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.

Background: Nursing students who suffer from co-occurring anxiety experience added difficulties when communicating and interacting with others in a healthy, positive, and meaningful way. Previous studies have found strong positive correlations between Internet addiction (IA) and anxiety, suggesting that nursing students who report severe IA are susceptible to debilitating anxiety as well. To date, however, network analysis (NA) studies exploring the nature of association between individual symptoms of IA and anxiety have not been published.Objective: This study examined associations between symptoms of IA and anxiety among nursing students using network analysis.Methods: IA and anxiety symptoms were assessed using the Internet Addiction Test (IAT) and the Generalized Anxiety Disorder Screener (GAD-7), respectively. The structure of IA and anxiety symptoms was characterized using “Strength” as a centrality index in the symptom network. Network stability was tested using a case-dropping bootstrap procedure and a Network Comparison Test (NCT) was conducted to examine whether network characteristics differed on the basis of gender and by region of residence.Results: A total of 1,070 nursing students participated in the study. Network analysis showed that IAT nodes, “Academic decline due to Internet use,” “Depressed/moody/nervous only while being off-line,” “School grades suffer due to Internet use,” and “Others complain about your time spent online” were the most influential symptoms in the IA-anxiety network model. Gender and urban/rural residence did not significantly influence the overall network structure.Conclusion: Several influential individual symptoms including Academic declines due to Internet use, Depressed/moody/nervous only while being off-line, School grades suffering due to Internet use and Others complain about one's time spent online emerged as potential targets for clinical interventions to reduce co-occurring IA and anxiety. Additionally, the overall network structure provides a data-based hypothesis for explaining potential mechanisms that account for comorbid IA and anxiety.

Clozapine remains one of the most commonly used antipsychotic medications in China. As China has the largest population internationally on clozapine treatment, its experience and research findings are of keen interest to Western psychiatrists. However, most of the related papers have hitherto been published only in Chinese language journals. Here we review mainly Chinese-language publications on the use of clozapine in China. A descriptive study based on literature identified from searches of Medline and the China National Knowledge Infrastructure (CNKI) databases (1979-2007), and other hand-picked references. Unlike the situation in other countries, clozapine is still widely used for a number of psychiatric disorders in China, though the prescription of other second-generation antipsychotics (SGAs) is also increasing. About 25-60% of all treated patients with schizophrenia receive clozapine; and clozapine is preferred by some as a first-line treatment for schizophrenia. Clozapine is also used for other conditions such as mania, treatment-resistant depression and drug abuse. The average daily dose is between 200 and 400 mg. The incidence of leukopenia is 3.92% and agranulocytosis 0.21% in China, with about one third of reported cases of patients with agranulocytosis dying. Weight gain and clozapine-associated diabetes are also commonly reported in the Chinese population. Clozapine is currently the most commonly used treatment for schizophrenia in China. Chinese psychiatrists need to pay more attention to its potential toxic side effects when they make drug choices.