Efficacy of anti-Toxoplasma medications on symptom severity and cognition in patients with schizophrenia or schizoaffective disorder: systematic review and meta-analysis.

OBJECTIVE

This systematic review and meta-analysis assessed the efficacy of anti-Toxoplasma medications on schizophrenia spectrum disorders. Given the emerging evidence linking Toxoplasma gondii infection to schizophrenia, understanding these results may provide targeted treatments for patients with schizophrenia who are infected with T. gondii.

METHODS

A comprehensive search of PubMed, Scopus, and Lilacs databases following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines identified studies on anti- Toxoplasma antibiotics in schizophrenia or schizoaffective disorder. The inclusion criteria were primary observational studies and randomized controlled trials, and the risk of bias was assessed using appropriate tools. Meta-analyses of the standardized mean differences were conducted to compare Positive and Negative Syndrome Scale scores from baseline to post-treatment. Statistical analyses were performed in R 4.3.1. Funnel plots and Egger's tests were applied to assess publication bias.

RESULTS

Of 5,491 screened studies, 19 met the inclusion criteria: 13 randomized controlled trials, four secondary analyses, one cross-sectional study, and one cohort study. A meta-analysis of the randomized controlled trials revealed that antibiotics had a small effect on symptom improvement (-3.12, 95%CI -5.82 to -0.41). Minocycline yielded mixed outcomes, showing improvements in negative symptoms and cognitive function in some studies but no effect on others. Other antibiotics, like azithromycin and artemisinin, showed limited benefits regarding T. gondii immunoglobulin Gpositive patients, although artemether did not. No publication bias was detected.

CONCLUSION

Anti-Toxoplasma antibiotics may offer potential benefits as adjunctive therapy for schizophrenia. However, the studies' heterogeneity and methodological limitations make it difficult to draw conclusions. Large-scale randomized controlled trials are needed to further clarify the role of anti- Toxoplasma antibiotics in schizophrenia treatment.