Assessment of Suvorexant and Eszopiclone as Alternatives to Benzodiazepines for Treating Insomnia in Patients With Major Depressive Disorder

Abstract

ObjectivesWe investigated the utility of switching from benzodiazepines to suvorexant or eszopiclone to manage benzodiazepine-unresponsive insomnia in patients with major depressive disorder (MDD) in a randomized, open-label study.MethodsPatients with MDD who have insomnia symptoms (a score of >7 on the Insomnia Severity Index Japanese version [ISI-J]), who had received benzodiazepine treatment for more than 2 weeks (n = 18) were randomized to 4 weeks of suvorexant (20 or 15 mg/d) or eszopiclone (3 or 2 mg/d) treatment. The primary endpoint was an improvement in insomnia severity from baseline assessed by the ISI-J score at 2 and 4 weeks after switching from benzodiazepines. The secondary endpoints included changes in the scores of the Pittsburgh Sleep Quality Index Japanese version, the Beck Depression Inventory II, Generalized Anxiety Disorder 7, the digit span test, and the digit symbol substitution test from baseline. Adverse events were recorded throughout the study.ResultsPatients taking suvorexant or eszopiclone had improved ISI-J scores (−4.3 for suvorexant and −4.1 for eszopiclone at week 4; P = 0.04 for eszopiclone). Both drugs tended to improve the Beck Depression Inventory II and Generalized Anxiety Disorder 7 scores 2 and 4 weeks after switching. The Pittsburgh Sleep Quality Index Japanese version, digit symbol substitution test, and digit span test scores and the incidence of adverse events did not change from baseline.ConclusionsSwitching to suvorexant or eszopiclone was well tolerated and improved the severity of benzodiazepine-unresponsive insomnia in MDD patients. Both drugs could be beneficial alternatives to benzodiazepines for treating insomnia in MDD patients.

Alliance for Sleep Clinical Practice Guideline on Switching or Deprescribing Hypnotic Medications for Insomnia

“…In an open-label, randomized study, 18 subjects with comorbid insomnia and major depressive disorder were investigated. Participants were currently taking various benzodiazepine hypnotics for at least 2 weeks but had residual insomnia (Insomnia Severity Index (ISI) score > 7) [ 33 ]. Subjects were randomized to receive either suvorexant or eszopiclone, and benzodiazepine dosage was reduced by half during the first 2 weeks of treatment and then discontinued.…”

“…Neither group reported rebound insomnia, and there were no changes in Pittsburgh Sleep Quality Index (PSQI) scores or increased adverse events compared to baseline. Depression and anxiety scores tended to improve, although this was only significant for reduced anxiety in the eszopiclone group [ 33 ].…”

Factors Associated with Prescriptions for an Orexin Receptor Antagonist Among Japanese Patients with Insomnia: Analysis of a Nationwide Japanese Claims Database

“…e Facility with ≥ 20 beds disorder (except for one case report [32]), anxiety disorder, or schizophrenia (except for one case report [33]) at the time of conducting our analyses. Very recently, Shigetsura et al reported a new finding that switching from BZD to suvorexant was associated with a significant improvement of insomnia in patients with major depressive disorder [34]. Overall, the findings published to date suggest that ORA is an effective and tolerable treatment option for insomnia in patients with a wide variety of psychiatric comorbidities, and that physicians may be becoming more familiar with their use in this setting.…”