Prozac Treatment of Major Depression: Discontinuation Study

Major Depression Clinical Trial

Official title:

Prozac Treatment of Major Depression: Discontinuation Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00427128
• Other study ID #: 4099R
• Secondary ID: RO1 MH56058
• Status: Completed
• Phase: Phase 4
• First received: January 24, 2007
• Last updated: December 14, 2011
• Start date: November 1995
• Est. completion date: March 2003

Study information

• Verified date: December 2011
• Source: New York State Psychiatric Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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 At week 12 "non-responders" were withdrawn from the study and received open label treatment; responders were randomized in double-blind fashion to either fluoxetine continuation (20-80mg daily) at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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 627
• Est. completion date: March 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depression

Intervention

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

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	New York State Psychiatric Institute	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York State Psychiatric Institute	Massachusetts General Hospital

Country where clinical trial is conducted

United States, 

References & Publications (1)

McGrath PJ, Stewart JW, Quitkin FM, Chen Y, Alpert JE, Nierenberg AA, Fava M, Cheng J, Petkova E. Predictors of relapse in a prospective study of fluoxetine treatment of major depression. Am J Psychiatry. 2006 Sep;163(9):1542-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	MDD section of Mood Disorders Module of Structured Clinical Interview for DSM-IV (SCID)		up to 9 mos.	No
Primary	Ham-D		up to 9 mos.	No
Primary	CGI		up to 9 mos.	No

External Links

•   official site of Depression Evaluation Service