D-cycloserine Not Effective as an Augmentation Strategy for CBT in Pediatric OCD

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Some of the strategies to improve memory extinction aim at plasticity pathways in the brain with the use of NMDA receptor-modulating drugs, such as D-cycloserine.
Some of the strategies to improve memory extinction aim at plasticity pathways in the brain with the use of NMDA receptor-modulating drugs, such as D-cycloserine.

In a placebo-controlled, randomized clinical trial, D-cycloserine (DCS) did not augment the efficacy of cognitive behavioral therapy (CBT) in youth patients diagnosed with OCD, according to the findings of a new study published in JAMA Psychiatry.1

It is well established that the N-methyl-D-aspartate receptors (NMDARs) are critically involved in cognitive processes, and that DCS, a partial agonist at the glycine recognition site (NR1/NR2B) of the NMDAR, augments various forms and phases of learning and memory. In 1989, Monahan and colleagues were first to report the beneficial behavioral effects of DCS as a cognitive enhancer.2 The cognitive modifying properties of DCS are used as a strategy to enhance memory extinction and thereby augment CBT for many psychiatric conditions, including anxiety, social phobia, panic disorder, depression, posttraumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD).1,3

In the current study, the researchers affiliated with University of California at Los Angeles, University of South Florida, and Harvard Medical School employed DCS in an effort to augment CBT among 142 youth patients [mean (SD) age was 12.7 (2.9) years] diagnosed with OCD.3 They used a validated measure, Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS),4 to evaluate OCD symptom severity.

During the last 6 (out of 10) family-based CBT sessions, one hour before the start of the session, children weighing 25 kg to 45 kg received 25 mg of DCS or placebo, and children weighing more than 45 kg received 50 mg of DCS or placebo.

The findings indicate that there was a significant effect of time, but no significant group x time interaction for the CY-BOCS score (the mean score at randomization was 23.82). In other words, individuals in the experimental group (DCS+CBT; -2.31, 95% CI, -2.79 to -1.83) experienced comparable improvements in severity of OCD symptoms relative to youth patients who received placebo (placebo+CBT; -2.03, 95% CI, -2.47 to -1.58).1

“Further research [should] identify specific characteristics of youth with OCD who may benefit from this treatment approach…. and, other safe and tolerable approaches to enhance fear extinction should be explored,” the authors noted.   

To date, only 2 other studies involved youth participants (aged 8-18) diagnosed with OCD in order to examine whether DCS-augmented CBT is safe and effective in this group of patients. In one study, with a relatively small sample size, researchers found that youth who received DCS (N=15) displayed small-to-moderate reductions in OCD symptoms compared with participants in the control group.5 In the other study, DCS-augmented CBT also produced significant improvements in severity of OCD symptoms.6 These results are in line with previously reported findings in adult OCD.7

Although DCS therapy did not augment CBT relative to placebo, the current study shows that family-based CBT is effective in youth with OCD, and “highlights the importance of CBT dissemination”, the authors concluded.

References

1. Storch EA, Wilhelm S, Sprich S, et al. Efficacy of augmentation of cognitive behavior therapy with weight-adjusted D-cycloserine vs placebo in perdiatric obsessive-compulsive disorder: a randomized clinical trial. JAMA Psychiatry. 2016. doi: 10.1001/jamapsychiatry.2016.1128.

2. Monahan JB, Handelmann GE, Hood WF, Cordi AA. D-cycloserine, a positive modulator of the N-methyl-D-aspartate receptor, enhances performance of learning in rats. Pharmacol Biochem Behav. 1989;34(3):649-653.

3. Ganasen KA, Ipser JC, Stein DJ. Augmentation of cognitive behavioral therapy with pharmacotherapy. Psychiatr Clin North Am. 2010;33(3):687-699.

4. Scahill L, Riddle MA, McSwiggin-Hardin M, et al. Children's Yale-Brown Obsessive Compulsive Scale: reliability and validity. J Am Acad Child Adolesc Psychiatry. 1997;36(6):844-852.

5. Storch EA, Murphy TK, Goodman WK, et al. A preliminary study of D-cycloserine augmentation of cognitive-behavioral therapy in pediatric obsessive-compulsive disorder. Biol Psychiatry. 2010;68(11);1073-1076.

6. Farrell LJ, Waters AM, Boschen MJ, et al. Difficult-to-treat pediatric obsessive-compulsive disorder: feasibility and preliminary results of a randomized pilot trial of D-cycloserine-augmented behavior therapy. Depress Anxiety. 2013;30(8):723-731.

7. Sulkowski ML, Geller DA, Lewin AB, et al. The future of D-cycloserine and other cognitive modifiers in obsessive-compulsive and related disorders. Curr Psychiatry Rev. 2014;10(4):317-324.

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