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

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. 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. 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. 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.