D-Cycloserine enhances durability of social skills training in autism spectrum disorder

Logan K Wink,Ryan Adams,Ernest V Pedapati,Craig A Erickson,Noha F Minshawi,Paul S Horn,Tori L Schaefer,Naomi B Swiezy,Martin H Plawecki,Christopher J Mcdougle,Rebecca C Shaffer,David J Posey

doi:10.1186/s13229-017-0116-1

Abstract

Backgroundd-Cycloserine (DCS) enhances extinction learning across species, but it has proven challenging to identify consistent benefit of DCS when added to therapeutic interventions. We conducted a placebo-controlled trial of DCS to potentiate social skills training in autism spectrum disorder (ASD) but found substantial improvement in both the DCS and placebo groups at the conclusion of active treatment. Here, we assess the impact of DCS 11 weeks following active treatment to evaluate the impact of DCS on treatment response durability.MethodsStudy participants included 60 outpatient youth with ASD, ages 5–11 years, all with IQ above 70, and significantly impaired social functioning who completed a 10-week active treatment phase during which they received weekly single doses of 50 mg of DCS or placebo administered 30 min prior to group social skills training. Following the 10-week active treatment phase, blinded follow-up assessments occurred at week 11 and week 22. The primary outcome measure for our durability of treatment evaluation was the parent-rated social responsiveness scale (SRS) total raw score at week 22.ResultsAnalysis of the SRS total raw score demonstrated significant decrease for the DCS group compared to the placebo group (p = 0.042) indicating greater maintenance of treatment effect in the DCS group. DCS was well tolerated, with irritability being the most frequently reported adverse effect in both groups.ConclusionsThe findings of this study suggest that DCS may help youth with ASD to maintain skills gained during sort-term social skills training. Larger-scale studies with longer follow-up will be necessary to further understand the long-term impact of DCS paired with structured social skills training.Trial registrationClinicalTrials.gov, NCT01086475

Highlights

D-Cycloserine (DCS) enhances extinction learning across species, but it has proven challenging to identify consistent benefit of DCS when added to therapeutic interventions
Trial design and participants This study evaluated blinded week 22 durability of treatment data collected following a 10-week randomized, double-blind, placebo-controlled DCS plus peer-mediated social skills group intervention in high functioning youth with autism spectrum disorder (ASD) completed between August 4, 2009 and January 23, 2014 at Indiana University School of Medicine (IUSM) and Cincinnati Children’s Hospital Medical Center (CCHMC)
Adjunctive DCS significantly increased the sustained benefit from short-term social skills intervention 3 months after treatment cessation

Summary

Introduction

D-Cycloserine (DCS) enhances extinction learning across species, but it has proven challenging to identify consistent benefit of DCS when added to therapeutic interventions. We conducted a placebo-controlled trial of DCS to potentiate social skills training in autism spectrum disorder (ASD) but found substantial improvement in both the DCS and placebo groups at the conclusion of active treatment. Social impairment is a defining feature and key predictor of long-term outcome in autism spectrum disorder (ASD) [1, 2]. Adolescent social skills groups consistently demonstrate immediate improvements in social and communication skills in participants during treatment; One possible way to improve long-term outcomes of social skills training would be to potentiate the effect of the intervention with adjunctive pharmacotherapy. DCS appears to potentiate extinction learning, with most significant benefit from intermittent dosing immediately prior to behavioral conditioning in animals or psychotherapy session in humans [10]. The ability of DCS to augment learning appears to be related to NMDA receptor-dependent neural

Methods

Results

Discussion

Conclusion