TB drug could make PTSD treatment quicker, longer lasting, more effective

By Steve Tokar

Charles Marmar M.D. -----

Researchers at the San Francisco VA Medical Center are beginning a study to evaluate effectiveness of a medication that could make treatment for posttraumatic stress disorder (PTSD) quicker and longer-lasting and leave patients less suject to relapse.

The medication, D-cycloserine (DCS), has been approved for human use for many years as a treatment for tuberculosis. However, recent research indicates that it also has the potential to accelerate the rate at which fears and phobias can be extinguished, according to principal investigator Charles Marmar, MD, associate chief of staff of mental health at SFVAMC. DCS belongs to a class of compounds called NMDA receptor partial agonists, which act directly on the underlying mechanism in the brain that affects learning and memory.

“DCS is a safe, low cost, and widely available compound,” notes Marmar, who is also professor and vice chair of psychiatry at the University of California, San Francisco. “We believe that it has the potential to dramatically improve treatment of PTSD.”

Marmar and his fellow researchers are currently recruiting northern California combat veterans who have served in Iraq or Afghanistan since 2001 to participate in the study, which will compare the effectiveness of cognitive behavior therapy (CBT) - the current standard treatment for PTSD - with CBT in combination with DCS.

Participants in the double-blind, placebo-controlled study will be randomly assigned to one of two groups.

The first group will receive 16 sessions, plus two one-hour booster sessions, of state-of-the-art CBT that has proven effective in preventing long-term PTSD in accident and assault victims. These sessions will include a technique called imaginal exposure, in which participants safely confront the situations and memories that are causing them stress. One half hour prior to each imaginal exposure session, participants in this group will take one 50-milligram capsule of DCS, which has no known side effects in humans at that dose.

The second group will receive identical treatment, but will be given a placebo rather than a dose of the drug.

The investigators predict that both groups will achieve significant reductions in PTSD symptoms by the end of treatment. However, they predict that the CBT-plus-DCS group will show much more rapid improvement. Moreover, they believe that DCS will render the treatment more effective over time, and that subjects who have taken it will be less likely to re-experience symptoms of PTSD when they are exposed to stressful situations later in life.

Marmar notes that least one million Americans are expected to serve in Iraq and Afghanistan, of whom approximately 17 percent are expected to return with PTSD. “Not only do we have the opportunity to improve the lives of thousands of veterans,” he observes, “but, by accelerating and improving treatment, we also can potentially free up resources to treat more veterans more quickly.”
All Northern California combat veterans of Operation Iraqi Freedom or Operation Enduring Freedom who are interested in participating in the study, whether they served in regular armed services, the National Guard, or Reserve, should call Tracy Sway at (415) 418-4360, or toll-free at (888) 567-6337.

If successful, the study will serve as a foundation for larger studies at Veterans and Department of Defense medical sites around the United States.

Co-investigators of the study are Thomas Neylan, MD, of SFVAMC and UCSF, and Suzanne Best, PhD, of UCSF.

The research is supported by funds from the United States Department of Defense that are administered by the Northern California Institute for Research and Education.

NCIRE is the largest research institute associated with a VA medical center. Its mission is to improve the health and well-being of veterans and the general public by supporting a world-class biomedical research program conducted by the UCSF faculty at SFVAMC.

SFVAMC has the largest medical research program in the national VA system, with more than 200 research scientists, all of whom are faculty members at UCSF.

UCSF is a leading university that consistently defines health care worldwide by conducting advanced biomedical research, educating graduate students in the life sciences, and providing complex patient care.