Is Aripiprazole an Effective Adjunct to Reduce Metabolic Adverse Effects Caused by Clozapine in Patients With Schizophrenia—A Systematic Review

Clozapine is an atypical antipsychotic used in the treatment of schizophrenia. However, its use is associated with significant metabolic adverse effects, including hyperglycaemia, dyslipidaemia, and weight gain. Aripiprazole, a newer atypical antipsychotic with a different pharmacological profile, has been suggested to mitigate some of these metabolic side effects when used adjunctively. This systematic review assessed the evidence for the effectiveness of adjunctive Aripiprazole in reducing clozapine‐induced metabolic adverse effects. A systematic search was conducted across five academic databases, resulting in 52 articles. Following inclusion and exclusion criteria, eight studies were selected for narrative synthesis. These included randomized controlled trials, cohort studies, and case reports. The key metabolic outcomes assessed were glucose levels, lipid profiles, body weight, and waist circumference. Adjunctive Aripiprazole was associated with improvements in LDL and total cholesterol levels, as well as reductions in body weight in several studies. Fasting glucose levels and waist circumference showed limited or inconsistent changes. The overall evidence remains limited, particularly in terms of high‐quality, long‐term trials. This review suggests that Aripiprazole may offer some benefit in managing clozapine‐induced dyslipidaemia and weight gain. However, variability in outcomes, study design, and patient characteristics highlight the need for further research. Future studies should focus on larger, longer duration trials, broader patient demographics, and optimal dosing strategies to better evaluate the clinical utility of this combination therapy.