Does formulation matter? A systematic review and meta-analysis of oral versus long-acting antipsychotic studies

Recently, many authors highlighted the potential advantages of a broader prescription of long-acting injectable antipsychotics (LAIs) based on various assumptions, including favorable pharmacokinetic features. In this systematic review, data from randomized controlled trials comparing LAIs versus the oral formulation of the same antipsychotic were meta-analyzed in order to ascertain whether the route of administration may be associated with a different efficacy and tolerability profile. Of 21 included studies, 18 contributed to the meta-analysis, providing data for risperidone, olanzapine, aripiprazole, zuclopenthixol, fluphenazine and haloperidol. For all drugs, the number of dropouts for any reason (primary outcome) did not differ between the two formulations, except for a small effect in favor of LAI aripiprazole (2 comparisons; 986 patients; relative risk (RR) 0.78; 95% confidence interval (CI) 0.64 to 0.95). Similarly, no differences emerged in terms of dropouts for adverse events, extrapyramidal symptoms, prolactin increase (except for a small advantage for LAI risperidone), weight gain, non-response rate, relapse rate, and dropouts for inefficacy (except for a small advantage for oral olanzapine). Data on aripiprazole proved to be of high quality according to the GRADE approach (Grading of Recommendations, Assessment, Development and Evaluation), therefore we are confident that the effect estimate is close to the true effect. Data on risperidone were of moderate quality, while data on olanzapine, fluphenazine, zuclopenthixol and haloperidol were of low quality. In conclusion, there is no robust evidence to support doctors in choosing LAI instead of oral formulations in order to obtain better tolerability and efficacy.