Comparative Effectiveness of Amisulpride and Clozapine in the Treatment of Schizophrenia: A Systematic Review and Meta-Analysis

In approximately one-third of individuals with schizophrenia, the illness demonstrates a poor response to standard antipsychotic treatments. Although a relatively small proportion fails to achieve remission after the initial exposure to either first- or second -generation antipsychotic drugs, the condition often becomes progressively more resistant to medication following subsequent relapses. We conducted comprehensive searches in databases such as PubMed and PubMed Central, extracting and assessing data quality using the Cochrane risk -of -bias tool for randomized clinical trials (RCTs). A random effects model was employed to calculate the pooled prevalence and explore heterogeneity, utilizing the I-2 statistic. Subgroup analyses differentiated between experimental and placebo groups, while sensitivity analyses assessed the robustness of our findings, and publication bias was examined. Our meta -analysis included a sample size of 323 patients from seven studies out of the 10 selected articles. The pooled sample evaluated the effectiveness of amisulpride and clozapine in treating schizophrenia, with Positive and Negative Syndrome Scale (PANSS)positive and PANSS-negative scores used in the subgroup analysis. The analysis revealed a heterogeneity of 78% and a statistically significant p -value of <0.05, favoring amisulpride and clozapine for treating schizophrenia either as monotherapy or in combination. These findings indicate that the effectiveness of these drugs is statistically significant. Our study underscores the necessity of conducting larger RCTs to further elucidate the optimal dosage and guideline criteria for prescribing amisulpride, clozapine, or their combination for patients resistant to first- and second -generation antipsychotics.