Efficacy and Safety of Alpha-Lipoic Acid as an Adjunctive Therapy in Schizophrenia
Gabriel Caruso Novaes Tudella, Maria Antônia Oliveira Machado Pereira, Augusto Utida Klostermann, João Victor Pereira Gonzalez, Ocílio Ribeiro Gonçalves, Kenzo Ogasawara Donato, Luiz Arthur de Oliveira Nantes, Anderson Matheus Pereira da Silva, Ana Rízzia Cunha Cordeiro Forte, Marianna Letícia Vasconcelos Patrocínio, Tatiana de Queiroz Oliveira, Silvânia Maria Mendes VasconcelosBackground:
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.