D-Cycloserine Plus Behavioral Therapy Lessens OCD Symptoms

Pauline Anderson

March 14, 2008

March 14, 2008 – A short course of D-cycloserine (DCS) (Seromycin, Eli Lilly) added to behavioral therapy could improve outcomes for patients with obsessive-compulsive disorder (OCD), a new study suggests.

The study, published in the March issue of the American Journal of Psychiatry, showed that patients receiving DCS had a 52% decrease in the Yale-Brown OCD scale after only 5 behavioral therapy sessions.

"This is a really fast and clinically meaningful response," said Sabine Wilhelm, PhD, associate professor at Harvard Medical School and director of the OCD and related disorders program and the cognitive-behavioral therapy program at Massachusetts General Hospital, in Boston. The study "shows that DCS speeds up the therapeutic effect inherent in behavior therapy and that patients can reach subclinical OCD levels after only very few sessions."

"Fast and Clinically Meaningful"

Unlike agents that target serotonin receptors, DCS interferes with the subtype of glutamate receptor called N-methyl-D-aspartic acid (NMDA). Originally approved by the Food and Drug Administration for the treatment of tuberculosis, DCS has been tested as a treatment for neurocognitive deficits in schizophrenia and Alzheimer’s disease. More recently, it has been used to augment exposure-based behavior therapy for several anxiety disorders.

This current double-blind, placebo-controlled trial included 23 patients with OCD enrolled through Massachusetts General Hospital or the Institute of Living, in Hartford, Connecticut. The patients received either placebo or DCS in addition to behavioral therapy sessions. The groups did not differ in the proportion of patients currently receiving psychiatric medications or in their pretreatment Yale Brown OCD Scale or Beck Depression Inventory- 11 total scores.

All study participants received 10 1-hour individual behavioral therapy sessions scheduled twice a week. One hour before each session, the subjects received their treatment (placebo or DCS). Additional sessions were held at mid-treatment (after 5 sessions) and posttreatment (after 10 sessions) and at 1-month follow-up.

Symptom Severity Dropped to Mild Range

At mid-treatment, there was a significant 52% decrease in OCD symptom severity scores among patients in the DCS group. "OCD symptom severity had dropped from the severe range to the mild range, and 70% of DCS patients, vs only 8% of the patients who received [exposure and response prevention] ERP and placebo, met criteria for clinical remission," Dr. Wilhelm added in an e-mail interview.

Dr. Wilhelm referred to another, larger OCD trial that took much longer to demonstrate such positive results. In that study, patients showed a 55% decrease in OCD symptom severity after receiving 2 information sessions, 30 hours of ERP, and 2 relapse-prevention sessions. "This is comparable to our response after 1 treatment planning and 5 ERP sessions," she noted.

Narrow Therapeutic Range

The dose of 100 mg used in the study — a dose that is much lower than the 250 mg used in at least 1 other study — might fall into a narrow ideal therapeutic range for the drug. The larger dose did not have as positive results and could have had an attenuated effect on fear extinction compared with the lower dose, according to the study authors. Dr. Wilhelm said that if she were to do another study on this drug she would choose the same lower dose.

The timing of the drug administration — 1 hour before each therapy session — could also have contributed to the positive results, said Dr. Wilhelm. She added that in a recent OCD study in which DCS was given 4 hours before ERP, the results were negative and that other research suggests that "it's best to administer DCS closer to extinction training."

The spacing of the therapy sessions — twice weekly — may be another important factor. Longer studies might include more between-session homework assignments that are not accompanied by DCS, and this greater frequency of nonaugmented homework exposure may obscure the effects of DCS, the study authors write.

Effects Time Limited

It appears that the positive effects of DCS may be time limited. Although the study found a large effect after 5 therapy sessions, that was not the case at the end of study. Over time, differences between DCS and placebo augmentation tend to decrease. "Thus, D-cycloserine administration over a shorter period of time may be critical for augmenting exposure-based treatment," write the authors.

Adding DCS to behavior therapy may decrease the high treatment dropout rate, because patients might be more likely to begin and less likely to abandon a treatment that reduces their anxiety faster and is less time-consuming. "It might give them a boost in their motivation if they see results more quickly and they have to take less time away from other activities such as work to see those results,” Dr. Wilhelm told Medscape Psychiatry.

In addition, DCS could reduce the cost of care, as DCS is inexpensive and fewer treatment sessions are required to reach clinically meaningful results.

The study also found that DCS-augmented behavioral therapy was superior to placebo for depressive symptoms posttreatment.

Dr. Wilhelm receives research support from the National Institute of Mental Health (NIMH) and Forest (medication only) and royalties from Guilford Press and New Harbinger Publications. Coauthor Dr. David F. Tolin receives research support from NIMH and royalties from Oxford University Press. Coauthor Dr. Scott L. Rauch receives research funding through Massachusetts General Hospital (Medtronics, Cyberonics, and Cephalon); honoraria from Neurogen, Sepracor, Cyberonics, and Novartis during the past 12 months; funding of postdoctorate fellows from Pfizer; and consulting fees from Novartis. Coauthors Drs. Suzanne A. Meunier and Godfrey D. Pearlson receive current research support from Massachusetts General Hospital. The remaining authors report no competing interests.

Am J Psychiatry. 2008;165:335-341. Abstract

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