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.

Using Richardson and Davidson’s model and the sciences of pharmacokinetics and clinical pharmacopsychology, this article reviewed the: (1) poor life expectancy associated with treatment-resistant schizophrenia (TRS), which may be improved in patients who adhere to clozapine; (2) findings that clozapine is the best treatment for TRS (according to efficacy, effectiveness and well-being); and (3) potential for clozapine to cause vulnerabilities, including potentially lethal adverse drug reactions such as agranulocytosis, pneumonia, and myocarditis. Rational use requires: (1) modification of the clozapine package insert worldwide to include lower doses for Asians and to avoid the lethality associated with pneumonia, (2) the use of clozapine levels for personalizing dosing, and (3) the use of slow and personalized titration. This may make clozapine as safe as possible and contribute to increased life expectancy and well-being. In the absence of data on COVID-19 in clozapine patients, clozapine possibly impairs immunological mechanisms and may increase pneumonia risk in infected patients. Psychiatrists should call their clozapine patients and families and explain to them that if the patient develops fever or flu-like symptoms, the psychiatrist should be called and should consider halving the clozapine dose. If the patient is hospitalized with pneumonia, the treating physician needs to assess for symptoms of clozapine intoxication since halving the dose may not be enough for all patients; consider decreasing it to one-third or even stopping it. Once the signs of inflammation and fever have disappeared, the clozapine dose can be slowly increased to the prior dosage level.

Patient-reported outcome measures (PROMs) are self-rated scales and indices developed to improve the detection of the patients’ subjective experience. Given that a considerable number of PROMs are available, it is important to evaluate their validity and usefulness in a specific research or clinical setting. Published guidelines, based on psychometric criteria, do not fit in with the complexity of clinical challenges, because of their quest for homogeneity of components and inadequate attention to sensitivity. Psychometric theory has stifled the field and led to the routine use of scales widely accepted yet with a history of poor performance. Clinimetrics, the science of clinical measurements, may provide a more suitable conceptual and methodological framework. The aims of this paper are to outline the major limitations of the psychometric model and to provide criteria for clinimetric patient-reported outcome measures (CLIPROMs). The characteristics related to reliability, sensitivity, validity, and clinical utility of instruments are critically reviewed, with particular reference to the differences between clinimetric and psychometric approaches. Of note is the fact that PROMs, rating scales, and indices developed according to psychometric criteria may display relevant clinimetric properties. The present paper underpins the importance of the clini­metric methodology in choosing the appropriate PROMs. CLIPROM criteria may also guide the development of new indices and the validation of existing PROMs to be employed in clinical settings.

Although telepsychiatry in the form of videoconferencing has been well received in terms of increasing access to care and user satisfaction, few data on treatment outcomes and efficacy from telepsychiatry applications are available at the present time. This paper evaluates the efficacy of telepsychiatry through videoconference in the treatment of mental disorders by comparing to face-to-face conventional (F2FC) treatment. We carried out a randomized clinical trial where 140 psychiatric outpatients were randomized to either F2FC treatment or videoconference telepsychiatry (VCTP) treatment. Patients were diagnosed according to International Classification of Diseases, 10th edition (ICD-10) criteria using the Composite International Diagnostic Interview. Treatment involves eight consultations lasting 30 minutes over the 24-week study period. Patients received pertinent psychotropic medication plus cognitive– behavioral therapy during sessions. The same psychiatrist diagnosed and treated all the patients that were recruited from the Community Mental Health Centre of San Sebastian de la Gomera, in the Canary Islands. Change in psychiatric test scores served as the primary efficacy criterion. Efficacy was determined by comparing baseline (visit 1) Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) scales as well as Global Indexes (GSI, PSDI, and PST) from SCL-90R with scores obtained at the end of the study period (week 24). Response was defined as a CGI-I score of 1 or 2. Reliable Change Indexes were computed in SCL-90R Global Indexes scores. Of 140 patients randomized, 130 completed 24 weeks of treatment. Only 4 patients dropped out prematurely from the study in VCTP and 6 in F2FC. The study involves 534 teleconsultations, 522 F2FC consultations, and more than 500 hours of clinical practice. Significant improvements were found on the CGI and SCL-90- R Global Indexes scores of both treatment groups, showing clear clinical state improvement. No statistically significant differences were observed when the efficacy of VCTP treatment was compared to F2FC psychiatric treatment efficacy. This study demonstrated that telepsychiatry treatment through videoconference has equivalent efficacy to F2FC psychiatric treatment. Telepsychiatry showed to be an effective mean of delivering mental health services to psychiatric outpatients living in remote areas with limited resources.

The COVID-19 pandemic has created great uncertainty around the world, and due to the pandemic, nurses have been exposed to an increase in highly stressful clinical situations. This study examines the relationships between perceived stress and emotional disorders among nurses who have provided direct patient care during the COVID-19 pandemic and explores the mediating role of resilience in these relationships. In an online cross-sectional design, we asked Spanish nurses (N = 214) to complete self-reported scales, and we performed correlation and mediation analyses between perceived stress (Perceived Stress Scale, PSS-4), resilience (Wagnild Resilience Scale, RS-14), wellbeing (World Health Organization Wellbeing Index, five items, WHO-5), anxiety (PHQ-2) and depression (GAD-2). The nurses self-reported moderate levels of perceived stress, considerable psychological distress and high resilience. We found resilience to be significantly negatively correlated with the reported levels of perceived stress, anxiety and depression (p < 0.001). The mediating analysis revealed that resilience played a protective role in the direct relationships of stress with depression, anxiety, and psychological distress. To conclude, our findings supported the hypothesis that resilience mediated the relationship between stress and mental health.

Although clozapine is underprescribed in many countries, it may be the most efficacious antipsychotic and the best for treatment-refractory schizophrenia. Moreover, a meta-analysis¹ reported significantly lower deaths in patients continuously treated with clozapine compared to other antipsychotics.