This systematic review found a small but positive evidence base to support the efficacy of prazosin therapy for nightmares. Twelve studies comprising 259 patients were identified, in addition to 9 case reports. Four of the studies were randomized placebo-controlled trials of good quality but were limited by small sample sizes (total of 96 patients, not including patients randomized to receive behavioral intervention). 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.
Common prazosin usage patterns and results were observed throughout these studies. Initial prazosin dose was 1 mg before bedtime to test for first-dose hypotension, and subsequent increases varied from 1 mg every 2 to 3 days earlier in the titration to 2 to 5 mg every week later in the titration. The final doses ranged from 1 to 16 mg/d, with patients at both age extremes (7-83 years) successfully treated with lower doses of up to 4 mg/d. Civilian patients, most of whom were female, also only needed lower mean ± SD doses of less than 3.1±3 mg/d. Symptom improvement occurred within a few days to a few weeks, and duration of therapy continued for several months. Regularly, nightmares returned rapidly when prazosin therapy was discontinued and resolved when reintroduced. Prazosin was well tolerated, and common adverse effects consisted of transient dizziness and orthostatic hypotension.
One of the objectives of this systematic review was to identify evidence for the use of prazosin to treat non–PTSD-related nightmares. We did not find any such evidence. Patients in these studies all had a diagnosis of PTSD (or were presumed to meet the criteria for PTSD), subsyndromal PTSD, or acute stress disorder, which can be considered a precursor of PTSD. It seems logical to extend the use of prazosin therapy to non–PTSD-related nightmares, especially if the nature of recurrent nightmares suggests an underlying PTSD diagnosis. However, there are likely differences in the severity and nature of PTSD- vs non–PTSD-related nightmares that affect the efficacy of prazosin. Given the relative lack of significant adverse effects when used for PTSD-related nightmares, research should be conducted for its use in recurrent non–PTSD-related nightmares.
Our systematic review agrees with other recent narrative reviews of the use of prazosin to treat PTSD-related nightmares.38-42
We used a method that would be reproducible for future updates, and we assessed the risk of bias for the randomized studies. 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.38
There are several limitations to the present literature review. One is the relatively small number of studies and total number of patients. There is also heterogeneity of the studies, including the variability of inclusion criteria, psychiatric comorbidities, follow-up periods, outcome measures, and allowance for concurrent medications. A formal meta-analysis would be difficult because of the heterogeneity. Another potential bias is related to the commonality of the research groups, with all but 1 of the 12 studies originating from or including the senior author(s) from the VA Puget Sound Health Care System. Of interest, a study that examined the diffusion of knowledge about prazosin for treatment of PTSD concluded that it diffused quickly in the local Puget Sound area but not so fast in farther geographic areas.11
Of the 1 study not from that group, the finding of decreased nightmares was not replicated, although there were other possible reasons for that finding, including lower baseline severity of nightmares.18
Nightmares are difficult to treat, and further positive results using prazosin would be welcome but would have to be replicated by different research groups and in other patient populations.