Changes in Dosing and Dose Timing of D-Cycloserine Explain Its Apparent Declining Efficacy for Augmenting Exposure Therapy for Anxiety-related Disorders: An Individual Participant-data Meta-analysis

David Rosenfield, Jasper A.J. Smits, Stefan G. Hofmann, David Mataix-Cols, Lorena Fernández de la Cruz, Erik Andersson, Christian Rück, Benedetta Monzani, Ana Pérez-Vigil, Paolo Frumento, Michael Davis, Rianne A. de Kleine, Jo Ann Difede, Boadie W. Dunlop, Lara J. Farrell, Daniel Geller, Maryrose Gerardi, Adam J. Guastella, Gert Jan Hendriks, Matt G. KushnerFrancis S. Lee, Eric J. Lenze, Cheri A. Levinson, Harry McConnell, Jens Plag, Mark H. Pollack, Kerry J. Ressler, Thomas L. Rodebaugh, Barbara O. Rothbaum, Eric A. Storch, Andreas Ströhle, Candyce D. Tart, David F. Tolin, Agnes van Minnen, Allison M. Waters, Carl F. Weems, Sabine Wilhelm, Katarzyna Wyka, Margaret Altemus, Page Anderson, Judith Cukor, Claudia Finck, Gary R. Geffken, Fabian Golfels, Wayne K. Goodman, Cassidy A. Gutner, Isobel Heyman, Tanja Jovanovic, Adam B. Lewin, Joseph P. McNamara, Tanya K. Murphy, Seth Norrholm, Paul Thuras, Cynthia Turner, Michael W. Otto

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

The apparent efficacy of d-cycloserine (DCS) for enhancing exposure treatment for anxiety disorders appears to have declined over the past 14 years. We examined whether variations in how DCS has been administered can account for this “declining effect”. We also investigated the association between DCS administration characteristics and treatment outcome to find optimal dosing parameters. We conducted a secondary analysis of individual participant data obtained from 1047 participants in 21 studies testing the efficacy of DCS-augmented exposure treatments. Different outcome measures in different studies were harmonized to a 0-100 scale. Intent-to-treat analyses showed that, in participants randomized to DCS augmentation (n = 523), fewer DCS doses, later timing of DCS dose, and lower baseline severity appear to account for this decline effect. More DCS doses were related to better outcomes, but this advantage leveled-off at nine doses. Administering DCS more than 60 minutes before exposures was also related to better outcomes. These predictors were not significant in the placebo arm (n = 521). Results suggested that optimal DCS administration could increase pre-to-follow-up DCS effect size by 50%. In conclusion, the apparent declining effectiveness of DCS over time may be accounted for by how it has been administered. Optimal DCS administration may substantially improve outcomes. Registration: The analysis plan for this manuscript was registered on Open Science Framework (https://osf.io/c39p8/).

Original languageEnglish
Article number102149
JournalJournal of Anxiety Disorders
Volume68
DOIs
StatePublished - Dec 2019

Keywords

  • augmentation
  • d-cycloserine
  • decline effect
  • dosing
  • exposure

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