Abstract: BACKGROUND: Different effectiveness profiles among second-generation antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to affect long-term outcome. The aim of this study was to compare the clinical effectiveness of aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up. 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 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on the intention-to-treat principle was conducted in the analysis for clinical efficacy. RESULTS: The overall dropout rate at 3 years reached 19.3%. Treatment discontinuation rates were significantly different among treatment groups (aripiprazole=73.08%, ziprasidone=79.03%, and quetiapine=95.16%) (?2=11.680; P=.001). Statistically significant differences in terms of nonefficacy, nonadherence, and side effects were observed among treatment groups along the 3-year follow-up determining significant differences in time to all-cause discontinuation (log-rank=32.260; P=.001). Significant differences between treatments were found in the categories of sleepiness/sedation (?2=9.617; P=.008) and increased sleep duration (?2=6.192; P=.004). No significant differences were found in the profile of extrapyramidal symptoms. Patients on aripiprazole were more likely to be prescribed benzodiazepines. CONCLUSIONS: First-episode psychosis patients on quetiapine were more likely to discontinue treatment due to nonefficacy. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.

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