A randomized controlled trial of the effect of d-cycloserine on exposure therapy for spider fear

Adam J. Guastella*, Mark R. Dadds, Peter F. Lovibond, Philip Mitchell, Rick Richardson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

126 Citations (Scopus)


Previous research [Hofmann SG, Meuret AE, Smits JA, Simon NM, Pollack MH, Eisenmenger K, et al. Augmentation of exposure therapy for social anxiety disorder with d-cycloserine. Archives of General Psychiatry 2006;63:298-304; Ressler KJ, Rothbaum BO, Tannenbaum L, Anderson P, Graap K, Zimand E, et al. Cognitive enhancers as adjuncts to psychotherapy: use of d-cycloserine in phobic individuals to facilitate extinction of fear. Archives of General Psychiatry 2004;61:1136-44] suggests that d-cycloserine (DCS) facilitates the reduction of clinical fear in humans. We used a well established intervention to evaluate the effectiveness of administering DCS as an adjunct to exposure therapy in a heightened, but sub-clinical, fear population. Over two studies, 100 spider-fearful participants were allocated to DCS or placebo before treatment and were assessed at pre-, immediate post-, and 3.5 weeks post-treatment. Significant treatment effects and return of fear was observed at follow-up, particularly in non-treatment contexts; however, both studies failed to demonstrate any enhancing effects of DCS (50 or 500 mg). DCS did not enhance the reduction of spider fears or the generalisation of treatment of a single session of exposure-based therapy. These results suggest that DCS may not enhance loss of non-clinical levels of fear in human populations.

Original languageEnglish
Pages (from-to)466-471
Number of pages6
JournalJournal of Psychiatric Research
Issue number6
Publication statusPublished - Sep 2007
Externally publishedYes


  • Anxiety disorders
  • d-Cycloserine
  • Exposure therapy
  • Extinction
  • Generalisation
  • Phobia


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