Role of Adjunctive Melatonin in Patients with Chronic Schizophrenia: A Prospective Comparative Cohort Study of Cognitive Function and Inflammatory Markers

Abstract Background: Schizophrenia is a chronic neuropsychiatric disorder with cognitive impairment and inflammatory dysregulation. Melatonin’s antioxidant, anti-inflammatory, and neuroprotective properties may improve cognition and clinical outcomes as adjunctive therapy. Aim: To evaluate the association of adjunctive melatonin therapy with cognitive function and inflammatory markers in patients with chronic schizophrenia. Materials and Methods: This hospital-based prospective comparative cohort study included 77 patients with chronic schizophrenia. Patients receiving adjunctive melatonin (10 mg/day) with standard antipsychotic therapy constituted the melatonin-exposed group ( n = 39), while those receiving standard antipsychotic therapy alone constituted the comparison group ( n = 38). Cognitive function and psychopathology were assessed using Cognition Self-Assessment Rating Scale for Patients with Schizophrenia (C-SARS) and Positive and Negative Syndrome Scale (PANSS). Serum interleukin-6 (IL-6), interleukin-18 (IL-18), and C-reactive protein were measured at baseline and at 4, 8, and 16 weeks. Between-group comparisons were performed using independent Student’s t test or chi-square test, as appropriate. Results: Baseline characteristics were broadly comparable, although IL-18 was higher in the melatonin-exposed group ( t = 2.12, P = 0.037). C-SARS scores were lower in the melatonin group at 8 weeks ( t = -3.24, P = 0.002) and 16 weeks ( t = -6.36, P < 0.001). PANSS total scores were lower at 4 weeks ( t = -2.15, P = 0.034) and 16 weeks ( t = -5.96, P < 0.001), and PANSS negative scores were lower at 4, 8, and 16 weeks. C-reactive protein and IL-6 showed no significant between-group differences during the follow-up. IL-18 declined in the melatonin group, but the 16-week between-group difference was not significant. Conclusion: Adjunctive melatonin was associated with lower C-SARS and PANSS scores during the follow-up, while inflammatory markers showed inconsistent changes. Given the nonrandomized allocation, these findings are hypothesis-generating and do not establish the causal treatment effect.