D-Cycloserine Augmentation Ineffective in Pediatric OCD

Megan Brooks

July 13, 2016

Augmenting cognitive-behavioral therapy (CBT) with D-cycloserine provides no added benefit in children and adolescents with obsessive compulsive disorder (OCD), according to results of a large, randomized, placebo-controlled trial.

"This study confirms that for kids with average-severity OCD, CBT works really well and shows that D-cycloserine doesn't confer additional benefit above and beyond that. We had a truncated [CBT] treatment course, and we still saw massive effects," first author Eric Storch, PhD, Department of Pediatrics, University of South Florida, in St. Petersburg, told Medscape Medical News.

The study was published online June 29 in JAMA Psychiatry.

D-Cycloserine is a partial glutamatergic N-methyl-D-aspartate agonist. Some small studies have suggested that when administered before CBT sessions, the drug amplifies the response to CBT in young people and adults with OCD.

The current study included 142 children and adolecents aged 7 to 17 years (mean age, 12.7 years, 53.5% female) with a primary diagnosis of OCD. Half were randomly allocated to receive 10 sessions of family-based CBT with either D-cycloserine (25 or 50 mg) or placebo, administered 1 hour before sessions 4 through 10.

A mixed-effects model using all available data indicated significant declines in total scores on the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) and the Clinical Global Impressions–Severity (CGI-Severity). For both measures, comparable changes over time occurred for both patients who received D-cycloserine plus CBT and those who received placebo plus CBT.

Measure D-Cycloserine (95% CI) Placebo (95% CI)
CY-BOCS total score -2.31 (-2.79 to -1.83) -2.03 (-2.47 to -1.58)
CGI-Severity -0.29 (-0.35 to -0.22) -0.23 (-0.29 to -0.17)

95% CI, 95% confidence interval


Use of antidepressant medication at baseline did not have an effect on changes in either group.

It is possible, the researchers note, that between-group differences may be "overshadowed" by the strong efficacy of CBT.

"Because both treatment groups exhibited a large response, there may be a ceiling effect for further and faster improvement with CBT, which has been demonstrated by others," they write.

For young people with OCD, symptoms at presentation can be heterogeneous and can include both fear-based and non–fear-based symptoms.

"Because D-cycloserine enhances fear extinction, it may be that its augmentation properties only affected fear-based symptoms. Therefore, a more individualized symptom-level analysis may be needed to detect its benefit," the investigators write.

"What we don't know is whether children who had more successful exposure sessions benefited from D-cycloserine more than those who didn't, and that's something that other studies have found," said Dr Storch.

Premature Enthusiasm?

"This is an important study [and] great news that a journal of this caliber decided to publish negative findings," David Mataix-Cols, PhD, Karolinska Institutet Department of Clinical Neuroscience, Child and Adolescent Psychiatry Research Center, Stockholm, Sweden, who was not involved in the study, told Medscape Medical News.

"The study is methodologically sound and the first to be adequately powered to test the hypothesis [regarding D-cycloserine augmentation] in children with OCD. All previous pediatric OCD trials were too small to draw meaningful conclusions. The results suggest that our initial enthusiasm for [D-cycloserine] as an augmentation strategy for OCD may have been premature. The message for clinicians and families is that [D-cycloserine] is currently not recommended for use in regular clinical practice," Dr Mataix-Cols said.

In an accompanying editorial, Stefan Hofmann, PhD, Department of Psychological and Brain Sciences, Boston University, Massachusetts, notes that the study results "do not prove that D-cycloserine is categorically ineffective as an augmentation strategy. 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.

"There is a good chance that D-cycloserine will not be a reliable pharmacological agent to augment any particular treatment. However, the effort so far has been well worth it because it has initiated a paradigm shift of clinical research by encouraging investigators to explore new ways to study and improve psychological therapies," Dr Hoffman notes.

The study was supported by the National Institute of Mental Health. The original articles include complete lists of author disclosures.

JAMA Psychiatry. Published online June 29, 2016. Abstract, Editorial


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