Evaluation of the glycine transporter inhibitor Org 25935 as augmentation to
cognitive-behavioral therapy for panic disorder: a multicenter, randomized,
double-blind, placebo-controlled trial.
Author(s): Nations KR, Smits JA, Tolin DF, Rothbaum BO, Hofmann SG, Tart CD, Lee A, Schipper
J, Sjogren M, Xue D, Szegedi A, Otto MW.
Affiliation(s): Merck Research Laboratories, Rahway, NJ 07065, USA. kari100@att.net
Publication date & source: 2012, J Clin Psychiatry. , 73(5):647-53
OBJECTIVE: A growing body of evidence supports the efficacy of D-cycloserine
(DCS), a partial agonist at the N-methyl-D-aspartate (NMDA) glutamate receptor,
as augmentation to cognitive-behavioral therapy (CBT) in the treatment of anxiety
disorders. Org 25935 is a glycine transporter 1 inhibitor that acts to increase
synaptic glycine levels and enhance NMDA-mediated glutamatergic activity. The aim
of this study was to examine the efficacy of a glutamatergic compound other than
DCS in a CBT augmentation paradigm.
METHOD: This was a randomized, double-blind, placebo-controlled, parallel-group
clinical trial for which participants were recruited from November 2008 through
February 2010. Eligible adult patients diagnosed (DSM-IV) with panic disorder
with or without agoraphobia (N = 40) were scheduled to receive 5 manualized CBT
treatment sessions. Participants were randomly assigned to receive either a dose
of Org 25935 (4 mg or 12 mg) or placebo 2 hours prior to the start of CBT
sessions 3, 4, and 5. The primary endpoint was symptomatic change as measured by
the Panic Disorder Severity Scale (PDSS) 1 week following the last CBT session.
RESULTS: Although mean PDSS total scores decreased significantly from baseline to
end of treatment in every group, no statistically significant benefit was
observed for Org 25935 (4 or 12 mg) over placebo on the primary endpoint or on
any secondary efficacy endpoint. Org 25935 showed no safety issues at either dose
but was much better tolerated at the 4-mg dose level than at the 12-mg dose
level.
CONCLUSIONS: Org 25935 demonstrated no benefit over placebo in augmenting CBT for
panic disorder. Study limitations and implications are discussed.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00725725.
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