1 École de Psychologie, Université Laval, 2325 Rue Des Bibliothèques, Québec, Québec, G1V 0A6, Canada.
2 Centre de recherche CERVO/Brain Research Center, 2301 Av. D'Estimauville, Québec, Québec, G1E 1T2, Canada.
3 Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
4 Department of Health, Kinesiology and Applied Physiology, Concordia University, 7141 Sherbrooke Street West, Montréal, Québec, H4B 1R6, Canada.
5 Centre de Recherche de L'Institut Universitaire de Gériatrie de Montréal (CRIUGM), CIUSSS du Centre-Sud-de-L'île-de-Montréal, 4565 Queen Mary Road, Montréal, Québec, H3W 1W5, Canada.
6 Medical Sciences, University of Toronto, 399 Bathurst St, MP7, 421, Toronto, Ontario, M5T 2S8, Canada.
7 Department of Psychology, Toronto Metropolitan University, 350 Victoria Street, Toronto, Ontario, M5B 2K3, Canada.
8 School of Psychology, University of Ottawa, 136 J

Introduction: Insomnia is a prevalent yet under-characterized disorder, particularly regarding the heterogeneity of patients and their associated responses to different treatment modalities. This often leads to suboptimal management. There is a need to consider personalized approaches tailored to the characteristics of insomnia phenotypes with regard to objective evidence of shortened sleep duration (< 6 h). This study will examine whether there is a differential treatment response to cognitive behavioral therapy for insomnia (CBT-I) versus pharmacotherapy (lemborexant) as a function of insomnia phenotypes (i.e., ± 6 h of sleep).

Methods: This study is a three-arm pragmatic randomized clinical trial, which will enroll 90 adults with chronic insomnia disorder and anxiety/depressive symptoms. Eligible participants will be randomized to one of three conditions (1:1:1) involving CBT-I, lemborexant (Dual Orexin Receptor Antagonist) or placebo medication. Treatment outcomes will be assessed at post-treatment and 6-month follow-up. Insomnia symptom severity as measured by the Insomnia Severity Index will serve as the primary outcome for treatment comparisons. Secondary outcomes will include daily sleep/wake variables derived from the Consensus Sleep Diary, subjective measures of fatigue, mood, mental well-being, functional impairments, and sleep-related beliefs and attitudes. In addition, changes in cognitive performance will be examined as an exploratory outcome. Sleep reactivity and arousal level will be evaluated as potential mediators of treatment-related changes in CBT-I and pharmacotherapy.

Discussion: This study will contribute to the development of personalized medicine for managing different insomnia phenotypes and will have implication for knowledge mobilization of sleep research.

Trial registration: ClinicalTrials.gov. Identifier: NCT06779149. Registered on 12 January 2025.