Prazosin effects on objective sleep measures and clinical symptoms in civilian trauma posttraumatic stress disorder: a placebo-controlled study.

BACKGROUND: Prazosin, a central nervous system (CNS) active alpha-1 adrenoreceptor antagonist, has reduced nightmares and sleep disturbance in placebo-controlled studies of combat-related posttraumatic stress disorder (PTSD). We evaluated objective sleep parameters and PTSD symptoms in a placebo-controlled prazosin trial for civilian trauma-related PTSD. METHODS: Thirteen outpatients with chronic civilian trauma PTSD, frequent nightmares, and sleep disturbance participated in a randomized placebo-controlled crossover trial of prazosin. Sleep parameters were quantified at home with the REMView (Respironics, Pittsburgh, Pennsylvania). The PTSD symptoms were quantified with the Clinician Administered PTSD Scale (CAPS) "recurrent distressing dreams" and "disturbed sleep" items, a non-nightmare distressed awakenings scale, the PTSD Dream Rating Scale (PDRS), the PTSD Checklist-Civilian (PCL-C), and the Clinical Global Impression of Improvement (CGI-I). RESULTS: Prazosin compared with placebo significantly increased total sleep time by 94 min; increased rapid eye movement (REM) sleep time and mean REM period duration without altering sleep onset latency; significantly reduced trauma-related nightmares, distressed awakenings, and total PCL scores; significantly improved CGI-I scores; and changed PDRS scores toward normal dreaming. CONCLUSIONS: Prazosin reductions of nighttime PTSD symptoms in civilian trauma PTSD are accompanied by increased total sleep time, REM sleep time, and mean REM period duration in the absence of a sedative-like effect on sleep onset latency.

Daytime prazosin reduces psychological distress to trauma specific cues in civilian trauma posttraumatic stress disorder.

BACKGROUND: Persons with posttraumatic stress disorder (PTSD) whose trauma-related nightmares improve or resolve with bedtime administration of the alpha-1 adrenergic antagonist prazosin often continue to experience PTSD symptoms during the day. This study addressed whether daytime prazosin compared to placebo would alleviate psychological distress provoked experimentally by a trauma-related word list included in the emotional Stroop (E-Stroop) paradigm. METHODS: Eleven persons with civilian trauma PTSD who continued to experience daytime PTSD symptoms despite a stable bedtime prazosin dose that suppressed trauma-related nightmares were studied. Prazosin and placebo were administered on two different occasions in the early afternoon followed two hours later by the E-Stroop. Effects of drug on psychological distress were assessed by the Profile of Mood States (POMS). RESULTS: POMS total score and an "emotional distress" POMS subscale score following trauma-related words were significantly lower in the prazosin than placebo condition. There were no treatment effects on E-Stroop completion time. In 10 subjects who continued open label daytime prazosin, there was a reduction in global PTSD illness severity at 2-week follow-up. CONCLUSIONS: Daytime prazosin pretreatment reduced psychological distress specifically to trauma cues. Adding daytime prazosin to bedtime prazosin may further reduce overall PTSD illness severity and distress.