By Stephen Spotswood

Col. Kris Peterson, Chief of the Psychiatry Department at Madigan, Tammy Williams, Licensed Clinical Social Worker, and Dr. Murray Raskind of the Puget Sound VA, want to help soldiers deal with combative nightmares. Photo by Melissa Renahan

HOUSTON — As researchers delve deeper into the pathophysiology of PTSD, the complex interplay among the disease’s symptoms becomes more transparent, opening the possibility of new treatments.

One area of treatment that remains very limited, however, is medication.

Currently, the only two drugs approved by the FDA for PTSD are sertraline (Zoloft) and paroxetine (Paxil), both SSRI-type antidepressants. While physicians have been known to prescribe other types of medications, including tranquilizers, beta-blockers, anticonvulsants and atypical antipsychotics, all of those are off-label.

Researchers conducting a study at the Michael E. DeBakey VA Medical Center (MEDVAMC) in Houston are hoping to add at least one more drug — the antihypertension drug doxazosin — to the frustratingly short list of approved medications.

“The current medication treatments for PTSD are essentially limited to antidepressants,” said Thomas Newton, MD, a MEDVAMC physician and associate professor at Baylor College of Medicine. “And the biggest trouble with those is that they don’t work for everybody. They have side effects for those willing to take them, and they’re not profoundly effective. Things like sleep can still be very affected.”

Some of the potential side effects can mimic problems already faced by PTSD sufferers, including agitation and restlessness, irritability, insomnia, headache and loss of appetite. SSRIs also can take weeks to become effective.

Doxazosin would have few of those problems, if found to be effective.

Newton honed in on the drug after seeing the success of Seattle VA researchers in using another alpha blocker, prazosin, to treat PTSD-related nightmares. Prazosin is an alpha-adrenergic blocker designed to treat high blood pressure and anxiety. It makes users less sensitive to the effects of adrenaline — something that can be produced in excess in PTSD patients.

Murray Raskind, MD, a psychiatrist, and his colleagues with the VA Puget Sound Health Care System have been prescribing prazosin to Vietnam-era PTSD sufferers for years, having found that the drug significantly reduced the intense nightmares associated with the disorder.

Raskind also conducted three positive controlled trials using prazosin to treat PTSD-related sleep disorders in Vietnam-era veterans and in active duty soldiers at Joint Base Lewis-McChord. This was the first joint VA-Army study on behavioral disorders in active duty servicemembers.

VA has been conducting a nationwide study on prazosin and PTSD nightmares that was scheduled to wrap up this year, though results have yet to be released.

Seeing Raskind’s success, Newton began looking at alpha-blockers as potential treatment for a larger range of PTSD symptoms. He chose doxazosin, which is in the same class of drug but only needs to be taken once a day, instead of two or three times, as with prazosin.

Newton is recruiting patients into a double-blind study that will compare doxazosin to placebo. Over the course of many weeks, the dose will be gradually increased. The veterans will undergo exposure therapy using an Iraq/Afghanistan virtual reality computer simulation to help determine optimal dosage and to prove effectiveness.

Newton and his fellow researchers are hoping the treatment not only reduces current PTSD symptoms but prevents the onset of new symptoms.

While not all drugs work for everyone, this class of medication is less unpredictable than SSRIs and works much more quickly.

“This is a completely different mechanism of action, and it works for many indications right away,” Newton said. “We don’t know if it will work on PTSD right away but, based on [what we know of the drug], it should.”

This could be key when treating veterans with PTSD who are suffering from exhausting, sometimes debilitating, symptoms. They will be more likely to stick with the treatment program if they can see immediate results.

An additional benefit of doxazosin is its side effects. While it might have been designed to decrease blood pressure, it also reduces anxiety, enhances sleep and blocks nightmares.

If doxazosin is proven to be effective, that opens the door to a number of other drugs in the same class, Newton said.

“There’s a bunch of other medications that do similar things. And all should be investigated as potential treatment options.”

Another advantage is that doxazosin could be combined with other approved medications with relative ease.

“This is a completely orthogonal approach,” Newton said. “It could be applied with current treatment; it could be used as a sole treatment; or it could be used to augment ongoing treatment. It could have a big impact on how people [with PTSD] are cared for if it works.”

Veterans seeking to enroll or physicians looking to learn more about the project can call 1-877-228-5777.