OBJECTIVES

To assess the comparative efficacy and safety of lurasidone, brexpiprazole and cariprazine in the treatment of schizophrenia in a network meta-analysis.

METHODS

A systematic review was conducted to identify randomised controlled trials comparing lurasidone, brexpiprazole and cariprazine with each other or placebo in patients with schizophrenia. Searches were carried out in a range of bibliographic databases and other information sources. The key outcomes included effect on Positive and Negative Syndrome Scales (PANSS) and Clinical Global Impression-Severity (CGI-S) scores; and cardiovascular and metabolic parameters. A feasibility assessment evaluated the trials’ suitability for inclusion in a Bayesian Network Meta Analysis.

Random effects models were used, with half-Cauchy priors for the between-study variance term for the continuous outcomes and informative priors from Turner et al. (2015) for the binomial outcomes. Uninformative priors were used for the treatment effects. Each drug and dose combination was considered as a separate node in the networks.

RESULTS

Searches conducted in February 2020 identified 1,138 records; 19 RCTs contributed to the NMA. There was evidence that lurasidone doses of 40mg/d and above performed better than placebo in terms of change in PANSS and CGI-S scores at 6 weeks, with increasing dose leading to higher effect estimates. The lowest doses of all treatments were not found to be better than placebo.

When comparing brexpiprazole and cariprazine against lurasidone 40 mg/d, the 95% credible interval contained ‘no difference’ regardless of dose.

The safety outcomes were relatively variable; for all treatments, the 95% credible intervals usually contained ‘no difference’. Active treatments were generally associated with lower odds of discontinuation due to any cause, and higher odds of experiencing any adverse event.

CONCLUSIONS

Lurasidone was found to be comparable to brexpiprazole and cariprazine for the efficacy and safety outcomes assessed at 6 weeks.