1097 Effect of Lemborexant on Individual Domains of the Hamilton Depression Rating Scale in Patients with Insomnia Disorder and Depression

Abstract Introduction Insomnia and mood disorders are commonly comorbid. Many patients with partial remission of depression have insomnia symptoms remaining. In a recent study of lemborexant (LEM), a dual orexin-receptor antagonist approved for the treatment of insomnia, open-label LEM significantly improved symptoms of both insomnia and depression in a comorbid patient population. We report the symptoms on the Hamilton Depression Rating Scale (HAM-D-17) impacted by LEM. Methods This multicenter, prospective intervention study enrolled participants with insomnia disorder diagnosed with major depressive disorder (MDD) or bipolar disorder (BD) receiving stable antidepressant treatment. MDD add-on (n=29) and BD add-on (n=15) cohorts included participants with prior insomnia medication; MDD mono (n=23) and BD mono (n=15) cohorts included participants without concomitant hypnotic medication. LEM starting dose was 5 mg and could be titrated up/down. Mood disorder severity was measured with HAM-D-17 at baseline (BL) and Weeks 4/8/12. HAM-D-17 assesses severity of depression over the past week; higher scores indicate more severe depression, and 3 items (rating scale 0–2) evaluate insomnia symptoms (items 4–6; early, middle, and late insomnia, respectively). This analysis considered each item to determine those affected by LEM treatment. Results As previously reported, total HAM-D-17 scores for the 4 cohorts decreased significantly (improved) compared with BL at 4 weeks; these improvements were maintained over 12 weeks. This was also true when the 3 items associated with insomnia were excluded. At Week 12, significant decreases (improvements) in scores for HAM-D-17 items 1–8, 10, 11, and 13–15 were observed. However, the item scores most impacted by LEM treatment were the 3 insomnia items, as well as the overall depression item (rated on a scale from 0–4). The magnitude of change from BL was at least 0.4 points in the total patient population (early insomnia: BL 1.21, Week 4 −0.71; middle insomnia: BL 1.21, Week 4 −0.50; late insomnia: BL 0.91, Week 4 −0.53; depression: BL 1.56, Week 4 −0.44). Conclusion The majority of change (improvement) on the HAM-D-17 with LEM treatment was related to changes in sleep symptoms in this comorbid patient population. Support (if any) Eisai Inc.