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 current paper introduces the actual International College of Neuro-Psychopharmacology clinical guidelines for the treatment of bipolar disorder. The current clinical guidelines are based on evidence-based data, but they also intend to be clinically useful, while a rigid algorithm was developed on the basis of firm evidence alone. Monotherapy was prioritized over combination therapy. There are separate recommendations for each of the major phases of bipolar disorder expressed as a 5-step algorithm. The current International College of Neuro-Psychopharmacology clinical guidelines for the treatment of bipolar disorder are the most up-to-date guidance and are as evidence based as possible. They also include recommendations concerning the use of psychotherapeutic interventions, again on the basis of available evidence. This adherence of the workgroup to the evidence in a clinically oriented way helped to clarify the role of specific antidepressants and traditional agents like lithium, valproate, or carbamazepine. The additional focus on specific clinical characteristics, including predominant polarity, mixed features, and rapid cycling, is also a novel approach. Many issues need further studies, data are sparse and insufficient, and many questions remain unanswered. The most important and still unmet need is to merge all the guidelines that concern different phases of the illness into a single one and in this way consider BD as a single unified disorder, which is the real world fact. However, to date the research data do not permit such a unified approach.

The aim of the current study was to assess the reliability, validity and psychometric properties of the Greek translation of the Center for Epidemiological Studies- Depression Scale (CES-D). 40 depressed patients 29.65 ± 9.38 years old, and 120 normal controls 27.23 ± 10.62 years old entered the study. In 20 of them (12 patients and 8 controls) the instrument was re-applied 1-2 days later. Translation and Back Translation was made. Clinical Diagnosis was reached by consensus of two examiners with the use of the SCAN v.2.0 and the IPDE. Statistical Analysis included ANOVA, the Pearson Product Moment Correlation Coefficient, Principal Components Analysis and Discriminant Function Analysis and the calculation of Cronbach's alpha (α) Both Sensitivity and specificity exceed 90.00 at 23/24, Chronbach's alpha for the total scale was equal to 0.95. Factor analysis revealed three factors (positive affect, irritability and interpersonal relationships, depressed affect and somatic complains). The test-retest reliability was satisfactory (Pearson's R between 0.45 and 0.95 for individual items and 0.71 for total score). The Greek translation of the CES-D scale is both reliable and valid and is suitable for clinical and research use with satisfactory properties. Its properties are similar to those reported in the international literature. However one should always have in mind the limitations inherent in the use of self-report scales.