The alpha-1 adrenergic receptor prazosin failed to improve recurring nightmares or sleep quality compared with placebo in veterans with PTSD in a 26-week randomized trial of 304 adult veterans.
In several previous randomized trials lasting fewer than 15 weeks, veterans with PTSD and recurring nightmares who received prazosin showed benefits, including improved sleep quality and PTSD symptoms, compared with placebo patients, wrote Murray A. Raskind, MD, of the Department of Veterans Affairs Puget Sound Health Care System, Seattle, and his colleagues.
In a study published in the New England Journal of Medicine, the researchers randomized 152 veterans with sleep problems and PTSD to prazosin and 152 to a placebo. The participants were recruited from 12 VA medical centers. The average age of the participants was 52 years, more than 96% were male, and about two-thirds were white. Demographics were similar between the two groups.
After 10 weeks and after 26 weeks, there were no significant differences between the two groups in changes from baseline measures of recurring nightmares, using the mean change from baseline in Clinician-Administered PTSD Score item B2 (recurrent distressing dreams). Similarly, no significant differences appeared between the two groups based on Pittsburgh Sleep Quality Index scores.
“A possible explanation for these negative results is selection bias resulting from recruitment of patients who were mainly in clinically stable condition, since symptoms in such patients were less likely to be ameliorated with antiadrenergic treatment,” reported Dr. Raskind and his colleagues.
The average maintenance dose of prazosin was 14.8 mg, compared with 16.4 mg in the placebo group; 187 male study participants reached the maximum dose of 20 mg/day (54% of the prazosin group and 70% of the placebo group).
After 10 weeks, no significant differences were found between the two groups in changes from baseline measures of “recurring distressing dreams,” using the mean change from baseline in Clinician-Administered PTSD Score item B2 (recurrent distressing dreams). The between group difference was 0.2. In addition, no significant differences were found at 10 weeks in the average change from baseline Pittsburgh Sleep Quality Index scores.
Similarly, no significant differences appeared between the two groups at 26 weeks. “ since symptoms in such patients were less likely to be ameliorated with antiadrenergic treatment,” the researchers said.
On average, patients in the prazosin group had significantly greater decreases in blood pressure, compared with the placebo group. In addition, they had fewer reports of new or worsening suicidal ideation, compared with the placebo group (8% vs.15%).
“Given the concern about suicide among veterans, it is noteworthy that the specifically solicited adverse event of new or worsening suicidal ideation was less common in the prazosin group than in the placebo group, but the absolute number of events was small; this issue warrants further study,” the researchers said.
The study was limited by several factors, including the absence of screening for sleep apnea or sleep-disordered breathing, Dr. Raskind and his colleagues noted. However, the results suggest that “further studies with more refined characterization of autonomic nervous system activity and nocturnal behaviors are needed to determine whether there might be subgroups of veterans with PTSD who can benefit from prazosin.”
Dr. Raskind had no financial conflicts to disclose. The study was supported by the Department of Veterans Affairs Cooperative Studies Program.
SOURCE: Raskind MA et al. N Engl J Med. 2018 Feb 8;378:507-17. doi: 10.1056/NEJMoa1507598.