ABSTRACT
BACKGROUND: In randomized trials, prazosin, an α1-adrenoreceptor antagonist, has been effective in alleviating nightmares associated with post-traumatic stress disorder (PTSD) in military veterans. METHODS: We recruited veterans from 13 Department of Veterans Affairs medical centers who had chronic PTSD and reported frequent nightmares. Participants were randomly assigned to receive prazosin or placebo for 26 weeks; the drug or placebo was administered in escalating divided doses over the course of 5 weeks to a daily maximum of 20 mg in men and 12 mg in women. After week 10, participants continued to receive prazosin or placebo in a double-blind fashion for an additional 16 weeks. The three primary outcome measures were the change in score from baseline to 10 weeks on the Clinician-Administered PTSD Scale (CAPS) item B2 ("recurrent distressing dreams"; scores range from 0 to 8, with higher scores indicating more frequent and more distressing dreams); the change in score from baseline to 10 weeks on the Pittsburgh Sleep Quality Index (PSQI; scores range from 0 to 21, with higher scores indicating worse sleep quality); and the Clinical Global Impression of Change (CGIC) score at 10 weeks (scores range from 1 to 7, with lower scores indicating greater improvement and a score of 4 indicating no change). RESULTS: A total of 304 participants underwent randomization; 152 were assigned to prazosin, and 152 to placebo. At 10 weeks, there were no significant differences between the prazosin group and the placebo group in the mean change from baseline in the CAPS item B2 score (between-group difference, 0.2; 95% confidence interval [CI], -0.3 to 0.8; P=0.38), in the mean change in PSQI score (between-group difference, 0.1; 95% CI, -0.9 to 1.1; P=0.80), or in the CGIC score (between-group difference, 0; 95% CI, -0.3 to 0.3; P=0.96). There were no significant differences in these measures at 26 weeks (a secondary outcome) or in other secondary outcomes. At 10 weeks, the mean difference between the prazosin group and the placebo group in the change from baseline in supine systolic blood pressure was a decrease of 6.7 mm Hg. The adverse event of new or worsening suicidal ideation occurred in 8% of the participants assigned to prazosin versus 15% of those assigned to placebo. CONCLUSIONS: 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 .).
Subject(s)
Adrenergic alpha-1 Receptor Antagonists/administration & dosage , Dreams/drug effects , Prazosin/administration & dosage , Sleep Wake Disorders/drug therapy , Stress Disorders, Post-Traumatic/drug therapy , Veterans , Adrenergic alpha-1 Receptor Antagonists/adverse effects , Adult , Combined Modality Therapy , Dose-Response Relationship, Drug , Double-Blind Method , Female , Hospitals, Veterans , Humans , Male , Middle Aged , Prazosin/adverse effects , Psychiatric Status Rating Scales , Psychotherapy , Sleep/drug effects , Stress Disorders, Post-Traumatic/psychology , Stress Disorders, Post-Traumatic/therapy , Suicidal Ideation , Treatment Failure , United StatesABSTRACT
BACKGROUND: Excessive brain responsiveness to norepinephrine appears to contribute to post-traumatic stress disorder (PTSD), particularly at night. Prazosin, a brain active alpha-1 adrenergic receptor antagonist, significantly reduced trauma nightmares and sleep disturbance in 10 Vietnam War combat veterans in a previous placebo-controlled crossover study. The current parallel group trial in a larger sample of veterans evaluated prazosin effects on trauma nightmares, sleep quality, global clinical status, dream characteristics, and comorbid depression. METHODS: Forty veterans (mean age 56 +/- 9) with chronic PTSD and distressing trauma nightmares and sleep disturbance were randomized to evening prazosin (13.3 +/- 3 mg/day) or placebo for 8 weeks. RESULTS: In the evaluable sample (n = 34), primary outcome measures demonstrated that prazosin was significantly superior to placebo for reducing trauma nightmares and improving sleep quality and global clinical status with large effect sizes. Prazosin shifted dream characteristics from those typical of trauma-related nightmares toward those typical of normal dreams. Blood pressure changes from baseline to end study did not differ significantly between prazosin and placebo. CONCLUSIONS: Prazosin is an effective and well-tolerated treatment for trauma nightmares, sleep disturbance and global clinical status in veterans with chronic PTSD.
Subject(s)
Adrenergic alpha-Antagonists/therapeutic use , Dreams/drug effects , Prazosin/therapeutic use , Sleep Wake Disorders/drug therapy , Stress Disorders, Post-Traumatic/complications , Veterans , Aged , Blood Pressure/drug effects , Case-Control Studies , Combat Disorders/complications , Combat Disorders/drug therapy , Combat Disorders/psychology , Cross-Over Studies , Dose-Response Relationship, Drug , Double-Blind Method , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Sleep Wake Disorders/etiology , Stress Disorders, Post-Traumatic/psychology , Treatment OutcomeABSTRACT
Iraq and Afghanistan War veterans were grouped by level of posttraumatic stress disorder (PTSD) symptomatology and compared on self-report measures of trait anger, hostility, and aggression. Veterans who screened positive for PTSD reported significantly greater anger and hostility than those in the subthreshold-PTSD and non-PTSD groups. Veterans in the subthreshold-PTSD group reported significantly greater anger and hostility than those in the non-PTSD group. The PTSD and subthreshold-PTSD groups did not differ with respect to aggression, though both groups were significantly more likely to have endorsed aggression than the non-PTSD group. These findings suggest that providers should screen for anger and aggression among Iraq and Afghanistan War veterans who exhibit symptoms of PTSD and incorporate relevant anger treatments into early intervention strategies.