Placebo-controlled comparison of prazosin and cognitive-behavioral treatments for sleep disturbances in US Military Veterans

Abstract

Objective Pharmacological and cognitive-behavioral treatments targeting insomnia and nightmares have been shown to be effective in the treatment of military veterans with sleep complaints comorbid with symptoms of stress-related disorders, including Post-Traumatic Stress Disorder (PTSD), but the two approaches have not been directly compared. This randomized controlled trial compared the effects of prazosin vs. a behavioral sleep intervention (BSI), targeting nightmares and insomnia against a placebo pill control condition on sleep and daytime symptoms. Methods Fifty United States military veterans (mean age 40.9 years, SD = 13.2 years) with chronic sleep disturbances were randomized to prazosin (n = 18), BSI (n = 17), or placebo (n = 15). Each intervention lasted eight weeks. Participants completed self-report measures of insomnia severity, sleep quality, and sleep disturbances. All kept a sleep diary throughout the intervention period. Polysomnographic studies were conducted pre- and post-intervention. Results Both active treatment groups showed greater reductions in insomnia severity and daytime PTSD symptom severity. Sleep improvements were found in 61.9% of those who completed the active treatments and 25% of those randomized to placebo. Conclusion BSI and prazosin were both associated with significant sleep improvements and reductions in daytime PTSD symptoms in this sample of military veterans. Sleep-focused treatments may enhance the benefits of first-line PTSD treatments.

Treatment of Nightmares With Prazosin: A Systematic Review

“…Already, our review includes 2 recent studies from 2010 and 2012 that other recent reviews were unable to include, and the significance is that one of these studies reported a negative finding and the other study reported less impressive results than the earlier studies. 18,22 With the continued traumas of today's world, both from civilian and military causes, further prazosin trials can help clarify its efficacy compared with that reported in the older studies and whether continued optimism insofar as its efficacy is justified. Upcoming results from 2 large clinical trials of use of prazosin to treat PTSD symptoms (a 13-site VA study of 320 veterans and a single-site study of 120 soldiers on active duty), expected to be completed in late 2012, will add greatly to our knowledge.…”

“…The first 3 trials of similar design reported superiority of prazosin over placebo, but the most recent study did not. 18 The 4 open-label trials, also described as case series, reported that 26 of 31 patients (83.9%) experienced greater than 50% reduction in nightmares. The remaining medical record reviews also found statistically significant improvement in the nightmare scores, with the exclusion of one study that measured only CGI-C and not a nightmare score.…”

“…18 Fifty-eight percent met criteria for PTSD, and the remaining 42% endorsed subthreshold PTSD symptoms. Concurrent medications were also continued unchanged.…”

“…12 For the randomization categories, only 2 studies mentioned the method of sequence generation. 4,18 None of the studies described the details of the allocation concealment sufficient for assessment. All of the studies seemed to use adequate blinding techniques, eg, with how the placebos were provided.…”

“…In the most recent study, the fate of all randomized patients was described, and discontinuations were spread similarly between the prazosin and placebo groups. 18 However, there still seemed to be missing data in the analysis, which was not explained, leading to concern about potential bias of the results. Also, the primary outcomes of clinician-and patient-reported CGI-I were not reported numerically, and the text commented only on the lack of a statistically significant difference between the active treatment groups vs the placebo group using the CGI-I, without specifying clinicianvs patient-reported CGI-I.…”