title: Effect of decreasing afferent vagal activity with ondansetron on symptoms of bulimia nervosa: a randomised, double-blind trial.
abstract: BACKGROUND
  Several lines of evidence have led us to postulate that afferent vagal hyperactivity could be an important factor in the pathophysiology of the eating disorder bulimia nervosa. Ondansetron is a peripherally active antagonist of the serotonin receptor 5-HT3, and is marketed for prevention of vagally-mediated emesis caused by cancer chemotherapeutic agents. We investigated the effects of ondansetron on bulimic behaviours in patients with severe and chronic bulimia nervosa in a randomised, double-blind, placebo-controlled study.
  
  
  METHODS
  We enrolled patients with severe bulimia nervosa (at least seven coupled binge/vomit episodes per week). The patients were otherwise healthy, their weight was normal, and they were not receiving medical or psychiatric treatment. During the first week of the study, patients recorded all eating-behaviour events to establish a baseline. In the second week, all patients received placebo, but were told that they were receiving either placebo or active drug. At the end of this single-blind phase, patients were randomly assigned placebo or ondansetron (24 mg daily) for a further 4 weeks. The primary outcome measure was the number of binge/vomit episodes per week. Data were analysed by intention to treat.
  
  
  RESULTS
  29 patients met the inclusion criteria, of whom 28 completed the baseline study, and 26 completed the single-blind placebo week. 12 patients were assigned placebo, and 14 ondansetron; one patient in the ondansetron group dropped out owing to accidental injury. During the 4th week of double-blind treatment, mean binge/vomit frequencies were 13.2 per week (SD 11.6) in the placebo group, versus 6.5 per week (3.9) in the ondansetron group (estimated difference 6.8 [95% CI 4.0-9.5]; p<0.0001). The ondansetron group also showed significant improvement, compared with the placebo group, in two secondary indicators of disease severity. The amount of time spent engaging in bulimic behaviours was decreased on average by 7.6 h per week in the ondansetron group, compared with 2.3 h in the placebo group (estimated difference 5.1 [0.6-9.7]). Similarly, the number of normal meals and snacks increased on average by 4.3 normal eating episodes without vomiting per week in the ondansetron group, compared with 0.2 in the placebo group (estimated difference 4.1 [1.0-7.2]).
  
  
  CONCLUSIONS
  The decrease in binge-eating and vomiting under ondansetron treatment was not achieved by compensatory changes in eating behaviour such as by a smaller number of binges of longer duration, or by not eating, or by binge-eating without vomiting. Instead, our findings indicate a normalisation of the physiological mechanism(s) controlling meal termination and satiation. Since meal termination and satiety are mainly vagally mediated functions, since binge-eating and vomiting produce intense stimulation of vagal afferent fibres, and since ondansetron and other 5-HT3 antagonists decrease afferent vagal activity, the symptom improvement may result from a pharmacological correction of abnormal vagal neurotransmission.
authors.affiliation: Department of Psychiatry, University of Minnesota Medical School, Minneapolis 55455, USA. faris001@umn.edu
authors.forename: P L
authors.initials: PL
authors.lastname: Faris
authors.forename: S W
authors.initials: SW
authors.lastname: Kim
authors.forename: W H
authors.initials: WH
authors.lastname: Meller
authors.forename: R L
authors.initials: RL
authors.lastname: Goodale
authors.forename: S A
authors.initials: SA
authors.lastname: Oakman
authors.forename: R D
authors.initials: RD
authors.lastname: Hofbauer
authors.forename: A M
authors.initials: AM
authors.lastname: Marshall
authors.forename: R S
authors.initials: RS
authors.lastname: Daughters
authors.forename: D
authors.initials: D
authors.lastname: Banerjee-Stevens
authors.forename: E D
authors.initials: ED
authors.lastname: Eckert
authors.forename: B K
authors.initials: BK
authors.lastname: Hartman
mesh_terms: D000293:Adolescent; D000328:Adult; D000344:Afferent Pathways / Q000187:drug effects / Q000503:physiopathology; D000932:Antiemetics / Q000009:adverse effects / Q000627:therapeutic use*; D002032:Bulimia / Q000188:drug therapy* / Q000503:physiopathology; D004311:Double-Blind Method; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D006801:Humans; D008875:Middle Aged; D017294:Ondansetron / Q000009:adverse effects / Q000627:therapeutic use*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012528:Satiety Response / Q000187:drug effects / Q000502:physiology; D012702:Serotonin Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D014630:Vagus Nerve / Q000187:drug effects* / Q000503:physiopathology
chemical_list: D000932:Antiemetics; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017294:Ondansetron