Long-acting injectable antipsychotics in patients with schizophrenia: Systematic review and mixed treatment meta-analysis

Long-acting injectable antipsychotics (LAIs) are recommended for schizophrenic patients who cannot adhere to oral medication. We systematically reviewed randomized controlled trials of 6 LAIs available in Thailand including fluphenazine, flupentixol, haloperidol, zuclopenthixol, paliperidone, and risperidone in PubMed/MEDLINE and the Cochrane library (1955-Nov 2013). Inclusion was limited to studies of schizophrenia ≥24 weeks duration published in English. We selected 17 of 1,245 articles including 1,904 patients. The number of patients ranged from 19 to 747 per study (median 54). Mean study duration was 52.3 weeks (24-96 weeks) and median quality score using a Jadad scoring method was 4 (2-5). We applied a Bayesian model with a mixed treatment comparison approach for 3 competing risk outcomes including relapse, and discontinuation because of adverse events or other reasons. Based on the random effect model preferred by a goodness of fit analysis, risperidone had the lowest 52 week probability of relapse (mean ± SD, 0.26 ± 0.321) followed by paliperidone (0.30 ± 0.314). Zuclopenthixol had the lowest probability of discontinuation because of an adverse event (0.07 ± 0.159) or other reasons (0.26 ± 0.295). Risperidone had the highest probability of preventing relapse (0.35 ± 0.476) or discontinuation for other reasons (0.31 ± 0.461). Zuclopenthixol had the highest probability of preventing discontinuation because of adverse effects (0.31 ± 0.464). All 6 LAIs tended to have a lower risk of relapse compared with placebo. Differences between LAIs preventing any treatment discontinuation or relapse were seen, but limited in our analysis.