TUCSON, ARIZ. — Prazosin, an α1-adrenergic blocker, substantially reduces posttraumatic stress disorder-related nightmares and sleep disturbances among veterans.
The drug is a safe and inexpensive treatment for night symptoms and also several daytime PTSD symptoms such as irritability, hypervigilance, and flashbacks, Dr. Murray Raskind reported at a psychopharmacology conference sponsored by the University of Arizona. “Many veterans say, 'It changed my life,'” he said.
Industry-supported trials in PTSD patients are unlikely for prazosin, which has been used for years as a generic antihypertensive. But Dr. Raskind, a professor at the University of Washington in Seattle and director of mental health services for the Veterans Administration Puget Sound, has compiled a growing body of evidence supporting the use of prazosin in this group.
He presented data from a parallel group study in which 34 Vietnam veterans with PTSD-related nightmares and sleep disturbances were randomized to prazosin at an average dose of 14 mg at bedtime or placebo. At 8 weeks, scores for the recurrent distressing dreams item of the Clinician-Administered PTSD Scale were significantly improved (6.5 at baseline to 2.9) among 17 prazosin patients, compared with 17 placebo patients (6.1 to 5.2).
Clinical Global Impression-Change scores were moderately or markedly improved in 12 of 17 prazosin patients and in only 2 of 17 placebo patients.
Another recent study included 28 combat veterans from Iraq who were treated with an average dose of 2 mg of prazosin every night for nightmares. Among the 23 patients with follow-up data, 20 had complete elimination of their nightmares, 2 had reduced frequency or intensity, and 1 had no change at 8 weeks (Military Med. 2005;170:513–5).
Sales of prazosin have risen in the Seattle area by about 30% since 1999 by word of mouth alone. But the drug has been criticized, because the results had not been replicated in a randomized trial, he said.
Although civilian trauma PTSD is helped somewhat by paroxetine (Paxil) and sertraline (Zoloft), results for selective serotonin reuptake inhibitors (SSRIs) have been disappointing among Vietnam veterans, especially for nightmares and sleep disruption.
Dr. Raskind opted to take a different approach based on evidence that enhanced responsiveness of central nervous system α1-adrenergic receptors contributes to PTSD pathophysiology, particularly at night. An initial clinical experience with the β-adrenergic blocker, propranolol, failed as the β-blocker drugs can intensify dreams. Brain α1-adrenergic effects are often opposed to brain β-adrenergic effects, so he turned to prazosin.
Treatment was started in a single patient at a low dose of 1 mg nightly to avoid the “first-dose” hypotension that has earned prazosin and other α1-blockers a black box warning. After 2 weeks of gradual dose increases to 6 mg nightly, the tortuous dreams of a Vietnam veteran who had accidentally killed his friend disappeared. After 8 years, the veteran is still nightmare free.
But several episodes of unintentional discontinuation led to a rapid return of intense nightmares. Therefore, Dr. Raskind recommends the drug be taken every night, starting at 1 mg for 3 nights, then 2 mg for 4 nights, and increasing by 2 mg weekly until a therapeutic dose is achieved. Some older, Vietnam veterans may need 20 mg nightly. Adding small doses in the morning is helpful for daytime flashbacks and hypervigilance.
Adverse effects can include first-dose hypertension, increased risk of priapism with concurrent use of trazodone, nasal congestion, peripheral edema, and headache. Caution should be used with Viagra. Long-acting Cialis and Levitra should be avoided. Helpful side effects include gentle blood pressure reduction, enhanced urine flow in older men with prostate hypertrophy, and enhanced erectile function, he said.
Scores for recurrent distressing dreams were significantly improved from 6.5 at baseline to 2.9. DR. RASKIND