A randomized controlled trial of the effect of d-cycloserine on exposure therapy for spider fear
Introduction
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, 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, 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.
Section snippets
Method and materials
Following the procedures of previous research1 (Mineka et al., 1999, Rodriguez et al., 1999), university students participated in this study if (1) they scored 15+ (M = 21.02, range = 15–28) on the Spider Phobia Questionnaire (SPQ; Klorman et al., 1974) or (2) they were unable to approach within a metre of a clear perspex box containing a spider (final sample = 49 female, 14 male; age = 20.9 years
Study 2
The aim of this study was to test the effects of both the 50 and 500 mg dose of DCS in a heightened spider fearful sample when only partial ET treatment is provided. Like the first study, this study aimed to assess whether DCS could enhance the effects of ET by increasing treatment response and the generalisation of treatment.
General discussion
The results of these studies indicate that DCS does not enhance the reduction of fear in a heightened spider fear population. DCS-treated subjects were no different to placebo controls on self-reports, behavioural proximity tasks, and heart rate responses post-treatment or at follow-up. Despite a failure to find an effect of DCS, this study was able to replicate the effects of other variables thought to impede ET, specifically, stimulus and context shifts (Rodriguez et al., 1999, Rowe and
Acknowledgements
This research was supported by the NHRMC, #350963. We thank Jayson Mystowski, Michelle Craske, and Kristy Johnstone for providing treatment manuals and advice upon which our procedures were based. We also thank Dr. David Sutherland, the external medical monitor for our participants, and our research assistants, Sally Ramke and Kristy Attwool.
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