D-cycloserine (Seromycin) is a prescription medication used for the treatment of specific phobia, such as fear of spiders (arachnophobia) or a fear of heights (acrophobia). However, D-cycloserine is not helpful as a sole treatment for specific phobia- it is prescribed as an adjunctive treatment to exposure therapy. D-cycloserine helps to facilitate fear extinction during exposure sessions.
D-cycloserine is a coagonist with glutamate at the NMDA receptor. When utilized for phobias, D-cycloserine binds to the glycine site of the NMDA receptor, and this allows glutamate (released during exposure therapy) to bind to the NMDA receptor, facilitating glutamate neurotransmission, and this facilitates fear extinction in the amygdala.
But without exposure therapy, glutamate would not be released, and hence fear extinction would not occur in phobias. So it is the combination of D-cycloserine and exposure therapy which leads to facilitation of the glutamate neurotransmission, leading to fear extinction and the eradication of the phobia.
In fact, all of the prescription medication treatments for specific phobia are adjunctive treatment to exposure therapy. Prescription medication treatment is not adequate alone to treat specific phobia. Exposure therapy is the primary treatment for specific phobia, while a few medications can be added to help facilitate the treatment.
Benzodiazepines such as lorazepam (Ativan) and clonazepam (Klonopin) can be used in addition to exposure therapy for the treatment of specific phobia. The benzodiazepines can help to decrease the phobic anxiety and the anticipatory anxiety associated with exposure sessions. In contrast, D-cycloserine is not an anxiolytic, as it does not decrease phobic or anticipatory anxiety immediately. However D-cycloserine helps by facilitating fear extinction during the exposure sessions, which is seen weeks to months later when fear is reduced when presented with the feared stimulus.
Remarkably, after two doses of D-cycloserine each given prior to an exposure session, subjects with acrophobia (fear of heights) showed a significant decrease in fear up to 3 months after only these 2 doses (Ressler et al., 2004).