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.

The psychometric characteristics of the Spanish version are similar to those of the original version. In the Spanish adaptation of the MDQ, seven positive responses to hypomanic symptoms show a good discriminative capacity for BD in patients attending psychiatric outpatient facilities; therefore, this cut-off score is proposed for the detection of BD in psychiatric outpatients.

In the above-mentioned article, the spelling of 5 authors last names has been wrong and these names have been corrected.This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.

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Introduction Evidence supports clozapine as the best treatment in terms of efficacy, effectiveness and well-being, and as the gold standard in treatment-resistant psychotic disorders. Clozapine remains still underused, suffering initiation delays from 1.1 to 9.7 years. Furthermore, there is a scarcity of data about patterns of use, showing high variability worldwide (0.6-189.2/100. 000 inhabitants). Objectives The main objective of this work is to carry out an analysis of the use of clozapine in our mental health catchment area. Thus, off-label use, the percentage of patients with clozapine depending on diagnosis, age and sex, and its use in mono and polytherapy are established. Besides, dosage and time between the first contact and the start of treatment with clozapine are recorded. Methods A descriptive study has been developed on the patients with clozapine who consulted in the catchment area of the Jerez Mental Health Service between 2018 and 2019. Data were extracted from medical records. Results From our population of 456.752 inhabitants, 449 patients received clozapine. 278 (61.9%) had a schizophrenia diagnosis; 33 (7.3%) delusional disorder and 34 (7,6%) schizoaffective disorder. The off-label use of clozapine was 19,1 %. The average mean dose used was 246,2 mg/day and 59% of the patients on clozapine were on polytherapy. Only 14,7% of these patients had a previous trial with clozapine on monotherapy. Conclusions Rates of polytherapy, previous trials of clozapine monotherapy, off label use, rates of discontinuation and other variables are to be considered to precisely map the adequate use of clozapine in clinical settings. Disclosure No significant relationships.