Dose Timing of D-Cycloserine to Augment Exposure Therapy for Social Anxiety Disorder: A Randomized Clinical Trial

Key PointsQuestionWhat is the best dosing regimen for augmenting exposure therapy for social anxiety disorder with D-cycloserine? FindingsIn this double-blind, placebo-controlled, randomized clinical trial involving 152 adults with social anxiety disorder, D-cycloserine augmented the treatment effects when administered before or after the exposure sessions. A tailored approach based on exposure success, as defined by low fear at the end of exposure practice, did not facilitate the therapy effects. MeaningD-cycloserine augments exposure therapy for social anxiety disorder, although further optimizing the effects of D-cycloserine augmentation requires research on identifying the targets for tailored approaches. This randomized clinical trial examines whether D-cycloserine administration augments exposure therapy for adults with social anxiety disorder. ImportanceFindings suggest that the efficacy of D-cycloserine (DCS) for enhancing exposure therapy may be strongest when administered after sessions marked by low fear at the conclusion of exposure practice. These findings have prompted investigation of DCS dosing tailored to results of exposure sessions. ObjectiveTo compare tailored postsession DCS administration with presession DCS administration, postsession DCS administration, and placebo augmentation of exposure therapy for social anxiety disorder. Design, Setting, and ParticipantsThis double-blind randomized clinical trial involved adults with social anxiety disorder enrolled at 3 US university centers. Symptom severity was assessed at baseline, weekly during treatment, and at 1-week and 3-month follow-up. Data analysis was performed from September 2019 to March 2020. InterventionsParticipants completed a 5-session treatment and received pills commensurate with their condition assignment at sessions 2 through 5, which emphasized exposure practice. Main Outcomes and MeasuresSymptom severity was evaluated by the Liebowitz Social Anxiety Scale and Social Phobic Disorders-Severity Form as administered by independent evaluators. ResultsA total of 152 participants were enrolled (mean [SD] age, 29.24 [10.16] years; 84 men [55.26%]). Compared with placebo, presession and postsession conditions showed greater symptom improvement (b=-0.25; 95% CI, -0.37 to -0.13; P<.001; d=1.07; and b=-0.20; 95% CI, -0.32 to -0.07; P=.002; d=0.85) and lower symptom severity (b=-0.51; 95% CI, -0.81 to -0.21; P<.001; d=0.76; and b=-0.49; 95% CI, -0.80 to -0.18; P=.002; d=0.72) at 3-month follow-up. No differences were found between presession and postsession conditions. The tailored condition showed no advantage over placebo. Compared with the tailored condition, presession and postsession conditions evidenced greater decreases (b=-0.22; 95% CI, -0.34 to -0.10; P<.001; d=0.94; and b=-0.17, 95% CI, -0.29 to -0.04; P=.008; d=0.72) and lower symptom severity (b=-0.44, 95% CI, -0.73 to -0.14; P=.004; d=0.64; and b=-0.41, 95% CI, -0.72 to -0.11; P=.008; d=0.61) at 3-month follow-up. Conclusions and RelevanceAdministration of DCS enhanced exposure therapy for social anxiety disorder when given before or after the exposure session. However, the study failed to achieve the aim to develop a tailored clinical application. Trial RegistrationClinicalTrials.gov Identifier: NCT02066792