Antidepressant Agomelatine Improves Sleep and Mood Disorders in Epilepsy

In a recently published retrospective study, findings study that agomelatine, a melatonergic antidepressant, showed greater improvement in treating anxiety and sleep than escitalopram in patients with epilepsy. Furthermore, agomelatine demonstrated a better overall safety profile, suggesting it may be a more optimal therapeutic option for these symptoms than escitalopram in this patient population.¹

Senior investigator Xue-Wu Liu, department of neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, and colleagues collected data on 133 patients with epilepsy treated with either agent over an 8-week period. Depression and anxiety were explored through the Hamilton Depression (HAMD) and Hamilton Anxiety (HAMA) scales, respectively, while sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI). The goal of the study was to provide important references for the rational use of psychotropic drugs in patients with epilepsy who also suffer from sleep or mood disorders.

Between the agomelatine (n = 52) and escitalopram (n = 61) groups, there were no significant differences in patient age, gender, age of onset of epilepsy, etiology, seizure type, and antiseizure medication (ASM) type (P >.05). Throughout the study, the ASMs used included phenytoin, valproic acid, oxcarbazepine, carbamazepine, levetiracetam, topiramate, lamotrigine, parampanel, lacosamide, and zonisamide.

After 8 weeks of treatment, both groups showed significant reductions in the HAMA, HAMD, and PSQI scales (P <.001). There was no significant difference in HAMD score reduction rate between the groups (P >.791); however, HAMA D scores were significantly lower in agomelatine-treated patients (P = .001 <.05). In addition, this group showed significantly lower PSQI D scores as well (P <.001). Investigators observed no significant difference in HAMA D scores of the HAMD score between the groups (P = .712 >.05).

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Between the groups, there were slightly lower rates of adverse events (AEs) in the agomelatine group (13.46%; n = 7) than escitalopram (14.75%; n = 9). No serious AEs were observed and no significant abnormalities in blood routine test, liver and kidney function, and electrolyte, were identified. For both treatment cohorts, the AEs observed included dizziness and headache (agomelatine: n = 3; escitalopram: n = 4), nausea and vomiting (n = 2; n = 3), loss of appetite (n = 0; n = 1), drowsiness (n = 1; n = 1), an physical strength decline (n = 1; n = 0).

"One of causes of sleep disorders in PWE is circadian disruption," the study authors wrote. "Agomelatine antagonizes the 5-HT2C receptor to increase total sleep time, reduce arousals and promote slow wave sleep; similar to escitalopram. Agomelatine is also a receptor agonist that concurrently affects both MT1 and MT2 melatonin receptors, which exert sleep-promoting effects to restore sunchronization of disordered biorhythm."

In a correlation analysis using Kendall’s tau-b test, only the correlation coefficient between the kinds of ASMs and HAMD scale exhibited significance (P = –0.320; P <.01), indicating a weak negative correlation between the types of ASMs and HAMD values.

The study was limited by the retrospective design, which could potentially lead to a bias in the patient selection and statistical analysis. Investigators did not observe long-term prognostic outcomes, nor was there sufficient data on treating epilepsy itself, the interaction between epilepsy and complications, and the interaction between complications. Liu et al concluded that this study can only preliminarily analyze the relationship between adjuvant drugs and the efficacy of epileptic complications.

REFERENCE
1. Jiang J, Wu Y, Yan C, et al. Efficacy and safety of agomelatine in epilepsy patients with sleep and mood disorders: an observational, retrospective cohort study. Epileps & Behav. 2024;152:109641. doi:10.1016/j.yebeh.2024.109641