Reduction of Nightmares and Other PTSD Symptoms in Combat Veterans by Prazosin: A Placebo-Controlled Study

University of California, San Diego, San Diego, California, United States
American Journal of Psychiatry (Impact Factor: 12.3). 03/2003; 160(2):371-3. DOI: 10.1176/appi.ajp.160.2.371
Source: PubMed


Prazosin is a centrally active alpha(1) adrenergic antagonist. The authors' goal was to evaluate prazosin efficacy for nightmares, sleep disturbance, and overall posttraumatic stress disorder (PTSD) in combat veterans.
Ten Vietnam combat veterans with chronic PTSD and severe trauma-related nightmares each received prazosin and placebo in a 20-week double-blind crossover protocol.
Prazosin (mean dose=9.5 mg/day at bedtime, SD=0.5) was superior to placebo for the three primary outcome measures: scores on the 1) recurrent distressing dreams item and the 2) difficulty falling/staying asleep item of the Clinician-Administered PTSD Scale and 3) change in overall PTSD severity and functional status according to the Clinical Global Impression of change. Total score and symptom cluster scores for reexperiencing, avoidance/numbing, and hyperarousal on the Clinician-Administered PTSD Scale also were significantly more improved in the prazosin condition, and prazosin was well tolerated.
These data support the efficacy of prazosin for nightmares, sleep disturbance, and other PTSD symptoms.

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Available from: Eric C Petrie, Oct 10, 2015
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    • "The first RCT was a double-blind placebo-controlled crossover study performed in 10 veterans (Raskind et al., 2003). Prazosin or placebo in random order were begun at an initial dose of 1 mg at bedtime and titrated upward for 3 weeks to a dose that eliminated trauma nightmares or to a maximum dose of 10 mg HS. "
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    ABSTRACT: Research on the neurobiology of the stress response in animals has led to successful new treatments for Post-Traumatic Stress Disorder (PTSD) in humans. Basic research has found that high levels of catecholamine release during stress rapidly impair the top-down cognitive functions of the prefrontal cortex (PFC), while strengthening the emotional and habitual responses of the amygdala and basal ganglia. Chronic stress exposure leads to dendritic atrophy in PFC, dendritic extension in the amygdala, and strengthening of the noradrenergic (NE) system. High levels of NE release during stress engage low affinity alpha-1 adrenoceptors, (and likely beta-1 adrenoceptors), which rapidly reduce the firing of PFC neurons, but strengthen amygdala function. In contrast, moderate levels of NE release during nonstress conditions engage higher affinity alpha-2A receptors, which strengthen PFC, weaken amygdala, and regulate NE cell firing. Thus, either alpha-1 receptor blockade or alpha-2A receptor stimulation can protect PFC function during stress. Patients with PTSD have signs of PFC dysfunction. Clinical studies have found that blocking alpha-1 receptors with prazosin, or stimulating alpha-2A receptors with guanfacine or clonidine can be useful in reducing the symptoms of PTSD. Placebo-controlled trials have shown that prazosin is helpful in veterans, active duty soldiers and civilians with PTSD, including improvement of PFC symptoms such as impaired concentration and impulse control. Open label studies suggest that guanfacine may be especially helpful in treating children and adolescents who have experienced trauma. Thus, understanding the neurobiology of the stress response has begun to help patients with stress disorders.
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    • "Inclusive results have also been found in studies examining the preventive efficacy of the α2-agonists guanfacine and clonidine that both pharmacologically reduce the release of noradrenaline from the presynaptic terminal into the synaptic cleft.8 The delivery of the α1 antagonist prazosin, however, seems to dispose of a more promising preventive potential, as has been shown in several randomized controlled trials (RCTs) in patients already suffering from PTSD.18-22 Prazosin's pronounced positive effect on trauma-related sleep disturbances and nightmares makes it a promising candidate also in prophylactic interventional studies.23,24 This indication, however, still requires proper pharmacological investigation. "
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    • "Antagonism of both α-1 adrenergic receptors and CRF1Rs reduces excessive alcohol drinking and other dependence-related behaviors in animals.64, 65, 66, 67 Indeed, the brain norepinephrine systems are being investigated as a therapeutic target for PTSD.68, 69, 70 "
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