A PROSPECTIVE STUDY OF THE CLINICAL OUTCOME FOLLOWING TREATMENT DISCONTINUATION AFTER 2 YEARS IN FIRST-EPISODE SCHIZOPHRENIA

Abstract

Background: An important unanswered question in the management of schizophrenia is how long antipsychotic treatment should be continued after a first psychotic episode. This study assessed the clinical consequences of antipsychotic discontinuation after 2 years of uninterrupted treatment in patients treated for a first episode of schizophrenia or related illness. This is a pre-specified interim analysis after 1 year of treatment discontinuation. Methods: This study is an extension of a previously published 24month, open-label study in which 50 patients with first-episode schizophrenia, schizophreniform disorder, or schizoaffective disorder were treated with flexible doses of risperidone long-acting injection (RLAI). At the completion of that study, patients were offered enrolment in this follow-up study evaluating the effects of treatment discontinuation. Patients opting to participate in the discontinuation trial had RLAI tapered over a period of up to 6 weeks, with follow-up while off antipsychotic therapy or until relapse, defined operationally. Following RLAI discontinuation, patients were assessed every 2 months. RLAI was immediately re-instituted when relapse was identified. This is a pre-specified interim analysis of all subjects who completed 1 year of follow-up. Relapse rates, time to relapse, and antecedents to relapsewere evaluatedwith Positive and Negative Syndrome Scale (PANSS) and Patient-assessed Global Impression of Change (PGI-C) scores. Results: Of the 50 patients who completed the 2-year treatment study,19men and 14women (mean age 27.5±7.9 years and baseline PANSS score of 45.0±7.4) entered the discontinuation study and were followed for 1 year or until relapse. At baseline, 28 patients (84.8%) were in remission. 26 patients (79%) relapsed within 1 year. Kaplan-Meier estimate of median time to relapse was 163 days (95% CI 96–199). 8 patients were hospitalized as a result of relapse. There were no differences between those who relapsed and those who did not in terms of baseline PANSS scores or remission status. PANSS total scores remained similar to those at baseline up until (and including) the visit prior to relapse. Discussion: Similar to previously reported studies with oral and depot antipsychotics,2,3 relapse rates were high within 1 year of treatment discontinuation in patients who had been treated with RLAI for firstepisode of schizophrenia for 2 years. First relapses occurred suddenly, without clear-cut warning signs. These findings have important clinical implications, suggesting that antipsychotic discontinuationafter 2 years of treatment may not be in the best interest of the majority of patients.