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.

Impairments of attention and memory are evident in early psychosis, and are associated with functional disability. In a group of stable, medicated women patients, we aimed to determine whether participating in aerobic exercise or yoga improved cognitive impairments and clinical symptoms. A total of 140 female patients were recruited, and 124 received the allocated intervention in a randomized controlled study of 12 weeks of yoga or aerobic exercise compared with a waitlist group. The primary outcomes were cognitive functions including memory and attention. Secondary outcome measures were the severity of psychotic and depressive symptoms, and hippocampal volume. Data from 124 patients were included in the final analysis based on the intention-to-treat principle. Both yoga and aerobic exercise groups demonstrated significant improvements in working memory (P<0.01) with moderate to large effect sizes compared with the waitlist control group. The yoga group showed additional benefits in verbal acquisition (P<0.01) and attention (P=0.01). Both types of exercise improved overall and depressive symptoms (all P⩽0.01) after 12 weeks. Small increases in hippocampal volume were observed in the aerobic exercise group compared with waitlist (P=0.01). Both types of exercise improved working memory in early psychosis patients, with yoga having a larger effect on verbal acquisition and attention than aerobic exercise. The application of yoga and aerobic exercise as adjunctive treatments for early psychosis merits serious consideration. This study was supported by the Small Research Funding of the University of Hong Kong (201007176229), and RGC funding (C00240/762412) by the Authority of Research, Hong Kong.