Efficacy and Safety of Daridorexant in Patients With Major Depressive Disorder and Insomnia

Insomnia is an extensively studied condition, yet its interactions with major depressive disorder (MDD) remain insufficiently understood. This study aims to evaluate the efficacy and safety of Daridorexant in MDD patients with comorbid insomnia. The primary objective is to determine whether Daridorexant improves the severity of insomnia, as measured by the Insomnia Severity Index (ISI), while assessing its impact on depressive symptoms will be considered the secondary objective. A prospective, double-blind, randomized, multicenter, placebo-controlled trial will be conducted in major depressive disorder outpatient clinic of the psychiatry department. Eligible patients will be randomized to Daridorexant versus placebo. Neither participants nor investigators will be aware of the treatment allocation. Standardized procedures for blinding and emergency unblinding will be implemented across all centers. The main outcome will be the improvement of Insomnia Severity Index (ISI) but additionally total sleep time, wake after sleep onset time, sleep latency and sleep efficiency will be measured. Data collection will include the Pittsburgh Sleep Quality Index (PSQI), depressive symptoms measured by the Montgomery-Åsberg Depression Rating Scale (MADRS), suicidal thoughts measured by the MINI-Neuropsychiatry Scale, quality of life measured by EuroQol, Dysfunctional Beliefs and Attitudes about Sleep (DBAS) and Polysomnography at baseline and 3 months. The study aims to demonstrate improvements in patient's subjective experience of insomnia, and additionally objective quantifiable improvements of objective sleep measurements via polysomnography, without an associated increase in depressive symptoms.