Antidepressants May Inhibit D-Cycloserine From Improving Symptoms in People With OCD

Cognitive-behavioral therapy (CBT) is a proven approach to help people overcome obsessive-compulsive disorder (OCD), though not everyone will respond quickly or fully. Researchers have been looking for pharmacological agents that might help augment CBT, and one promising agent that has emerged is D-cycloserine (DCS), an antibiotic that can also interact with some receptors in the brain.

“DCS has been one of the truly exciting recent innovations in psychiatry,” said Eric Storch, Ph.D., a professor of clinical psychology at the University of South Florida and clinical director of OCD services at Rogers Behavioral Health-Tampa Bay. “However, the early promise has given way to mixed results in early clinical trials, which shows we still don’t know enough about how DCS works or whom it works best for.”

New research from the Karolinska Institute in Sweden may have provided a significant answer: antidepressants can interact with DCS and block its ability to help people with OCD extinguish the anxieties and fears that trigger their compulsions.

These findings, published May 13 in JAMA Psychiatry, arose from a clinical study of 128 adults with OCD who received CBT with either DCS or placebo for 12 weeks. Previous DCS trials had involved 20 to 30 participants, making this the largest trial conducted by far.

In this new trial, led by Christian Ruck, M.D., Ph.D. of Karolinska’s Osher Center for Integrative Medicine, DCS supplementation did not improve CBT effectiveness among patients as a whole, either at the end of the 12-week treatment regimen or at follow-up three months later.

However, when patients were classified based on their medications status, big discrepancies in response appeared; 60 percent of the antidepressant-free patients on the DCS + CBT therapy achieved a remission of their symptoms at follow-up, compared with only 24 percent of patients on antidepressants. In comparison, the remission rate in the CBT-only group was 50 percent for patients taking antidepressants and those who were not.

“Given the good safety profile for DCS, these findings provide a basis to include DCS pharmacotherapy as part of a CBT strategy for some patients,” Michael Jenike, M.D., a professor of psychiatry at Harvard Medical School and founder of the OCD Program at Massachusetts General Hospital, told Psychiatric News.

“DCS also has similar properties to drugs like Rapastinel that are used as adjuncts to boost the effectiveness of antidepressants,” he continued. “These adjuncts are typically not used alone, but some of them might also be able to augment behavioral therapy, which potentially opens up many new clinical windows.”

Jenike had conducted one of the earlier DCS trials back in 2008. His study did not identify any long-term benefits related to OCD symptoms—perhaps because 16 of his 25 patients were taking antidepressants—but it did find evidence that DCS can improve depressive symptoms. According to Jenike, such findings suggest that if a patient receives a diagnosis of OCD with associated depression, DCS plus CBT may be able to serve as a first-line strategy, and an antidepressant can be added later, if needed.

One challenge to this treatment strategy is that many patients are not medication-naïve when they seek help for OCD, as this condition frequently associates with anxiety and depression. “In these cases, it’s not as simple as telling someone to stop taking their antidepressant for a few weeks while they try CBT,” Storch said. “For one, we don’t yet know whether a recent medication user would respond the same as someone who never took an antidepressant. Second, we’re still not sure how to best take someone off of antidepressant therapy.”

Storch believes these two areas should be targets for more research, as well as looking into how different types of CBT benefit from DCS; this particular study employed a therapist-supported Internet CBT approach (which is useful from a research standpoint, as it can be standardized and has slightly higher retention), but in-person therapies might be more or less sensitive to DCS.

The study was funded by the Swedish Research Council. ■

An abstract of “D-Cycloserine vs Placebo as Adjunct to Cognitive-Behavioral Therapy for Obsessive-Compulsive Disorder and Interaction With Antidepressants” can be accessed here.