Body Dysmorphic Disorder: Pharmacological enhancement of fear extinction; a randomized placebo controlled, double blind study.

Body Dysmorphic Disorder (BDD) is a chronic and severe psychiatric disorder
which affects 1-7% of the general population. Cognitive Behavioural Therapy is
currently the treatment of choice for BDD and aims to help patients changing
their thoughts and behaviours. High rates of suicide attempts, severe
impairment in psychosocial functioning and decreasing daily functioning are
very common among BDD patients. Procedurally, CBT is based on altering negative
appraisal of body imaging and core beliefs as well as extinction of conditioned
fear. Recent work in rodents and humans has demonstrated that acute treatment
with D-cycloserine (DCS) a partial agonist of the NMDA-receptor enhances the
learning and memory processes underlying extinction of fear. Adding DCS to
behavioural exposure therapy might improve treatment outcome in BDD.

The objective for this study is threefold. First we will determine whether DCS
addition to behavioural exposure therapy may enhance fear extinction and
improve symptoms in BDD. Our hypothesis is that improvement will occur and at a
faster rate than with no addition of DCS. Furthermore, we will examine the
underlying pathophysiologic mechanisms of fear extinction in BDD with
neuro-imaging studies. The brain activity of the amygdale and cortico-striatal
circuits will be assessed in fifty patients before and after treatment with
citalopram and before and after exposure treatment with DCS by means of
functional magnetic resonance imaging (fMRI) in a fear extinction paradigm.
Finally, we will examine if DCS has an effect on learning, memory and executive
tasks. We hypothesize based on rodent and limited human studies that DCS is a
performance enhancer in different learning, memory and executive tasks.

A randomized, double blind, placebo-controlled fixed dose study.

Half of the subjects will be randomly assigned to the placebo condition and the
other half will be randomly assigned to receive DCS. All subject will receive
24 weeks CBT including exposure therapy. During week 2-8 subjects will receive
the assigned study medication 30 minutes prior to exposure therapy.

Side-effects of D-Cycloserine are limited, since study dosing is low (50 mg).
Exept for this small chance on side effects, there are serious risks associated
to this study. Advantages to the subjects can be expected because of the
potential therapeutic effect (faster reduction in OCD-symptoms and lower
drop-out rates). Futhermore, the results can offer insight into the
pathofysiology of OCD and may lead to future development of more effective
treatmentmethods.