Anxiety, OCD, PTSD Benefit From CBT Plus Agonist

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D-cycloserine can augment the effect of cognitive behavioral therapy for anxiety, OCD, and PTSD.
D-cycloserine can augment the effect of cognitive behavioral therapy for anxiety, OCD, and PTSD.

D-cycloserine (DCS) has a small augmentation effect on cognitive behavioral therapy (CBT) for anxiety, obsessive-compulsive disorder, and post-traumatic stress disorder (PTSD), although more research is warranted to fully understand this effect of this agonist, according to a study published in JAMA Psychiatry.1

Researchers from the Child and Adolescent Psychiatry Research Center, department of neuroscience, at the Karolinska Institutet, Stockholm, Sweden, collected individual participant data to observe the interaction between DCS and antidepressants, and to identify whether DCS performed better than placebo in boosting the effects of CBT. Positive results for DCS could be useful in determining a CBT with better long-tem results and symptom relief.

Raw data from 21 studies including 1047 participants were considered for this meta-analysis, in which DCS proved to have a statistically significant augmentation effect over placebo during posttreatment (regardless of antidepressant treatment). Follow-up failed to give DCS a similarly significant advantage.

Several factors hindered this study: Since only 4 studies involving pediatric samples were included, result interpretation for younger populations is limited. Also, due to the fact that different studies used different outcome metrics, the researchers had to use rank scores to achieve a universal measurement. Additionally, the inability to observe in-session experiences meant that DCS efficacy in CBT could not be fully appreciated.

On the other hand, this study did include 97% of all eligible raw data. “We had greater than 80% power to detect an effect size as small as a Cohen d value of 0.20 for the treatment effects and individual-level moderators,” lead researcher David Mataix-Cols, PhD, said. “This represents a substantial improvement on previous aggregate-data meta-analyses, which were only powered to detect large effect sizes.”2-6

Still, while the data demonstrated a small augmentation effect on exposure-based CBT, Dr Mataix-Cols advised that additional research on DCS efficacy would be beneficial.


  1. Mataix-Cols D, Fernández de la Cruz L, Monzani B, Rosenfield D, et al.D-cycloserine augmentation of exposure-based cognitive behavior therapy for anxiety, obsessive-compulsive, and posttraumatic stress disorders: a systematic review and meta-analysis. JAMA Psychiatry [published online January 25, 2017]. doi: 10.1001/jamapsychiatry.2016.3955
  2. Bontempo A, Panza KE, Bloch MH. D-cycloserine augmentation of behavioral therapy for the treatment of anxiety disorders: a meta-analysis. J Clin Psychiatry. 2012;73(4):533-537. doi: 10.4088/JCP.11r07356
  3. Rodrigues H, Figueira I, Lopes A, Gonçalves R, et al. Does D-cycloserine enhance exposure therapy for anxiety disorders in humans? A meta-analysis. PLoS One. 2014;9(7):e93519. doi: 10.1371/journal.pone.0093519. eCollection 2014
  4. Ori R , Amos T, Bergman H, Soares-Weiser K, et al. Augmentation of cognitive and behavioural therapies (CBT) with d-cycloserine for anxiety and related disorders. Cochrane Database Syst Rev [published online May 10, 2015]. doi: 10.1002/14651858.CD007803.pub2
  5. Xia J, Du Y, Han J, Liu G, et al. D-cycloserine augmentation in behavioral therapy for obsessive-compulsive disorder: a meta-analysis. Drug Des Devel Ther. 2015;9:2101-2117. doi: 10.2147/DDDT.S68994
  6. Norberg MM, Krystal JH, Tolin DF. A meta-analysis of D-cycloserine and the facilitation of fear extinction and exposure therapy. Biol Psychiatry. 2008;63(12):1118-1126.  doi: 10.1016/j.biopsych.2008.01.012
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