d-Cycloserine Facilitation of Exposure Therapy Improves Weight Regain in Patients With Anorexia Nervosa: A Pilot Randomized Controlled Trial

Objective: Exposure therapy in anorexia nervosa has preliminarily been shown to be effective for increasing food intake. d-Cycloserine is a glutamatergic N-methyl-d-aspartate receptor agonist that has been shown to facilitate the benefits of exposure therapy for anxiety disorders by enhancing the emotional learning in the exposures; therefore, we examined d-cycloserine-facilitation of exposure therapy to increase body mass index (BMI) in patients with anorexia nervosa.

Method: Participants (N = 36) with anorexia nervosa (diagnosed via DSM-IV) were recruited from a partial hospitalization eating disorder clinic between February 2013 and November 2013. Participants were randomly assigned to receive exposure therapy plus d-cycloserine (n = 20) or placebo (n = 16). Participants completed psychoeducation and 4 sessions of exposure therapy, with medication (d-cycloserine vs placebo) given prior to the first 3 exposure sessions. They also completed a 1-month follow-up.

Results: As hypothesized, participants in the d-cycloserine group showed a significantly greater increase in BMI than those in the placebo group (Wilk Λ = 0.86, F3,32 = 2.20, P = .043, ηp2 = 0.12). d-Cycloserine participants gained 3 pounds relative to 0.5 pounds in the placebo group. Both groups experienced significantly decreased anxiety over the course of therapy (Wilk Λ = 0.80, F3,32 = 3.32, P = .023, ηp2 = 0.20).

Conclusions: This study preliminarily demonstrates that d-cycloserine facilitates exposure therapy for anorexia nervosa, leading to increased weight gain. A potential mechanism is that participants who receive d-cycloserine may generalize learning from within-session exposures to food intake during other similar meals, resulting in sustained increases in BMI. Further research is needed to confirm these findings and test the putative mechanism that generalized learning from exposure therapy can increase BMI and stabilize a healthy weight.

Trial Registration: ClinicalTrials.gov identifier: NCT01996644