Randomized Controlled Trial
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Mar 19, 2020; 10(3): 21-28
Published online Mar 19, 2020. doi: 10.5498/wjp.v10.i3.21
Double-blind randomized controlled study of the efficacy, safety and tolerability of eszopiclone vs placebo for the treatment of patients with post-traumatic stress disorder and insomnia
Sheila M Dowd, Alyson K Zalta, Helen J Burgess, Elizabeth C Adkins, Zerbrina Valdespino-Hayden, Mark H Pollack
Sheila M Dowd, Mark H Pollack, Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, Chicago, IL 60601, United States
Alyson K Zalta, Department of Psychological Science, University of California Irvine, Irvine, CA 92697, United States
Helen J Burgess, Sleep and Circadian Research Laboratory, Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, United States
Elizabeth C Adkins, Center for Behavioral Intervention Technologies | Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, United States
Zerbrina Valdespino-Hayden, Department of Psychology, Montclair State University, Montclair, NJ 07043, United States
Author contributions: Pollack MH designed the research; Pollack MH, Dowd SM, Zalta AK, Adkins EC and Valdespino-Hayden Z performed the research; Valdespino-Hayden Z and Burgess HJ scored and analyzed the sleep data; Pollack MH, Dowd SM, Zalta AK, Burgess HJ, Adkins EC and Valdespino-Hayden Z wrote the paper.
Supported by National Institute of Mental Health, No. 5R34MH91338-03 and No. K23 MH103394 (to Zalta AK).
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board of Rush University Medical Center.
Clinical trial registration statement: The study was registered on ClinicalTrials.gov. The registration identification number is NCT01605253.
Informed consent statement: Informed consent was obtained prior to the initial assessment.
Conflict-of-interest statement: Dr. Dowd reports grants from NIMH, during the conduct of the study; other from The Wellness Network, grants from Janssen Pharmaceuticals, grants from National Institutes of Health, outside the submitted work.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Sheila M Dowd, PhD, Associate Professor, Department of Psychiatry and Behavioral Sciences, Rush University Medical Center, 1645 West Jackson Blvd Suite 400, Chicago, IL 60601, United States. sheila_dowd@rush.edu
Received: November 13, 2019
Peer-review started: November 13, 2019
First decision: January 15, 2020
Revised: February 10, 2020
Accepted: February 23, 2020
Article in press: February 23, 2020
Published online: March 19, 2020
Processing time: 113 Days and 10.4 Hours
ARTICLE HIGHLIGHTS
Research background

Sleep disturbance is a frequent concern and an important component of post-traumatic stress disorder (PTSD). It is associated with several adverse consequences and may be a marker and risk factor for developing PTSD. It is also possible that it contributes to the difficulty treating PTSD. Preclinical studies have found impaired extinction learning in fear conditioned rats, a possible explanation for the impact of sleep disturbance.

Research motivation

There are few studies focused on the use of pharmacotherapy targeting sleep disturbance. However there is evidence that sleep disturbance among patients with PTSD are associated with increased rates of depression, suicidal ideation, increased use of alcohol and substances and poorer functioning.

Research objectives

The main objective was to examine the possible benefits of eszopiclone on sleep disturbance in PTSD.

Research methods

The study was a randomized controlled parallel study of participants with PTSD and sleep disturbance. We collected both self-report and clinician administered measures of PTSD and sleep quality. In addition, actigraphy data were collected and compared to patient’s self-report sleep logs.

Research results

The study did not find a significant relative improvement for those treated with eszopiclone compared to placebo. Those participants receiving eszopiclone experienced significant improvement in symptoms of PTSD and sleep disturbance, as did the participants receiving placebo. However, clinician and self-report measures of PTSD were correlated with improvement in sleep for the eszopiclone, but not placebo-treated patients, suggesting the potential importance of this specific association for the active treatment vs placebo effect. Interestingly, there were greater amounts of dropouts amongst the eszopiclone vs placebo treated patients. In addition, there were higher rates of past alcohol and substance abuse in the eszopiclone treated patients with two factors approaching, but not achieving statistical significance. Due to the small sample size, the potential role for eszopiclone in the treatment of PTSD remains uncertain until a larger more definitive trial is undertaken

Research conclusions

The findings of this study have contributed to the mixed evidence exploring pharmacotherapy in the treatment of sleep disturbance in patients with PTSD.

Research perspectives

Further work is needed to determine the potential role for pharmacotherapy targeting sleep disturbance in patients with PTSD.