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Clinician's Digest III

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Old Pills, New Promises for PTSD

By Jared DeFife

With nearly eight million Americans affected by the symptoms of post-traumatic stress disorder (PTSD) and tens of thousands of troops returning from military operations in Iraq and Afghanistan, researchers are hard at work trying to identify new, effective treatments for the disorder. Currently, there are only two FDA-approved medications for the treatment of PTSD: sertraline (Zoloft) and paroxetine (Paxil). The evidence of the effectiveness of these antidepressants and other medications used "off-label" for PTSD-related symptoms is limited, and the medications often cause problematic side effects, such as sexual dysfunction, weight gain, and fatigue, which many users find disagreeable. New studies suggest that two drugs previously used for very different purposes may provide hope for PTSD sufferers. Unlike other psychiatric medications, these drugs aren't intended to treat the symptoms of PTSD directly--they're meant to augment traditional psychotherapy approaches for the disorder.

The first drug, ethylenedioxymethamphetamine (MDMA), is better known by its street name: Ecstasy. MDMA proponents suggest that the mood-mellowing effects of the drug may allow for more controlled and efficient processing of traumatic material in psychotherapy sessions. After years of campaigning, researchers from the Medical University of South Carolina and the Multidisciplinary Association for Psychedelic Studies in California received federal approval for the first randomized controlled clinical trial of this illegal recreational psychedelic party drug for patients with chronic PTSD. Under close clinical monitoring and in conjunction with intensive psychotherapeutic engagement (two eight-hour experimental sessions), 20 participants were randomized to administrations of either MDMA or placebo. In this admittedly small trial sample, 83 percent of the MDMA group exhibited substantial treatment response compared to 25 percent in the placebo group. The study results suggested that MDMA could be administered without severe adverse effects and may provide significant clinical results where other treatments have failed.

The second drug being investigated isn't found on the streets but behind the pharmacy counter. D-cycloserine is a broad-spectrum antibiotic commonly used for the treatment of tuberculosis infection. Researchers discovered that, in addition to its ability to fight off infections, the drug activates neural receptors in the brain associated with learning and memory formation. When treated with d-cycloserine, both rats and humans can learn fear extinction more quickly, requiring far fewer trials to extinguish fear of a nonharmful stimulus (e.g., a flashing light) that had previously been conditioned with an aversive stimulus (by pairing the light with a painfully loud noise, for example). This accelerated learning curve, researchers suggest, may hasten the effects of behavioral psychotherapies targeting the extinction of PTSD symptoms.

A recent clinical trial found that giving d-cycloserine to patients participating in exposure therapy for severe and persistent PTSD led to improved outcomes for the behavioral treatment. Rianne de Kleine, a researcher form the Centre for Anxiety Disorders in the Netherlands, the study's first author, said "Our study showed that some PTSD patients respond well and fast to exposure [psychotherapy] and, for them, there seems no need to augment the therapy. In contrast, those patients with severe PTSD symptoms who fail to respond to exposure sessions may benefit from augmentation with d-cycloserine."

While experimental findings for these old drugs in new bottles are exciting, the research is still in its infancy. MDMA may go the way of its psychedelic-assisted therapy predecessor LSD, and d-cycloserine may fail to live up to its promises, just as other psychiatric wonder drugs have. Yet, if these drugs prove successful, therapists might one day ask their anxious patients to "turn on, tune in, and drop out," while a drug once geared to a disease of the lungs may help soothe the traumatized mind.

Resources

New Pills for PTSD: Journal of Psychopharmacology 25, no. 4 (April 2011): 439-52; Biological Psychiatry 71, no. 11 (June 1, 2012): 962-68.

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