Pakistan Journal of Pharmaceutical Sciences

Abstract: Background: Schizophrenia is a severe mental disorder characterized by hallucinations, delusions and cognitive dysfunction, imposing a substantial burden on individuals and society. While antipsychotic medications such as risperidone effectively control positive symptoms, their efficacy in ameliorating cognitive impairment and aggressive behavior remains limited. Repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, has recently demonstrated potential in adjunctively improving cognitive and behavioral dimensional symptoms in schizophrenia patients. However, the effects of combined rTMS-risperidone therapy on these symptoms and associated serum biomarkers are not yet adequately supported by clinical evidence. Objective: This study aimed to evaluate the effects of repetitive transcranial magnetic stimulation (rTMS) combined with risperidone on cognitive function, aggressive behavior and serum biomarkers in patients with schizophrenia. Method: Eighty patients were randomly assigned to a risperidone monotherapy group or a combination therapy group (40 each) for a 4-week intervention. Results: Results showed that the combination group achieved significantly greater reductions in cognitive factor scores (11.39±2.44 vs. 12.84±2.13) and aggressive behavior scores compared to the monotherapy group (all P<0.05). Serum analysis revealed that the combination group also demonstrated superior modulation of biomarkers, including greater reductions in pro-inflammatory factors (TNF-?, IL-8, IL-18) and greater increases in anti-inflammatory (IL-10) and neurotrophic factors (BDNF, VEGF-A, FGF-2) (all P<0.05), while no significant differences were observed in PDGF-BB and HGF between the two groups. Conclusion: These findings suggest that rTMS combined with risperidone more effectively improves cognitive and aggressive symptoms in schizophrenia and is associated with favorable changes in serum inflammatory and neurotrophic markers.