Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans

Raskind, Murray A.; Peskind, Elaine R.; Chow, Bruce K.; Harris, Crystal L.; Davis-Karim, Anne; Holmes, Hollie; Hart, Kimberly; McFall, Miles; Mellman, Thomas A.; Reist, Christopher; Romesser, Jennifer; Rosenheck, Robert; Shih, Mei‐Chiung; Stein, Murray B.; Swift, Robert; Gleason, Theresa; Lü, Ying; Huang, Grant D.

doi:10.1056/nejmoa1507598

Cited by 271 publications

(210 citation statements)

References 30 publications

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“…The AASM recommended prazosin as an adjunct therapy for PTSD, including nightmares (Aurora et al., , on behalf of the AASM). However, there was a recent large‐scale multicentre trial that did not yield any improvements (Raskind et al., ) and another trial in which patients returned to their baseline levels after treatment was discontinued (Raskind et al., ). These conflicting data caused the AASM to downgrade their advice regarding prazosin from “recommended” to “may be used” and to name other pharmaceuticals that “may be used” as well (Morgenthaler et al., , on behalf of the AASM).…”

Section: The Treatment Of Nightmare Disordermentioning

confidence: 99%

Aetiology and treatment of nightmare disorder: State of the art and future perspectives

Gieselmann

Aoudia²,

Carr

et al. 2019

Journal of Sleep Research

166

159

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This consensus paper provides an overview of the state of the art in research on the aetiology and treatment of nightmare disorder and outlines further perspectives on these issues. It presents a definition of nightmares and nightmare disorder followed by epidemiological findings, and then explains existing models of nightmare aetiology in traumatized and non‐traumatized individuals. Chronic nightmares develop through the interaction of elevated hyperarousal and impaired fear extinction. This interplay is assumed to be facilitated by trait affect distress elicited by traumatic experiences, early childhood adversity and trait susceptibility, as well as by elevated thought suppression and potentially sleep‐disordered breathing. Accordingly, different treatment options for nightmares focus on their meaning, on the chronic repetition of the nightmare or on maladaptive beliefs. Clinically, knowledge of healthcare providers about nightmare disorder and the delivery of evidence‐based interventions in the healthcare system is discussed. Based on these findings, we highlight some future perspectives and potential further developments of nightmare treatments and research into nightmare aetiology.

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Section: The Treatment Of Nightmare Disordermentioning

confidence: 99%

Aetiology and treatment of nightmare disorder: State of the art and future perspectives

Gieselmann

Aoudia²,

Carr

et al. 2019

Journal of Sleep Research

166

159

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“…Several RCTs with varying sample sizes of veterans and civilians demonstrate safety, tolerability and efficacy of prazosin to reduce nightmares, sleep impairment, and overall PTSD symptom severity [1,18,51–53,59,68], as well as AUD severity [59,60]. However, the largest RCT to date examining prazosin in the treatment of PTSD ( N = 304) [49] resulted in null findings. Veterans in this study were recruited from 13 VA hospitals across the nation.…”

Section: Discussionmentioning

confidence: 99%

“…It is necessary for future studies to explore the possibility that some Veterans might benefit from initiating prazosin earlier in their course of treatment or sooner after PTSD onset. In the [49] study, approximately one third of participants with similar distributions between medication conditions received individual or group psychotherapy ( n = 43; 28%) and the majority of participants were prescribed antidepressants (95% and 89% in the prazosin vs. placebo group, respectively). Thus, an additional consideration posed by the authors is that prazosin is less efficacious in the context of an established course of evidence-supported medications and/or psychotherapy to treat PTSD.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have examined the use of prazosin, an alpha-1 noradrenergic blocker approved by the U.S. Food and Drug Administration (FDA) for hypertension and benign prostatic hyperplasia, in the treatment of PTSD, AUD and comorbid AUD/PTSD. The findings have been mixed with some studies showing significant reduction in AUD symptoms [15,59,60] and reduction in PTSD symptoms, particularly nightmares, sleep disruption and daytime hyperarousal symptoms [18,50,52], while other studies find no significant differences in prazosin vs. placebo for AUD or PTSD symptoms [41,49]. Several studies suggest that pre-treatment blood pressure may represent a biomarker to help identify who will respond favorably to prazosin, or potentially other alpha-1 blockers [48,74].…”

Section: Introductionmentioning

confidence: 99%

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Doxazosin for the treatment of co-occurring PTSD and alcohol use disorder: Design and methodology of a randomized controlled trial in military veterans

Back¹,

Flanagan²,

Jones³

et al. 2018

Contemporary Clinical Trials

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Posttraumatic stress disorder (PTSD) and alcohol use disorders (AUD) are two of the most common mental health disorders affecting civilians as well as military populations. If left untreated, individuals with co-occurring PTSD/AUD are at increased risk for developing other mental health problems (e.g., depression, anxiety), physical health problems, reduced resiliency and military readiness, and vocational and social impairment. Substantial gaps in the treatment of co-occurring PTSD/AUD exist and there is a critical need to develop more effective pharmacological treatments. The current study addresses this gap in the literature by testing the efficacy and safety of doxazosin, a long-acting and selective alpha-1 adrenergic antagonist, as compared to placebo in reducing PTSD and AUD severity among U.S. military veterans. Noradrenergic dysregulation has been implicated in the development and maintenance of PTSD and AUD, and pilot studies examining doxazosin in PTSD-only or AUD-only samples have shown promise. This is the first study, however, to evaluate doxazosin in a comorbid PTSD/AUD sample. This paper describes the rationale, design and methodology of a randomized, double-blind, placebo-controlled trial of doxazosin (16 mg/day) delivered over 12 weeks among military veterans with current PTSD and AUD. In addition, functional magnetic resonance imaging (fMRI) is applied at pre- and post-treatment to investigate the underlying pathophysiology of comorbid PTSD/AUD and identify prognostic indicators of treatment outcome. This study is designed to accelerate research on co-occurring PTSD/AUD and provide empirical evidence to inform clinical practice.

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“…6 However, a recent large multisite clinical trial in Veterans with PTSD and nightmare disorder showed no benefit of sleep symptoms with prazosin. 51 Clonazepam has also been tried. While clonazepam did improve sleep onset and maintenance insomnia symptoms in a pilot study of patients with combat-related PTSD, it did not improve nightmares associated with combat-related PTSD.…”

Section: Treatmentmentioning

confidence: 99%

Trauma-Associated Sleep Disturbances: a Distinct Sleep Disorder?

Rachakonda

Balba

Lim

2018

Curr Sleep Medicine Rep

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Purpose of review This paper describes a newly proposed sleep disorder, trauma-associated sleep disorder (TSD). Whether or not this represents a truly unique condition is controversial. In this paper, we describe the overlapping features and differences between TSD, post-traumatic stress disorder (PTSD) and Rapid Eye Movement (REM) sleep behavior disorder (RBD). Recent findings While REM sleep without atonia (RWA) and dream enactment are part of the diagnostic criteria for both RBD and TSD, only TSD features nightmares that occur both in non-REM and REM. A key difference between TSD and PTSD is the presence of symptoms during wakefulness in the latter, though the relationship between the two disorders is, as of yet, unclear. It is unknown whether or not a relationship exists between TSD and neurodegeneration, thus this needs to be explored further. Summary Additional research, such as application of TSD diagnostic criteria to more diverse population, would help to determine whether or not TSD is a distinct clinical entity, its relationships to PTSD, as well as the association of this condition with the development of neurodegeneration.

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Trial of Prazosin for Post-Traumatic Stress Disorder in Military Veterans

Abstract: In this trial involving military veterans who had chronic PTSD, prazosin did not alleviate distressing dreams or improve sleep quality. (Funded by the Department of Veterans Affairs Cooperative Studies Program; PACT ClinicalTrials.gov number, NCT00532493 .).

Cited by 271 publications

References 30 publications

Aetiology and treatment of nightmare disorder: State of the art and future perspectives

Aetiology and treatment of nightmare disorder: State of the art and future perspectives

Doxazosin for the treatment of co-occurring PTSD and alcohol use disorder: Design and methodology of a randomized controlled trial in military veterans

Trauma-Associated Sleep Disturbances: a Distinct Sleep Disorder?

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