SEATTLE -- A generic drug already used by millions of Americans for high blood pressure and prostate problems has been found to improve sleep and lessen trauma nightmares in veterans with posttraumatic stress disorder (PTSD).
"This is the first drug that has been demonstrated effective for PTSD nightmares and sleep disruption," said Murray A. Raskind, MD, executive director of the mental health service at the Veterans Affairs Puget Sound Health Care System and lead author of a study appearing April 15 in Biological Psychiatry.
The randomized trial of 40 veterans compared a nightly dose of prazosin (PRAISE-oh-sin) with placebo over eight weeks. Participants continued to take other prescribed medications over the course of the trial.
At the end of the study, veterans randomized to prazosin reported significantly improved sleep quality, reduced trauma nightmares, a better overall sense of well being, and an improved ability to function.
"These nighttime symptoms are heavily troublesome to veterans," said Raskind, who also is director of VA's VISN 20 (Veterans Integrated Service Network #20) Mental Illness Research, Education and Clinical Centers program (MIRECC). "If you get the nighttime symptoms under control, veterans feel better all around."
Raskind, also a professor of psychiatry and behavioral sciences at the University of Washington, estimates that of the 10 million U.S. veterans and civilians with PTSD, about half have trauma-related nightmares that could be helped with the drug.
Participants were given 1 mg of prazosin per day for the first three days. The dose was gradually increased over the first four weeks to a maximum of 15 mg at bedtime. The average dose of prazosin in the trial was 13.3 mg. By comparison, typical prazosin doses for controlling blood pressure or treating prostate problems range from 3 mg to 30 mg per day in divided doses.
The drug did not affect blood pressure compared to placebo, though some participants reported transient dizziness when standing from a sitting position during the first weeks of prazosin titration. Other occasional side effects included nasal congestion, headache, and dry mouth, but these were all minor, according to the authors.
"This drug has been taken by many people for decades," said Raskind. "If there were serious long-term adverse side effects, it is likely we would know about them by now."
The relatively small size of the study was due to the easy availability of this generic drug, Raskind said. "If you are doing a study with a new drug, the only way people can get it is to be in the study. With prazosin, we have approximately 5,000 veterans with a PTSD diagnosis taking it already in the Northwest alone. So we had to find veterans with PTSD who were not [taking it]."
For treating PTSD, prazosin costs 10 to 30 cents a day at VA contract prices. It is not a sedating sleeping pill, emphasized Raskind. "It does not induce sleep. But once you are asleep, you sleep longer and better."
And better sleep can make a big difference. "This drug changes lives," Raskind said. "Nothing else works like prazosin."
Trauma nightmares appear to arise during light sleep or disruption in REM sleep, whereas normal dreams--both pleasant and unpleasant-- occur during normal REM sleep. Prazosin works by blocking the brain's response to the adrenaline-like neurotransmitter norepinephrine. Blocking norepinephrine normalizes and increases REM sleep. In this study, veterans taking prazosin reported that they resumed normal dreaming.
One dose of prazosin works for 6 to 8 hours. Unlike similar drugs, prazosin does not induce tolerance; people can take it for years without increasing the dose. But when veterans stop taking it, Raskind said, the trauma nightmares usually return.
Aside from the VA-funded study he just published, Raskind is working on three larger studies of prazosin. One, a VA cooperative study slated to start this month, will enroll about 300 veterans at 12 VA facilities. The second, a collaborative study with Walter Reed Army Medical Center and Madigan Army Medical Center, will enroll active-duty soldiers who have trauma nightmares. The third study, funded by the National Institute of Mental Health, will look at prazosin in the treatment of civilian trauma PTSD.