Prazosin Prevented Nightmares in Veterans with Posttraumatic Stress Disorder

Marlene Busko
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April 30, 2007 Prazosin a generic drug used for years for hypertension and urine-flow obstruction was substantially more effective than placebo in reducing trauma nightmares and sleep disturbance in a study of 34 middle-aged combat veterans with posttraumatic stress disorder (PTSD).

The study is published in the April 15 issue of Biological Psychiatry.

Lead author Murray A. Raskind, MD, from the University of Washington, in Seattle, told Medscape that PTSD is the most common anxiety disorder among the civilian population and a huge problem among military personnel. "When they do get to sleep, often with the help of some alcohol, they wake up anxious and sweaty with a terrifying nightmare of a life-threatening traumatic event. During the day, they often have memories of it and sometimes even vivid recollections. . . . Prazosin helps that." He added that prazosin is a very safe, inexpensive generic drug, which is rarely sedating and has been given to millions of older men over the years for benign prostatic hypertrophy.

Dr. Raskind explained that the group previously published a study showing that prazosin significantly reduced trauma nightmares and sleep disturbance among 10 Vietnam War combat veterans. "It was clear that although some of their daytime PTSD symptoms were helped modestly by some other medications, nothing was helpful at night," he said. Clinical studies suggested that the brain's norepinephrine system was not shutting down as it should during normal sleep, and enhanced adrenergic receptor responsiveness to norepinephrine contributed to PTSD.

Prazosin is an alpha-1 adrenergic receptor antagonist that had been developed during the 1970s to treat hypertension and that easily crosses the blood-brain barrier, Dr. Raskind explained. "It turned out that the alpha-1 receptor, which is blocked by prazosin, is the one that appears to be overly responsive in PTSD," he said.

The current larger, parallel-group, placebo-controlled study aimed to evaluate the effectiveness of prazosin for reducing trauma nightmares, improving sleep quality, and improving global clinical status in veterans with PTSD.

The study comprised 40 veterans with chronic PTSD who had a mean age of 56 years plus or minus 9 years and were mainly veterans from the Vietnam War (n = 32), but also from World War II ( 2), the Korean War (3), the Panama invasion (1), and the first Gulf War (2). The subjects were randomized to receive prazosin or placebo for 8 weeks. The prazosin dose was titrated to a mean achieved daily dose of 13 mg plus or minus 3 mg, taken at bedtime.

The 3 primary outcome measures were:

* The Clinician Administered PTSD Scale (CAPS) questionnaire, recurrent distressing dreams question score: from 0 to 8 (daily occurrence, extreme distress).
* The self-reported Pittsburgh Sleep Quality Index (PSQI) score: from 0 to 21.
* The investigator-rated Clinical Global Impression of Change (CGIC) score: from 1 (markedly improved) to 7 (markedly worse).

Secondary outcome measures included assessments of dream content and depression.

Of the 40 randomized subjects, 6 did not complete the study, leaving 34 subjects who were evaluated.

At 8 weeks, prazosin produced significantly and substantially greater improvements in the frequency and intensity of trauma-related nightmares (CAPS distressing dream question), sleep quality (PSQI), and global clinical status (CGIC).

Primary Outcome Scores at 8 Weeks, Prazosin vs Placebo
Outcome

Prazosin)

Placebo

P
CAPS distressing dreams

3.2 2.6

5.5 2.2

.02
PSQI

9.7 3.9

12.6 4.1

.008
CGIC

2.41 1.1

3.65 1.2

.002
CAPS = Clinician Administered PTSD Scale.
PSQI = Pittsburgh Sleep Quality Index.
CGIC = Clinical Global Impression of Change.

At the end of the study, the CGIC scores were moderately or markedly improved in 71% of subjects who had received prazosin vs 12% of subjects who had received placebo.

Prazosin also shifted dream characteristics from trauma nightmares to typical normal dreams, and there was a trend to less depression. The drug was well tolerated and did not lower study-end blood pressure more than did placebo.

"If clinicians have a patient with trauma-related nightmares and sleep disruptions, or even if they have sleep disruption and used to have nightmares but the nightmares have gone, then it's reasonable to give prazosin a try," said Dr. Raskind. He added that it is important to follow the Physicians' Desk Reference instructions to start at a low dose and then titrate it up gradually.

http://www.medscape.com/viewarticle/555848

Brillante, thanks for the info. I was thinking at one point on using medications but I am finally OK with the pain and turture of the childhood. EMDR is working for now