Prozac Treatment of Major Depression: Discontinuation Study

Study Overview
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Brief Summary
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This study randomized two stratifications of acute phase MDD SSRI responders, categorized as having either true drug response or placebo response pattern, to continuation with SSRI vs placebo in a double-blind trial to determine if stratification category predicted continuation outcome.

Detailed Description
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This study enrolled 627 subjects with Major Depressive illness at New York State Psychiatric Institute and Massachusetts General Hospital. Subjects were treated with fluoxetine 10-60mg over a 12 week period. The responder group was defined by those no longer meeting criteria for Major Depression at week 12, along with CGI ratings of much improved or very much improved as determined by an independent evaluator. At week 12 non-responders were withdrawn from the study and received open label treatment; responders were randomized in double-blind fashion to either fluoxetine continuation (20-80mg daily) at response dose or placebo switch for up to 24 weeks. The responder group was stratified by specific or true drug response (late onset and persistent once attained) and nonspecific or placebo response (early onset or nonpersistent) patterns. Subjects were evaluated at one week and two week intervals at different phases of continuation treatment, and depression relapse was determined by agreement between study psychiatrist and independent evaluator CGI and Ham-D ratings, as well as administration of the MDD section of the Mood Disorders Module of the Structured Clinical Interview for DSM-IV Disorders at those visits. A subset of study participants also provided DNA samples to determine whether there are any DNA markers of response type. Data were analyzed to test the following hypotheses: that during continuation fluoxetine treatment improved patients with a true drug acute response pattern randomized to placebo had a poorer outcome than those maintained on active drug; that during continuation fluoxetine treatment improved patients with a placebo acute response pattern randomized to placebo had no worse an outcome than those maintained on drug; that during continuation fluoxetine treatment patients with a true drug acute response pattern randomized to continue on fluoxetine were more likely to maintain their benefit than those with a placebo pattern.

Official Title
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Prozac Treatment of Major Depression: Discontinuation Study

Conditions
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Major Depression

Intervention / Treatment
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* Drug: fluoxetine
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: men and women ages 18-65 meets criteria for DSM IV Major Depression signs informed consent and able to comply with study Exclusion Criteria: pregnant women and women of child-bearing potential who are not using a medically accepted means of contraception. women taking oral contraceptives, the initiation of which was temporally associated with the onset of depression; women who are breast-feeding. Patients with serious suicidal risk, including any patient who became suicidal with previous discontinuation of an antidepressant. Patients with a history of seizure disorder. Patients with unstable physical disorders (cardiovascular, hepatic, renal, respiratory, endocrine, neurologic, or hematologic) or any physical disorder judged to significantly affect CNS function. Patients meeting criteria for the following DSM-IV diagnoses: organic mental disorders; substance use disorders, including alcohol, active within the last 6 months; schizophrenia; delusional disorder; psychotic disorders; bipolar disorder; antisocial personality disorder; or presence of psychotic features Patients with a history of non-response to an adequate trial of a selective serotonin reuptake inhibitor in a past or current depressive episode, defined as a four-week trial of a minimum of 40mg/day of fluoxetine or paroxetine, or 100mg/day of sertraline. Concurrent use of exclusionary drugs Clinical or laboratory evidence of hypothyroidism without adequate stable replacement (eg, low total T4 or elevated TSH by a high sensitivity method).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: fluoxetine|10mg/day increased over 12 weeks to 20-80 mg/day; 20-80 mg/day maintained from week 13-36.|
|Drug: placebo|Week 13-36.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MDD section of Mood Disorders Module of Structured Clinical Interview for DSM-IV (SCID) |  | up to 9 mos. | 
| Ham-D |  | up to 9 mos. | 
| CGI |  | up to 9 mos. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Major Depression, true drug response, placebo response pattern, continuation treatment outcomes