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The article is a systematic review of randomized controlled trials (RCTs) that evaluated the safety and efficacy of ondansetron and simvastatin as potential adjunctive treatment for patients with schizophrenia. Ondansetron is an antiemetic drug that acts on the 5-HT3 receptor, and simvastatin is a lipid-lowering drug that inhibits the enzyme HMG-CoA reductase. Both drugs have been proposed to have beneficial effects on schizophrenia symptoms by modulating inflammation, oxidative stress, glutamate and dopamine neurotransmission.
The authors searched four databases (PubMed, Scopus, Web of Science and Cochrane Library) for RCTs that compared ondansetron or simvastatin plus antipsychotics with placebo plus antipsychotics in adult patients with schizophrenia. They assessed the quality of the studies using the Cochrane risk of bias tool and performed a narrative synthesis of the results.
They identified six RCTs for ondansetron (n = 341) and four RCTs for simvastatin (n = 253) that met their inclusion criteria. The studies varied in terms of sample size, duration, dosage, outcome measures and quality. The results showed that ondansetron was superior to placebo in improving positive, negative and general symptoms of schizophrenia, as well as cognitive function and quality of life. Simvastatin was superior to placebo in improving negative and general symptoms of schizophrenia, but not positive symptoms or cognitive function. Both drugs were well tolerated and did not cause significant adverse effects or interactions with antipsychotics.
The authors concluded that ondansetron and simvastatin may be effective and safe adjunctive treatments for patients with schizophrenia, especially for those who are resistant or partially responsive to antipsychotics. However, they acknowledged the limitations of their review, such as the heterogeneity, small sample size and low quality of the included studies. They recommended more high-quality RCTs with larger samples, longer duration, standardized outcome measures and subgroup analyses to confirm their findings and to explore the mechanisms of action and the optimal dosage of these drugs.