Efficacy of melatonin as an adjunct to first-line therapy in epileptic patients.

Abstract

Objective: To determine the efficacy of melatonin as an adjunct to first-line antiepileptic therapy in reducing seizure severity, seizure frequency, and electroencephalographic (EEG) abnormalities in pediatric patients with generalized epilepsy. Study Design: Quasi-experimental Comparative study. Setting: Department of Pediatrics, Pakistan Institute of Medical Sciences (PIMS), Islamabad. Period: July 2025 to Dec 2025. Methods: A total of 60 children aged 2–12 years with generalized epilepsy and suboptimal seizure control despite first-line antiepileptic therapy were enrolled using consecutive sampling. Patients were allocated into two groups: the treatment group (n=30) received melatonin as an adjunct to first-line therapy, while the control group (n=30) received placebo with first-line therapy. Melatonin was administered at bedtime for 12 weeks (1 mg for children <5 years and 2 mg for ≥5 years). Seizure severity was assessed using the Chalfont-National Hospital Seizure Severity Scale (NHS-3), while seizure frequency over a three-month period and EEG findings were recorded at baseline and follow-up. Data were analyzed using SPSS version 25.0, and a p-value of less than 0.05 was considered statistically significant. Results: The two groups showed no significant differences in baseline demographic and clinical characteristics. At 12 weeks, seizure severity scores were significantly reduced in the melatonin group compared to the placebo group (10.7 ± 2.4 vs. 17.9 ± 4.3; p < 0.001), with a mean reduction of 7.9 ± 3.1 versus 1.5 ± 1.6, respectively. Seizure frequency also showed a significant reduction in the melatonin group compared to placebo (mean reduction: 3.1 ± 1.1 vs. 0.4 ± 0.9; p < 0.001). 50% of patients in the melatonin group showed significant EEG normalizationin contrast to 26% in the placebo group (p = .03). Conclusion: Adjunctive use of melatonin with first-line antiepileptic therapy results in significant improvement in seizure severity, seizure frequency, and EEG findings in pediatric patients with generalized epilepsy, supporting its safety and effectiveness as an additional treatment option in children with inadequate seizure control.