March 12, 2012 (Prague, Czech Republic) — A systematic review of the literature supports the use of prazosin to treat nightmares related to posttraumatic stress disorder (PTSD).
Simon Kung, MD, assistant professor of psychiatry and consultant in psychiatry at the Mayo Clinic in Rochester, Minnesota, presented the results of this review at a poster session here at the EPA 2012: 20th European Congress of Psychiatry.
Dr. Kung explained that his team reviewed all 12 studies of prazosin published before January 9, 2012, which involved 276 patients, and concluded that the studies are of fair to good quality. In addition, they reviewed 9 case reports.
All the patients had PTSD, subsyndromal PTSD, or acute stress disorder. The researchers did not find any studies evaluating prazosin for nightmares not associated with PTSD or its related conditions.
Two outcome measures — the Clinician Administered PTSD Scale (CAPS) and the Clinical Global Impression of Change (CGI-C) — were used in all studies.
Majority of Studies Show Benefit of Prazosin
Four of the 12 studies were randomized, 4 were open label, and 4 were retrospective chart reviews. "Probably about a good 10 of them are positive reviews," showing that prazosin can be helpful, Dr. Kung told Medscape Medical News.
There were consistent improvements in the CGI-C score and CAPS items B2 (recurrent distressing dreams) and D1 (difficulty falling or staying asleep). In the 9 case reports, nightmares improved in all but 2 patients. Four of the case reports involved children, and all were positive for improvement.
Dr. Kung explained that he sometimes has to use prazosin for several weeks before patients see relief, but some patients will report benefit within a few days. In most of the studies in this systematic review, the period of use was 6 to 8 weeks.
Mean daily doses of prazosin in the studies and case reports ranged from 1 mg/day to 13 mg/day.
There are "very few side effects with this medication — some transient headaches and transient dizziness was mostly what was noted." Adverse effects reported in any of the studies were sporadic mild orthostatic hypotension symptoms, transient lethargy, dry mouth, morning sedation, nausea, and urinary incontinence. In general, the drug was well tolerated by patients of all ages, even at higher dosages.
Prazosin is an alpha-adrenergic blocker originally used to treat hypertension. "The reason we think it works in the setting of nightmares is that prazosin crosses the blood–brain barrier, so it gets into the brain and kind of dampens the norepinephrine effects, which we think contribute to nightmares," he said.
Limitations of the systematic review include the small number of studies and of patients, the fact that most of the trials were from related researchers (all from the United States), and the variability of inclusion criteria, psychiatric comorbidities, follow-up period, outcome measures, and concurrent medications allowed.
Murray Raskind, MD, director of the Department of Veterans Affairs Northwest Network Mental Illness Research, Education and Clinical Center and Professor and vice-chair of the Department of Psychiatry and Behavioral Sciences at the University of Washington School of Medicine in Seattle, told Medscape Medical News: "I thought they did a nice job pulling the studies together, such as they are. Most of them, obviously, come from our group."
Trauma Nightmares Are Not Just Bad Dreams
Dr. Raskind explained that when a patient with PTSD is treated with prazosin, as the trauma nightmares go away, normal dreams return. As for anyone, some of the dreams are pleasant, others unpleasant.
The difference between a normal bad dream and a trauma nightmare is that trauma nightmares are extremely realistic. "They classically are reenactments of the traumatic situation that happened," Dr. Raskind said. "The trauma nightmares are true-life situations, and they are accompanied by an adrenaline storm." The patient experiences a rapid heartbeat, sweating, and rapid breathing, and needs to get out of bed to check the environment for danger.
He said the person is confused because the experience is so real and has trouble getting back to sleep. Unlike normal dreams during rapid eye-movement sleep, in which the body's muscles are essentially paralyzed, trauma nightmares are often accompanied by muscle activity that can be dangerous to a bed partner.
Dr. Raskind noted that nightmares are not just an adrenergic effect, but are specific to the alpha-adrenergic receptor. One of the adverse effects of propranolol, a beta-adrenergic receptor blocker, is vivid dreams and sleep disturbance.
Dr. Raskind explained that he first used prazosin in 1995 in a Vietnam War combat veteran with intractable PTSD trauma nightmares; I gave him propranolol and his nightmares became worse."
He said prazosin is worth a try even in patients who do not have PTSD but who have recurrent nightmares, awaken sweaty, and have trouble going back to sleep. "It's possible that prazosin will be helpful for that, but no one has tested that to this point," he said.
A primary care physician should easily be able to prescribe the drug. "It's a lot easier than most general medical regimens," Dr. Raskind said. "You just have to start low, and keep pushing the dose up until [the nightmares] either go away or someone has a side effect, and side effects are pretty rare. The mistake people make is that they don't give enough [prazosin]. They quit too soon."
Dr. Raskind is now writing a paper involving active-duty soldiers. Some soldiers receive up to 25 mg/day of prazosin — 5 mg in morning and 20 mg at night. He has had some patients who require as much as 40 mg/day.
"We've found it is important to not only give a dose at night, but to give smaller doses during the day if a person has persistent hyperarousal symptoms and reexperiences symptoms during the day," he said. Daytime dosing seems to be helpful for irritability, hypervigilance, and flashbacks in PTSD.
Adverse effects are rare, but generally appear when first starting the drug, "especially if you increase it too quickly or start at too high a dose or someone is taking an erectile dysfunction drug, like [sildenafil citrate], or they're taking other antihypertensives," Dr. Raskind advised.
The right dose is when a patient says the nightmares have gone away. As little as 2 mg can be effective for some people; others require much more. The therapeutic dose is unpredictable and does not correlate with blood levels. "People need not to be afraid of this drug," Dr. Raskind said, and they should dose it to effect. The drug is generic and costs "just pennies a pill."
He warned that if a patient stops prazosin even after 10 years of effective treatment, "the nightmares will come back 9 times out of 10." Prazosin does not seem to interfere with and may even be helpful in some of the exposure-based psychotherapies for PTSD.
Jonathan Davidson, MD, professor emeritus of psychiatry and former director of the Anxiety and Traumatic Stress Program at Duke University Medical Center in Durham, North Carolina, agrees that this systematic review is a useful contribution to the literature.
But, he warned, "prazosin is quite a complicated drug, in that the doses are all over the place in the different studies and in real practice. Patients are often on other medicines, and there may be more issues with side effects than in controlled trials, which weed out such patients."
The study received no commercial funding. Dr. Kung and Dr. Raasskind have disclosed no relevant financial relationships. Dr. Davidson, who did not participate in the work that Dr. Kung presented, reports being a speaker for GlaxoSmithKline and the CME Institute of Physicians Postgraduate Press; being an advisor to AstraZeneca; and receiving royalties/license fees from Connor-Davidson Resilience Scale, Multi-Health Systems for the Davidson Trauma Scale, Guilford Publications, the American Psychiatric Association, and the Social Phobia Inventory.
EPA 2012: 20th European Congress of Psychiatry: Abstract P-1094. Presented March 6, 2012.
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