Blood-based oxidation markers in medicated and unmedicated schizophrenia patients: A meta-analysis

Increased reactive species due to the effect of antipsychotics on oxidative stress may be involved in the development of schizophrenia. However, antipsychotics may have different direct antioxidant effects due to their chemical structures. The present meta-analysis aimed to investigate whether the cause increased oxidant status in schizophrenia patients is due to the illness or induction by antipsychotics. Studies published from 1964 to 2021 were selected from Pubmed and Scopus databases. Data were analysed using Comprehensive Meta-Analysis version 2. Effect sizes were calculated and compared between unmedicated and medicated patients and healthy controls. Heterogeneity and publication bias were assessed. Subgroup analyses were conducted on drug-free and drug-naïve patients, and patients treated with atypical and typical antipsychotics. We found that medicated patients had significantly higher malondialdehyde (MDA), thiobarbituric acid reactive substances (TBARS) and total oxidant status (TOS). Meanwhile, significantly increased plasma/serum MDA and nitric oxide (NO) were observed in unmedicated patients only. Higher lipid peroxidation in the drug-naïve group may be associated schizophrenia. However, both atypical and typical antipsychotics may worsen lipid peroxidation. Antipsychotic discontinuation in the drug-free group led to significantly increased plasma/serum NO, with larger effect size than the atypical antipsychotic group. In conclusion, medicated schizophrenia patients were more suffered from increased oxidative stress. Therefore, future study may focus on the mechanism of action of specific antipsychotic on oxidative stress.