LAI formulations of paliperidone, aripiprazole, olanzapine have highest effect sizes

Long-acting injectable formulations of paliperidone, aripiprazole and olanzapine had the highest effect sizes and certainty of evidence for relapse prevention and acceptability, researchers noted in American Journal of Psychiatry.

“There has been a growing interest around the role of long-acting antipsychotics to prevent relapse in schizophrenia and other chronic psychoses; however, current evidence and guidelines do not pragmatically help clinicians in the choice of the best treatment,” Giovanni Ostuzzi, MD, PhD, of the department of neuroscience, biomedicine and movement sciences, section of psychiatry, at the University of Verona in Italy, told Healio Psychiatry. “We chose the methodological approach of the network meta-analysis in order to provide a comprehensive overview of the most effective and safe long-acting treatments. Furthermore, this methodology gives relevance to the quality of the evidence included in the analysis, also providing interesting insights for novel research.”

Ostuzzi and colleagues aimed to compare relapse prevention and acceptability of long-acting injectable (LAI) antipsychotics in the maintenance treatment of adults with nonaffective psychoses. They searched five databases, as well as online registers, for randomized controlled trials published until June 2020. They used random-effects pairwise and network meta-analysis to pool relative risks and standardized mean differences. Relapse rate and all-cause discontinuation served as the primary outcomes. The researchers included 78 trials, with 11,505 total participants, in the meta-analysis.

Results showed most of the 12 LAIs assessed outperformed placebo in relapse prevention. A 3-month formulation of paliperidone, as well as aripiprazole, had the largest point estimates and best rankings of LAIs vs. placebo. Further, the researchers found moderate to high Grading of Recommendations Assessment, Development and Evaluation (GRADE) certainty for superior relapse prevention vs. placebo in descending ranking order for risperidone, pipothiazine, olanzapine and 1-month formulation of paliperidone. Head-to-head LAI comparisons revealed only haloperidol was inferior to aripiprazole, fluphenazine and paliperidone. Most LAIs outperformed placebo for acceptability, with moderate to high GRADE certainty in descending ranking order for zuclopenthixol, aripiprazole, 3-month formulation of paliperidone, olanzapine, flupenthixol, fluphenazine and 1-month formulation of paliperidone. Head-to-head comparisons revealed only LAI aripiprazole had superior acceptability to other LAIs, including bromperidol, fluphenazine, 1-month formulation of paliperidone, pipothiazine and risperidone.

“We hope that data from this study can effectively inform future guidelines aimed at supporting frontline practitioners in their everyday practice,” Ostuzzi said. “Tailoring the choice of medications to patients' characteristics is at the core of modern psychopharmacology. Moreover, as long-acting antipsychotics might represent a valuable tool in many settings, including low- and middle-income countries, we believe that results from this article can support the evidence-based update of the WHO Essential Medicines List.”