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.

Abstract

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.

• Authors: Kari R Nations, Jasper A J Smits, David F Tolin, Barbara O Rothbaum, Stefan G Hofmann, Candyce D Tart, Allen Lee, Jacques Schipper, Magnus Sjogren, Dixi Xue, Armin Szegedi, Michael W Otto
• Journal: The Journal of clinical psychiatry (J Clin Psychiatry) Vol. 73 Issue 5 Pg. 647-53 (May 2012) ISSN: 1555-2101 [Electronic] United States
• PMID: 22394471 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © Copyright 2012 Physicians Postgraduate Press, Inc.

Chemical References

• Glycine Plasma Membrane Transport Proteins
• N-methyl-N-(6-methoxy-1-phenyl-1,2,3,4-tetrahydronaphthalen-2-ylmethyl)aminomethylcarboxylic acid
• Nootropic Agents
• Tetrahydronaphthalenes

Topics

• Adult
• Cognitive Behavioral Therapy (methods)
• Combined Modality Therapy
• Double-Blind Method
• Drug-Related Side Effects and Adverse Reactions
• Female
• Glycine Plasma Membrane Transport Proteins (antagonists & inhibitors)
• Humans
• Male
• Nootropic Agents (administration & dosage, adverse effects)
• Panic Disorder (drug therapy, therapy)
• Tetrahydronaphthalenes (administration & dosage, adverse effects)