D-Cycloserine and Virtual Reality Exposure Therapy

Social Anxiety Disorder (social phobia) is the most common psychiatric disorder in the US. It negatively impacts health-related quality of life, educational and economic achievement, and it leads to attempted suicide in as many as 21% of affected individuals. A critical barrier to progress in reducing the negative impact of this disorder is that 75-92% of sufferers do not receive treatment. Social phobia self-help programs delivered via computer are designed to increase access to treatment and can be effective. Compliance and completion rates of such programs are, however, quite poor, greatly limiting their impact and accessibility. Furthermore, self-help programs for social phobia do not directly administer a critical component of treatment - exposure therapy. The direct administration of self-guided exposure therapy, using virtual reality is an innovation that would increase the accessibility and impact of computer delivered treatment.

Exposure therapy is based on well-researched fear extinction learning paradigms, where individuals confront what they fear in a therapeutic manner and learn that the feared outcome will not occur. Ressler et al's groundbreaking translational research showed that D-cycolserine (DCS), an analogue of D-alanine and a partial agonist at the NMDA receptor, facilitates the process of fear extinction. DCS is different from other pharmacological agents used to treat social phobia which are prescribed chronically (daily) over a period of months or years to maintain a therapeutic dose; one pill of DCS is taken immediately before exposure therapy sessions. This work sparked a flurry of research showing that DCS augments exposure therapy for a variety of anxiety disorders; people who take DCS show benefit from therapist-assisted exposure therapy more quickly than those who take placebo. Two randomized double-blind, placebo-controlled studies of social phobia conclude that the combination of DCS and therapist-assisted exposure therapy improves treatment response when participants complete fewer exposure sessions. The ability of DCS to speed up the response to exposure therapy is especially valuable for sufferers using self-guided treatment, because they are not generally compliant with the full exposure protocol. The combination of DCS and self-guided exposure therapy would increase access to effective treatment. The use of DCS with self-guided exposure, however, has never been tested.

Specific Aims

1. Adapt an existing computer program to deliver self-guided VRE for social phobia via iPad, and
2. Test the comparative efficacy of DCS vs placebo plus self-guided VRE.

Hypothesis: Participants who receive self-guided VRE plus DCS will show less self-reported social anxiety and less avoidance during a laboratory based behavioral test following a 5-week intervention than those who received self-guided VRE plus placebo.

The investigators seek to shift current clinical practice in the treatment of social phobia so that more people with the disorder receive exposure therapy. The investigators will improve access to evidence-based treatment for social phobia with delivery of exposure via a computer - a modality that capitalizes on the fact that people with severe social phobia spend extensive hours on the computer; exposure therapy can come to people with social phobia "where they are." The investigators also will be the first to test the delivery of exposure therapy on an iPad. The study design improves the approach of existing research on computer-delivered programs for social phobia by testing how treatment affects real behavior - existing research has relied exclusively on self-report measures and assessment of diagnostic status. No studies have assessed actual behavior - either in the lab or in the real-world. This study will improve scientific knowledge by answering the question of whether or not DCS augments self-guided exposure therapy. The combination of a self-help program with DCS addresses many of the obstacles to treatment with therapist-guided exposure therapy. For example, there are not enough mental health providers trained in exposure therapy. Furthermore, social anxiety disorder is characterized by the fear and avoidance of social situations, and psychotherapy is inherently a social encounter. The effective combination of DCS and self-guided virtual reality exposure is an avenue for treatment to any sufferer with access to a computer and a prescribing physician. When the proposed aims are achieved, an innovative treatment will exist that did not before - self-guided VRE delivered via computer.

The investigators have developed and tested a self-help program delivered via computer, with minimal therapist support. The self-help program was tested in a small (N=10) uncontrolled trial of 8 sessions, and results showed decreases in scores on standardized self-report measures of social anxiety from pre- to post-treatment and follow-up. Large effect sizes were observed at post-treatment (d = 1.22-1.53) and follow-up (d = 1.41 - 2.39).

Using standardized measures of software usability, participants described the program as easy-to-use, including a participant who had never before used a computer. Since this study, the program has been updated with new virtual environments, as well as shortening the treatment down. The proposed project will adapt an existing program for delivery via a tablet and to collect data via the computer.

Finally, the investigative team completed a double-blind, placebo controlled trial that tested the combination of DCS vs placebo combined with therapist-guided VRE for specific phobia.

Thus, the investigative team is well-positioned to complete the specific aims of adapting a computer program that delivers self-guided exposure therapy for social phobia via a tablet and testing following hypothesis: Participants who receive self-guided exposure therapy plus DCS will show less self-reported social anxiety and less avoidance during a laboratory based behavioral test following a 5-week intervention than those who received self-guided exposure therapy plus placebo.