Cognitive Enhancers as Adjuncts to Psychotherapy - Use of D-Cycloserine in Phobic Individuals to Facilitate Extinction of Fear
Ressler KJ, Rothbaum BO, Tannenbaum L, Anderson P, et al. ;
Commented by , 22 Nov 2004
Aims of the study
To investigate whether cognitive enhancers can facilitate extinction of fear in patients who are treated with behavioural exposure therapy for acrophobia.
A double-blind, randomised controlled study. 27 patients with acrophobia were assigned to 3 treatment groups: behavioural exposure therapy plus placebo, and behavioural exposure therapy plus two different dosages of a cognitive enhancer.
Behavioral exposure therapy consisted in two 35- to 45-minute sessions of virtual reality exposure therapy (VRET) in which participants stood in a virtual glass elevator and were able to peer over a virtual railing.
Study medication consisted in 50 and 500 mg of D-cycloserine (DCS). Participants were instructed to take the study medication 2 to 4 hours before each one of the two VRET sessions.
The two therapy sessions were separated by 1 to 2 weeks.
Outcome measures included ratings of Subjective Units of Discomfort (SUDs) as well as other measures, from pretest to post-test at three months after treatment.
- During the second (but not during the first) session, participants in the DCS groups experienced significantly lower SUDs than participants in the placebo group.
- One week after the second session, participants in the DCS groups experienced significantly lower SUDs than participants in the placebo group. The improvement was maintained at three months.
- Post-treatment assessment at 1 week and three months of general avoidance of heights, and of general attitudes towards heights, showed significantly more improvement in the DCS groups.
- At post-treatment assessment, patients in the DCS groups reported a significantly bigger increase of exposures in the real world than those in the placebo group.
In both humans and animals, repeated exposure to a feared stimulus, in the absence of adverse consequences, leads to a reduction of fear of this same stimulus. The reduction of fear following repeated exposure is known as fear extinction.
In a previous study (ref. 1), the authors have shown that DCS improves NMDA synaptic transmission and facilitates extinction of fear in rats. As revealed by the results of the present study, DCS may play a similar role in the extinction of fear in humans. The effects of cognitive behavioral therapy may be facilitated by combining DCS with exposure therapy. Two sessions of VRET in combination with DCS were sufficient to produce extinction of fear within the virtual environment. To obtain a similar result without DCS, at least three times more sessions of VRET would have been necessary.
The study is based on a small number of participants and is concerned exclusively with patients suffering from acrophobia. As such, the results may not apply to other anxiety disorders, or even other phobias.
In spite of these limitations, this is an important study. The results suggest that cognitive enhancers, such as DCS, may facilitate the learning process of fear extinction during behavioral exposure therapy. Provided that the results of the study can be replicated, this could be a major breakthrough in the treatment of phobic (as well as possibly other) anxiety disorders. In particular, cognitive enhancers may significantly reduce the duration of psychotherapy, and, consequently, contribute to reduce the costs of treatment for phobic disorders.
1. Walker DL, Ressler KJ, Lu KT, Davis M. Facilitation of conditioned fear extinction by systemic administration or intra-amygdala infusions of D-cycloserine as assessed with fear-potentiated startle in rats. Journal of Neurosciences, 2003, 117: 341-349. (Note: Free full text article)