Melatonin Prolonged-Release May Improve Insomnia and Depression in Epilepsy Patients

Insomnia is a common sleep disorder that is highly prevalent among patients with epilepsy. Despite the known benefits of melatonin for insomnia and its potential anticonvulsive effects, clinical evidence regarding its efficacy in epilepsy patients with comorbid insomnia remains limited. This pilot study aimed to evaluate the efficacy and safety of prolonged-release (PR) formulation of melatonin in epilepsy patients with insomnia.

We prospectively enrolled 34 adult patients with epilepsy from March 2024 to February 2025. The insomnia severity index (ISI) and the Korean version of the Neurological Disorders of Depression Inventory for Epilepsy (K-NDDI-E) were assessed before and after 12 weeks of melatonin PR intake. Data were analyzed using the Wilcoxon signed-rank test. Changes in seizure status before and after treatment were analyzed using McNemar's test.

A total of 25 patients (nine males, mean age 53.5±11.6 years) completed the study. Of these, 23 had focal-onset seizures and two had generalized-onset seizures. After 12 weeks of treatment, ISI scores significantly improved from 16.0±4.4 to 12.2±5.2 (p=0.001). Similarly, K-NDDI-E scores showed a significant reduction from 11.3±4.2 to 9.8±3.2 (p=0.041). Seizure status remained unchanged following treatment, with no statistically significant difference observed before and after melatonin PR administration (p=1.000). No patients discontinued the medication due to seizure aggravation.

Our findings demonstrate that melatonin PR effectively improves both sleep quality and depression in epilepsy patients with insomnia. These results suggest that melatonin PR could be a potential therapeutic option for managing comorbid insomnia and depression in patients with epilepsy.