Context: Antidepressant medication is frequently prescribed for patients with anorexia nervosa.

Objective: To determine whether fluoxetine can promote recovery and prolong time-to-relapse among patients with anorexia nervosa following weight restoration.

Design, setting, and participants: Randomized, double-blind, placebo-controlled trial. From January 2000 until May 2005, 93 patients with anorexia nervosa received intensive inpatient or day-program treatment at the New York State Psychiatric Institute or Toronto General Hospital. Participants regained weight to a minimum body mass index (calculated as weight in kilograms divided by the square of height in meters) of 19.0 and were then eligible to participate in the randomized phase of the trial.

Interventions: Participants were randomly assigned to receive fluoxetine or placebo and were treated for up to 1 year as outpatients in double-blind fashion. All patients also received individual cognitive behavioral therapy.

Main outcome measures: The primary outcome measures were time-to-relapse and the proportion of patients successfully completing 1 year of treatment.

Results: Forty-nine patients were assigned to fluoxetine and 44 to placebo. Similar percentages of patients assigned to fluoxetine and to placebo maintained a body mass index of at least 18.5 and remained in the study for 52 weeks (fluoxetine, 26.5%; placebo, 31.5%; P = .57). In a Cox proportional hazards analysis, with prerandomization body mass index, site, and diagnostic subtype as covariates, there was no significant difference between fluoxetine and placebo in time-to-relapse (hazard ratio, 1.12; 95% CI, 0.65-2.01; P = .64).

Conclusions: This study failed to demonstrate any benefit from fluoxetine in the treatment of patients with anorexia nervosa following weight restoration. Future efforts should focus on developing new models to understand the persistence of this illness and on exploring new psychological and pharmacological treatment approaches.

Trial registration: clinicaltrials.gov Identifier: NCT00288574.