Official Title: “Prozac Treatment of Major Depression: Discontinuation Study”

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.

Study Type: Interventional

Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study

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 At week 12 "non-responders" were withdrawn from the study and received open label treatment; responders were randomized in double-blind fashion to either fluoxetine continuation (20-80mg daily) at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.

Intervention(s) in this Clinical Trial

• 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.

Primary Measures

• MDD section of Mood Disorders Module of Structured Clinical Interview for DSM-IV (SCID)
  • Time Frame: up to 9 mos.
    Safety Issue?: No
• Ham-D
  • Time Frame: up to 9 mos.
    Safety Issue?: No
• CGI
  • Time Frame: up to 9 mos.
    Safety Issue?: No

Inclusion Criteria:

• 1. men and women ages 18-65
• 2. meets criteria for DSM IV Major Depression
• 3. signs informed consent and able to comply with study

Exclusion Criteria:

• 1. pregnant women and women of child-bearing potential who are not using a medically accepted means of contraception.
• 2. women taking oral contraceptives, the initiation of which was temporally associated with the onset of depression; women who are breast-feeding.
• 3. Patients with serious suicidal risk, including any patient who became suicidal with previous discontinuation of an antidepressant.
• 4. Patients with a history of seizure disorder.
• 5. Patients with unstable physical disorders (cardiovascular, hepatic, renal, respiratory, endocrine, neurologic, or hematologic) or any physical disorder judged to significantly affect CNS function.
• 6. 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
• 7. 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.
• 8. Concurrent use of exclusionary drugs
• 9. Clinical or laboratory evidence of hypothyroidism without adequate stable replacement (eg, low total T4 or elevated TSH by a high sensitivity method).

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: New York State Psychiatric Institute

Overall Clinical Trial Officials and Contacts

Patrick J McGrath, MD Principal Investigator New York State Psychiatric Institute  

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00427128

Study ID Number: 4099R

ClinicalTrials.gov Identifier: NCT00427128

Health Authority: United States: Institutional Review Board

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