D-cycloserine for Anxiety Disorders

D-Cycloserine as an Adjunctive Therapy Fear extinction is a major area of anxiety research, and researchers continue to investigate novel and effective ways to reduce the salience of painful memories and replace them with more neutral ones.

One such pathway is the N-methyl-D-aspartate (NMDA) receptor in the basolateral amygdala, which is known to play an important role in controlling neuroplasticity and memory. Recent studies have shown that NMDA activity can modulate fear extinction. Thus, a compound known as D-cycloserine (DCS) has been shown to enhance extinction learning as a partial NMDA agonist.Since DCS has long been used in high doses to treat tuberculosis, it could be used as a safe cognitive enhancer at lower doses and for shorter durations in exposure therapy for anxiety disorders. As a result, a significant amount of research has focused on translating preclinical basic neuroscience findings about DCS into clinical trials in patients with anxiety disorders.

Efficacy of D-Cycloserine

For the first time, D-cycloserine has shown promising results in human trials as an augmentation strategy for exposure in patients with anxiety.

A study of patients with acrophobia who were given a single dose of DCS prior to exposure showed that DCS significantly enhanced extinction learning after two acute treatments and at a 3-month follow-up. Subsequently, patients randomized to the DCS group reported less avoidance of heights in their daily activities after the study was completed.

Thus, DCS appears to enhance memory of successful exposure experiences and influence subsequent willingness to face fearful situations. This promising research has led to further studies aimed at elucidating the augmentative effects of DCS for various anxiety disorders. Subsequent studies in social anxiety disorder and panic disorder have found similarly successful results with DCS as an augmentation strategy.

However, other studies have shown no effect. Of particular interest is a trial in post-traumatic stress disorder (PTSD). The study found that patients who received DCS reported more symptoms after treatment than those who received a placebo. As will be discussed further in this article, this study suggests that DCS may also enhance the reconsolidation of fear memories and, therefore, may have a counter-therapeutic effect in some cases. These studies reveal a complex therapeutic and counter-therapeutic effect of DCS. Three major findings from the literature should be carefully considered when using DCS for exposure therapy: (1) the effects of dose and timing of administration; (2) DCS as an accelerator of early treatment response; and (3) specific circumstances in which DCS may lead to fear reconsolidation and symptom exacerbation.

D-cycloserine as an accelerator of early treatment response

DCS is not directly targeted at anxiolytics, but rather is used to enhance the consolidation of therapeutic learning provided by CBT. Because DCS is a cognitive enhancer, it is expected that DCS will enhance the benefits of CBT through faster learning.

Studies examining the use of DCS in obsessive-compulsive disorder (OCD) found that the effects of DCS diminished with subsequent administrations. These results are the first to suggest that DCS exerts its effects early in treatment primarily by accelerating the therapeutic response.

Furthermore, with repeated exposures, studies have shown that single exposures can ultimately show effects similar to the initial DCS-enhancing effects. This apparent catch-up effect has also been demonstrated in animal models and human trials of social anxiety disorder, agoraphobia, and panic disorder.

Although these studies did not show an advantage in D-cycloserine remission rates at the end of treatment, a faster treatment response could have far-reaching consequences. For example, rapid reductions in pain and disability along with faster onset of effect are associated with lower discontinuation rates.