Clozapine Rechallenge or Continuation Despite Neutropenia, an Extended Follow-up of a Consecutive Quebec Case Series.

BACKGROUND: Clozapine is the most efficacious antipsychotic for treatment-resistant schizophrenia. However, clozapine-induced neutropenia may warrant treatment discontinuation, hindering recovery. Several case reports describe clozapine rechallenge or continuation despite neutropenia, although many are subject to selective reporting, with incomplete information and short follow-up periods. Thus, consecutive case series, devoid of such bias, with long-term comprehensive follow-up are needed to better assess this practice. This study aimed to describe consecutively the evolution of every patient in the Québec City catchment area for whom clozapine was either reintroduced after neutropenia during a previous clozapine trial or was maintained despite a first neutropenia. METHODS: Patients were identified through clozapine's national hematological monitoring database and their medical records between January 1, 2000, and October 22, 2017. RESULTS: Twenty-three patients were identified, 8 continued clozapine despite neutropenia, while 15 discontinued clozapine and attempted rechallenge; among the latter, 4 patients were successfully rechallenged after agranulocytosis without the use of granulocyte colony-stimulating factors, which is the largest published consecutively. A total of 6 patients experienced further neutropenia episodes. Every patient who had a neutropenia recurrence also had a possible explanation for neutropenia other than exposure to clozapine. After a median follow-up of 4.8 years, 16 patients were still on clozapine and 3 cases discontinued because of a hematological event. CONCLUSIONS: This study adds further data on the subject of clozapine rechallenge or continuation despite neutropenia. Clozapine rechallenge after agranulocytosis may be less perilous than first thought, but a systematic review on this specific subject is needed.

[Psychopharmacology of First Episode Psychosis: An Approach Based on Recovery]. / Une approche de la psychopharmacologie des premiers épisodes psychotiques axée sur le rétablissement.

Objectives Individuals with first-episode psychosis (FEP) are poorly represented in clinical trials leading to drug approval. As a result, there is a relative paucity of empirical data to guide the psychopharmacological treatment of these youths. This article provides a synthesis of this literature, informed by the authors' clinical experience in treating FEP over the past 25 years. Methods This selective review of the literature focuses on the psychopharmacological treatment of FEP and includes both randomized trials and observational studies. It is organized around the following themes for FEP: response and remission rates; relapse rates; specifics regarding susceptibility to adverse events; comparisons of efficacy, safety and relapse prevention among various molecules and dosage forms; recommendations for duration of treatment; approach to treatment resistance; and use of clozapine. For each of these themes, research data are interpreted and supplemented by commentary based on the authors' clinical experience, with a strong focus on the individual's recovery. Results Symptom remission is achieved in approximately 75% of individuals during the initial treatment of a FEP, its maintenance being a very strong predictor of functional recovery. The rate of psychotic relapse during the three years following a FEP is about 60%, the problem of adherence to treatment being the main cause of these relapses. The FEP population is distinguished by a greater propensity for adverse events, including weight gain and extrapyramidal reactions. With the exception of treatment-resistant FEP, no clear difference has been demonstrated in the efficacy of the various molecules, but they do differ in their adverse events profile and formulations. As such, the use of long-acting injectable antipsychotics (LAIs) is superior to oral agents in preventing relapse. While the guidelines recommend continued treatment for 18 months after remission is achieved, these recommendations are based on empirical data that are still unclear, necessitating the use of a shared-decision approach with the patient and his/her family. In the group of people who do not achieve a satisfactory response after two trials of antipsychotics, clozapine is effective in up to 80% of people. Conclusions The FEP population is characterized by a high response rate, relapses frequently related to non-adherence to treatment, and increased susceptibility to adverse events. Tailoring pharmacological treatment for FEP aims at sustained remission of all symptom dimensions combined with proactive management of adverse events, including through judicious use of LAIs and clozapine.