(Reuters) — The blood pressure drug prazosin, widely prescribed to relieve symptoms of post-traumatic stress disorder (PTSD), has failed to show it can reduce distressing dreams or improve sleep quality in a trial of 304 military veterans at 13 Veterans Affairs medical centers.
After 10 weeks of therapy with the generic drug, which costs about a nickel per pill, recipients had no significant reduction in recurrent nightmares or easier sleep compared to veterans receiving placebo.
Sixteen weeks later, even after doctors were allowed to add some other treatments, there was still no difference between the two groups.
The study, known as PACT, did find a lower rate of new or worsening suicidal thoughts among prazosin recipients. The rate with placebo was 15 percent versus 8 percent with the drug. However, that trend surfaced as part of an evaluation of side effects; suicidal ideation was not a primary outcome and the number of cases was small.
Experts in PTSD familiar with the research have been shocked by the findings, chief author Dr. Murray Raskind told Reuters Health in a telephone interview.
But it's also likely that the drug is effective in some veterans with more severe PTSD who have trauma nightmares, waking up sweaty after thrashing around in bed. They were excluded from the study for safety reasons. In normal nightmares, sleepers are usually unable to move.
The results should discourage doctors from giving prazosin as a one-size-fits-all therapy and encourage them to identify veterans who will find it effective, he said.
"It should put the focus on personalized precision medicine. Fortunately, our patients will tell us" when it's working and will ask for it if they're taken off the drug and their symptoms return, said Raskind, director of the VA's Northwest Network Mental Illness Research Education and Clinical Center.
An estimated 5 percent to 10 percent of the U.S. population has PTSD, with much higher rates among veterans and active-duty soldiers.
It manifests itself in many ways but nightmares and sleep problems are often cited as the worst aspects.
When veterans reported that the medicine, when given for high blood pressure, seemed to be alleviating their nightmares, the drug was quickly embraced as a PTSD treatment. Some clinical trials have affirmed its reputation.
"Thus, the failure of this new, large, multisite trial to replicate the previous studies is surprising and disappointing," Dr. Kerry Ressler of McLean Hospital in Belmont, Massachusetts, said in an editorial in The New England Journal of Medicine, where the study appears.
Ressler said the drug may not have seemed effective because patients with social instability or veterans who were already benefiting from another drug were not included. Some volunteers may also have been suffering from undiagnosed sleep apnea, which might have masked the benefits of the drug.
The study allowed for the daily dose to be adjusted upward — up to 20 milligrams per day for men and 12 mg for women - to try for maximal alleviation of nightmares without serious adverse effects. Among the 187 men, 54% of the prazosin recipients and 70% getting placebo reached the maximum dose.
"We found out from our referring doctors that the very distressed vets who had these trauma nightmares — waking up sweaty, thrashing around — were not put in the study," said Dr. Raskind. "So we got a sample of quite stable veterans who reported enough symptoms for PTSD and had nightmares. But we had to exclude people with psychosocial instability because we didn't want to risk giving placebo to someone who would harm themselves, harm others, get in trouble with the law, or lose their jobs because they were randomized to placebo for 6 months. So I think what we did was recruit a very treatment-resistant, stable sample."
Not surprisingly, prazosin lowered blood pressure more than placebo, and it still may be given for that purpose, said Raskind, who is also a professor of psychiatry at the University of Washington School of Medicine in Seattle.
Rates of serious side effects were comparable in the two groups. Prazosin patients had higher rates of dizziness, lightheadedness and urinary incontinence. Two veterans, both in the placebo group, were hospitalized following suicidal ideation.