Lack of Efficacy of Simvastatin Adjunctive Therapy for Patients with Schizophrenia: A Meta-Analysis of Randomized Controlled Trials

Background: The adjunctive therapeutic potential of simvastatin in schizophrenia treatment has generated interest due to its antiinflammatory and neuroprotective properties. This meta-analysis aims to assess the efficacy of simvastatin as an adjunct treatment for schizophrenia, synthesizing results from various controlled trials. Methods: We performed a comprehensive search of databases including PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) evaluating the efficacy of simvastatin as an adjunct therapy in patients with schizophrenia. The primary outcome measures were improvements in the Positive and Negative Syndrome Scale (PANSS) scores. Secondary outcomes included changes in overall clinical condition and level of functioning. Data were pooled using random-effects models, and heterogeneity was Results: The four RCTs included in the analysis represented 425 participants. The combined results demonstrated no significant advantage of simvastatin over placebo in reducing PANSS total scores with a pooled effect size (Standard Mean Difference, SMD) of -0.36 (95% Confidence Interval, CI: -0.82 to 0.11) at 1 month, and -1.80 (95% Confidence Interval, CI: -4.82 to 1.21) at 3 months, indicating minimal to no effect. Similarly, analyses of secondary outcomes showed no significant improvements in overall clinical condition and level of functioning. The studies exhibited low heterogeneity (I2 = 0%). Conclusion: This meta-analysis provides evidence that simvastatin, used as adjunctive therapy, does not significantly improve the symptomatic outcomes of schizophrenia compared to placebo. Although simvastatin is well-tolerated, its role in enhancing antipsychotic treatment efficacy in patients with schizophrenia appears limited. These findings suggest that simvastatin should not be recommended as an adjunctive treatment in the clinical management of schizophrenia. Further research may explore the potential subgroups that could benefit from such treatment or identify the biological reasons for the lack of efficacy.