Long-term antipsychotic effectiveness in First Episode of Psychosis: a 3-year follow-up randomized clinical trial comparing aripiprazole, quetiapine and ziprasidone.

Background: Different effectiveness profiles among second generation antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis (FEP) to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of aripiprazole, ziprasidone and quetiapine in the treatment of FEP 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-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 3-year 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 =0.001). Statistically significant differences in terms of non-efficacy, non-adherence 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 =0.001). Significant differences between treatments were found in the categories of sleepiness/sedation (χ2 =9.617; p = 0.008) and increased sleep duration (χ2 =6.192; p = 0.004). No significant differences were found in the profile of extrapyramidal symptoms. Patients on aripiprazole were more likely to be prescribed benzodiazepines.

Conclusions: FEP patients on quetiapine were more likely to discontinue treatment due to non-efficacy. Identifying different discontinuation patterns may contribute to optimize treatment selection after FEP. ClinicalTrials.gov Identifier: NCT02526030 | https://clinicaltrials.gov/show/NCT02526030.