title: D-cycloserine facilitation of cognitive behavioral therapy for delusions in schizophrenia.
abstract: Glutamatergic N-methyl-D-aspartate (NMDA) receptor hypofunction has been proposed as a mechanism underlying psychosis. D-cycloserine, a partial agonist at the glycine site of the NMDA receptor, enhances learning in animal models, although tachyphylaxis develops with repeated dosing. Once-weekly dosing of D-cycloserine produces persistent improvement when combined with cognitive behavioral therapy (CBT) in anxiety disorders. Delusional beliefs can be conceptualized as a learning deficit, characterized by the failure to use contradictory evidence to modify the belief. CBT techniques have been developed with modest success to facilitate such reality-testing (or new learning) in delusional beliefs. The current study evaluated whether D-cycloserine could potentiate beneficial effects of CBT on delusional severity. Twenty-one outpatients with schizophrenia or schizoaffective disorder and moderately severe delusions were randomized in a double-blind cross-over design to receive a single-dose of either D-cycloserine 50mg or placebo in a counterbalanced order on two consecutive weeks 1h prior to a CBT intervention involving training in the generation of alternative beliefs. Assessments were completed at baseline, 7 days following the first study drug administration and 7 days following the second study drug administration. Contrary to prediction, there was no significant d-cycloserine treatment effect on delusional distress or severity as measured by the SAPS or PSYRATS. An unexpected finding was an order effect, whereby subjects who received D-cycloserine first had significantly reduced delusional severity, distress, and belief conviction on PSYRATS compared to subjects who received placebo first. However, this finding is consistent with animal models in which D-cycloserine enhances learning only when accompanying the first exposure to training.
authors: Dartmouth Medical School, Department of Psychiatry/Dartmouth Psychiatric Research Center, 105 Pleasant Street, Concord, NH 03301, USA. Jennifer.D.Gottlieb@dartmouth.edu
authors: Jennifer D
authors: JD
authors: Gottlieb
authors: Corinne
authors: C
authors: Cather
authors: Meghan
authors: M
authors: Shanahan
authors: Timothy
authors: T
authors: Creedon
authors: Eric A
authors: EA
authors: Macklin
authors: Donald C
authors: DC
authors: Goff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000963:Antimetabolites / Q000627:therapeutic use*; D015928:Cognitive Behavioral Therapy / Q000379:methods*; D003469:Culture; D003523:Cycloserine / Q000627:therapeutic use*; D003702:Delusions / Q000209:etiology / Q000523:psychology / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000150:complications; D012189:Retrospective Studies; D012559:Schizophrenia / Q000150:complications; D055815:Young Adult
chemical_list: D000963:Antimetabolites; D003523:Cycloserine