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.
The NMDA partial agonist d-cycloserine (DCS) facilitates extinction of learned fear in rats when administered before, after, or 60 min post-extinction training (Richardson et al., 2004 and Walker et al., 2002), while it has no impact in the absence of extinction training. It has been suggested that DCS strengthens extinction memories so they may be more easily retrieved during subsequent exposures to fear-relevant cues. Recent research has also suggested that DCS may facilitate the therapeutic effects of exposure therapy (ET) for clinical anxiety in humans. In a first pilot study (Ressler et al., 2004), 27 height-phobic subjects were assigned to three conditions: placebo, 50 mg DCS, or 500 mg DCS, and all received two sessions of virtual reality (VR) ET. At 1 week and 3-months post-treatment, participants in the DCS condition, regardless of dose, experienced less fear as indicated by fear levels in a virtual reality environment, self-reported attitudes and beliefs about acrophobia, and the number of self-exposures to real-world environments. A second study by Hofmann et al. (2006) also found that DCS given before each of four ET sessions decreased social anxiety symptoms reported one month post-treatment.
These findings have the potential to significantly advance the practice of fear/anxiety management, and warrant careful replication in varying populations. The aim of this study was to use a well developed laboratory-based treatment to test the efficacy of combining DCS with ET for spider fears. These laboratory-based exposure therapy treatments have been used previously to demonstrate the impact of internal and external context shifts, stimulus shifts, and session-spacing effects on exposure outcomes (Mineka et al., 1999, Mystkowski et al., 2003, Rodriguez et al., 1999, Rowe and Craske, 1998a and Rowe and Craske, 1998b). Our aim was to test whether DCS would enhance exposure therapy treatment effects in a heightened spider fear population. Ressler et al. (2004) results also suggest that DCS effects generalise to settings outside of the treatment context (i.e., number of self-exposures), so we tested whether the hypothesised benefits of DCS generalised to non-treatment settings in our participants.
