Assessing the metabolic impact of aripiprazole versus risperidone in the treatment of schizophrenia: a randomized double-blind controlled clinical trial.

BACKGROUND

Antipsychotic-induced metabolic side effects remain a major challenge in schizophrenia management, contributing to cardiovascular morbidity and reduced life expectancy. Aripiprazole and risperidone are among the most widely prescribed second-generation antipsychotics (SGAs), yet their differential metabolic effects, particularly in real-world patient populations extending beyond first-episode psychosis, require further clarification.

OBJECTIVE

To compare the short-term metabolic impact of aripiprazole versus risperidone in patients with schizophrenia, with specific attention to changes in body mass index (BMI), lipid profiles, appetite regulation, and other cardiometabolic parameters.

METHODS

In this 7-week, randomized, double-blind, controlled trial, 60 patients with schizophrenia were allocated to aripiprazole (5-30 mg/day) or risperidone (2-10 mg/day). Eligible patients were either antipsychotic-naïve or had undergone at least a one-week washout period. Primary outcome was change in BMI. Secondary outcomes included waist circumference, blood pressure, fasting lipids, treatment-emergent adverse events (TEAEs), and changes in appetite. Compliance was assessed via pill counts and structured patient interviews. Missing data were handled using generalized estimating equations (GEE).

RESULTS

Fifty-seven patients completed the study. Risperidone was associated with significantly greater BMI increases than aripiprazole (mean change: +1.1 ± 0.3 vs. +0.4 ± 0.2; p < 0.001). Trends favored aripiprazole for triglycerides (+ 7.3 vs. +28.1 mg/dL) and total cholesterol (+ 0.1 vs. +5.1 mg/dL), though differences did not reach statistical significance. Appetite effects diverged sharply: decreased appetite occurred more often with aripiprazole (60.7% vs. 20.7%; p = 0.002), whereas increased appetite was more common with risperidone (55.2% vs. 39.3%). Baseline demographics, illness duration, and Positive and Negative Syndrome Scale (PANSS) scores were comparable across groups, and both treatments significantly reduced PANSS scores over time.

CONCLUSIONS

Aripiprazole demonstrated a more favorable short-term metabolic profile compared to risperidone, with significantly less weight gain and appetite suppression as a potential mechanistic correlate. Appetite changes may serve as an early, clinically accessible predictor of long-term metabolic trajectories. These findings support integrating appetite monitoring into routine clinical practice and highlight the need to individualize antipsychotic selection based on metabolic risk.

TRIAL REGISTRATION: IRCT201305233930N26.