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.

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Background: Improving patients’ perception of social support is significant not only for their re-adaptation to life but also for alleviating caregivers’ burden. Aim: This study aims to examine an integrated model regarding social support, psychotic symptoms and caregiver burden. Methods: Persons with schizophrenia ( N1 = 300) and their family caregivers ( N2 = 300) in Xinjin County, Chengdu, China, completed the survey to report their demographics, patients’ perception of social support (Duke Social Support Index), psychotic symptoms (Positive and Negative Syndrome Scale) and caregiver burden (Burden Scale for Family Caregivers, Short Version). Structural equation modelling was utilised to test the proposed model. Results: The degree of caregiver burden differed significantly within subgroups of patients’ gender and education, as well as caregivers’ gender, education and employment. Caregiver burden was negatively related to patients’ age and household income. Social interaction partially mediated the relationship between instrumental and subjective social support (total effect = 0.451, p < .01). Subjective social support fully mediated the impact of social interaction on psychotic symptoms (total effect = −0.099, p < .05). In the final model, instrumental social support was positively associated with social interaction ( p < .001) and increased subjective social support ( p < .05). Increased subjective social support showed correlation with a lower degree of psychotic symptoms ( p < .01), which was related to a lower level of caregiver burden ( p < .001). Conclusion: This study shows the associations of patients’ social support with psychotic symptoms and caregiver burden. Culture-specific psychosocial interventions should be provided for both patients and caregivers to enrich external support and reduce psychotic symptoms and caregivers’ burden within the health care environment.

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