Changes in Weight and Metabolic Indices after Switching to Aripiprazole Once-Monthly in Patients with Schizophrenia According to Prior Oral Antipsychotics.

Abstract

Introduction: Antipsychotic-induced weight gain and metabolic disturbance are common in schizophrenia, but liability varies across agents. Aripiprazole has a relatively favorable metabolic profile, yet evidence on aripiprazole once-monthly, its long-acting injectable formulation, remains limited. We hypothesized that switching from a higher liability antipsychotic would yield a greater weight reduction than switching from a lower liability agent.

Methods: This 16-week, prospective, open-label, multicenter study enrolled patients with stable schizophrenia. Participants were stratified by the metabolic liability of their prior oral antipsychotic (high vs. low). Participants received aripiprazole once-monthly 400 mg intramuscularly every 4 weeks, with cross-titration of the prior agent. Anthropometric and metabolic parameters were assessed every 4 weeks from baseline. Weight changes at week 16 were the principal outcome, and all analyses were exploratory. Mixed models for repeated measures evaluated changes over time, adjusting for covariates.

Results: Among the 151 participants (100 low-risk and 51 high-risk participants), weight, body mass index, and waist circumference decreased significantly in the high-risk group only, and more high-risk patients reached clinically meaningful improvement. Most lipid and glycemic indices changed little, although low-density lipoprotein cholesterol and total cholesterol decreased in both groups. Psychiatric symptoms remained stable. In a subgroup switched from oral aripiprazole (n=73), anthropometric and metabolic parameters were all unchanged.

Discussion: In patients previously exposed to high-metabolic-risk antipsychotics, switching to aripiprazole once-monthly was associated with short-term reductions in weight and central adiposity-consistent with the reversal of the prior agents' metabolic burden-while psychiatric stability was maintained. Longer-term studies are needed to confirm their durability and clinical significance.