Effect of n-3 polyunsaturated fatty acids on the treatment of schizophrenia: an updated systematic review and meta-analysis.

BACKGROUND: Schizophrenia is a chronic disorder, and treatment options for its negative and cognitive symptoms are limited. Omega-3 fatty acids have potential neuroprotective effects, but evidence of their efficacy in schizophrenia and ultra-high risk group is inconsistent. This study aimed to provide an updated meta-analysis of randomized controlled trials evaluating the effectiveness of omega-3 fatty acid supplementation in patients with schizophrenia and ultra-high risk group. METHODS: A PRISMA-guided meta-analysis of randomized controlled trials comparing omega-3 fatty acids with placebo in schizophrenia was conducted. The literature search was concluded on November 12, 2024, and was conducted without any restrictions on language or timeframe. Data were extracted and analyzed using fixed or random-effects model depending on heterogeneity. Subgroup, sensitivity, and bias assessments were performed. RESULTS: The meta-analysis, which included 16 trials with 1,435 participants, revealed no significant difference between omega-3 fatty acids and placebo in schizophrenia at the endpoint of intervention (standard mean difference = - 0.123; 95% confidence interval = - 0.267 to 0.021; p = 0.095), and ultra-high risk of schizophrenia at the endpoint of follow-up after intervention (standard mean difference = - 0.070; 95% confidence interval = - 0.425 to 0.285; p = 0.699). A small number of subgroup analyses suggested potential benefits for patients with first-episode schizophrenia and treatment over 24 weeks, and those receiving adjunctive antioxidant treatment. Publication bias was minimal. CONCLUSIONS: Omega-3 fatty acid supplementation generally has no significant benefits for treating schizophrenia and ultra-high risk group. However, subgroup findings highlight the need for future trials focusing on early-stage patients, longer supplementation, and exploring synergistic effects with adjunctive antioxidant interventions. Clinical application should remain cautious until further confirmatory evidence emerges.