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
Abstract
BACKGROUND

Sleep disturbance is a core feature of post-traumatic stress disorder (PTSD). Given the relationship between sleep disturbance and PTSD, there has been a relative paucity of studies examining the potential therapeutic impact of using pharmacotherapy to target sleep disturbance in patients with PTSD. Eszopiclone (ESZ) is a non-benzodiazepine y-aminobutyric acid-A receptor agonist indicated for the treatment of sleep and may affect sleep in patients with PTSD.

AIM

To evaluate the efficacy of ESZ vs placebo (PBO) for patients with PTSD and insomnia.

METHODS

The study was a 12-wk, double blind, randomized controlled trial with 3 mg of ESZ (n = 13) or PBO (n = 12).

RESULTS

Patients in both arms experienced significant improvement in PTSD symptoms as assessed by the Clinician-Administered PTSD Scale for DSM-IV (CAPS): ESZ (t11 = -3.12, P = 0.005) and PBO (t11 = -3.5, P = 0.002) and by self-report with the Short PTSD Rating Interview (ESZ t11 = -3.38, P = 0.003 and PBO t11 = -4.48, P = 0.0005). There were no significant differences between treatments on the CAPS (t22 = -0.13, P = 0.70) or the Short PTSD Rating Interview (t22 = -0.58, P = 0.56). Similarly, both treated groups improved on sleep measures as assessed by the Pittsburgh Sleep Quality Index with PTSD Addendum (PSQI) and on total sleep time (TST) and sleep latency assessed by actigraphy with no significant differences between groups (PSQI t22 = -0.24, P = 0.81; total sleep time t10 = 0.13, P = 0.90 and sleep latency t10 = 0.68, P = 0.50). There was a significant correlation between improvement in sleep and overall improvement in PTSD as measured by change scores on the PSQI and CAPS, r(8) = 0.79, P = 0.01 for ESZ treated subjects, but not for those treated with PBO r(9) = 0.16, P = 0.69. Adverse events of ESZ were consistent with the known profile of the medication including dysgeusia (30%, mild), sedation (20%, mild) and headache (20%, moderate to severe).

CONCLUSION

Results do not support the hypothesis of a specific positive effect of ESZ compared to PBO for measures of PTSD and associated sleep disturbance.

Keywords: Trauma, Sleep disturbance, Hypnotic, Post-traumatic stress disorder

Core tip: Sleep disturbance is a core feature of post-traumatic stress disorder (PTSD) yet few studies have examined the impact of psychopharmacotherapy. Results from this randomized controlled parallel study in individuals with PTSD and sleep disturbance did not demonstrate a significant relative improvement for eszopiclone (ESZ) vs placebo treated patients. Although patients receiving ESZ did experience significant improvement in measures of PTSD and sleep disturbance, placebo treated patients also significantly improved on these outcomes. Thus the potential role for ESZ in the treatment of PTSD remains uncertain until a larger more definitive trial is undertaken.