The antihypertensive drug guanfacine, which lowers brain norepinephrine activity, does not reduce the symptoms of posttraumatic stress disorder (PTSD), according to results of an 8-week study appearing in the December 1st issue of the American Journal of Psychiatry.

“This was surprising,” Dr. Thomas C. Neylan told Reuters Health, “because there is evidence from a variety of studies that norepinephrine is over-activated in PTSD. Because of this, experts in the field have recommended guanfacine and clonidine (both in the same drug class) as possibly effective in PTSD. However, prior to our study, there were no data from randomized controlled trials.”

In the U.S., guanfacine is sold under the trade name Tenex and clonidine, under the trade name Catapres.

Neylan, from the University of California, San Francisco and the San Francisco VA Medical Center, and colleagues randomly assigned 63 veterans with chronic PTSD who were medication-free or who met the full criteria for a diagnosis of PTSD, even though they were on stable doses of psychiatric medications, to receive guanfacine or placebo for 8 weeks.

The subjects in the guanfacine group received weekly doses of the drug, which was increased by 0.5 milligrams per day until the target dose, ranging from 1.0 to 3.0 mg at bedtime, was reached.

Compared with placebo, “guanfacine did not result in greater improvement in PTSD symptoms, depression, general psychological distress, sleep quality or quality of life,” the team reports.

Because the effect was “zero,” the findings suggest that guanfacine offers no promise of efficacy “even with larger samples,” they add.

Moreover, guanfacine was associated with a number of side effects, including sleepiness, lightheadedness and dry mouth.

For chronic PTSD, “the key message is to avoid guanfacine,” Neylan said, and “be wary of using a similar drug clonidine - at least until there are results from randomized controlled studies.”

Neylan noted that another antihypertensive medication, prazosin, which has a different mechanism of action than guanfacine and clonidine, has shown promise for the treatment of chronic PTSD in randomized, controlled trials.

“The important distinction between guanfacine and prazosin is that the latter drug does not lower brain norepinephrine release.” Rather, it blocks the effect of norepinephrine on one particular receptor (alpha 1), he added.

SOURCE: American Journal of Psychiatry, December 1, 2006.