Time to Initiation of Clozapine Treatment in Children and Adolescents with Early-Onset Schizophrenia

Abstract

Early-onset schizophrenia (EOS) has a poor prognosis and is difficult to treat, which often leads to the initiation of clozapine treatment. Studies in adults have shown that the initiation of clozapine treatment is often delayed. There is a lack of studies concerning the initiation of clozapine in children and adolescents with EOS. The aim of this study was to investigate the time span from first EOS-related psychiatric hospitalization to clozapine initiation. We retrospectively studied a consecutive cohort of children and adolescents with EOS and first-time clozapine prescriptions from a tertiary care child and adolescent psychiatric center in Germany. Clinical records with data on clozapine initiation were available for 112 patients (35.7% females, mean age: 15.2±1.6 years). The mean time from first EOS-related hospitalization to clozapine initiation was 1.1 (±1.0) years, with an average of 2.3 (±1.1) prior antipsychotic treatment episodes. Higher age and higher IQ predicted earlier clozapine initiation. At the time of clozapine initiation, 40.2% of patients received antipsychotic polypharmacy. Prior to clozapine, 33.9% of patients had received 3 or more antipsychotic treatment episodes. In our study, clozapine treatment was initiated markedly earlier than in the few existing studies, which may partly be due to the expected poor prognosis of EOS. The significant portion of patients undergoing 3 or more antipsychotic trials or antipsychotic polypharmacy prior to clozapine may indicate a need for improved dissemination of knowledge on the effectiveness of clozapine in treatment-resistant schizophrenia in order to promote timely clozapine prescriptions in these cases.

International trends in clozapine use: a study in 17 countries

“…Concerning age, in most countries the clozapine use prevalence peaked in middle age, which is about 10 years later than the known average age of onset in adult‐onset schizophrenia , and which might indicate a delay in the initiation of clozapine treatment, which is not an uncommon finding in clinical practice (review: ). In the majority of countries, clozapine use in men peaked several years earlier than in women (Fig.…”

“…onset in adult-onset schizophrenia (59), and which might indicate a delay in the initiation of clozapine treatment, which is not an uncommon finding in clinical practice (review: (60)). In the majority of countries, clozapine use in men peaked several years earlier than in women (Fig.…”

Naturalistic study on the use of clozapine in the early phases of non-affective psychosis: A 10-year follow-up study in the PAFIP-10 cohort

“…Despite this, about 60% of subjects eligible for clozapine initiation received more than two treatments (three to seven) before starting clozapine. In the efforts of psychiatric associations to redefine prescribing guidelines, the initiation of clozapine continues to be delayed for up to five to nine years in patients with early-onset schizophrenia (Doyle et al, 2017;Trinczek et al, 2016), and despite limited evidence supporting this clinical practice, most patients receive numerous antipsychotics, alone or in combination (Moore et al, 2007), worsening the prognosis and increasing side effects (Üçok et al, 2015).…”

Lost in Translation: Challenges in the Diagnosis and Treatment of Early-Onset Schizophrenia

“…Current guidelines [88] recommend the use of clozapine in EOS patients who have failed to respond to two adequate trials with different antipsychotics and provide detailed schedules of assessments to evaluate and assess potential ADRs both before initiation and throughout the treatment [89][90][91][92].…”