IMPORTANCE The mental health consequences of conflict and violence are wide-ranging and pervasive. Scalable interventions to address a range of mental health problems are needed. OBJECTIVE To test the effectiveness of a multicomponent behavioral intervention delivered by lay health workers to adults with psychological distress in primary care settings. DESIGN, SETTING, AND PARTICIPANTS A randomized clinical trial was conducted from November 1, 2014, through January 28, 2016, in 3 primary care centers in Peshawar, Pakistan, that included 346 adult primary care attendees with high levels of both psychological distress and functional impairment according to the 12-item General Health Questionnaire and the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0). INTERVENTIONS Lay health workers administered 5 weekly 90-minute individual sessions that included empirically supported strategies of problem solving, behavioral activation, strengthening social support, and stress management. The control was enhanced usual care. MAIN OUTCOMES AND MEASURES Primary outcomes, anxiety and depression symptoms, were independently measured at 3 months with the Hospital Anxiety and Depression Scale (HADS). Secondary outcomes were posttraumatic stress symptoms (Posttraumatic Stress Disorder Checklist for DSM-5), functional impairment (WHODAS 2.0), progress on problems for which the person sought help (Psychological Outcome Profiles), and symptoms of depressive disorder (9-item Patient Health Questionnaire). RESULTS Among 346 patients (mean [SD] age, 33.0 [11.8] years; 78.9% women), 172 were randomly assigned to the intervention and 174 to enhanced usual care; among them, 146 and 160 completed the study, respectively. At baseline, the intervention and control groups had similar mean (SD) HADS scores on symptoms of anxiety (14.16 [3.17] vs 13.64 [3.20]; adjusted mean difference [AMD], 0.52; 95% CI, −0.22 to 1.27) and depression (12.67 [3.27] vs 12.49 [3.34]; AMD, 0.17, 95% CI, −0.54 to 0.89). After 3 months of treatment, the intervention group had significantly lower mean (SD) HADS scores than the control group for anxiety (7.25 [3.63] vs 10.03 [3.87]; AMD, −2.77; 95% CI, −3.56 to −1.98) and depression (6.30 [3.40] vs 9.27 [3.56]; AMD, −2.98; 95% CI, −3.74 to −2.22). At 3 months, there were also significant differences in scores of posttraumatic stress (AMD, −5.86; 95% CI, −8.53 to −3.19), functional impairment (AMD, −4.17; 95% CI, −5.84 to −2.51), problems for which the person sought help (AMD, −1.58; 95% CI, −2.40 to −0.77), and symptoms of depressive disorder (AMD, −3.41; 95% CI, −4.49 to −2.34). CONCLUSIONS AND RELEVANCE Among adults impaired by psychological distress in a conflict-affected area, lay health worker administration of a brief multicomponent intervention based on established behavioral strategies, compared with enhanced usual care, resulted in clinically significant reductions in anxiety and depressive symptoms at 3 months.

This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas’ original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300–600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75–150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175–300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100–200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250–400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150–300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300–600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.

We aimed to do a systematic review and meta-analysis of studies describing suicidal ideation, suicide attempts and suicide and associated risk factors during COVID-19 pandemic. We searched following electronic databases using relevant search terms: Medline, Embase, PsycInfo and CINAHL and systematically reviewed the evidence following PRISMA guidelines. The meta-analysis of prevalence of suicidal ideation was done using random effect model. The search returned 972 records, we examined 106 in full text and included 38 studies describing 120,076 participants. Nineteen studies described suicide or attempted self-harm, mostly in case reports. Out of 19 studies describing suicidal ideations, 12 provided appropriate data for meta-analysis. The pooled prevalence of suicidal ideation in these studies was 12.1% (CI 9.3-15.2). Main risk factors for suicidal ideations were: low social support, high physical and mental exhaustion and poorer self-reported physical health in frontline medical workers, sleep disturbances, quarantine and exhaustion, loneliness, and mental health difficulties. We provide first meta-analytic estimate of suicidal ideation based on large sample from different countries and populations. The rate of suicidal ideations during COVID pandemic is higher than that reported in studies on general population prior to pandemic and may result in higher suicide rates in future.