title: Enhancement of Psychosocial Treatment With D-Cycloserine: Models, Moderators, and Future Directions.
abstract: Advances in the understanding of the neurobiology of fear extinction have resulted in the development of d-cycloserine (DCS), a partial glutamatergic N-methyl-D-aspartate agonist, as an augmentation strategy for exposure treatment. We review a decade of research that has focused on the efficacy of DCS for augmenting the mechanisms (e.g., fear extinction) and outcome of exposure treatment across the anxiety disorders. Following a series of small-scale studies offering strong support for this clinical application, more recent larger-scale studies have yielded mixed results, with some showing weak or no effects. We discuss possible explanations for the mixed findings, pointing to both patient and session (i.e., learning experiences) characteristics as possible moderators of efficacy, and offer directions for future research in this area. We also review recent studies that have aimed to extend the work on DCS augmentation of exposure therapy for the anxiety disorders to DCS enhancement of learning-based interventions for addiction, anorexia nervosa, schizophrenia, and depression. Here, we attend to both DCS effects on facilitating therapeutic outcomes and additional therapeutic mechanisms beyond fear extinction (e.g., appetitive extinction, hippocampal-dependent learning).
authors.affiliation: Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts. Electronic address: mwotto@bu.edu.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Otto
authors.affiliation: Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts.
authors.forename: M Alexandra
authors.initials: MA
authors.lastname: Kredlow
authors.affiliation: Institute for Mental Health Research and Department of Psychology, University of Texas at Austin, Austin, Texas.
authors.forename: Jasper A J
authors.initials: JAJ
authors.lastname: Smits
authors.affiliation: Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts.
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Hofmann
authors.affiliation: Department of Psychological and Brain Sciences, Boston University, Boston, Massachusetts; Institute for Mental Health Research and Department of Psychology, University of Texas at Austin, Austin, Texas; Overwaal Centre for Anxiety Disorders, Pro Persona, Radboud University Nijmegen, Behavioral Science Institute, Nijmegen, The Netherlands; Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Psychiatry, Rush University Medical Center, Chicago, Illinois.
authors.forename: David F
authors.initials: DF
authors.lastname: Tolin
authors.affiliation: Overwaal Centre for Anxiety Disorders, Pro Persona, Radboud University Nijmegen, Behavioral Science Institute, Nijmegen, The Netherlands.
authors.forename: Rianne A
authors.initials: RA
authors.lastname: de Kleine
authors.affiliation: Overwaal Centre for Anxiety Disorders, Pro Persona, Radboud University Nijmegen, Behavioral Science Institute, Nijmegen, The Netherlands.
authors.forename: Agnes
authors.initials: A
authors.lastname: van Minnen
authors.affiliation: Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: A Eden
authors.initials: AE
authors.lastname: Evins
authors.affiliation: Department of Psychiatry, Rush University Medical Center, Chicago, Illinois.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Pollack
mesh_terms: D000963:Antimetabolites / Q000494:pharmacology*; D001008:Anxiety Disorders / Q000188:drug therapy / Q000523:psychology / Q000534:rehabilitation; D003131:Combined Modality Therapy; D003523:Cycloserine / Q000627:therapeutic use*; D005108:Extinction, Psychological / Q000502:physiology*; D006801:Humans; D007171:Implosive Therapy / Q000379:methods*
chemical_list: D000963:Antimetabolites; D003523:Cycloserine
keywords: Addiction; Anxiety; DCS; Depression; Extinction; d-cycloserine