A Systematic Literature Review Of Randomized Controlled Trials Evaluating Primary Chronic Insomnia Treatments

Insomnia is a common disorder affecting up to 6-10% of the adult population which can contribute to significant functional impairments at work and is linked to reduced quality of life. However, additional evidence is needed to understand the relative effectiveness and safety of available therapies to guide treatment decisions. We performed a systematic literature review (SLR) for randomized controlled trials (RCTs) for interventions used in the treatment of primary chronic insomnia to evaluate efficacy and safety data available across treatments that could inform future comparative effectiveness studies. Studies were retrieved from Embase and Pubmed databases, using relevant search strategies for primary chronic insomnia. Medication therapies (including lembroexant, suvorexant, eszopiclone, zolpidem, and ramelteon), cognitive behavioral therapy for insomnia (CBT-I), and known prescription and non-prescription digital therapeutics were included in the search. Study characteristics, patient demographics, clinical efficacy, and safety data were extracted. Efficacy endpoints extracted for review included sleep efficiency [SE], total sleep time [TST], wake after sleep onset [WASO], number of awakenings [NOA], sleep onset latency [SOL], and insomnia severity index [ISI]. In total, 1,013 potentially relevant studies were identified. Following the screening of abstracts and full-text publications, 72 papers were included. Included studies were published between 1997 and 2020, including 25 studies focused on medication-based treatments (Eszopiclone: 6; Ramelteon: 7; Zolpidem: 6; Suvorexant: 4; Lembroexant: 2), 10 on prescription digital therapeutics, and 37 for traditional CBT-I. Across the reviewed studies, only 7 reported data on every endpoint of interest, while the remainder reported one or more endpoints of interest (SE: 16; TST: 22; WASO: 19; NOA: 10; ISI: 31). Sufficient evidence exists to compare available medications, CBT-I, and digital therapeutics in chronic insomnia. Findings from this study will be used in future comparative effectiveness studies.