Anorexia nervosa (AN) is a major psychiatric disorder associated with life-threatening medical complications, significant chronicity, and less than optimal outcomes including high mortality rates. Startlingly, there has been limited study of the treatment of AN. Treatment studies to date, including the use of pharmacologic agents such as the serotonin (5-HT) selective reuptake inhibitors (SSRIs), show limited success in AN. Previous studies of CSF metabolites, pharmacological neuroendocrine and behavioral responses, and PET imaging studies have shown that low weight patients with AN have decreased pre- and post-synaptic 5-HT responsiveness. Similar studies have shown increasing 5-HT responsiveness as patients gain weight and achieve symptom remission. Dysregulation of 5-HT function in AN is potentially quite important as it may play a significant role in the disabling behavioral symptoms, as well as in the tendency for relapse and chronicity. Decreased central nervous system 5-HT function may contribute to the refractoriness of the disorder to pharmacological interventions. Given the potential importance of these findings in suggesting new treatment approaches for AN, this study examines the possible therapeutic implications of precursor augmentation to enhance 5-HT functioning in patients with AN. This study utilizes a double-blind randomized placebo-controlled design to test the hypothesis that, in subjects with AN, short-term augmentation with a 5- HT precursor enhances 5-HT function in comparison to an SSRI alone as measured by behavioral and neuroendocrine responses. Subjects include 54 women with AN, 36 women who have recovered from AN, and 54 healthy controls. AN and control subjects are randomized to one of three short-term medication conditions: placebo, fluoxetine, or fluoxetine plus 5- hydroxytryptophan (5-HTP). Recovered AN subjects are randomized to short-term placebo or fluoxetine conditions. Results of this project will help to clarify the usefulness of precursor augmentation as a possible new treatment approach for this devastating disorder.
