Article

Fluoxetine After Weight Restoration in Anorexia Nervosa

University of Toronto, Toronto, Ontario, Canada
JAMA The Journal of the American Medical Association (Impact Factor: 30.39). 07/2006; 295(22):2605-12. DOI: 10.1001/jama.295.22.2605
Source: PubMed

ABSTRACT Antidepressant medication is frequently prescribed for patients with anorexia nervosa.
To determine whether fluoxetine can promote recovery and prolong time-to-relapse among patients with anorexia nervosa following weight restoration.
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.
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.
The primary outcome measures were time-to-relapse and the proportion of patients successfully completing 1 year of treatment.
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).
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.
clinicaltrials.gov Identifier: NCT00288574.

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    • "Patient outcome: Studies investigating comparable patient populations found 1 year relapse rates after hospital treatment of around 70% (Walsh et al., 2006). Other relapse prevention studies have reduced rates (30–50%; Pike et al., 2003). "
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    • "Although medications in most psychotropic medication classes have been studied in small case series or trials in adults, none of them consistently demonstrate systematic effectiveness. There was enthusiasm for the potential for SSRIs (e.g., fluoxetine) as possibly useful to prevent weight loss after acute weight restoration, but a large study now suggests that this is not likely (Walsh et al., 2006). Also, atypical antipsychotics, because of their propensity to lead to weight gain as well as their anxiolytic properties, have been considered potentially useful. "
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    ABSTRACT: Anorexia nervosa (AN) is characterized by restricted eating and a relentless pursuit of thinness that tends to present in females during adolescence according to DSM-IV (Table 1). Individuals with AN exhibit an ego-syntonic resistance to eating and a powerful pursuit of weight loss, yet are paradoxically preoccupied with food and eating rituals to the point of obsession. Individuals have a distorted body image and, even when emaciated, tend to see themselves as "fat," express denial of being underweight, and compulsively overexercise. Two types of eating-related behavior are seen in AN. In restricting-type anorexia (AN), individuals lose weight purely by dieting without binge eating or purging. In binge-eating/purging-type anorexia, individuals also restrict their food intake to lose weight but have a periodic disinhi-bition of restraint and engage in binge eating and/or purging, also seen in bulimia nervosa (BN). Anorexia nervosa is often kept hidden by patients who are excessively preoccupied by their current body weight/ shape and are ashamed of any compensatory behaviors they engage in. Illness often becomes apparent when patients become emaciated from gradually losing weight or in the purging subtype when patients become physiologically unsta-ble from excessive self-induced loss of fluids or electrolytes. Onset is typically around puberty and is usually preceded by anxiety disorders and followed by a prolonged clinical course with the highest mortality for any psychiatric illness. Outcome is often hindered by an unwillingness to seek treatment. A limited understanding of etiological mecha-nisms and the lack of powerful treatments are major impediments to providing effective care. Still, there is evidence supporting cautious optimism regarding the development of more effective therapy. For example, although there are no U.S. Food and Drug Administration (FDA) approved medications for AN, some short-term studies suggest that sec-ond-generation antipsychotics may be beneficial. For adolescents who develop AN before the age of 18, Maudsley fam-ily therapy may be an effective alternative. HISTORY The term "anorexia nervosa" is derived from the Greek for lack of appetite and the Latin for nervous origin. The earliest known medical account of AN was from 1689 by Richard Morton, an English physician and a specialist in tuberculosis, who care-fully described the case of an 18-year-old girl who "…fell into a total suppression of her Monthly Courses from a multitude of Cares and Passions of her Mind, but without any Symptom of the Green-Sickness following upon it….I do not remember that I did ever in all my Practice see one, that was conversant with the Living so much wasted with the greatest degree of a Consumption, (like a Skel-eton only clad with skin) yet there was no Fever, but on the contrary a coldness of the whole Body; no Cough, or difficulty of Breathing, nor an appear-ance of any other distemper of the Lungs, or of any other Entrail: No loosness, or any other sign of a Colliquation, or Preternatural expence of the Nu-tritious Juices" (1). In the late 19th century an interest in this condi-tion developed in Europe, after publication of case series of AN by Sir William Gull in England and Charles Lasegue in France, respectively (2, 3). As Sir Gull noted in some patients, "It seemed hardly possible that a body so wasted could undergo exer-cise so agreeably." This illness seems just as perplex-ing more than a century later.
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