. “For example, people with higher purpose are more proactive in taking care of their health, have better impulse control, and engage in healthier activities.”

Past APA President Dilip Jeste, M.D. (pictured above), director of the UC San Diego Center for Healthy Aging, said the results are supportive of a large body of research emerging in the last decade showing an association between psychological well-being and measures of physical health.

Similarly, he said a robust literature has linked speed of walking and hand grip to biological age. “These two discrete measures have come to be regarded as a shorthand for biological age, a clinical marker for aging,” he said.

Finding meaning and purpose in life is especially critical—and can be challenging—for adults who have retired from jobs that for years may have served as their identity. “There’s no single answer to the purpose of life and it will be different for different people,” Jeste told Psychiatric News. “Clinicians can help with this task and should ask their older patients, ‘What’s your purpose in life?’ because patients may not bring the subject up themselves.”

For related information, see Positive Psychiatry: A Clinical Handbook, coedited by Dilip Jeste, M.D.

Study Estimates 630K Infants With Fetal Alcohol Spectrum Disorder Born Globally Each Year

One of every 13 women worldwide who consumed alcohol during pregnancy is estimated to have had a child with fetal alcohol spectrum disorder (FASD), according to a study published today in JAMA Pediatrics. Based on these global estimates, some 630,000 infants with FASD are born each year.

The analysis also revealed FASD is notably more frequent among aboriginal populations, children in foster care and residing in orphanages, incarcerated populations, and those in psychiatric care.

“The higher prevalence emphasizes that these high-risk populations deserve special attention for the planning and organization of targeted screening strategies, improved access to diagnostic services, and prevention of maternal alcohol consumption,” wrote senior author Svetlana Popova, Ph.D., of the Centre for Addiction and Mental Health in Toronto and colleagues.

Popova and colleagues first conducted a meta-analysis of 24 separate studies that assessed FASD rates; these studies included over 1,400 children with FASD in eight countries: Australia, Canada, Croatia, France, Italy, Norway, South Africa, and the United States. They then used available global data on alcohol consumption rates by women to predict FASD prevalence in the remaining countries.

The global prevalence of FASD was estimated to be around 7.7 per 1,000 children, while the prevalence in the United States was higher at 15.2 per 1,000 children. South Africa had the highest individual country prevalence of FASD at 111.1 per 1,000 children, while Europe had the highest regional prevalence at 19.8 per 1,000 children.

“The current findings emphasize that FASD is not restricted to disadvantaged groups but rather occurs throughout society, regardless of socioeconomic status, educational attainment, or ethnicity,” the authors wrote. “Given the current trend in unplanned pregnancies in developing and developed countries (39% and 47%, respectively), efforts should be made to educate all women of childbearing age about the potential detrimental effects of prenatal alcohol exposure on the developing fetus.”

“Most individuals with FASD living today and those yet to be born will never receive a diagnosis,” wrote Albert Chudley, M.D., of the University of Manitoba’s Max Rady College of Medicine in a related editorial. “Priority for screening and identifying children at risk for FASD should begin with those in the highest-risk categories, such as certain minority groups, children in care, youth involved with the law, and children with learning difficulties and mental health issues.”

For related information, see the Psychiatric News article “NIAAA Proposes Updated Guidelines for Fetal Alcohol Spectrum Disorders.”

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Dialectic Behavioral Therapy May Lead to Improvements in Children With Disruptive Mood Dysregulation Disorder

There are no established treatments for disruptive mood dysregulation disorder (DMDD), a disorder characterized by chronic irritability and severe, recurrent outbursts in children. A study in the Journal of the American Academy of Child and Adolescent Psychiatry suggests dialectical behavioral therapy for children (DBT-C) may offer an advantage over individual therapy for preadolescent children with the disorder.

“Emotion regulation, defined as intrinsic capabilities individuals use to modulate the experience and expression of emotions based on internal or external demands, appears to be a core deficit in DMDD,” wrote Francheska Perepletchikova, Ph.D., of Weill Cornell Medical Center in New York and colleagues. “DBT is an empirically validated therapy designed to treat emotional regulation, suicidal thoughts, and non-suicidal self-injury associated with borderline personality disorder.”

For the study, Perepletchikova and colleagues randomly assigned 43 children aged 7 to 12 to DBT-C or treatment as usual (TAU) over 32 weeks. DBT-C consisted of weekly, 90-minute sessions conducted individually with each family; sessions were divided into child counseling, parent training, and skills training with parents and children. Children in the TAU group received up to 32 weeks of individual therapy, with each clinician determining session duration, frequency, and treatment approach. Assessments were conducted at the beginning of the study, followed by every 8 weeks until the end of 32 weeks, and again at a follow-up three months later.

After 32 weeks, the rate of positive response (“much improved” or “very much improved” on the Clinical Global Impressions Improvement Scale) was 90.4% for children receiving DBT-C and 45.5% for those receiving TAU. Children receiving DBT-C also showed higher rates of symptom remission (52.4% vs. 27.3%) and lower use of psychiatric medications (19.1% vs. 54.4%). 

The DBT-C group also had much higher retention than the TAU group, though the authors noted this may have been due to the fact DBT-C was provided free of charge while TAU participants had to pay through insurance. 

“A confirmatory efficacy trial is needed with a more structured TAU, with built-in strategies for retention and without requirement for payment,” the authors wrote. “Further research needs to examine the effects of DBT-C on specific outcomes, including depression and anxiety, as well as ... mediating factors, including emotion regulation, creation of validating environment, and treatment duration.”

For related information, see the Psychiatric News article “How to Diagnose and Treat Disruptive Mood Dysregulation Disorder.”

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Poor Vision May Be Associated With Worse Cognition in Older Adults

Poor vision appears to be associated with worse cognitive function in older U.S. adults, according to a study published today in JAMA Ophthalmology.

“This is the first evidence, to our knowledge, of a strong, clear association between self-reported [visual impairment] and cognitive impairment in a large-scale, broadly representative sample of the U.S. population,” senior author Suzann Pershing, M.D., M.S., of the Stanford University School of Medicine and colleagues wrote. This association remained after adjusting for demographics as well as age-related predictors of cognitive decline including hearing and physical function impairments, the authors noted.

To examine the relationship between visual impairment and cognition in older U.S. adults, the researchers analyzed two national data sets, the National Health and Nutrition Examination Survey (NHANES), 1999-2002, and the National Health and Aging Trends Study (NHATS), 2011-2015. Vision was measured at distance and near and by self-report in the NHANES and by self-report alone in the NHATS. The NHANES measured Digit Symbol Substitution Test (DSST) score and relative DSST impairment (DSST score ≤28, lowest quartile in study cohort), and the NHATS measured possible or probable dementia (based on self-report and performance on cognitive tests).

The NHANES included 2,975 respondents aged 60 years and older who completed the DSST measuring cognitive performance. The NHATS included 30,202 respondents aged 65 years and older with dementia status assessment. In the NHANES, distance visual impairment (odds ratio [OR], 2.8) and subjective visual impairment (OR, 2.7) were both associated with lower DSST scores and higher odds of DSST impairment. The NHATS data corroborated these results, with all vision variables associated with higher odds of dementia (distance visual impairment: OR, 1.9; near visual impairment: OR, 2.6).

The authors cautioned that “the results presented in this cross-sectional analysis are purely observational. A causative relationship between [visual impairment] and cognitive dysfunction cannot be established without longitudinal studies.” 

Nonetheless, they concluded that “should causality be established, this may contribute to the value of vision screening, not only to identify patients who may benefit from treatment of correctable eye diseases but also to suspect broader limitations in function from cognitive and directly visual tasks.”

Numerous questions remain, wrote Jennifer Evans, Ph.D., of the London School of Hygiene and Tropical Medicine in a related editorial. “If the results of this investigation are not a measurement artifact and not confounding, and visual impairment and cognition are indeed associated, then the next question is: which came first? … Would successful intervention for visual impairment (where possible) reduce the risk of cognitive impairment? Or is sensory impairment an early marker of decline?”

For related information, see the Psychiatric News article “Dual-Task Gait Testing Identifies MCI Patients Likely to Develop Dementia.”

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Billing for Psychotherapy Drops After 2013 Changes to CPT Psychiatry Codes

The proportion of psychiatric visits billed as psychotherapy declined significantly in the period following the 2013 update of Current Procedural Terminology (CPT) codes used for psychiatry, according to an analysis appearing in Psychiatric Services in Advance. Moreover, the most frequently billed psychiatric codes were those for evaluation and management (E/M).

“Given that the majority of visits to psychiatrists included E/M services only, efforts and incentives could be used to increase care coordination, treatment in teams, and colocation of mental health services to support the provision of mental health care,” wrote Tami L. Mark, Ph.D., of RTI International, William J. Olesiuk, Ph.D., of Truven Analytics, and colleagues at the Substance Abuse and Mental Health Services Administration.

On January 1, 2013, the Centers for Medicare and Medicaid Services (CMS) implemented significant revisions to the CPT code set for psychiatry and psychotherapy services, eliminating more than 30 of the most commonly used psychiatry CPT codes and introducing several new codes. The 2013 CPT revisions, formulated by the American Medical Association CPT Editorial Board, were designed to improve the ability of the codes to account for varying levels of work involved in psychotherapy and medical management, among other factors.

For the analysis, Mark, Olesiuk, and colleagues used 2012–2014 data from the Truven Health Analytics MarketScan Commercial Claims and Encounters (MarketScan) database. The MarketScan database reflects the entire claims experience of approximately 30 million individuals with private insurance annually. The sample in this study was restricted to office visits to psychiatrists in 2012 (prior to the CPT code changes) and in 2013 and 2014 (the two years after the CPT code changes).

After controlling for factors related to the patient, practice, and health plan, the authors found that the percentage of visits billed as psychotherapy dropped from 51% in 2012 to 41% in 2013, and 42% in 2014. In 2013, the most common CPT code was the E/M code 99213 (established patient office visit, low to moderate severity), followed by the E/M code 99214 (established patient office visit, moderate severity), and the 90833 add-on code (individual psychotherapy, 16–37 minutes).

“The change in CPT psychiatric billing codes resulted in a significant decline in documented psychotherapy by psychiatrists among privately insured patients,” the researchers stated. “Whether this was due to a change in actual treatments provided or a clarification of the extent to which psychotherapy was actually being provided … is an issue that requires further investigation.”

For questions and answers about CPT coding, see the Psychiatric News article “CPT Coding Q&As From Helpline.”

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Process Open for Submitting Proposals to Update DSM

The publicly accessible portal on the APA website for submitting proposed changes and updates to DSM-5 will turn a year old soon, and past APA President Paul Appelbaum, M.D., chair of the DSM Steering Committee, wants to be sure clinicians, researchers, and members of the public know they have a role to play in making DSM a “living document.”

The portal, which was launched in December 2016, was the first step in a process meant to allow incremental updates as new research evidence accumulates. Instead of engaging in an extremely expensive and time-consuming process that characterized the development of past editions of the diagnostic manual, the DSM Task Force wanted to seize on the opportunity afforded by digital communication by creating a process for changes to be made incrementally, as they become warranted by the weight of new evidence. Since the portal opened late last year, however, proposed revisions have been very few and relatively minor—for example, an editorial correction to the criteria for acute stress disorder and the addition of ICD-10-CM codes for substance use disorder in remission.

Appelbaum said he believes it is most likely that clinicians and researchers are not sufficiently aware that the process exists. "We want to make an effort to spread the word and publicize the existence of this process,” he said.

Visitors to the portal are guided through steps to submit proposals for the following specific kinds of revisions:

• Changes to an existing diagnostic criteria set that would markedly improve its validity.
• Changes to an existing diagnostic criteria set that would markedly improve reliability without an undue reduction in validity.
• Changes to an existing diagnostic criteria set that would markedly improve clinical utility without an undue reduction in validity or reliability.
• Changes to an existing diagnostic criteria set that would substantially reduce deleterious consequences associated with the criteria set without a reduction in validity.
• Addition of a new diagnostic category or specifier.
• Deletion of an existing diagnostic category or specifier/subtype.
• Corrections and clarifications, including changes aimed at improving the understanding and application of an ambiguous diagnostic criterion, specifier, or text.

For more information, see the Psychiatric News article “Process for Updating DSM-5 Is Up and Running.”

Regular Phone Check-Ins With Mental Health Clinician May Reduce Symptoms of Postpartum Depression

A telephone-based depression care management (DCM) program is effective at improving the symptoms of postpartum depression, particularly in women who experienced childhood sexual abuse, reports a study in the Journal of Clinical Psychiatry.

“Childhood maltreatment confers life-long risk for general and mental health disorders and affects the development of stress-responsive neuropsychiatric symptoms,” wrote Katherine Wisner, M.D., of Northwestern University and colleagues. “The regular (and crisis) telephone availability of a supportive clinician is a comforting and empowering resource that appears to be particularly therapeutic to women with childhood sexual abuse.”  

The trial involved 628 women who screened positive for depression (a score of 10 or greater on the Edinburgh Postnatal Depression Scale) four to six weeks after giving birth. The women were randomly assigned to receive either DCM or enhanced usual care (EUC). The DCM program involved regularly scheduled calls from a clinician who provided ongoing education, assisted with decisions about medication use during breastfeeding, monitored patient symptoms and progress, facilitated access to mental health services, and more. Women in the EUC group were given educational materials, encouraged to contact their health plan to facilitate treatment, and received one follow-up call.

Independent evaluators followed up with women in both groups at three, six, and 12 months postpartum to assess their health, functioning, and use of health care services. At 12 months, both groups showed significant improvements, with SIGH-ADS (Structured Interview Guide for the Hamilton Depression Rating Scale with Atypical Depression Supplement) and function scores significantly improving by at least 50% from baseline. Women in both groups reported similar health service use as well.

Women with a history of childhood sexual abuse (about 20% of the participants) responded more favorably to the DCM program compared with the EUC condition. For example, the SIGH-ADS scores of women with a history of childhood sexual abuse decreased by about 1 point during the follow-up period in the DCM group, but rose 1.7 points in the group receiving EUC.

“Why might monthly telephone contact with a mental health clinician benefit women with childhood sexual abuse significantly more than nonabused depressed postpartum women? Women with childhood sexual abuse may have difficulty coping with pregnancy due to the need for intimate examinations and birth, which may trigger traumatic memories,” the authors wrote.

For related information, see the Psychiatric News article “Researcher Discusses Goals and Challenges of Perinatal Mental Illness” and the Psychiatric Services article “Incremental Benefit-Cost of MOMCare: Collaborative Care for Perinatal Depression Among Economically Disadvantaged Women.”

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CBT Improves Functioning in Parents of Children With ASD

Parents of children with autism spectrum disorder (ASD) can benefit from involvement in their children’s cognitive-behavioral therapy (CBT), according to a pilot study posted online August 1 in the Journal of Autism and Developmental Disorders.

“Treatment effects occurred across all parents in depression, emotional regulation, perceptions of their children, and mindful parenting,” wrote Andrea L. Maughan and Jonathan A. Weiss, Ph.D., of York University in Toronto.

Investigators examined changes in the parents’ mental health, parenting skills, and expressed emotion following participation with their children in a randomized, controlled trial of 10 sessions of a CBT program developed to improve emotional regulation in children with ASD. CBT has emerged as an effective treatment for anxiety disorders in children with ASD who do not have an intellectual disability, the researchers noted.

Participants included 57 children with ASD and one parent of each child. Of the 57 parents, 80.7% were mothers of children with ASD (91.2% males). The children’s IQ scores ranged from 79 to 140. About 70% of parents had undergraduate university degrees. More than 90% of the children met criteria for at least one mental health problem on the Anxiety Disorders Interview Schedule for DSM-IV. Parent psychopathology and stress were measured using the Depression Anxiety Stress Scale. Child psychopathology and improvement were measured by the Clinical Global Impression Scale–Severity and Improvement.

Of the parents who had depression, their symptoms from pre- to post-intervention were significantly reduced, and overall the parents’ emotional regulation improved. 

“It may be that helping children to practice the emotion regulation strategies from the CBT program also resulted in parents learning strategies that are relevant to their own coping approach,” the researchers noted. 

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High-Risk Drinking, Alcohol Use Disorder Rises Significantly Over Past Decade

Between 2001-2002 and 2012-2013, the percentage of U.S. adults who engaged in regular high-risk drinking increased by almost 30%, and the percentage of people meeting criteria for alcohol use disorder (AUD) grew by 49.4%, according to a report published today in JAMA Psychiatry.

“Increases in all of these outcomes were greatest among women, older adults, racial/ethnic minorities, and individuals with lower educational level and family income,” Bridget F. Grant, Ph.D., of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and colleagues wrote.

Grant and colleagues compared information collected during face-to-face interviews from two nationally representative surveys of U.S. adults: NIAAA’s 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and the 2012-2013 NESARC-III. Survey participants were asked identical questions regarding 12-month alcohol consumption and how often they engaged in high-risk drinking (four or more standard drinks containing alcohol [for example 12 oz. beer or 5 oz. wine] on any given day for women; five or more standard drinks for men); for this study, high-risk drinking was defined as exceeding the daily drinking limits at least weekly. Participants were considered to have a DSM-IV AUD diagnosis if they met criteria for alcohol dependence or abuse in the past 12 months.

The study sample included 43,093 participants in the NESARC and 36,309 participants in the NESARC III. Between 2001-2002 and 2012-2013, alcohol use in the United States increased from 65.4% to 72.7% (11.2% increase), high-risk drinking increased from 9.7% to 12.6% (29.2% increase), and the prevalence of DSM-IV AUD increased from 8.5% to 12.7% (49.4% increase). 

“While the prevalence of AUD among both 12-month alcohol users and 12-month high-risk drinkers increased, the prevalence of AUD among high-risk drinkers (46.5% in 2001-2002 and 54.5% in 2012-2013) was much greater than the prevalence of AUD among 12-month users (12.9% in 2001-2002 and 17.5% in 2012- 2013), highlighting the critical role of high-risk drinking in the increase in AUD between 2001-2002 and 2012-2013,” the authors wrote. 

In a related editorial, Marc A. Schuckit, M.D., a professor of psychiatry at the University of California, San Diego, described the costs associated with alcohol-related problems and noted that the populations that appear to be at greatest risk may also be least likely to have access to care.

The article “makes a compelling case that the United States is facing a crisis with alcohol use, one that is currently costly and about to get worse,” he wrote. It is also a reminder that “the chilling increases in opioid-related deaths reflect a broader issue regarding additional substance-related problems.”

The findings “highlight the urgency of educating the public, policymakers, and health care professionals about high-risk drinking and AUD, destigmatizing these conditions, and encouraging those who cannot reduce their alcohol consumption on their own, despite substantial harm to themselves and others, to seek treatment,” Grant and colleagues wrote.

For related information, see the Psychiatric News article “Why Treat Alcohol Use Disorders in Primary Care?” and the AJP article “Vulnerability for Alcohol Use Disorder and Rate of Alcohol Consumption.”

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Oregon Governor to Veto Psychologist Prescribing Bill

Oregon Gov. Kate Brown (D) announced yesterday she will veto legislation (Oregon HB 3355) that would have authorized the Oregon State Board of Psychologist Examiners to issue prescriptive authority to licensed psychologists who meet specified requirements. 

“Access to appropriate and timely mental health services is a serious issue in Oregon,” Brown said in a statement. “I share the concerns about inadequate services that arose during the debate on this bill, particularly for children, vulnerable populations, and rural communities. Unfortunately, [HB 3355] is not a proven solution. There remains a lack of evidence that psychologist prescribing will improve access or quality of care. While prescription drugs may be appropriate mental health treatment for some patients, there are also significant health risks with some drug therapies. HB 3355 contains several flaws that prevent the policy from being implemented safely.”

Brown’s announcement is a victory for the Oregon Psychiatric Physicians Association (OPPA) and APA’s Department of Government Relations, which advocated against the bill along with state representatives from child psychiatry, academic psychiatry, and patient and community advocates. 

One of those efforts included an op-ed published in the June 24 Register Guard (in Eugene, Ore.)  by leaders of the OPPA, the Oregon Council on Child and Adolescent Psychiatry, and others who called HB 3355 “a reckless experiment.” They wrote, “There is no question that Oregon needs more mental health services, both from trained physicians and other mental health providers. Letting psychologists practice medicine is not the answer. … Not only would HB 3355 fail to deliver more or better care, it would endanger patients’ lives.” 

The op-ed appeared under the byline of Jim Lace, M.D., chair of the Oregon Medical Association’s Legislative Committee, and Martin Rafferty, executive director of the nonprofit Youth M.O.V.E. Oregon. It was co-signed by Jonathan Betlinski, M.D., president of OPPA; David Jeffery, M.D., president of the Oregon Council on Child and Adolescent Psychiatry; Ajit Jetmilani, M.D., director of child and adolescent psychiatry at Oregon Health and Science University; and Sandy Bumpus, executive director of the Oregon Family Support Network.

“We applaud Gov. Brown for her decision to reject this bill as a solution to the problem of access to care, and we congratulate the leaders of the Oregon district branch for their tireless work advocating for patient safety,” said APA CEO and Medical Director Saul Levin, M.D., M.P.A. “APA will continue to support members in Oregon and elsewhere in their efforts to expand access to care through appropriate means, including expansion of integrated care and telepsychiatry.”

For related information, see the Psychiatric News article “Psychologist Prescribing Bills Defeated in Many States.”

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Lithium, Divalproex Appear Effective, Well-Tolerated in Older Adults With Bipolar Mania

Lithium and divalproex are both well-tolerated and effective at controlling mania in older adults with bipolar disorder, reports a study in AJP in Advance. The observed rates of response or remission were similar to rates reported in younger patients with bipolar disorder despite this study using lower medication dosages and serum concentrations. 

“Our main findings, if confirmed, have implications for geriatric practice and investigation,” wrote lead author Robert Young, M.D., of Weill Cornell Medicine and colleagues. “Treatment with lithium or divalproex with conservative serum concentration targets, combined with limited use of rescue and adjunctive medications, was tolerated by older patients with mania, and it benefited a substantial proportion of them.” 

For the study, Young and colleagues compared the tolerability and efficacy of lithium and divalproex in 224 inpatients and outpatients aged 60 years or older with bipolar I disorder who presented with a manic, hypomanic, or mixed episode. The patients were randomly assigned to either lithium (target serum concentration, 0.80–0.99 mEq/L) or divalproex (target serum concentration, 80–99 μg/mL) for nine weeks. All study participants received standard behavioral interventions, such as a reduction of excess social stimuli.

During the first three weeks of treatment, patients received lorazepam if they had significant anxiety, agitation, or insomnia, and then oral risperidone if they failed to respond to the lorazepam and behavioral intervention. Only 17% and 14% of the participants taking lithium and divalproex, respectively, required rescue risperidone.

After nine weeks, manic symptoms, as assessed by the Young Mania Rating Scale (YMRS), improved significantly in both groups, with the lithium group averaging 3.90 points better. Response rates (50% or greater reduction in YMRS score) were 78.6% for lithium and 73.2% for divalproex; rates of remission (YMRS score ≤9) were 69.6% for lithium and 63.4% for divalproex. 

Contrary to expectations based on existing literature, divalproex did not induce higher rates of sedation than lithium. However, as has been previously found, lithium did result in more cases of tremor. Other side effects, including nausea and weight gain, were similar in both groups.

For related information, see the Psychiatric News PsychoPharm article “Lurasidone May Work Better as Monotherapy in Older Patients With Bipolar Depression.”

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Integrated Behavioral Health Home Program May Benefit Patients With Psychotic, Bipolar Disorders

Participation in a behavioral health home (BHH) program by patients with serious mental illness was associated with significant reductions in emergency department (ED) visits and psychiatric hospitalizations, and increased HbA1c monitoring, according to a study in Psychiatric Services in Advance.

“The study extends existing literature by evaluating a clearly defined BHH program that was implemented in a safety-net institution for use by adults with schizophrenia spectrum disorders or bipolar disorder,” wrote lead author Miriam C. Tepper, M.D., a psychiatrist affiliated with Cambridge Health Alliance in Somerville, Mass., and colleagues. 

Data were collected from electronic health records (EHRs) in an urban academic medical system in Massachusetts that provides a full continuum of care to more than 140,000 patients annually. Records of 424 patients (n=369, psychotic disorder; n=55, bipolar disorder) assigned to BHH were compared with 1,521 individuals with the same diagnoses who were not enrolled in the BHH. 

The BHH implemented four key general medical and psychiatric service enhancements: 1) On-site medical care, health promotion, support for care coordination and transitions, and peer-to-peer engagement opportunities; 2) Enhanced EHR functionality including provider alerts for patient transitions, a registry for monitoring individuals’ health status and service delivery, acute care discharge reports to facilitate follow-up, and a performance measurement dashboard; 3) The addition of three new positions—a nurse practitioner, care manager, and program manager—to supplement the existing clinical team; and 4) Shifting clinical practice toward fully integrated, team-based care organized around group therapy modalities, health promotion, chronic disease screening and monitoring, social inclusion, and population management.

During the 12-month study period, the total number of ED visits per capita among BHH patients decreased significantly from 1.45 to 1.19 visits, while total ED visits rose in the control group from 0.99 to 1.16. Total psychiatric hospitalizations per capita declined for the BHH patients (from 0.22 to 0.10), but remained stable in the control group (from 0.145 to 0.147). Screening rates for HbA1c increased more among BHH patients (from 0.49 to 0.64) than among control group patients (from 0.40 to 0.46). 

The BHH had no effect on rates of general medical hospitalization or LDL screening or on values of metabolic parameters for diabetic patients over the 12-month period. 

“The lack of association between BHH participation and reductions in general medical inpatient utilization was unexpected,” the authors wrote. “One possible explanation is that intervention components emphasize health promotion activities that are designed to improve long-term health rather than stem acute medical service utilization.”

For related information, see the Psychiatric News article “New York State’s Path to Behavioral Health Integration,” by Jay Carruthers, M.D., and Lloyd Sederer, M.D.

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APA Member McCance-Katz Confirmed First HHS Assistant Sec’y for MH/SU; Adams Confirmed Surgeon General

Elinore McCance-Katz, M.D., Ph.D., was confirmed yesterday by the U.S. Senate as the first Assistant Secretary for Mental Health and Substance Use in the Department of Health and Human Services (HHS), and Jerome Adams, M.D., M.P.H., was confirmed as U.S. Surgeon General.

Both nominees were endorsed by APA. McCance-Katz and Adams were confirmed by the Senate, along with three other nominees for HHS leadership roles. Hearings were held on Tuesday before the Senate Committee on Health, Labor, and Pensions, during which McCance-Katz and Adams both vowed to focus on the nation’s opioid crisis.

The confirmation of McCance-Katz, an APA member, is especially good news, bringing psychiatric leadership to a crucial new position at the Substance Abuse and Mental Health Services Administration (SAMHSA), where she will manage and direct SAMHSA and coordinate mental health and substance use programs and research across the federal government. McCance-Katz previously served in SAMHSA as the first chief medical officer of the agency.

The assistant secretary post was created in the 21st Century Cures Act, a bipartisan bill that President Barack Obama signed into law in December 2016.

At the hearing on Tuesday, McCance-Katz said that in addition to the opioid epidemic, her priority would be services for people with serious mental illness.

“Dr. McCance-Katz is an accomplished physician and the ideal person to guide our nation’s treatment of mental health and substance use disorders,” APA CEO and Medical Director Saul Levin, M.D., M.P.A., said in a press release. “We are delighted that the Senate confirmed her as Assistant Secretary for Mental Health and Substance Use. We look forward to working with her to provide quality mental health care to everyone who needs it.”

McCance-Katz is currently the chief medical officer for the Rhode Island Department of Behavioral Healthcare, Developmental Disabilities, and Hospitals. She is also a professor of psychiatry and human behavior and professor of behavioral and social sciences at the Alpert Medical School at Brown University.

Levin also hailed the confirmation of Adams for Surgeon General. “Dr. Adams has worked throughout his career to improve public health,” he said in a press release. “His expertise in combatting opioid addiction is particularly needed as physicians and elected officials work together to reduce the toll of this epidemic. On behalf of our 37,000 members, I congratulate Dr. Adams on his confirmation and look forward to working with him to improve well-being of all Americans, including those needing treatment for mental health or substance use disorders. We commend him for ensuring that people with serious mental illness are a part of his agenda.” Currently, Adams is the Indiana State Health Commissioner.

Internet-Based, Guided Self-Help Program May Benefit Some Patients With Binge-Eating Disorder

An internet-based, guided self-help program may not improve the symptoms of adults with binge-eating disorder (BED) as quickly as face-to-face cognitive-behavioral therapy (CBT), but it may be as effective in the long run, reports a study published yesterday in JAMA Psychiatry.

Past studies show CBT can benefit patients with BED, but many patients do not have access to this specialized treatment, lead author Martina de Zwaan, M.D., of Hannover Medical School in Germany and colleagues wrote. “An alternative to traditional face-to-face CBT and a potential means to disseminate adequate treatment is structured self-help,” the authors suggested.

To compare the efficacy of internet-based, guided self-help (GSH-I) to traditional CBT, de Zwaan and colleagues randomly assigned 178 patients with full or subsyndromal BED to receive 20, 50-minute individual face-to-face CBT sessions or complete 11 Internet modules and receive weekly emails. Both treatments lasted four months, and the patients were assessed at the beginning, middle, and end of the treatment.

After the end of the treatment period, the authors found that CBT was more effective than GSH-I at reducing the number of binge eating days in the past four weeks (10.4 vs. 11.7 days, respectively) and increasing abstinence from binge eating (61% vs. 36%). CBT was also more effective at reducing overall patient psychopathology, as measured with the Eating Disorder Examination–Interview.

The superiority of CBT was still evident at a six-month follow-up visit; however, differences were no longer evident at a second follow-up visit 12 months later. At the 18-month follow-up visit, for example, binge-eating abstinence rates were 46% for CBT and 43% for GSH-I.

“Overall, our results suggest that face-to-face CBT is likely to be a better initial treatment option compared with GSH-I,” de Zwaan and colleagues wrote. “However, given that improvements were significant in both treatment conditions, the effect size of the difference of the main outcome between treatment conditions was small, and there were no statistical differences between the treatment conditions at 1.5 years after treatment, GSH-I remains a viable, low-threshold treatment alternative for this patient population, for example, in a stepped-care approach.”

For related information, see the Handbook of Assessment and Treatment of Eating Disorders.

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Internet Searches of ‘Suicide’ Increased Following Netflix Series About Teen Suicide

Google searches using terms related to suicidal ideation rose significantly in the days following the March 31, 2017, release of “13 Reasons Why”—a Netflix series about a teenage girl who dies by suicide.

The finding was reported in a research letter published Monday in JAMA Internal Medicine by researchers from multiple institutions. They found that searches using the terms “how to commit suicide,” “commit suicide,” and “how to kill yourself” were all significantly higher following the series’ release.

“13 Reasons Why” explores the suicide of a fictional teenage girl, and the final episode of the series includes a three-minute, graphic scene of her death. The series has generated widespread interest, as well as debate about its public health implications.

The researchers compared Internet searches using some 20 terms related to “suicide” in the 19 days following the premier of “13 Reasons Why” (March 31, 2017, through April 18, 2017) with expected search volumes assuming the series had never been released. Statistical modeling, using daily trends from January 15, 2017, to March 30, 2017, was used to forecast expected volumes.

All suicide queries were cumulatively 19% higher for the 19 days following the release of “13 Reasons Why,” reflecting 900,000 to 1.5 million more searches than expected. For 12 of the 19 days studied, suicide queries were significantly greater than expected, ranging from 15% higher on April 15 to 44% higher on April 18. Searches using the terms “how to commit suicide” were 26% higher during this period.

Notably, searches for suicide hotlines were also elevated, including “suicide hotline number” (21%) and “suicide hotline” (12%), as were searches using the terms “suicide prevention” (23%) and “teen suicide” (34%).

“It is unclear whether any query preceded an actual suicide attempt,” John W. Ayers, Ph.D., M.A., of San Diego State University and colleagues wrote. “However, suicide search trends are correlated with actual suicides. … The deleterious effects of shows such as 13 Reasons Why could possibly be curtailed by following the World Health Organization’s (WHO) media guidelines for preventing suicide, such as removing scenes showing suicide, or addressed by including suicide hotline numbers in each episode. These strategies could be retrofitted to the released episodes, included in the planned second season, or applied to other programs.”

“I think the points in the research letter about not glamorizing suicide are on point,” said immediate past APA President Maria A. Oquendo, M.D., Ph.D. (pictured above), an internationally recognized expert on suicide. “This is especially important for adolescents who are impressionable. Anything that makes anyone dying by suicide appear heroic, larger than life, or unusually sympathetic is a disservice.”

Oquendo echoed the researchers in calling for adherence to WHO guidelines regarding publicity about suicide, especially highlighting the relationship of mental illness to suicide, and the fact that mental illness is treatable. “It is very important for parents to be talking to their kids if they are watching this show or others like it, emphasizing the relationship of suicide with mental illness, and that suicide is not a solution, but getting treatment is,” she told Psychiatric News.

For related information, see the APA blog post “13 Mental Health Questions about ‘13 Reasons Why’” and the Psychiatric News article “Experts Respond to Facebook's Updated Suicide Prevention Tools.”

(Image: courtesy Maria A. Oquendo, M.D., Ph.D.)

Clozapine May Lower Risk of Self-Harm in Patients With Treatment-Resistant Schizophrenia

Clozapine use by patients with treatment-resistant schizophrenia appears to have a protective effect against self-harm when compared with other antipsychotics, according to a report in AJP in Advance. The study also found that when compared with no antipsychotic treatment, clozapine use is associated with a decreased overall mortality rate.

Researchers in England and Denmark conducted a population-based cohort study of 2,370 individuals born in Denmark, who had been diagnosed with treatment-resistant schizophrenia after January 1, 1996. Patients were followed until death, first episode of self-harm, emigration, or June 1, 2013.

During the follow-up period, 1,372 individuals (58%) with treatment-resistant schizophrenia initiated clozapine treatment. After adjusting for confounding factors, nonclozapine antipsychotic treatment was associated with an elevated rate of self-harm (hazard ratio: 1.36) compared with clozapine. Moreover, the absence of clozapine treatment was associated with an elevated rate of all-cause mortality (hazard ratio: 1.88) compared with clozapine treatment. “This was driven mainly by periods of no antipsychotic treatment (hazard ratio: 2.50), with nonsignificantly higher mortality during treatment with other antipsychotics (hazard ratio: 1.45),” Theresa Wimberley, Ph.D., of Aarhus University in Denmark and colleagues wrote.

“Given that the authors focused their study on patients meeting their criteria for treatment-resistant schizophrenia, it is possible that their results actually underestimate the value of clozapine in reducing the risk of suicidality,” John Kane, M.D., the chair of psychiatry at the Zucker Hillside Hospital in Glen Oaks, N.Y., told Psychiatric News. Kane, who was not involved with the study, added that he believes the study indicates another benefit for a medication that he says is vastly underutilized.

The nonclozapine treatment group included some patients who had started but later discontinued clozapine. The authors found that rates of all-cause mortality were highest after clozapine discontinuation, particularly within the first year after clozapine discontinuation when compared with rates during clozapine treatment.

“The extent to which the observed excess mortality rate after clozapine discontinuation is caused by side effects from recent clozapine exposure, unobserved factors, or clozapine discontinuation remains to be investigated,” Wimberley and colleagues wrote. “This study suggests that clozapine discontinuation needs more attention with thorough evaluation, care, and monitoring of the patient.”

For related information, see the Psychiatric News article “Collaborative Effort Among Stakeholders Can Reduce Barriers to Clozapine Use” and the Psychiatric Services article “The Business Case for Expanded Clozapine Utilization.”

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