Efficacy of Anti-Toxoplasma Medications in Symptom Severity and Cognition in Patients with Schizophrenia or Schizoaffective Disorder: Systematic Review and Meta-analysis

ABSTRACT
Background: This systematic review and meta-analysis assess the efficacy of antiToxoplasma medications in treating schizophrenia spectrum disorders. Given the emerging evidence linking Toxoplasma gondii infection to schizophrenia, understanding these results may inform targeted treatments for patients with schizophrenia who are infected with Toxoplasma gondii.
Methods: A comprehensive search of PubMed, Scopus, and Lilacs databases following PRISMA guidelines identified studies on anti-Toxoplasma antibiotics in schizophrenia or chizoaffective disorder. Inclusion criteria focused on primary observational studies and randomized controlled trials (RCTs). 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 (PANSS) scores from baseline to post-treatment. Statistical analyses were performed using R version 4.3.1. Funnel plots and Egger’s tests were applied to assess publication bias.
Results: Nineteen studies met the inclusion criteria from 5,491 screened: 13 RCTs, four secondary analyses, one cross-sectional study, and one cohort study. A metaanalysis of RCTs revealed a small effect of antibiotics 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 in others. Other antibiotics, like azithromycin and artemisinin, showed limited benefit, except for artemether in T. gondii Immunoglobulins G positive patients. No publication bias was detected.
Conclusion: Anti-Toxoplasma antibiotics may offer potential benefits as adjunctive therapy for schizophrenia. However, heterogeneity and methodological limitations complicate conclusions. Large-scale RCTs are needed further to clarify the role of anti-Toxoplasma antibiotics in schizophrenia treatment.