Post Hoc Analysis of the Impact of Lemborexant on Patient-Reported Sleep and Insomnia Severity in Adults with Insomnia and Depression Histories
Bibliographic record
Abstract
Abstract Introduction The dual orexin receptor antagonist lemborexant (LEM) is approved in multiple countries including the United States, Japan, Canada, and Australia for insomnia treatment in adults. In phase 3 study E2006-G000-303 (Study 303; SUNRISE-2; NCT02952820), LEM provided significant benefit vs placebo (PBO) on subjective sleep outcomes over 6 months and was well tolerated. This post hoc analysis evaluated the effect of LEM on sleep outcome measures and insomnia severity as assessed by the Insomnia Severity Index (ISI) over 6 months in subjects with a lifetime history of depression (DepHx subgroup). We performed this analysis as insomnia in DepHx subjects could be a residual symptom of unresolved depression, and therefore, these subjects may respond differently to insomnia treatment. Methods Study 303 was a randomized, double-blind, 12 months global study in adults (≥18 years) with DSM-5 insomnia disorder. For 6 months (Treatment Period 1), subjects were randomized to PBO or LEM (5 mg [LEM5]; 10 mg [LEM10]). For the next 6 months (Treatment Period 2; not reported), PBO subjects were rerandomized to LEM and LEM subjects continued their original dose. The inclusion criteria allowed for participation of subjects with a lifetime DepHx, concomitant antidepressant medication use and/or mild depression (maximum Beck Depression Inventory II score of 19). Subjects had a baseline ISI total score (ISI-ts) ≥15. Results The Full Analysis Set comprised 949 subjects, including 112 subjects in the DepHx subgroup (PBO, n = 34; LEM5, n = 39; LEM10, n = 39). Baseline median subjective sleep onset latency (sSOL; minutes) was 52.9, 57.1, and 70.7 for PBO, LEM5, and LEM10, respectively. At 6 months, greater median decreases from baseline in sSOL were observed with LEM5 (−21.7) and LEM10 (−40.1) vs PBO (−12.9). Baseline mean subjective sleep efficiency (sSE; %) was 62.2, 59.2, and 62.4 for PBO, LEM5, and LEM10, respectively. At 6 months, greater mean (SD) increases from baseline in sSE were observed with LEM5 (17.2 [18.3]) and LEM10 (20.9 [19.0]) vs PBO (14.9 [15.4]). Baseline mean subjective wake after sleep onset (sWASO; minutes) was 123.7, 151.0, and 132.6 for PBO, LEM5, and LEM10, respectively. At 6 months, greater mean (SD) decreases from baseline in sWASO were observed with LEM5 (−52.7 [69.2]) and LEM10 (−68.8 [81.9]) vs PBO (−46.7 [69.4]). Mean baseline ISI-ts were 18.6, 19.9, and 19.0 PBO, LEM5, and LEM10, respectively. At 6 months, greater mean (SD) decreases from baseline in ISI-ts were observed with LEM5 (−9.1 [6.8]) and LEM10 (−10.0 [5.9]) vs PBO (−7.9 [5.6]). Treatment-emergent adverse event rates in the DepHx subgroup were similar to those in the overall study population. Discussion At 6 months, LEM improved patient-reported sleep outcomes and reduced patient-reported insomnia severity in subjects with DepHx. These results suggest that LEM may be a therapeutic option for patients with insomnia and DepHx. Funding Eisai, Inc.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".