Prozac Treatment of Major Depression: Discontinuation Study
Information source: New York State Psychiatric Institute
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Major Depression
Intervention: fluoxetine (Drug); placebo (Drug)
Phase: Phase 4
Status: Completed
Sponsored by: New York State Psychiatric Institute Official(s) and/or principal investigator(s):
Patrick J McGrath, MD, Principal Investigator, Affiliation: New York State Psychiatric Institute
Maurizio Fava, MD, Principal Investigator, Affiliation: Massachussets General Hospital
Summary
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.
Clinical Details
Official title: Prozac Treatment of Major Depression: Discontinuation Study
Study design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
Primary outcome: MDD section of Mood Disorders Module of Structured Clinical Interview for DSM-IV (SCID)Ham-D CGI
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withdrawn from the study and received open label treatment; responders were randomized in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
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Both.
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).
Locations and Contacts
Massachusetts General Hospital, Boston, Massachusetts 02114, United States
New York State Psychiatric Institute, New York, New York 10032, United States
Additional Information
official site of Depression Evaluation Service
Starting date: November 1995
Ending date: March 2003
Last updated: January 15, 2008
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