Enhancing cognitive behavioral therapy: Is the finish line in sight?

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Science Translational Medicine  01 Mar 2017:
Vol. 9, Issue 379, eaam9857
DOI: 10.1126/scitranslmed.aam9857


Augmentation of cognitive behavioral therapy with D-cycloserine (DCS) for anxiety disorders results in a small decrease in symptom severity.

Up to 30% of individuals will suffer in their lifetime from anxiety, obsessive-compulsive, and posttraumatic stress disorders that are characterized by deficits in fear responses and extinction. Although cognitive behavioral therapy (CBT) and serotonin reuptake inhibitors are efficacious in symptom alleviation, a substantial number of patients do not respond to these first-line treatments. Thus, the race toward identifying drugs that augment the effects of CBT has intensified over the last two decades. The current frontrunner in this race is D-cycloserine (DCS), a partial N-methyl-D-aspartate receptor agonist that has been shown in animal studies to facilitate fear extinction. The initial studies supported the notion that DCS's facilitates CBT to reduce symptoms in anxiety-related disorders, but larger, more recent trials have been equivocal in nature. Thus, Mataix-Cols and the DCS Anxiety Consortium conducted a systematic review of double-blinded randomized trials of DCS and performed a meta-analysis to (i) determine whether DCS is superior to placebo in augmenting CBT in those with anxiety disorders, and (ii) identify factors that might influence DCS’ efficacy.

Investigators identified 22 eligible studies via their systematic review and obtained raw data from 21 of them that included 1047 participants. Results controlling for antidepressant use indicated that DCS reduced symptoms from pre- to post-treatment, and post hoc analyses showed that those receiving DCS had fewer symptoms after treatment. Although a clear improvement, the beneficial effects of DCS were small, and the meta-analysis did not identify specific factors that influenced the effects of DCS on symptom relief. The authors concluded that DCS was associated with a small facilitation of CBT for anxiety disorders, with potential further improvement, provided future research identifies patient and therapy characteristics that maximize the beneficial effects of DCS on symptom alleviation during CBT. Although this meta-analysis helps us toward the finish line, these findings suggest that the race toward effective pharmacological augmentation of CBT for anxiety disorders is turning out to be a marathon and not a sprint.

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