D-cycloserine facilitation of cognitive behavioral therapy for delusions in
schizophrenia.
Author(s): Gottlieb JD, Cather C, Shanahan M, Creedon T, Macklin EA, Goff DC.
Affiliation(s): Dartmouth Medical School, Department of Psychiatry/Dartmouth Psychiatric Research
Center, 105 Pleasant Street, Concord, NH 03301, USA.
Jennifer.D.Gottlieb@dartmouth.edu
Publication date & source: 2011, Schizophr Res. , 131(1-3):69-74
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.
|