Treatment of first-episode non-affective psychosis: a randomized comparison of aripiprazole, quetiapine and ziprasidone over 1 year

[Rationale]: Discontinuation of antipsychotic treatment at early phases increases the risk of poor adherence to maintenance drug therapy. Differences among antipsychotics in terms of effectiveness may determine a good adherence to treatment. [Objectives]: The aim of this study is to compare the clinical effectiveness of aripiprazole, ziprasidone and quetiapine in the treatment of first-episode schizophrenia spectrum disorders at 1 year. [Method]: From October 2005 to January 2011 a prospective, randomized, open-label study was undertaken. Two hundred two first-episode drug-naïve patients were randomly assigned to aripiprazole (N = 78), ziprasidone (N = 62), or quetiapine (N = 62) and followed up for 1 year. The primary effectiveness measure was all-cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy. [Results]: The overall dropout rate at 1 year was 13.37 %. The treatment discontinuation rate differed significantly between treatment groups (aripiprazole = 43.6 %, ziprasidone = 66.1 % and quetiapine = 82.3 %) (χ 2 = 22.545; p < 0.001). Insufficient efficacy in the group of quetiapine is the most important reason for differences in discontinuation rates between agents (χ 2 = 19.436; p < 0.001). The mean time to all-cause discontinuation was significantly different between groups (LogRank = 30.732 p < 0.001). The profile of extrapyramidal symptoms varies between treatments. Patients on ziprasidone were more likely to be prescribed antidepressants. [Conclusions]: First episode patients treated with quetiapine have a higher risk of treatment discontinuation at midterm due to insufficient efficacy. Establishing differences between SGAs may help clinicians on prescribing decision for treatment of individuals presenting with first-episode non-affective psychosis.The present study was carried out at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following grant support: Instituto de Salud Carlos III PI020499, PI050427, PI060507, Plan Nacional de Drugs Research Grant 2005-Orden sco/3246/2004, SENY Fundació Research Grant CI 2005–0308007 and Fundación Marqués de Valdecilla API07/011.Peer Reviewe