D-cycloserine facilitation of cognitive behavioral therapy for delusions in schizophrenia

SCHIZOPHRENIA RESEARCH

卷:131

Article

Gottlieb, Jennifer D.^1,2  Cather, Corinne^2,3  Shanahan, Meghan²  Creedon, Timothy²  Macklin, Eric A.^3,4  Goff, Donald C.^2,3 

[1] Dartmouth Psychiat Res Ctr, Dept Psychiat, Dartmouth Med Sch, Concord, NH 03301 USA

[2] Massachusetts Gen Hosp, Schizophrenia Program, Freedom Trail Clin, Boston, MA 02114 USA

[3] Harvard Univ, Sch Med, Boston, MA 02115 USA

[4] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA

关键词: NMDA receptor hypofunction;    D-cycloserine;    Cognitive-behavioral therapy;    Psychosis;    Delusions;    Schizophrenia;   

DOI  :  10.1016/j.schres.2011.05.029

来源: Elsevier

【 摘 要 】

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 50 mg or placebo in a counterbalanced order on two consecutive weeks 1 h 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. (C) 2011 Elsevier B.V. All rights reserved.

【 授权许可】

Free