Prazosin and placebo exhibit similar efficacy in post-traumatic stress disorder: The PACT trial
1. In patients with nocturnal symptoms of post-traumatic stress disorder (PTSD), prazosin did not significantly reduce nightmares or improve quality of sleep compared to placebo at 10 or 26 weeks.
2. Although the number of serious adverse events between prazosin and placebo were similar, prazosin was associated with significantly fewer cases of new or worsening suicidal ideation compared to placebo.
Study Rundown: Nightmares are a common and difficult to treat manifestation of PTSD. Prazosin, an a1-adrenergic antagonistic medication with a level B recommendation for PTSD-associated nightmares, is widely used as adjunctive therapy for nocturnal symptoms of PTSD. Six placebo-controlled trials have supported prazosin's ability to reduce nocturnal symptoms of PTSD; however, all were of short duration and underpowered, making it difficult to draw conclusions. In the Prazosin and Combat Trauma PTSD (PACT) trial, the authors evaluated the efficacy of prazosin in a large group of participants with PTSD-associated nightmares over 10- and 26-week periods. No significant difference in nocturnal symptoms via multiple interview-based assessments were found at 10 weeks (primary outcome) or at 26 weeks (secondary outcome). These results challenge previous data that demonstrate beneficial effects of prazosin in treating nocturnal symptoms of PTSD.
This was a randomized, double-blinded, placebo-controlled trial with a sample size larger than any previous trial of prazosin in PTSD. The trial was limited by the low baseline adrenergic activity in the sample population and exclusion of clinically unstable patients, who may benefit most from prazosin. Additionally, the failure to screen for sleep apnea, a common co-morbidity in PTSD, may have masked beneficial effects of prazosin possibly found in subgroups of PTSD patients.
In-Depth [randomized controlled trial]: This randomized control trial was conducted between 2010 and 2013. Participants with PTSD (n = 304) according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, at multiple VA medical centers were randomized to either prazosin (n = 152) or placebo (n = 152). Primary outcomes were assessed at 10-weeks. Treatment was continued in a double-blind fashion for an additional 16 weeks and analyzed as secondary outcomes. Patients were excluded if they had an unstable medical or psychiatric condition, hypotension at baseline, substance abuse, psychosocial instability, or were taking an a1-adrenergic antagonistic medication during enrollment. No additional treatments to the trial regimen could be added during the first 10 weeks, while other therapy (besides trazodone or psychostimulants) could be added following analysis of the primary outcome. Outcomes were based on interview-based assessments starting at week 6 and conducted every 4 weeks thereafter. The primary assessments included the Clinician-Administered PTSD Scale (CAPS), Pittsburgh Sleep Quality Index (PSQI), and Clinical Global Impression of Change (CGIC) scale.
Among randomized participants, 271 completed 10-weeks and were evaluated in the primary outcome. The mean change in the CAPS “recurrent distressing dreams” item was -1.9 in the prazosin group and -1.7 in the placebo group (difference of 0.2; 95% confidence interval [CI], -0.3 to 0.8; p = 0.38), the mean change in the PSQI score was -2.3 and -2.4, respectively (difference of 0.1; 95% CI, -0.9 to 1.1; p = 0.80), and the mean change in the CGIC score was 3.3 and 3.3, respectively (difference of 0; 95% CI, -0.3 to 0.3; p = 0.96). Over the entire 26-week trial period, there was no significant difference in the least-squares mean change in total CAPS score (p = 0.48), PSQI score (p = 0.99), or CGiC score (p = 0.86). The number of serious adverse events were similar between the prazosin group or placebo (p = 0.72). New or worsening suicidal ideation was more common in the placebo group compared to those treated with prazosin (p = 0.048). The prazosin group had significantly greater decreases in supine and standing blood pressure than placebo and higher rates of dizziness, lightheadedness, and urinary incontinence.
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