D-Cycloserine Augmentation of Exposure and Response Prevention Treatment for Obsessive-Compulsive Disorder

Exposure and response prevention (ERP) has proven efficacy for OCD treatment in adults. Yet,
ERP does not help all individuals, and those who benefit often remain somewhat symptomatic.
Behavioral models for OCD treatment are based on two components. First, fears are acquired
by the development of an association between a neutral stimulus and an aversive stimulus
such the former acquires the aversive properties of the latter. The neutral stimulus is then
designated as a conditioned stimulus (CS), and the original aversive stimulus is called an
unconditioned stimulus (UCS). Second, the acquired fears can be unlearned through
presentation of the CS in the absence of the UCS, a process known as extinction. On a neural
level, ERP incorporates similar mechanisms to those involved in fear conditioning.
Antagonists at the glutamatergic NMDA receptor, which is involved in learning and memory,
block both fear learning and extinction. D-Cycloserine (DCS), a partial agonist at the
N-methyl-D-aspartate (NMDA) glutamate receptor subtype, augments learning in animals and
humans. Clinical application in animals and humans suggest that DCS facilitates the fear
extinction process when taken prior to exposure to feared stimuli. An initial trial in
acrophobic adults provided support for acute DCS dosing as facilitating extinction to fear.
Given that ERP is based on extinction, it follows that DCS may augment ERP therapy providing
enhanced treatment effects. With this in mind, we propose to undertake an initial study of
DCS to determine whether it has any short-term clinical benefits when added to standard ERP
therapy in adults with OCD.