OBJECTIVES: To assess retrospectively the relative efficacy, safety and tolerability of brexpiprazole versus lurasidone in the acute and maintenance phases of schizophrenia.

METHODS: A systematic literature review identified RCTs of pharmacological treatments for adults with schizophrenia. Twelve acute studies (5 brexpiprazole, 7 lurasidone) and two maintenance studies (one brexpiprazole, one lurasidone) met pre-specified inclusion criteria. Bayesian indirect comparisons were conducted using both fixed (FE) and random-effect (RE) models.

RESULTS: RE model comparisons showed no meaningful difference between brexpiprazole and lurasidone for change from baseline (CFB) in PANSS total score and CGI-S in the acute phase (median difference [MD] vs. lurasidone=2.58 [95% credible interval (CrI): -0.67, 5.88]; MD=0.15 [95% CrI: -0.18, 0.51]). In the maintenance phase, brexpiprazole showed lower risk of relapse versus lurasidone (hazard ratio=0.44 [95% CrI: 0.20, 0.91]). In the acute phase, brexpiprazole was associated with fewer akathisia occurrences and study withdrawals due to adverse events compared to lurasidone (odds ratio [OR] =0.21 [95% CrI: 0.06, 0.62]; OR=0.45 [95% CrI: 0.20, 0.97], respectively). In the acute phase brexpiprazole showed a higher absolute CFB in body weight compared to lurasidone (MD=0.55 kg [95% CrI: 0.13, 0.97]), while the incidence of clinically significant weight gain (≥7% CFB) was within sampling error (OR=1.92 [95% CrI: 0.88, 4.16]). No differences between treatments were observed for remaining safety and tolerability outcomes in either phase. Conclusions were robust to model choice and sensitivity analyses.

CONCLUSIONS: These indirect analyses indicated that brexpiprazole had comparable efficacy to lurasidone in the acute phase and a lower risk of relapse during maintenance treatment. In the acute phase, brexpiprazole showed lower rates of akathisia and withdrawals due to AE but higher absolute body weight change versus lurasidone. Results suggest that clinicians may be able to tailor therapy to their patients’ needs when relevant comorbidities and risk factors for AEs are present.