Common PTSD Drug Is No More Effective Than Placebo

"There was no benefit at all, and there were several adverse side effects," says lead author Thomas Neylan, MD, medical director of the PTSD treatment program at SFVAMC. "People with symptoms of PTSD should probably stay away from this drug and others of its type."

The study appears in the December 1, 2006 issue of the American Journal of Psychiatry.

Guanfacine belongs to a class of medications known as alpha-2 agonists, which lower the brain's supply of the neurotransmitter norepinephrine. Neurotransmitters are chemicals that transmit electrical signals between nerve cells. They are responsible for many aspects of behavior.

"Norepinephrine is released in the brain during states of excited arousal, and PTSD is associated with that state -- patients startle easily, have trouble sleeping, and are hypervigilant and anxious," explains Neylan, who is also an associate professor of psychiatry at the University of California, San Francisco.

Guanfacine and clonidine, another alpha-2 agonist, are commonly prescribed for PTSD symptoms. "There are at least 20 peer-reviewed articles published in the field of PTSD that recommend drugs which lower norepinephrine," Neylan says. "However, ours was the first randomized, controlled study of alpha-2 agonists for symptoms of PTSD."

The double-blind study compared the effects of guanfacine and an identical looking placebo pill on 63 male and female veterans at four VA medical centers in California and Hawaii. Twenty-nine participants were randomly assigned to take weekly doses of the drug, and 34 were assigned the placebo, for eight weeks.

At the end of the study, the effect of guanfacine on PTSD symptoms was "zero," and there were no differences between men and women or older versus younger veterans. In addition, the subjects who took guanfacine had significantly more somnolence, lightheadedness, and dry mouth than those who took placebo.

The study authors conclude, "These results do not support the use of alpha 2 agonists in veterans with chronic PTSD."

Neylan speculates that instead of lowering the overall level of norepinephrine, a more effective approach might be to inhibit the ability of brain cells to respond to the neurotransmitter. He notes that this is the action of prazosin, a blood pressure medication that has been found by other researchers to decrease the incidence of nightmares in combat veterans with PTSD.

Study co-authors were Maryann Lenoci, MA, and Kristin W. Franklin, PhD, of SFVAMC; Thomas J. Metzler, MA, of UCSF and SFVAMC; Clare Henn-Haase, PsyD, of SFVAMC; Robert W. Hierholzer, MD, of UCSF and Fresno VA Medical Center, Fresno, Calif.; Steven E. Lindley, MD, PhD, of Stanford University and Palo Alto VA Medical Center, Palo Alto, Calif.; Christian Otte, MD, of UCSF, SFVAMC, and University Hospital Hamburg-Eppendorf, Germany; Frank B. Schoenfeld, MD, of UCSF and SFVAMC; Jerome A. Yesavage, MD, of Stanford University and PAVAMC; and Charles R. Marmar, MD, of SFVAMC and UCSF.

The study was funded by support from the Department of Veterans Affairs.