0
Get Alert
Please Wait... Processing your request... Please Wait.
You must sign in to sign-up for alerts.

Please confirm that your email address is correct, so you can successfully receive this alert.

Articles   |    
A Trial of Prazosin for Combat Trauma PTSD With Nightmares in Active-Duty Soldiers Returned From Iraq and Afghanistan
Murray A. Raskind, M.D.; Kris Peterson, M.D.; Tammy Williams, L.C.S.W.; David J. Hoff, PA-C; Kimberly Hart, PA-C; Hollie Holmes, B.A.; Dallas Homas, M.D.; Jeffrey Hill, M.D.; Colin Daniels, M.D.; Jess Calohan, P.M.H.N.P.; Steven P. Millard, Ph.D.; Kirsten Rohde, R.N.; James O’Connell, M.S.W.; Denise Pritzl, L.I.C.S.W.; Kevin Feiszli, B.S.; Eric C. Petrie, M.D.; Christopher Gross, M.D.; Cynthia L. Mayer, D.O.; Michael C. Freed, Ph.D.; Charles Engel, M.D.; Elaine R. Peskind, M.D.
Am J Psychiatry 2013;170:1003-1010. doi:10.1176/appi.ajp.2013.12081133
View Author and Article Information

Supported by the Department of Veterans Affairs, U.S. Army Medical Research and Materiel Command, Fort Detrick, Md.; and by NIH grant 1R01MH069867.

Dr. Raskind has been an advisory board member for Janssen Immunotherapy, Pfizer Laboratories, and Baxter Pharmaceuticals. Dr. Peterson has been on the speakers bureau for Otsuka and AstraZeneca. Dr. Peskind has been an advisory board member for Lilly Pharmaceuticals and Avanir and on the speakers bureau for Forest Laboratories and Novartis. The other authors report no financial relationships with commercial interests.

The views expressed are those of the authors and do not reflect the official policy of the Department of the Army, the Department of Defense, or the U.S. Government.

From the VISN 20 Northwest Network Mental Illness Research, Education, and Clinical Center (MIRECC), Seattle; Madigan Army Medical Center, Tacoma, Wash.; Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle; and the Uniformed Services University of the Health Sciences, Bethesda, Md.

Address correspondence to Dr. Raskind (murray.raskind@va.gov).

Copyright © 2013 by the American Psychiatric Association

Received August 29, 2012; Revised January 03, 2013; Revised March 08, 2013; Accepted March 13, 2013.

Abstract

Objective  The authors conducted a 15-week randomized controlled trial of the alpha-1 adrenoreceptor antagonist prazosin for combat trauma nightmares, sleep quality, global function, and overall symptoms in active-duty soldiers with posttraumatic stress disorder (PTSD) returned from combat deployments to Iraq and Afghanistan.

Method  Sixty-seven soldiers were randomly assigned to treatment with prazosin or placebo for 15 weeks. Drug was titrated based on nightmare response over 6 weeks to a possible maximum dose of 5 mg midmorning and 20 mg at bedtime for men and 2 mg midmorning and 10 mg at bedtime for women. Mean achieved bedtime doses were 15.6 mg of prazosin (SD=6.0) and 18.8 mg of placebo (SD=3.3) for men and 7.0 mg of prazosin (SD=3.5) and 10.0 mg of placebo (SD=0.0) for women. Mean achieved midmorning doses were 4.0 mg of prazosin (SD=1.4) and 4.8 mg of placebo (SD=0.8) for men and 1.7 mg of prazosin (SD=0.5) and 2.0 mg of placebo (SD=0.0) mg for women. Primary outcome measures were the nightmare item of the Clinician-Administered PTSD Scale (CAPS), the Pittsburgh Sleep Quality Index, and the change item of the Clinical Global Impressions Scale anchored to functioning. Secondary outcome measures were the 17-item CAPS, the Hamilton Depression Rating Scale, the Patient Health Questionnaire–9, and the Quality of Life Index. Maintenance psychotropic medications and supportive psychotherapy were held constant.

Results  Prazosin was effective for trauma nightmares, sleep quality, global function, CAPS score, and the CAPS hyperarousal symptom cluster. Prazosin was well tolerated, and blood pressure changes did not differ between groups.

Conclusions  Prazosin is effective for combat-related PTSD with trauma nightmares in active-duty soldiers, and benefits are clinically meaningful. Substantial residual symptoms suggest that studies combining prazosin with effective psychotherapies might demonstrate further benefit.

Abstract Teaser
Figures in this Article

Your Session has timed out. Please sign back in to continue.
Sign In Your Session has timed out. Please sign back in to continue.
Sign In to Access Full Content
 
Username
Password
Sign in via Athens (What is this?)
Athens is a service for single sign-on which enables access to all of an institution's subscriptions on- or off-site.
Not a subscriber?

Subscribe Now/Learn More

PsychiatryOnline subscription options offer access to the DSM-5 library, books, journals, CME, and patient resources. This all-in-one virtual library provides psychiatrists and mental health professionals with key resources for diagnosis, treatment, research, and professional development.

Need more help? PsychiatryOnline Customer Service may be reached by emailing PsychiatryOnline@psych.org or by calling 800-368-5777 (in the U.S.) or 703-907-7322 (outside the U.S.).

FIGURE 1. Effects of Prazosin on Symptom Ratings in Active-Duty Soldiers With Combat Trauma-Related PTSD With Nightmaresa

a Based on linear mixed-effects models. CAPS=Clinician-Administered PTSD Scale; CGI=Clinical Global Impressions Scale.

b Change from baseline to week 15 significantly greater for prazosin than placebo, p<0.001.

c Change from baseline to week 15 significantly greater for prazosin than placebo, p<0.01.

d Change from baseline to week 15 significantly greater for prazosin than placebo, p<0.05.

Anchor for Jump
TABLE 1.Medication Titration Schedule in a Study of Prazosin in Active-Duty Soldiers With Combat Trauma-Related PTSD With Nightmares
Table Footer Note

a The morning dose was taken between 10:00 and 11:00 a.m.

Anchor for Jump
TABLE 2.Demographic and Clinical Characteristics of Active-Duty Soldiers With Combat Trauma-Related PTSD With Nightmares in a Study of Prazosin
Table Footer Note

a Missing values for three participants in each group.

Table Footer Note

b All were on selective serotonin reuptake inhibitors (SSRIs) except one on amitriptyline, one on mirtazapine, and one on bupropion.

Table Footer Note

c All were on SSRIs except one on mirtazapine.

Anchor for Jump
TABLE 3.Adjusted Means and Differences in Behavioral Outcomes and Blood Pressure in Active-Duty Soldiers With Combat Trauma-Related PTSD With Nightmares, at Baseline and End of Studya
Table Footer Note

a CAPS=Clinician-Administered PTSD Scale (17-item); CGI=Clinical Global Impressions Scale; Adjusted means and differences in 15-week change from baseline between treatment groups are based on linear mixed-effects models that include terms for gender and antidepressant use (these covariates are set to their average value). Change from baseline is defined as value at baseline minus value at week 15. For the CGI change item, change from baseline is value at week 15. For CGI change item responders (see text for results), adjusted percentages are based on a generalized linear mixed-effects model with covariates.

Table Footer Note

b Total number of participants varies between time points and outcomes; at baseline, N=63–66; at week 15, N=48–50.

Table Footer Note

c Difference in 15-week change from baseline between treatment groups (change from baseline in the prazosin group minus change from baseline in the placebo group). For the CGI change item, score at week 15 for the placebo group minus score at week 15 for prazosin group. For CGI change item responders (see text for results), the odds ratio for the prazosin group compared with the placebo group (based on generalized linear mixed-effects model with covariates).

+

References

Thomas  JL;  Wilk  JE;  Riviere  LA;  McGurk  D;  Castro  CA;  Hoge  CW:  Prevalence of mental health problems and functional impairment among active component and National Guard soldiers 3 and 12 months following combat in Iraq.  Arch Gen Psychiatry 2010; 67:614–623
[CrossRef] | [PubMed]
 
Morgan  M;  Lockwood  A;  Steinke  D;  Schleenbaker  R;  Botts  S:  Pharmacotherapy regimens among patients with posttraumatic stress disorder and mild traumatic brain injury.  Psychiatr Serv 2012; 63:182–185
[CrossRef] | [PubMed]
 
Department of Veterans Affairs, Department of Defense: VA/DoD Clinical Practice Guideline: Management of Post-Traumatic Stress, version 2.0. Oct 2010 (http://www.healthquality.va.gov/PTSD-FULL-2010c.pdf)
 
van der Kolk  BA;  Dreyfuss  D;  Michaels  M;  Shera  D;  Berkowitz  R;  Fisler  R;  Saxe  G:  Fluoxetine in posttraumatic stress disorder.  J Clin Psychiatry 1994; 55:517–522
[PubMed]
 
Hertzberg  MA;  Feldman  ME;  Beckham  JC;  Kudler  HS;  Davidson  JRT:  Lack of efficacy for fluoxetine in PTSD: a placebo controlled trial in combat veterans.  Ann Clin Psychiatry 2000; 12:101–105
[CrossRef] | [PubMed]
 
Friedman  MJ;  Marmar  CR;  Baker  DG;  Sikes  CR;  Farfel  GM:  Randomized, double-blind comparison of sertraline and placebo for posttraumatic stress disorder in a Department of Veterans Affairs setting.  J Clin Psychiatry 2007; 68:711–720
[CrossRef] | [PubMed]
 
Southwick  SM;  Krystal  JH;  Morgan  CA;  Johnson  D;  Nagy  LM;  Nicolaou  A;  Heninger  GR;  Charney  DS:  Abnormal noradrenergic function in posttraumatic stress disorder.  Arch Gen Psychiatry 1993; 50:266–274
[CrossRef] | [PubMed]
 
Mellman  TA;  Kumar  A;  Kulick-Bell  R;  Kumar  M;  Nolan  B:  Nocturnal/daytime urine noradrenergic measures and sleep in combat-related PTSD.  Biol Psychiatry 1995; 38:174–179
[CrossRef] | [PubMed]
 
Geracioti  TD  Jr;  Baker  DG;  Ekhator  NN;  West  SA;  Hill  KK;  Bruce  AB;  Schmidt  D;  Rounds-Kugler  B;  Yehuda  R;  Keck  PE  Jr;  Kasckow  JW:  CSF norepinephrine concentrations in posttraumatic stress disorder.  Am J Psychiatry 2001; 158:1227–1230
[CrossRef] | [PubMed]
 
Blake  DD;  Weathers  FW;  Nagy  LM;  Kaloupek  DG;  Gusman  FD;  Charney  DS;  Keane  TM:  The development of a clinician-administered PTSD scale.  J Trauma Stress 1995; 8:75–90
[CrossRef] | [PubMed]
 
Berridge  CW:  The locus ceruleus-noradrenergic system and stress: implications for post-traumatic stress disorder, in  Post-Traumatic Stress Disorder: Basic Science and Clinical Practice . Edited by Shiromani  PJ;  Keane  TM;  LeDoux  JE.  New York,  Humana Press, 2009, pp 213–230
 
Menkes  DB;  Baraban  JM;  Aghajanian  GK:  Prazosin selectively antagonizes neuronal responses mediated by alpha1-adrenoreceptors in brain.  Naunyn Schmiedebergs Arch Pharmacol 1981; 317:273–275
[CrossRef] | [PubMed]
 
Raskind  MA;  Peskind  ER;  Kanter  ED;  Petrie  EC;  Radant  A;  Thompson  CE;  Dobie  DJ;  Hoff  D;  Rein  RJ;  Straits-Tröster  K;  Thomas  RG;  McFall  MM:  Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study.  Am J Psychiatry 2003; 160:371–373
[CrossRef] | [PubMed]
 
Raskind  MA;  Peskind  ER;  Hoff  DJ;  Hart  KL;  Holmes  HA;  Warren  D;  Shofer  J;  O’Connell  J;  Taylor  F;  Gross  C;  Rohde  K;  McFall  ME:  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; 61:928–934
[CrossRef] | [PubMed]
 
Germain  A;  Richardson  R;  Moul  DE;  Mammen  O;  Haas  G;  Forman  SD;  Rode  N;  Begley  A;  Nofzinger  EA:  Placebo-controlled comparison of prazosin and cognitive-behavioral treatments for sleep disturbances in US military veterans.  J Psychosom Res 2012; 72:89–96
[CrossRef] | [PubMed]
 
First  MB;  Spitzer  RL;  Gibbon  M;  William  JBW:  Structured Clinical Interview for DSM-IV Axis I Disorders–Patient Edition (SCID-IP, Version 2.0) .  New York,  Biometrics Research Department, New York State Psychiatric Institute, 1996
 
Buysse  DJ;  Reynolds  CF  3rd;  Monk  TH;  Berman  SR;  Kupfer  DJ:  The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research.  Psychiatry Res 1989; 28:193–213
[CrossRef] | [PubMed]
 
Guy  W:  ECDEU Assessment Manual for Psychopharmacology : Publication ADM 76-338.  Washington, DC,  US Department of Health, Education, and Welfare, 1976, pp 218–222
 
Hamilton  M:  A rating scale for depression.  J Neurol Neurosurg Psychiatry 1960; 23:56–62
[CrossRef] | [PubMed]
 
Kroenke  K;  Spitzer  RL;  Williams  JB:  The PHQ-9: validity of a brief depression severity measure.  J Gen Intern Med 2001; 16:606–613
[CrossRef] | [PubMed]
 
Frisch MB: Manual and Treatment Guide for the Quality of Life Inventory–QOLI. Minneapolis, MN, Pearson Assessments, 1994
 
Pinheiro  JC;  Bates  DM:  Mixed-Effects Models in S and S-PLUS .  New York,  Springer, 2000
 
R Development Core Team: R: A Language and Environment for Statistical Computing, version 2.11.1. Vienna, Austria, R Foundation for Statistical Computing, 2011 (http://www.R-project.org)
 
Pinheiro J, Bates D, DebRoy S, Sarkar D, R Core Team: nlme: Linear and Nonlinear Mixed Effects Models, R package, version 3.1-104, 2012. http://cran.r-project.org/web/packages/nlme
 
Bates D, Maechler M, Bolker B: lme4: Linear mixed-effects models using S4 classes, R package, version 0.999999-0, 2012. http://CRAN.R-project.org/package=lme4.
 
Westfall  TC;  Westfall  DP:  Adrenergic agonists and antagonists, in  Goodman and Gilman’s The Pharmacological Basis of Therapeutics , 11th ed. Edited by Brunton  L;  Lazo  T;  Barker  K.  New York,  McGraw-Hill, 2006, pp 237–296
 
Krystal  JH;  Rosenheck  RA;  Cramer  JA;  Vessicchio  JC;  Jones  KM;  Vertrees  JE;  Horney  RA;  Huang  GD;  Stock  C; Veterans Affairs Cooperative Study No. 504 Group:  Adjunctive risperidone treatment for antidepressant-resistant symptoms of chronic military service-related PTSD: a randomized trial.  JAMA 2011; 306:493–502
[CrossRef] | [PubMed]
 
Brady  K;  Pearlstein  T;  Asnis  GM;  Baker  D;  Rothbaum  B;  Sikes  CR;  Farfel  GM:  Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial.  JAMA 2000; 283:1837–1844
[CrossRef] | [PubMed]
 
Davidson  JRT;  Rothbaum  BO;  van der Kolk  BA;  Sikes  CR;  Farfel  GM:  Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder.  Arch Gen Psychiatry 2001; 58:485–492
[CrossRef] | [PubMed]
 
Tucker  P;  Zaninelli  R;  Yehuda  R;  Ruggiero  L;  Dillingham  K;  Pitts  CD:  Paroxetine in the treatment of chronic posttraumatic stress disorder: results of a placebo-controlled, flexible-dosage trial.  J Clin Psychiatry 2001; 62:860–868
[CrossRef] | [PubMed]
 
Marshall  RD;  Beebe  KL;  Oldham  M;  Zaninelli  R:  Efficacy and safety of paroxetine treatment for chronic PTSD: a fixed-dose, placebo-controlled study.  Am J Psychiatry 2001; 158:1982–1988
[CrossRef] | [PubMed]
 
Oberndorfer  S;  Saletu-Zyhlarz  G;  Saletu  B:  Effects of selective serotonin reuptake inhibitors on objective and subjective sleep quality.  Neuropsychobiology 2000; 42:69–81
[CrossRef] | [PubMed]
 
Taylor  FB;  Martin  P;  Thompson  C;  Williams  J;  Mellman  TA;  Gross  C;  Peskind  ER;  Raskind  MA:  Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma postraumatic stress disorder: a placebo-controlled study.  Biol Psychiatry 2008; 63:629–632
[CrossRef] | [PubMed]
 
Ruff  RL;  Ruff  SS;  Wang  XF:  Improving sleep: initial headache treatment in OIF/OEF veterans with blast-induced mild traumatic brain injury.  J Rehabil Res Dev 2009; 46:1071–1084
[CrossRef] | [PubMed]
 
Calohan  J;  Peterson  K;  Peskind  ER;  Raskind  MA:  Prazosin treatment of trauma nightmares and sleep disturbance in soldiers deployed in Iraq.  J Trauma Stress 2010; 23:645–648
[CrossRef] | [PubMed]
 
Mallick  BN;  Majumdar  S;  Faisal  M;  Yadav  V;  Madan  V;  Pal  D:  Role of norepinephrine in the regulation of rapid eye movement sleep.  J Biosci 2002; 27:539–551
[CrossRef] | [PubMed]
 
Vythilingam  M;  Anderson  GM;  Owens  MJ;  Halaszynski  TM;  Bremner  JD;  Carpenter  LL;  Heninger  GR;  Nemeroff  CB;  Charney  DS:  Cerebrospinal fluid corticotropin-releasing hormone in healthy humans: effects of yohimbine and naloxone.  J Clin Endocrinol Metab 2000; 85:4138–4145
[CrossRef] | [PubMed]
 
Birnbaum  S;  Gobeske  KT;  Auerbach  J;  Taylor  JR;  Arnsten  AF:  A role for norepinephrine in stress-induced cognitive deficits: alpha-1-adrenoceptor mediation in the prefrontal cortex.  Biol Psychiatry 1999; 46:1266–1274
[CrossRef] | [PubMed]
 
Thompson  CE;  Taylor  FB;  McFall  ME;  Barnes  RF;  Raskind  MA:  Nonnightmare distressed awakenings in veterans with posttraumatic stress disorder: response to prazosin.  J Trauma Stress 2008; 21:417–420
[CrossRef] | [PubMed]
 
Eftekhari  A;  Ruzek  JI;  Crowley  JJ;  Rosen  CS; National Center for PTSD:  Effectiveness of national implementation of prolonged exposure therapy in VA care.  JAMA Psychiatry  (in press)
 
References Container
+
+

Self-Assessment Quiz

Did you know? You can add a subscription now to earn CME Credits!

1.
The likely mechanism of action of prazosin in the treatment of combat PTSD is:
2.
Prazosin is effective for which components of PTSD in active duty combat experienced service members?
3.
Which was the only emergent adverse event significantly different in incidence between prazosin and placebo?
Submit a Comments
Please read the other comments before you post yours. Contributors must reveal any conflict of interest.
Comments are moderated and will appear on the site at the discertion of APA editorial staff.

* = Required Field
(if multiple authors, separate names by comma)
Example: John Doe



Web of Science® Times Cited: 13

Related Content
See Also...
Articles
Books
APA Practice Guidelines > Chapter 17.  >
The American Psychiatric Publishing Textbook of Psychopharmacology, 4th Edition > Chapter 56.  >
The American Psychiatric Publishing Textbook of Psychiatry, 5th Edition > Chapter 12.  >
APA Practice Guidelines > Chapter 17.  >
Gabbard's Treatments of Psychiatric Disorders, 4th Edition > Chapter 32.  >
Topic Collections
Psychiatric News
APA Guidelines
PubMed Articles