American Journal of Psychiatry

OBJECTIVES: The authors sought to study the safety of antipsychotic polypharmacy compared with monotherapy in specific dosage categories. METHODS: Patients with schizophrenia (N=61,889; median follow-up, 14.8 years [IQR=7.4-22.0]) were identified from the Finnish nationwide inpatient care register and followed up over the period 1996-2017. Antipsychotic polypharmacy was compared with monotherapy in seven dosage categories (<0.4, 0.4-<0.6, 0.6-<0.9, 0.9-<1...

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OBJECTIVE: Social anxiety disorder is common and impairing. The efficacy of pharmacotherapy is moderate, highlighting the need for alternative therapies. This study compared the efficacy of gaze-contingent music reward therapy (GC-MRT), an eye-tracking-based attention bias modification treatment, with a selective serotonin reuptake inhibitor (SSRI) treatment or a waiting list control condition in reducing social anxiety disorder symptoms. Superior clinical effects of similar magnitude were expected for the active treatments relative to the control condition...

OBJECTIVE: Negative symptoms are a primary cause of disability in schizophrenia for which there are no established pharmacotherapies. This study evaluated a novel psychosocial intervention that combined two evidence-based practices-motivational interviewing and cognitive-behavioral therapy (MI-CBT)-for the treatment of motivational negative symptoms. METHODS: Seventy-nine participants with schizophrenia and moderate to severe negative symptoms were included in a randomized controlled trial comparing the 12-session MI-CBT treatment with a mindfulness control condition...

OBJECTIVE: Overdose risk during a course of treatment with medication for opioid use disorder (MOUD) has not been clearly delineated. The authors sought to address this gap by leveraging a new data set from three large pragmatic clinical trials of MOUD. METHODS: Adverse event logs, including overdose events, from the three trials (N=2,199) were harmonized, and the overall risk of having an overdose event in the 24 weeks after randomization was compared for each study arm (one methadone, one naltrexone, and three buprenorphine groups), using survival analysis with time-dependent Cox proportional hazard models...

OBJECTIVE: Family history is an established risk factor for mental illness. The authors sought to investigate whether polygenic scores (PGSs) can complement family history to improve identification of risk for major mood and psychotic disorders. METHODS: Eight cohorts were combined to create a sample of 1,884 participants ages 2-36 years, including 1,339 offspring of parents with mood or psychotic disorders, who were prospectively assessed with diagnostic interviews over an average of 5...

OBJECTIVE: Trichotillomania and skin-picking disorder are underrecognized and often disabling conditions in which individuals repeatedly pull at their hair or pick at their skin, leading to noticeable hair loss or tissue damage. To date there is a severe paucity of evidence-based treatments for these conditions. In this study, the authors sought to determine whether memantine, a glutamate modulator, is more effective than placebo in reducing hair-pulling and skin-picking behavior. METHODS: One hundred adults with trichotillomania or skin-picking disorder (86 women; mean age, 31...

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) protocols increasingly use subgenual anterior cingulate cortex (sgACC) functional connectivity to individualize treatment targets. However, the efficacy of this approach is unclear, with conflicting findings and varying effect sizes across studies. Here, the authors investigated the effect of the stimulation site's functional connectivity with the sgACC (sgACC-StimFC) on treatment outcome to rTMS in 295 patients with major depression...

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One in three adults with major depressive disorder (MDD) do not experience clinically significant improvement after multiple sequential courses of antidepressants and have treatment-resistant depression (TRD). The presence of TRD contributes to the morbidity and excess mortality associated with MDD and has been linked to significantly increased health care expenses. In the absence of a consensus definition of TRD, this report takes a broad approach by considering inadequate response to one or more courses of antidepressants and focuses on atypical antipsychotics that are approved by the U...

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OBJECTIVE: The purpose of this study was to investigate the efficacy of cariprazine, a dopamine D3 -preferring D3 /D2 and serotonin 5-HT1A receptor partial agonist, as adjunctive therapy for patients with major depressive disorder and nonresponse to at least one antidepressant monotherapy. METHODS: In this double-blind placebo-controlled study, adults with major depressive disorder and inadequate response to antidepressants alone were randomized in a 1:1:1 ratio to placebo, cariprazine at 1...

OBJECTIVE: Moderate alcohol consumption is associated with decreased risk for depression, but it remains unclear whether this is a causal relationship or a methodological artifact. To compare the effects of consistent abstinence and occasional, moderate, and above-guideline alcohol consumption throughout early to middle adulthood on depression at age 50, the authors conducted a secondary analysis of the National Longitudinal Survey of Youth 1979 cohort and employed a marginal structural model (MSM) approach...

OBJECTIVE: The authors sought to determine the shared and unique changes in brain resting-state functional connectivity (rsFC) between patients with major depressive disorder who achieved remission with cognitive-behavioral therapy (CBT) or with antidepressant medication. METHODS: The Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) trial randomized adults with treatment-naive major depressive disorder to 12 weeks of treatment with CBT (16 1-hour sessions) or medication (duloxetine 30-60 mg/day or escitalopram 10-20 mg/day)...

OBJECTIVE: The authors investigated associations between polygenic liabilities for bipolar disorder, major depression, and schizophrenia and episode polarity among individuals with bipolar disorder. METHODS: The sample consisted of 2,705 individuals diagnosed with bipolar disorder at Danish psychiatric hospitals between January 1995 and March 2017. DNA was obtained from dried blood spots collected at birth as part of routine screening. Polygenic risk scores (PRSs) for bipolar disorder, major depression, and schizophrenia were generated using a meta-PRS method combining internally and externally trained components...

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