Prozac Treatment of Major Depression: Discontinuation Study

This study has been completed.
Sponsor:
Collaborator:
Massachusetts General Hospital
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT00427128
First received: January 24, 2007
Last updated: December 14, 2011
Last verified: December 2011
  Purpose

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.


Condition Intervention Phase
Major Depression
Drug: fluoxetine
Drug: placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Prozac Treatment of Major Depression: Discontinuation Study

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • MDD section of Mood Disorders Module of Structured Clinical Interview for DSM-IV (SCID) [ Time Frame: up to 9 mos. ] [ Designated as safety issue: No ]
  • Ham-D [ Time Frame: up to 9 mos. ] [ Designated as safety issue: No ]
  • CGI [ Time Frame: up to 9 mos. ] [ Designated as safety issue: No ]

Enrollment: 627
Study Start Date: November 1995
Study Completion Date: March 2003
Intervention Details:
    Drug: fluoxetine
    10mg/day increased over 12 weeks to 20-80 mg/day; 20-80 mg/day maintained from week 13-36.
    Other Name: Prozac
    Drug: placebo
    Week 13-36.
Detailed Description:

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 At week 12 "non-responders" were withdrawn from the study and received open label treatment; responders were randomized in double-blind fashion to either fluoxetine continuation (20-80mg daily) at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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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).
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00427128

Locations
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
United States, New York
New York State Psychiatric Institute
New York, New York, United States, 10032
Sponsors and Collaborators
New York State Psychiatric Institute
Massachusetts General Hospital
Investigators
Principal Investigator: Patrick J McGrath, MD New York State Psychiatric Institute
Principal Investigator: Maurizio Fava, MD Massachussets General Hospital
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT00427128     History of Changes
Other Study ID Numbers: 4099R, RO1 MH56058
Study First Received: January 24, 2007
Last Updated: December 14, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by New York State Psychiatric Institute:
Major Depression
"true drug" response
"placebo response" pattern
continuation treatment outcomes

Additional relevant MeSH terms:
Depression
Depressive Disorder
Depressive Disorder, Major
Behavioral Symptoms
Mood Disorders
Mental Disorders
Fluoxetine
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Serotonin Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2014