Hostname: page-component-586b7cd67f-g8jcs Total loading time: 0 Render date: 2024-11-29T03:31:37.408Z Has data issue: false hasContentIssue false
  • English
  • Français

Prazosin for treatment of post-traumatic stress disorder: a systematic review and meta-analysis

Published online by Cambridge University Press:  04 May 2020

Christopher Reist Open the ORCID record for Christopher Reist [Opens in a new window] ,
Elani Streja ,
Cynthia Crystal Tang ,
Bryan Shapiro ,
Jim Mintz  and
Michael Hollifield
Christopher Reist*
Affiliation:
Tibor Rubin Veteran Affairs Healthcare System, Long Beach, California, USA Department of Medicine, University of California, Irvine School of Medicine, Orange, California, USA Science 37, Playa Vista, California, USA
Elani Streja
Affiliation:
Tibor Rubin Veteran Affairs Healthcare System, Long Beach, California, USA Department of Medicine, University of California, Irvine School of Medicine, Orange, California, USA Department of Population Health and Disease Prevention, Program in Public Health, University of California, Irvine, Irvine, California, USA
Cynthia Crystal Tang
Affiliation:
Department of Population Health and Disease Prevention, Program in Public Health, University of California, Irvine, Irvine, California, USA
Bryan Shapiro
Affiliation:
Tibor Rubin Veteran Affairs Healthcare System, Long Beach, California, USA Department of Medicine, University of California, Irvine School of Medicine, Orange, California, USA
Jim Mintz
Affiliation:
Department of Psychiatry and Biobehavioral Sciences, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA Department of Epidemiology and Biostatistics, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA
Michael Hollifield
Affiliation:
Tibor Rubin Veteran Affairs Healthcare System, Long Beach, California, USA
*
*Christopher Reist, MD, Email: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Background

Prazosin has been an accepted treatment for patients with post-traumatic stress disorder (PTSD) who experience sleep disturbances, including nightmares. Results of a recent large randomized control trial did not find benefit of prazosin vs placebo in improving such outcomes. A meta-analysis that includes this most recent trial was conducted to examine the pooled effect of prazosin vs placebo on sleep disturbances and overall PTSD symptoms in patients with PTSD.

Methods

A systematic review of the published literature on trials comparing prazosin vs placebo for improvement of overall PTSD scores, nightmares, and sleep quality was conducted. Hedges’ g standardized mean differences (SMD) between prazosin and placebo were calculated for each outcome across studies.

Results

Six randomized placebo-controlled studies representing 429 patients were included in the analysis, including two studies with a crossover design. Results showed prazosin significantly improved overall PTSD scores (SMD = −0.31; 95% confidence intervals [CI]: −0.62, −0.01), nightmares (SMD = −0.75; 95% CI: −1.24, −0.27), and sleep quality (SMD = −0.57; 95% CI: −1.02, −0.13). In the largest trial, prazosin showed a reduction in clinical outcome measures similar to past studies, but a relatively large placebo effect size, particularly for nightmares, contributed to no treatment differences.

Conclusions

Despite the results of a recent, large randomized study, pooled effect estimates show that prazosin has a statistically significant benefit on PTSD symptoms and sleep disturbances. Limitations that should be considered include heterogeneity of study design and study populations as well as the small number of studies conducted and included in this meta-analysis.

Keywords

Post-traumatic stress disordernightmaressleepprazosinmeta-analysis
Type
Review
Information
CNS Spectrums , Volume 26 , Issue 4 , August 2021 , pp. 338 - 344
Copyright
© Cambridge University Press 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

The Management of Posttraumatic Stress Disorder Work Group. D.o.V.A., VA/DOD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. https://www.healthquality.va.gov/guidelines/MH/ptsd/VADoDPTSDCPGFinal.pdf.2017. Accessed October 23, 2019.Google Scholar
Hall, KS, Beckham, JC, Bosworth, HB, et al. PTSD is negatively associated with physical performance and physical function in older overweight military Veterans. J Rehabil Res Dev. 2014;51(2):285–295.10.1682/JRRD.2013.04.0091CrossRefGoogle ScholarPubMed
Ryder, AL, Azcarate, PM, Cohen, BE. PTSD and physical health. Curr Psychiatry Rep. 2018;20(12):116.10.1007/s11920-018-0977-9CrossRefGoogle ScholarPubMed
Hoerster, KD, Campbell, S, Dolan, M, et al. PTSD is associated with poor health behavior and greater body mass index through depression, increasing cardiovascular disease and diabetes risk among U.S. veterans. Prev Med Rep. 2019;15:100930.10.1016/j.pmedr.2019.100930CrossRefGoogle ScholarPubMed
Forehand, JA, Peltzman, T, Westgate, CL, et al. Causes of excess mortality in veterans treated for posttraumatic stress disorder. Am J Prev Med. 2019;57(2):145–152.10.1016/j.amepre.2019.03.014CrossRefGoogle ScholarPubMed
Steenkamp, MM, Litz, BT, Hoge, CW, Marmar, CR. Psychotherapy for military-related PTSD: a review of randomized clinical trials. JAMA. 2015;314(5):489–500.10.1001/jama.2015.8370CrossRefGoogle ScholarPubMed
Berger, W, Mendlowicz, MV, Marques-Portella, C, et al. Pharmacologic alternatives to antidepressants in posttraumatic stress disorder: a systematic review. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(2):169–180.10.1016/j.pnpbp.2008.12.004CrossRefGoogle ScholarPubMed
Raskind, MA, Dobie, DJ, Kanter, ED, et al. The alpha1-adrenergic antagonist prazosin ameliorates combat trauma nightmares in veterans with posttraumatic stress disorder: a report of 4 cases. J Clin Psychiatry. 2000;61(2):129–133.10.4088/JCP.v61n0208CrossRefGoogle ScholarPubMed
Taylor, FB, Martin, P, Thompson, C, et al. Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study. Biol Psychiatry. 2008;63(6):629–632.10.1016/j.biopsych.2007.07.001CrossRefGoogle ScholarPubMed
De Berardis, D,  Marini, S, Serroni, N, et al. Targeting the noradrenergic system in posttraumatic stress disorder: a systematic review and meta-analysis of prazosin trials. Curr Drug Targets. 2015;16(10):1094–1106.10.2174/1389450116666150506114108CrossRefGoogle ScholarPubMed
George, KC, Kebejian, L, Ruth, LJ, Miller, CW, Himelhoch, S. Meta-analysis of the efficacy and safety of prazosin versus placebo for the treatment of nightmares and sleep disturbances in adults with posttraumatic stress disorder. J Trauma Dissoc. 2016;17(4):494–510.10.1080/15299732.2016.1141150CrossRefGoogle ScholarPubMed
Ipser, JC, Stein, DJ. Evidence-based pharmacotherapy of post-traumatic stress disorder (PTSD). Int J Neuropsychopharmacol. 2012;15(6):825–840.10.1017/S1461145711001209CrossRefGoogle Scholar
Khachatryan, D, Groll, D, Booji, L, Sepehry, AA, Shutz, CG. Prazosin for treating sleep disturbances in adults with posttraumatic stress disorder: a systematic review and meta-analysis of randomized controlled trials. Gen Hosp Psychiatry. 2016;39:46–52.10.1016/j.genhosppsych.2015.10.007CrossRefGoogle ScholarPubMed
Singh, B, Hughes, AJ, Mehta, G, Erwin, PJ, Parsaik, AK. Efficacy of prazosin in posttraumatic stress disorder: a systematic review and meta-analysis. Prim Care Companion CNS Disord. 2016;18(4):doi: 10.4088/PCC.16r01943.Google ScholarPubMed
Raskind, MA, Peskind, E, Chow, B, et al. Trial of prazosin for post-traumatic stress disorder in military veterans. N Engl J Med. 2018;378(6):507–517.10.1056/NEJMoa1507598CrossRefGoogle ScholarPubMed
Morgenthaler, TI, Auerbach, S, Casey, K, et al. Position paper for the treatment of nightmare disorder in adults: an American Academy of Sleep Medicine Position Paper. J Clin Sleep Med. 2018;14(6):1041–1055.10.5664/jcsm.7178CrossRefGoogle ScholarPubMed
Slomski, A. Prazosin may not reduce nightmares in veterans with PTSD. JAMA. 2018;319(16):1649.Google Scholar
Ressler, KJ. Alpha-adrenergic receptors in PTSD—failure or time for precision medicine? N Engl J Med. 2018;378(6):575–576.10.1056/NEJMe1716724CrossRefGoogle ScholarPubMed
Anghelescu, I, Moschner, C. Prazosin for post-traumatic stress disorder. N Engl J Med. 2018;378(17):1648–1649.Google ScholarPubMed
Glue, P, Barak, Y. Prazosin for post-traumatic stress disorder. N Engl J Med. 2018;378(17):1649.Google ScholarPubMed
Mysliwiec, V, Brock, MS. Prazosin for post-traumatic stress disorder. N Engl J Med. 2018;378(17):1649.Google ScholarPubMed
Higgins, JP, Altman DG, Gøtzsche PC, et al. The Cochrane collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.10.1136/bmj.d5928CrossRefGoogle ScholarPubMed
Blake, DD, Weathers, FW, Nagy, LM, et al. The development of a clinician-administered PTSD scale. J Trauma Stress. 1995;8(1):75–90.10.1002/jts.2490080106CrossRefGoogle ScholarPubMed
Blanchard, EB, Jones-Alexander, J, Buckley, TC, et al. Psychometric properties of the PTSD Checklist (PCL). Behav Res Ther. 1996;34(8):669–673.10.1016/0005-7967(96)00033-2CrossRefGoogle Scholar
Buysse, DJ, Reynolds, CF III, Monk, TH, et al. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989;28(2):193–213.10.1016/0165-1781(89)90047-4CrossRefGoogle ScholarPubMed
Higgins, J, Green, S, ed. Cochrane Handbook for Systematic Reviews of Interventions Vol. Version 5.1.0. Chichester, England, UK: The Cochrane Collaboration; 2011. Accessed March 2019, www.handbook.cochrane.org.Google Scholar
Hedges, LV, Olkin, I. Statistical Methods for Meta-Analysis. San Diego, CA: Academic Press; 1985.Google Scholar
Raskind, MA, Peskind, ER, Kanter, ED, et al. Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am J Psychiatry. 2003;160(2):371–373.CrossRefGoogle ScholarPubMed
Raskind, MA, Peskind, ER, Hoff, DJ, et al. A parallel group placebo controlled study of prazosin for trauma nightmares and sleep disturbance in combat veterans with post-traumatic stress disorder. Biol Psychiatry. 2007;61(8):928–934.CrossRefGoogle ScholarPubMed
Germain, A, Richardson, R, Moul, DE, et al. Placebo-controlled comparison of prazosin and cognitive-behavioral treatments for sleep disturbances in US military veterans. J Psychosom Res. 2012;72(2):89–96.10.1016/j.jpsychores.2011.11.010CrossRefGoogle ScholarPubMed
Raskind, MA, Peterson, K, Williams, T, et al. A trial of prazosin for combat trauma PTSD with nightmares in active-duty soldiers returned from Iraq and Afghanistan. Am J Psychiatry. 2013;170(9):1003–1010.10.1176/appi.ajp.2013.12081133CrossRefGoogle ScholarPubMed
Boehnlein, JK, Kinzie, JD. Pharmacologic reduction of CNS noradrenergic activity in PTSD: the case for clonidine and prazosin. J Psychiatr Pract. 2007;13(2):72–78.CrossRefGoogle ScholarPubMed
Yamamoto, K, Shinba, T, Yoshii, M. Psychiatric symptoms of noradrenergic dysfunction: a pathophysiological view. Psychiatry Clin Neurosci. 2014;68(1):1–20.CrossRefGoogle ScholarPubMed
Mallick, BN, Majumdar, S, Faisal, M, et al. Role of norepinephrine in the regulation of rapid eye movement sleep. J Biosci. 2002;27(5):539–551.CrossRefGoogle ScholarPubMed
Birnbaum, S, Gobeske, KT, Auerbach, J, et al. A role for norepinephrine in stress-induced cognitive deficits: alpha-1-adrenoceptor mediation in the prefrontal cortex. Biol Psychiatry. 1999;46(9):1266–1274.CrossRefGoogle ScholarPubMed
Vythilingam, M, Anderson, GM, Owens, MJ, et al. Cerebrospinal fluid corticotropin-releasing hormone in healthy humans: effects of yohimbine and naloxone. J Clin Endocrinol Metab. 2000;85(11):4138–4145.Google ScholarPubMed
Daly, CM, Doyle, ME, Radkind, M, et al. Clinical case series: the use of prazosin for combat-related recurrent nightmares among Operation Iraqi Freedom combat veterans. Mil Med. 2005;170(6):513–515.10.7205/MILMED.170.6.513CrossRefGoogle ScholarPubMed
Friedman, MJ, Marmar, C, Baker, DG, et al. Randomized, double-blind comparison of sertraline and placebo for posttraumatic stress disorder in a Department of Veterans Affairs setting. J Clin Psychiatry. 2007;68(5):711–720.CrossRefGoogle Scholar
Rosenheck, RA, Krystal, JH, Lew, R, et al. Long-acting risperidone and oral antipsychotics in unstable schizophrenia. N Engl J Med. 2011;364(9):842–851.CrossRefGoogle ScholarPubMed
Supplementary material: File

Reist et al. supplementary material

Reist et al. supplementary material

Download Reist et al. supplementary material(File)
File 3.8 MB