Een gerandomiseerde placebo gecontroleerde studie naar de toegevoegde waarde van D-cycloserine aan exposure therapie bij pati??nten met een poststraumatische stress stoornis

After experiencing a traumatic event, such as rape or an armed robbery, people
may develop a Post Traumatic Stress Disorder (PTSD). PTSD is classified in the
Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV;
APA, 1994) as an anxiety disorder. Patients suffering from PTSD typically
re-experience the traumatic event again and again, as if it was happening here
and now, in flashbacks and nightmares. These re-experiences are highly fearful
to patients. Therefore they avoid as much as they can to think about the
traumatic event, and they avoid situations that may trigger such memories. In
addition, because they are afraid that something bad can happen again, they are
therefore continuously alert for possible threats, leading to severe sleeping
and concentration problems. Exposure-based treatments are thus far the most
effective treatment for patients with PTSD. These treatments are based on
emotionally processing the feared stimuli, in which two conditions are
necessary: fear activation and cognitive (un)learning. When these two
conditions are met, extinction can take place. However, there is a need for
improvement of the treatment approach to increase the number of patients who
benefit from the treatments, to lower the level of residual symptoms after
treatments and to lessen the emotional burden of the treatment. The present
study aims at the improvement of exposure therapy -at this moment the most
effective psychotherapeutic treatment programme- by augmentation with
D-cycloserine, a newly discovered drug for enhancing learning processes such as
extinction.
The augmentation of D-cycloserine to exposure therapy is a promising approach
to improve treatment results of exposure-based treatments in patients with
anxiety disorders.

The present study is aimed at testing the effects of D-cycloserine in addition
to exposure treatment sessions in PTSD patients, in a randomized double blind
placebo controlled study.

The proposed study is a randomized and placebo double blind controlled trial.
After inclusion, patients are randomized in two treatment conditions; (1)
exposure plus D-Cycloserine and (2) exposure plus placebo. Both groups receive
an effective therapy program for PTSD, exposure therapy. Both groups will
receive 8-12 sessions of imaginal exposure at the outpatient clinic. An hour
before the imaginal exposure sessions, the experimental group will use
D-cycloserine 50 mg. The control group will use a placebo an hour before the
exposure sessions.

The exposure treatment is manualized and consists of 8-12 weekly sessions. In
the first session patients are educated about PTSD symptoms and about the
treatment rationale. In the next sessions, patients are instructed to recount
aloud the traumatic event in the first person and in the present tense with
closed eyes. They are further instructed to imagine the traumatic event as
vividly as possible, as if the trauma is happening *here and now*. They are
asked to recount the traumatic memory and to focus on details of the event, as
well as their emotions, and thoughts. Throughout the imaginal exposure, anxiety
levels are monitored each 5 minutes using the SUDS (Subjective Units of
Distress Scale, range 0-10). Each exposure session is recorded and as
*homework*, patients are asked to listen to the recording five times a week at
home. In addition to this homework audiotape listening, patients are given
in-vivo exposure assignments. The in-vivo assignments are initiated after the
second imaginal exposure session, and include real life exposure to fearful
stimuli related to the trauma, such as visiting the trauma place or watching a
movie related to the trauma.
Note that the exposure treatment is the most effective treatment for PTSD
patients and is the treatment *as usual*. In addition, the exposure treatment
will be identical for both treatment groups. Groups only differ in the drug
they take before the exposure sessions at the clinic.

Given the limited time burden on patients, and the safety of the used drugs,
in our opinion, this study should be classified as a low or negligible risk
study.