D-cycloserine enhancement of fear extinction is specific to successful exposure sessions: evidence from the treatment of height phobia

Abstract

Background: Whereas some studies have shown clear evidence for an augmentation effect of D-cycloserine (DCS) on exposure therapy for anxiety disorders, other studies have shown weak effects or no effect at all. Some preclinical data suggest that the DCS augmentation effect is moderated by the success of extinction learning. Therefore, we conducted a reanalysis of existing data to examine whether the effects of DCS on clinical outcome would vary as a function of response to the exposure session (i.e., exposure success).

Methods: In a clinical trial, patients with height phobia received two sessions involving 30 minutes of virtual reality exposure therapy and were randomly assigned to a pill placebo (n = 14) or 50 mg of DCS (n = 15) immediately after each session.

Results: Mixed-effects regression analysis showed that the effects of DCS administration on clinical improvement was moderated by the level of fear experienced just before concluding exposure sessions. Patients receiving DCS exhibited significantly greater improvement in symptoms relative to patients who received placebo when fear was low at the end of the exposure. In contrast, when end fear was still elevated, patients receiving DCS improved less compared with those receiving placebo.

Conclusions: D-cycloserine appears to enhance the benefits of exposure treatment when applied after a successful session, but it seems to have detrimental effects when administered after inadequate/unsuccessful exposure sessions.

Trial registration: ClinicalTrials.gov NCT01102803.

Figure 1

CGI-I outcome effects of the interaction between drug condition and exposure adequacy as assessed by end fear scores. Note. CGI-I is the Clinical Global Impressions Improvement scale that uses a 7-point scale, with lower scores indicating greater improvement 7-point scale (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse). End Fear is the fear rating provided just prior to concluding the exposure exercises. Fear was rated 0-100 scale (0 = no fear; 50 = moderate fear; 100 = extreme fear or panic), and thus 0 indicates exposure success and higher ratings indicate less exposure success.