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Augmenting CBT with partial agonist ineffective for pediatric OCD

D-cycloserine augmentation of cognitive behavioral therapy was not superior to placebo among youth with obsessive-compulsive disorder, according to recent findings.

“It is hypothesized that acutely dosed D-cycloserine can augment exposure therapy, particularly when the anxiety-provoking trigger has been successfully extinguished,” Eric A. Storch, PhD, of University of South Florida, Tampa, and colleagues wrote. “Initial studies of D-cycloserine augmentation of exposure therapy in anxiety have yielded mixed results, with evidence supporting this approach for acrophobia, social phobia, posttraumatic stress, and panic disorder, while others have found limited benefit in treating social phobia, posttraumatic stress, and panic disorder.”

Eric A. Storch

To assess efficacy of weight-adjusted D-cycloserine augmentation of cognitive behavioral therapy (CBT) for obsessive-compulsive disorder (OCD), researchers conducted a placebo-controlled randomized clinical trial among 142 youth, aged 7 to 17 years, with a primary diagnosis of OCD. Study participants received either 10 sessions of D-cycloserine plus CBT or placebo plus CBT. D-cycloserine or placebo was taken 1 hour before sessions 4 and 10.

Mixed-effects model analysis indicated significant decreases in the Children’s Yale-Brown Obsessive Compulsive Scale total score and Clinical Global Impressions-Severity.

There was no significant interaction between treatment group and changes in the Children’s Yale-Brown Obsessive Compulsive Scale total score and Clinical Global Impressions-Severity, indicating that both treatment groups declined at a similar rate per assessment point.

Estimated changes in scores were –2.31 (95% CI, –2.79 to –1.83) for the D-cycloserine group and –2.03 (95% CI, –2.47 to –1.58) for the placebo group on the Children’s Yale-Brown Obsessive Compulsive Scale total score and 0.29 (95% CI, 0.35 to 0.22) and 0.23 (95% CI, 0.29 to 0.17) on Clinical Global Impressions-Severity, respectively.

Researchers did not observe group differences in secondary outcomes, which included Clinical Global Impressions-Severity or Clinical Global Impressions-Improvement, remission status, Children’s Depression Rating Scale, Multidimensional Anxiety Scale for Children, and Children’s Obsessive-Compulsive Impact Scale–Parent Version.

Baseline antidepressant use did not moderate changes for either treatment group.

“In the context of the current literature, do the findings by Storch and colleagues mean that D-cycloserine for OCD should be declared dead? It may well be that D-cycloserine is both alive and dead. In other words, the results do not prove that D-cycloserine is categorically ineffective as an augmentation strategy,” Stefan G. Hofmann, PhD, of Boston University, wrote in an accompanying editorial. “Rather, the D-cycloserine effect might be more complicated than initially assumed. Some of the post-hoc analyses suggest that the effect of D-cycloserine might depend on the success of the exposure practices and might also be moderated by the effects of antidepressants. More research on the moderators and mechanisms of D-cycloserine will be necessary.” – by Amanda Oldt

Disclosure: Storch reports receiving research support from the NIH, Agency for Healthcare Research and Quality, International OCD Foundation, and All Children’s Hospital Research Foundation; receiving royalties from Elsevier Publications, Springer, American Psychological Association, John Wiley & Sons Inc., and Lawrence Erlbaum; being a consultant for Prophase Inc and Rijuin Hospital in China; serving on the speaker’s bureau and scientific advisory board for the International OCD Foundation; and receiving research support from the All Children’s Hospital Guild Endowed Chair. Hofmann reports receiving support by grant R01AT007257 from the National Center for Complementary and Integrative Health, NIH; by grants R01MH099021, R34MH099311, R34MH086668, R21MH102646, R21MH101567, and K23MH100259 from the NIMH, NIH; and from the Department of the Army. Grant R34MH099311 examines dosing and dose timing of -cycloserine to augment cognitive behavior therapy for social anxiety disorder. Hofmann also reports receiving compensation for his work as an advisor from Palo Alto Health Sciences and from Otsuka Digital Health Inc. and for his work as a subject matter expert from John Wiley & Sons Inc. and SilverCloud Health Inc. and receiving royalties and payments for his editorial work from various publishers. This work is unrelated to the studies reported in this article. Please see the full study for a list of all authors’ relevant financial disclosures.