Long-Term Antipsychotic Effectiveness in First Episode of Psychosis: A 3-Year Follow-Up Randomized Clinical Trial Comparing Aripiprazole, Quetiapine, and Ziprasidone

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%) (χ2=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 (χ2=9.617; P=.008) and increased sleep duration (χ2=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.

Trial registration: ClinicalTrials.gov NCT02526030.

Figure 1.

Consort flow diagram of subject through the phases of the randomized trial.

Figure 2.

Kaplan-Meyer survival graph: All-cause discontinuation.