Fluoxetine to Prevent Relapse and Enhance Psychological Recovery in Women With Anorexia Nervosa

Fluoxetine After Weight Restoration in Anorexia Nervosa

This study will evaluate the effectiveness of fluoxetine versus placebo in reducing the rate of relapse of anorexia nervosa (AN) and enhancing the psychosocial and behavioral recovery of people who have been treated for AN.

Study Overview

• Status: Completed
• Conditions: Anorexia Nervosa; Eating Disorders
• Intervention / Treatment: Drug: Placebo; Drug: Fluoxetine

Detailed Description

Anorexia nervosa (AN), a type of eating disorder, is a serious psychiatric illness that is characterized by an extreme loss of appetite. People with AN view themselves as overweight and cannot bring themselves to eat, even though most are dangerously thin. Signs of the disorder include unusual eating habits, such as avoiding food and meals, picking out a few foods and eating them in small quantities, or carefully weighing and portioning food. Some people with AN fully recover after a single episode, some have a fluctuating pattern of weight gain and relapse, and others experience a chronic course of illness over many years. Effective drugs to treat the disorder are lacking. In addition, most past research has examined the effect of medications during the initial phase of treatment, a time when AN patients may not respond to medication because of the acute effects of starvation. Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that is commonly used to treat depression. This study will evaluate the effectiveness of fluoxetine versus placebo in reducing the rate of relapse of AN and enhancing the psychosocial and behavioral recovery of women who have already been treated for AN.

Participants in this double-blind study will be recruited immediately following completion of a treatment program for AN, in which they maintained a body mass index (BMI) of at least 19 kg/m2 for two weeks. Upon study entry, participants will be randomly assigned to receive either fluoxetine or placebo for 12 months. Participants will begin receiving medication one week prior to discharge from the hospital in which they received care for AN. Medication doses will be increased up to a target dose of 60 mg per day, and will not exceed 80 mg per day. Participants will receive 50 sessions of cognitive-behavioral therapy, lasting approximately 45 minutes each and occurring twice weekly for the first month following discharge from the hospital. After the first month, therapy sessions will occur once weekly until Month 9 and then every other week until Month 12. Participants will also report to the study site to meet with a psychiatrist once a week for the first month following discharge and then every other week for the remainder of the study. General medical status, evidence of AN relapse, medication dose, and side effects will be assessed at these visits. Upon completing treatment, follow-up telephone calls will occur at Months 15 and 21, and follow-up visits will be held at Months 18 and 24. Psychopathology associated with AN, including concern with weight and shape, depressive symptoms, anxiety, and obsessive behavior, will be assessed.

• Study Type: Interventional
• Enrollment (Actual): 93
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute/Columbia University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 41 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Meets DSM-IV criteria for anorexia nervosa (except the requirement for amenorrhea)
• Successfully completed treatment at one of the study sites in an inpatient or day-program setting immediately prior to study entry (BMI remained at least 19 kg/m2 for two weeks)

Exclusion Criteria:

• Currently taking any medications other than occasional lorazepam or zopiclone for anxiety or sleep disturbance
• Previous serious adverse reactions to fluoxetine (e.g., allergy)
• Currently at risk for suicide
• Any medical condition requiring treatment with other psychotropic medication (except the occasional use of anti-anxiety medication)
• Pregnant
• Any serious medical illness besides the eating disorder
• History of continuous illness (at a low weight with no periods of remission or return to normal functioning for more than 15 years)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo
Experimental: fluoxetine; fluoxetine up to 80 mg per day	Drug: Fluoxetine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients Remaining in Study at 1 Year	The primary outcome measure was the proportion of patients with AN successfully completing 1 year of treatment and maintaining > 85% Ideal Body Weight.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Weight Per Month During Treatment		12 months
Change Per Month in Psychological Symptoms During Treatment, Assessed With Beck Anxiety Inventory (BAI)	The Beck Anxiety Inventory is a 21 question self-report measure of anxiety symptoms during the past week. Possible scores range from 0 - 63, with higher scores indicating more severe symptoms. Random effects regression models were used to compare fluoxetine vs placebo groups over time, using data from all patients.	12 months
Change Per Month in Psychological Symptoms During Treatment, Assessed With Beck Depression Inventory (BDI)	The Beck Depression Inventory-II is a 21 question self-report measure of depressive symptoms. Possible scores range from 0 - 63, with higher scores indicating more severe symptoms.Random effects regression models were used to compare fluoxetine vs placebo groups over time, using data from all patients.	12 months
Change Per Month in Psychological Symptoms During Treatment, Assessed With the Rosenberg Self-Esteem Scale (RSES).	The RSES is a 10 item self-report measure of self-esteem. Possible scores range from 0 - 30, with lower scores indicating more severe symptoms. Random effects regression models were used to compare fluoxetine vs placebo groups over time, using data from all patients.	12 months
Change Per Month in Psychological Symptoms During Treatment, Assessed With the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q).	The Q-LES-Q is a 93 item self-report measure of enjoyment and satisfaction experienced by individuals in various areas of daily functioning. Each of the 93 items is scored on a five-point scale, and the total score is converted to a percentage of the maximum score possible. The range is therefore from 0 to 100, with a higher score indicating greater enjoyment or satisfaction. Random effects regression models were used to compare fluoxetine vs placebo groups over time, using data from all patients.	12 months
Change Per Month in Psychological Symptoms During Treatment, Assessed With the Eating Disorders Inventory (EDI), Drive for Thinness Subscale.	The EDI is a 64 item self-report measure of psychological and behavioral characteristics of eating disorders. The Drive for Thinness subscale is comprised of seven items indicating excessive concern with dieting, preoccupation with weight and entrenchment in an extreme pursuit of thinness. Possible scores range from 0 to 21, with higher scores indicating greater Drive for Thinness. Random effects regression models were used to compare fluoxetine vs placebo groups over time, using data from all patients.	12 months
Change Per Month in Psychological Symptoms During Treatment, Assessed With the Eating Disorders Inventory (EDI), Bulimia Subscale.	The EDI is a 64 item self-report measure of psychological and behavioral characteristics of eating disorders. The Bulimia subscale is comprised of seven items indicating the tendency towards episodes of uncontrollable overeating (binge eating). Possible scores range from 0 to 21, with higher scores indicating greater tendency. Random effects regression models were used to compare fluoxetine vs placebo groups over time, using data from all patients.	12 months
Change Per Month in Psychological Symptoms During Treatment, Assessed With the Eating Disorders Inventory (EDI), Body Dissatisfaction Subscale.	The EDI is a 64 item self-report measure of psychological and behavioral characteristics of eating disorders. The Body Dissatisfaction subscale is comprised of nine items indicating the belief that parts of the body are too large. Possible scores range from 0 to 27, with higher scores indicating greater dissatisfaction. Random effects regression models were used to compare fluoxetine vs placebo groups over time, using data from all patients.	12 months
Change Per Month in Psychological Symptoms During Treatment, Assessed With the Eating Disorders Inventory (EDI), Perfectionism Subscale.	The EDI is a 64 item self-report measure of psychological and behavioral characteristics of eating disorders. The Perfectionism subscale is comprised of six items Indicating excessive personal expectations for superior achievement. Possible scores range from 0 to 18, with higher scores indicating greater expectations. Random effects regression models were used to compare fluoxetine vs placebo groups over time, using data from all patients.	12 months
Change Per Month in Psychological Symptoms During Treatment, Assessed With the Yale Brown Cornell Obsessive Compulsive Scale for Eating Disorders (YBC-EDS)	The YBC-EDS is an eight item, clinician-rated instrument assessing eating related preoccupations and/or rituals. Possible scores range from 0 to 32, with higher scores indicating greater preoccupations. Random effects regression models were used to compare fluoxetine vs placebo groups over time, using data from all patients.	12 months

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: B. Timothy Walsh, MD, New York State Psychiatric Institute/Columbia University Medical Center; Principal Investigator: Allan Kaplan, MD, Toronto General Hospital

Publications and helpful links

General Publications

• Walsh BT, Kaplan AS, Attia E, Olmsted M, Parides M, Carter JC, Pike KM, Devlin MJ, Woodside B, Roberto CA, Rockert W. Fluoxetine after weight restoration in anorexia nervosa: a randomized controlled trial. JAMA. 2006 Jun 14;295(22):2605-12. doi: 10.1001/jama.295.22.2605. Erratum In: JAMA. 2006 Aug 23;296(8):934. JAMA. 2007 Nov 7;298(17):2008.

Study record dates

Study Major Dates

• Study Start: January 1, 2000
• Primary Completion (Actual): May 1, 2005
• Study Completion (Actual): May 1, 2005

Study Registration Dates

• First Submitted: February 6, 2006
• First Submitted That Met QC Criteria: February 6, 2006
• First Posted (Estimate): February 8, 2006

Study Record Updates

• Last Update Posted (Actual): December 13, 2017
• Last Update Submitted That Met QC Criteria: December 11, 2017
• Last Verified: December 1, 2017

More Information

Terms related to this study

• Keywords: Depression
• Additional Relevant MeSH Terms: Mental Disorders; Signs and Symptoms, Digestive; Anorexia; Anorexia Nervosa; Feeding and Eating Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Fluoxetine
• Other Study ID Numbers: #4703R; R01MH060271 (U.S. NIH Grant/Contract); R01MH060336 (U.S. NIH Grant/Contract); DSIR AT-P