D-cycloserine does not improve CBT for social anxiety disorder, but may accelerate early treatment gains


Clinical trials in the field of social anxiety to date have primarily focussed on the effect of either anxiolytic medication or cognitive behavioural therapy (CBT). At best these trials have demonstrated only moderate efficacy for either treatment independently (Davidson et al, 2004; Clark et al, 2003; Heimberg et al, 1998; Stein et al, 1998), and attempts to improve treatment response by combining the two specifically for social anxiety disorder have mostly shown disappointing results (Blomhoff et al, 2001; Otto et al, 2005).

There has been recent interest in D-cycloserine and its possible application in treatments for anxiety disorders; as it has been suggested that it may facilitate the process of extinction in learned fear. Hoffman and colleagues (Hoffman et al, 2013) aimed to test whether D-cycloserine can improve the speed and quality of response to a full course of CBT in adults with generalised social anxiety disorder.


This was a randomised, double-blind, placebo-controlled treatment trial involving 169 adults with social anxiety disorder. Participants were enrolled onto a 12 week programme of group CBT, and were given either 50mg of D-cycloserine or of a placebo one hour prior to five of the sessions. They were then followed-up over a six month period.

The primary outcomes for the study were:

Response: defined as “very much improved” or “much improved” on the Social Phobic Disorders Change Scale

Remission: defined as an improvement score on the Social Phobic Disorders Change Scale and a score of less than 30 on the Liebowitz Social Anxiety Scale


although D-cycloserine may not amplify the effects of CBT in the longer term it may temporarily accelerate early treatment gains

Although D-cycloserine may not amplify the effects of CBT in the longer term it may temporarily accelerate early treatment gains

  • There were improvements in response and remission rates within both groups and these were maintained at follow-up in both conditions. The difference between groups however was not statistically significant for either response or remission rate.
  • Post treatment there was a trend towards lower scores on the Liebowitz Social Anxiety Scale for those given D-cycloserine compared to placebo (estimated parameter for treatment effect: 5.22; t=1.75, df=146, p=.08).
  • Also at post treatment the D-cycloserine group had lower mean global illness severity scores than the placebo group (estimated parameter for treatment effect: 0.43; t=20.5, df=149, p=.04).
  • During treatment the D-cycloserine group showed a significantly faster rate of improvement than those on placebo in relation to:
    • Global illness severity (estimated parameter for treatment effect: 0.06; t=2.76, df=129, p=.006).
    • Social anxiety symptom severity score (estimated parameter for treatment effect: 0.65; t=2.18, df=147, p=.03).
    • Remission rate (estimated parameter for treatment effect: -0.10; t=2.59, df=1661, p=.01).


The overall conclusion of the study was that D-cycloserine did not improve treatment response when added to a full course of CBT for social anxiety disorder. This does not support the findings of the authors initial pilot study (Hoffman et al, 2006) and other previous research (Guastella et al, 2008).

The results however, in line with others (Siegmund et al, 2011; Hofmann et al, 2011), suggest that although D-cycloserine may not amplify the effects of CBT in the longer term it may temporarily accelerate early treatment gains and therefore suggest a possible role for D-cycloserine in reducing distress during exposure treatments.

It was suggested that variations in the dose or dose timings of D-cycloserine may yield different results, and that certain subgroups of people, such as those with a specific genotype or those who show greater within-session progress, may be more likely to benefit. This may therefore be worth exploring in the future.


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