D-cycloserine augmentation of cognitive behavioral therapy for delusions: A randomized clinical trial

Objective: D-cycloserine (DCS) promotes consolidation of extinction learning. This study extends earlier work by examining whether DCS can enhance cognitive behavioral therapy (CBT) for delusions. Methods: Adults reporting moderate or greater delusions were randomly assigned to receive 50 mg of DCS or placebo prior to 10 weekly CBT sessions. The primary outcome was change in severity of delusions measured with the Psychotic Symptom Rating Scale delusion subscale (PSYRATS-D). Secondary outcomes included persistence of response at 3 and 6 month follow-up and the effects of DCS on memory consolidation and cognitive flexibility. Fifty-eight participants were randomized and 44 completed the trial. Results: The DCS and placebo groups did not differ in change from baseline to end of CBT on PSYRATS-D, nor did DCS improve memory consolidation or cognitive flexibility compared to placebo. However, at the 3 month follow-up visit (week 24), 47% of participants who completed treatment with DCS reported a 20% or greater decrease on PSYRATS-D compared to 15% in the placebo group (p = .04). Change in distress across CBT sessions interacted with treatment group to predict change from baseline to week 24 in PSYRATS-D total score (p = .03) such that response at week 24 was greatest in DCS-treated participants who experienced a decrease in distress during CBT sessions. Conclusions: DCS augmentation of CBT did not improve delusions compared to placebo during treatment; however, DCS was associated with a higher response rate at 3-month follow-up. DCS may produce a delayed therapeutic effect, associated with successful CBT sessions, but this finding requires replication. (c) 2020 Elsevier B.V. All rights reserved.