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Prazosin for post-traumatic stress disorder

Last updated: August 2011

Traumatic events—military combat, natural disasters, personal assaults, auto accidents—can trigger a disabling anxiety condition known as post-traumatic stress disorder (PTSD). In the U.S., it affects about one of every four people who experience such things in a given year.

A majority of PTSD sufferers—70 percent to almost 90 percent—develop sleep disturbances because they relive traumatic experiences in their thoughts and dreams. People with the condition can have trouble getting to sleep or staying asleep, and are often disturbed by nightmares. They might try to avoid people, places, or situations that remind them of their traumatic experiences, and feel distant from friends and family.

The main nondrug treatments recommended by the U.S. Department of Veterans Affairs for PTSD are talk therapy, cognitive behavioral therapy, and eye movement desensitization and reprocessing. Two medications are also approved to treat PTSD, the antidepressants sertraline (Zoloft and generic) and paroxetine (Paxil and generic). They are effective in controlling symptoms but they usually don't improve the sleep problems that can accompany PTSD.

Prazosin (Minipress and generic), a drug that was developed to treat high blood pressure, has been found to be useful in managing sleep-related problems caused by PTSD. It works by blocking certain alpha-1 receptors in the brain, which might lead to better, deeper sleep.

For people with PTSD and sleep problems, "typically I don't use sedatives and hypnotics such as Ambien or Lunesta except for the short-term because they tend to lose their benefit with prolonged daily use and there is an addictive potential as well," says Matthew Jeffreys, M.D., medical director of the PTSD treatment program at the South Texas Veterans Health Care System. He recently helped revise the PTSD treatment guidelines for the VA.

Prazosin is prescribed "off label" to treat the severe nightmares and other sleep disturbances related to PTSD, meaning that it has not been approved by the Food and Drug Administration for that use. But doctors can legally prescribe any treatment they deem appropriate for a patient's condition. Both the American Psychiatric Association and the U.S. Department of Veterans Affairs say that prazosin has been effective in helping combat veterans who have nightmares.

Prazosin is the most thoroughly studied drug in regard to PTSD and sleep among the class of medications known as alpha-1 blockers. In addition to preventing nightmares and insomnia, it can help improve overall symptoms, such as flashbacks, startle response, and irritability or anger, and it can be taken with an antidepressant.

What is the evidence for this off-label use?

A number of trials have studied prazosin's effect on sleep disturbances caused by PTSD. Recent analysis of those studies by the American Society of Health-System Pharmacists found that the drug helps patients sleep longer and have fewer nightmares and awakenings. It also lessens the severity of other symptoms of PTSD, such as re-experiencing a traumatic event, avoiding certain experiences, or feeling hyper-aroused by them. Most of the clinical studies of prazosin have focused on male combat veterans. Doctors also prescribe it for female veterans and people with PTSD not related to combat, but more research is needed to determine if it's as effective for them.

In a controlled crossover trial (where each patient was given the drug and a placebo at different times), the participants, 13 nonmilitary people with PTSD, experienced fewer nightmares and sleep disturbances, plus an average of 94 minutes of increased total sleep time.

A 20-week double-blind crossover study of 10 Vietnam combat veterans and an eight-week study involving 40 veterans with chronic PTSD and severe, trauma-related nightmares tested prazosin vs. a placebo. Researchers found that the patients taking prazosin had a much higher quality of sleep, slept longer, and had fewer nightmares.

A 2010 study that compared prazosin with the antipsychotic quetiapine (Seroquel) in male combat veterans with sleep problems found the two drugs to be equally effective at six months. But those taking prazosin were more likely to have remained on it as long-term therapy, while those taking Seroquel were more likely to have stopped taking it due to adverse effects, such as gaining weight, rising cholesterol levels, the onset of type 2 diabetes, and daytime sedation.

Many experts say there should be more extensive research on prazosin, especially to determine how well it works for other patients, especially women and people with PTSD that's not related to combat. Such research could also better establish optimal dosages, how frequently a patient should take the medication, and for how long.

What are the risks and warnings?

Common adverse effects—some severe enough to cause people to stop taking prazosin—include low blood pressure, headaches, nausea, lethargy, and dizziness. The best way to manage them is to ask your doctor to lower the dose you take, or to change when or how often you take it.

And because prazosin reduces blood pressure, it can cause fainting and dizziness. If you have low blood pressure already, or you're taking medication to reduce your blood pressure or medication for erectile dysfunction, such as sildenafil (Viagra), tadalafil (Cialis), or vardenafil (Levitra), you might want to avoid prazosin, or talk with your doctor about adjusting your current regimen.

He or she should check to see if you have other sleep-related disorders (e.g., obstructive sleep apnea, restless legs syndrome, etc.), or ask if you drink large amounts of caffeine, which can make your sleep problems worse.

What precautions can you take?

If you're planning to have cataract surgery you should tell your ophthalmologist that you're taking prazosin because people who take alpha-1 blockers have experienced intraoperative floppy iris syndrome (IFIS), a complication of eye surgery.

There's some uncertainty about the optimal dosage of prazosin for PTSD. Some clinical trials started people on a low dose (usually 1 mg at bedtime) to minimize its effects on blood pressure, and gradually increased it until the symptoms were controlled. Daily doses as high as 20 mg have been used in some studies. Some experts think more-frequent daily dosing might be necessary.

Be particularly cautious when taking the first dose of the medication, because you don't know how it will affect your blood pressure. One risk is excessively low blood pressure (hypotension), which can cause loss of consciousness. And with the first dose, it's important to not drive or do any potentially hazardous tasks. In general, to avoid dangerous falls from dizziness, stand up slowly when getting out of bed or even from a sitting position, since blood pressure can fall precipitously, especially when arising from a lying position.

You might see some improvement in PTSD sleep-related problems in as little as five days, but it usually takes one to two weeks. When stopping prazosin, nightmares can return in as little as two days, but they can usually be resolved by taking the medication again. Experts don't know how long prazosin should be taken, but the longest trial we reviewed lasted 20 weeks.

Bottom line. Nightmares and sleep disturbances are common with PTSD. The safe and appropriate use of prazosin can help many patients sleep better and reduce other effects of the condition. You should discuss the details of your symptoms with your physician, outlining what prescription and over-the-counter medication you're already taking, and your use of alcohol and other substances. He or she should check to see if you might have other sleep-related disorders, which could make your problems worse. Talk about strategies to minimize the dizziness, low blood pressure, tiredness, nausea, and headaches that might be a result of taking prazosin.

This off-label drug use report is made possible through a collaboration between Consumer Reports Best Buy Drugs and the American Society of Health-System Pharmacists. This is the 28th in a series based on professional reports prepared by ASHP.

These materials were made possible by a grant from the state Attorney General Consumer and Prescriber Education Grant Program, which is funded by a multistate settlement of consumer fraud claims regarding the marketing of the prescription drug Neurontin (gabapentin).
   

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