TB Agent Helps in Obsessive-Compulsive Therapy

MINNEAPOLIS, July 20 -- For patients with obsessive-compulsive disorder, an anti-tuberculosis agent can jump start behavioral therapy, investigators here have found.
Patients given 125 mg of D-cycloserine (Seromycin), an N-methyl-D-aspartate (NMDA) partial receptor agonist, about two hours before an extinction-based exposure therapy session had significantly greater decreases in obsession-related stress after four sessions than placebo controls.
The D-cycloserine patients required fewer exposure sessions before they reached clinical milestones, and they had a much lower dropout rate than patients who took placebo, Matt Kushner, Ph.D., of the University of Minnesota, and colleagues, reported online in Biological Psychiatry.
"The dropout rate decreased dramatically," Dr. Kushner said. "Typically about 20 to 30% of people with OCD drop out of therapy. Only 7% of people who took the D-cycloserine dropped out."
In D-cylcoserine studies with rats, the drug accelerated extinction learning, speeding the loss of conditioned fear responses. In human studies, D-cycloserine has also been shown to improve responses to two sessions of exposure therapy in patients with social phobia, and four sessions in patients with acrophobia.
"Based on the earlier work," the authors wrote, "we predicted that D-cycloserine would also facilitate the capacity of exposure therapy to weaken the link between obsession-related stimuli (e.g., public restrooms) and feared outcomes (e.g., contamination), thereby reducing associated fear responding (e.g., distress) along with the need for rituals (e.g., washing) and avoidance."
The investigators randomly assigned patients with OCD to receive either placebo (17 patients) or D-cycloserine (15 patients) at 125 mg for 10 doses, to be taken about two hours before each session of cognitive behavioral therapy.
The patients had twice weekly sessions of cognitive behavioral therapy for five weeks, with standard exposure/ritual prevention therapy techniques applied by a trained psychologist.
Patients rated their 10-most disturbing stimuli on the 1-100 Subjective Unit of Distress Scale. The clinician then started working on the lower-rated stimuli first, and once a rating was decreased by at least 50%, a more challenging stimulus was tackled until all the ratings were cut by 50% of baseline, or until the 10th session was completed.
The authors found that the patients who received D-cycloserine had a more rapid decline in obsession-related fear rating through four exposure sessions, with the difference becoming significant at session four (t=2.3, P<0.05).
In addition, patients in the D-cycloserine group required an average of two fewer therapy sessions before reaching a greater than 50% decline in the distress scale ratings. At the end of their treatment sessions, however, there were no significant differences between the 14 remaining patients in the active drug group, or 11 patients in the placebo group.
"This offers another therapeutic approach where we can attempt to manipulate the memory process and the brain's reward/punishment system so people can learn healthier responses to various cues," Dr. Kushner said.
The investigators are currently exploring whether D-cycloserine might also help smokers abolish conditioned response to cues that trigger desire for a cigarette.
The authors acknowledged that the OCD study was limited by a lack of information on co-morbidities other than major depression or substance use disorder.
The work was supported in part by a grant to Dr. Kushner from the Obsessive-Compulsive Disorder Foundation. The journal did not provide authors conflict of interest information. Primary source: Biological PsychiatrySource reference: Kushner MG et al. "D-cycloserine Augmented Exposure Therapy for Obsessive-Complusive Disorder." Biol Pyschiatry 2007. doi:1-.1016/jbiopsych.2006.12.020