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.

ObjectiveThe objective of this paper is to assess the reliability and validity of the Spanish translation of the Clinical Outcomes in Routine Evaluation – Outcome Measure, a 34-item self-report questionnaire that measures the client’s status in the domains of Subjective well-being, Problems/Symptoms, Life functioning, and Risk.MethodSix hundred and forty-four adult participants were included in two samples: the clinical sample (n=192) from different mental health and primary care centers; and the nonclinical sample (n=452), which included a student and a community sample.ResultsThe questionnaire showed good acceptability and internal consistency, appropriate test–retest reliability, and acceptable convergent validity. Strong differentiation between clinical and nonclinical samples was found. As expected, the Risk domain had different characteristics than other domains, but all findings were comparable with the UK referential data. Cutoff scores were calculated for clinical significant change assessment.ConclusionThe Spanish version of the Clinical Outcomes in Routine Evaluation – Outcome Measure showed acceptable psychometric properties, providing support for using the questionnaire for monitoring the progress of Spanish-speaking psychotherapy clients.

ObjectivesThe notion of intrapsychic conflict has been present in psychopathology for more than a century within different theoretical orientations. However, internal conflicts have not received enough empirical attention, nor has their importance in depression been fully elaborated. This study is based on the notion of cognitive conflict, understood as implicative dilemma (ID), and on a new way of identifying these conflicts by means of the Repertory Grid Technique. Our aim was to explore the relevance of cognitive conflicts among depressive patients.DesignComparison between persons with a diagnosis of major depressive disorder and community controls.MethodsA total of 161 patients with major depression and 110 non-depressed participants were assessed for presence of IDs and level of symptom severity. The content of these cognitive conflicts was also analysed.ResultsRepertory grid analysis indicated conflict (presence of ID/s) in a greater proportion of depressive patients than in controls. Taking only those grids with conflict, the average number of IDs per person was higher in the depression group.In addition, participants with cognitive conflicts displayed higher symptom severity. Within the clinical sample, patients with IDs presented lower levels of global functioning and a more frequent history of suicide attempts.ConclusionsCognitive conflicts were more prevalent in depressive patients and were associated with clinical severity. Conflict assessment at pre-therapy could aid in treatment planning to fit patient characteristics.Practitioner points Internal conflicts have been postulated in clinical psychology for a long time but there is little evidence about its relevance due to the lack of methods to measure them. We developed a method for identifying conflicts using the Repertory Grid Technique. Depressive patients have higher presence and number of conflicts than controls. Conflicts (implicative dilemmas) can be a new target for intervention in depression. Cautions/Limitations A cross-sectional design precluded causal conclusions. The role of implicative dilemmas in the causation or maintenance of depression cannot be ascertained from this study.

BackgroundSince long ago it has been asserted that internal conflicts are relevant to the understanding and treatment of mental disorders, but little research has been conducted to support the claim. The aim of this study was to test the differential efficacy of group cognitive behavioral therapy (CBT) plus an intervention focused on the dilemma(s) detected for each patient versus group individual CBT plus individual CBT for treating depression. A comparative controlled trial with a 3‐month follow‐up was conducted.MethodsOne hundred twenty‐eight adults meeting criteria for MDD and/or dysthymia, presenting at least one cognitive conflict (implicative dilemma or dilemmatic construct, assessed by the repertory grid technique) and who had completed seven sessions of group CBT were randomly assigned to eight sessions of individual manualized CBT or dilemma‐focused therapy (DFT). The Beck Depression Inventory‐II was administered at baseline, at the end of therapy and after 3 months’ follow‐up.ResultsMultilevel mixed effects modeling yielded no significant differences between CBT and DFT with the intention‐to‐treat sample. Equivalent effect sizes, remission, and response rates were found with completers as well. In combination with group CBT, both individual CBT and DFT significantly reduced depressive symptoms.ConclusionsBoth conditions obtained comparable results to those in the literature. Thus, the superiority of the adjunctive DFT was not demonstrated. Working with dilemmas can be seen as a promising additional target in the psychotherapy of depression, but further research is still required.