Background: Prophylactic treatment for recurrence of febrile seizure generally consists of intermittent administration of diazepam or clobazam, or long-term treatment with valproic acid or phenobarbital. However, the adverse effects outweigh the benefits. A newer, effective, more tolerable drug treatment is warranted.

Objective: To study melatonin efficacy in prevention of recurrence of one or more episodes of either simple or complex febrile seizure compared to a control group.

Methods: A quasi-experimental study in children who were diagnosed with febrile seizure in Bhumibol Adulyadej Hospital, between 6 months to 5 years old, divided into two groups, melatonin group and control group, depending upon parental convenience. Melatonin was given 0.3 mg/kg/dose every 8 hours for 48 to 72 hours during febrile illness to melatonin group if body temperature was more than 37.5°C. Control group had no medicine. Patients were followed at 3 and 6 months.

Results: The study included 23 patients in the melatonin group and 41 in the control group. Mean age of diagnosed of febrile seizure onset was 17.3 and 21.6 months, respectively. In the melatonin group, 8.7% of patients had recurrent febrile seizure compared to 36.6% in the control group, which is statistically significant (P-value 0.015, RD −0.28(95%CI: −0.46 to −0.09)). There was no statistically significant difference in adverse effects between the two groups.

Conclusion: This study demonstrates the efficacy and safety of short-term melatonin use to prevent the recurrence of one or more episodes of either simple or complex-febrile seizure in children.