Improved Insomnia Symptoms and Sleep-Related Next-Day Functioning in Patients With Comorbid Major Depressive Disorder and Insomnia Following Concomitant Zolpidem Extended-Release 12.5 mg and Escitalopram Treatment: A Randomized Controlled Trial

Objective: This investigation was performed to assess the efficacy and safety of zolpidem extended-release in patients with insomnia associated with major depressive disorder (MDD).

Method: Patients (N = 385) received open-label escitalopram 10 mg/d and were randomized to concomitant zolpidem extended-release 12.5 mg/night or placebo for 8 weeks (phase 1) in a randomized, parallel-group, multicenter trial. Responders (≥ 50% in 17-item Hamilton Depression Rating Scale [HDRS17] score) continued 16 weeks of double-blind treatment (phase 2); escitalopram only was given during a 2-week run-out period. The study was conducted between February 2006 and June 2007. The primary efficacy measure was change from baseline in subjective total sleep time. Secondary efficacy measures included subjective sleep-onset latency, number of awakenings, wake time after sleep onset, sleep quality, sleep-related next-day functioning, HDRS17, Sleep Impact Scale score, Patient and Clinical Global Impressions of Insomnia Treatment, the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire, and the Quality of Life Enjoyment and Satisfaction Questionnaire. Adverse events were recorded throughout the study; sleep measures were also evaluated during the run-out period.

Results: Throughout phase 1, zolpidem extended-release led to significantly greater improvements in total sleep time (P < .0001), wake time after sleep onset, sleep onset latency, number of awakenings, and sleep quality (P ≤ .0003), and some measures of sleep-related next-day functioning but not in depressive symptoms or quality of life. During phase 2, improvements with the zolpidem extended-release/escitalopram group occurred for total sleep time (significant [P < .05] at weeks 12 and 16), as well as for a few other secondary efficacy measures but not in depressive symptoms or quality of life. The most common adverse events associated with combination treatment included nausea, somnolence, dry mouth, dizziness, fatigue, and amnesia.

Conclusions: Zolpidem extended-release administered concomitantly with escitalopram for up to 24 weeks was well tolerated and improved insomnia and some sleep-related next-day symptoms and next-day functioning in patients with MDD but did not significantly augment the antidepressant response of escitalopram.

Trial Registration: clinicaltrials.gov Identifier: NCT00296179

J Clin Psychiatry 2011;72(7):914-928

Submitted: July 30, 2009; accepted November 24, 2009.

Online ahead of print: December 28, 2010 (doi:10.4088/JCP.09m05571gry).

Corresponding author: Maurizio Fava, MD, MGH Clinical Trials Network and Institute, Massachusetts General Hospital, 55 Fruit St, Bulfinch 351, Boston, MA ([email protected]).