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Efficacy and Safety of Alpha-Lipoic Acid as an Adjunctive Therapy in Schizophrenia: A Systematic Review and
Gabriel Caruso Novaes Tudella1, Maria Antônia Oliveira Machado Pereira2, Augusto Utida Klostermann1
1Department of Medicine, Federal University of Santa Maria, Rio Grande do Sul.
Background:
Alpha-lipoic acid (ALA) is an antioxidant proposed to mitigate metabolic burden and psychopathology in schizophrenia. We systematically reviewed the efficacy and safety of ALA as an adjunct to antipsychotics.
Methods:
We searched MEDLINE, Embase, and the Cochrane Library from inception to September 2025 for human studies evaluating ALA in individuals with schizophrenia. Random-effects meta-analyses pooled mean differences (MDs) with 95% CIs for continuous outcomes and pooled proportions for adverse events and discontinuation.
Results:
Eight studies (n = 165) were included. In single-arm analyses, ALA showed no significant improvements in PANSS scores in pooled estimates, despite isolated findings in small subsets. A reduction in BMI was observed in the RCT subgroup but not in the overall analysis. No significant effects were found for HbA1c, waist circumference, or lipid profile. In ALA versus placebo comparisons, no significant differences were observed for PANSS scores, BMI, adverse events, or discontinuation. ALA was generally well tolerated, though findings were limited by small sample sizes and imprecision.
Conclusions:
Current evidence suggests adjunctive ALA may modestly influence selected PANSS subscales but does not improve metabolic outcomes. Larger, well-designed trials with standardized dosing and longer follow-up are needed to clarify clinical relevance and safety.