Major DepressionPhase 4NCT00427128
Prozac Treatment of Major Depression: Discontinuation Study
A Phase 4 study testing fluoxetine in people with Major Depression, run by New York State Psychiatric Institute at 2 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depression
- What is being tested?
- fluoxetine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 627 participants
- Where
- 2 sitesUnited States
- Study dates
- Nov 1995to Mar 2003
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- men and women ages 18-65
- meets criteria for DSM IV Major Depression
- signs informed consent and able to comply with study
Who cannot join
- 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
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- 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).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
New York State Psychiatric Institute
New York, New York, 10032
About this 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.
Read the 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.
- Conditions
- Major Depression
- Being tested
- fluoxetine, placebo
- Keywords
- Major Depression, "true drug" response, "placebo response" pattern, continuation treatment outcomes
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fluoxetineDrug
Also called Prozac
10mg/day increased over 12 weeks to 20-80 mg/day; 20-80 mg/day maintained from week 13-36.
placeboDrug
Week 13-36.
What is being measured
The primary outcome is the main question the study is designed to answer.
MDD section of Mood Disorders Module of Structured Clinical Interview for DSM-IV (SCID)
Measured: up to 9 mos.
Ham-D
Measured: up to 9 mos.
CGI
Measured: up to 9 mos.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2007 (estimated)
- Study startNov 1995
- Study completionMar 2003
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Major DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 627 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Massachusetts General Hospital
- Responsible party
- Sponsor
- Investigators
- Patrick J McGrath, MD, Principal investigator, New York State Psychiatric InstituteMaurizio Fava, MD, Principal investigator, Massachussets General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00427128
- Sponsor's protocol ID
- 4099R
- Other IDs
- RO1 MH56058
- Status last verified
- Dec 2011
- First submitted
- 24 Jan 2007
- Last updated
- 15 Dec 2011
- Results posted
- No
Publications
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. doi: 10.1176/ajp.2006.163.9.1542.
PubMed 16946178Posternak MA, Baer L, Nierenberg AA, Fava M. Response rates to fluoxetine in subjects who initially show no improvement. J Clin Psychiatry. 2011 Jul;72(7):949-54. doi: 10.4088/JCP.10m06098. Epub 2011 May 31.
PubMed 21672502Yang H, Sinicropi-Yao L, Chuzi S, Youn SJ, Clain A, Baer L, Chen Y, McGrath PJ, Fava M, Papakostas GI. Residual sleep disturbance and risk of relapse during the continuation/maintenance phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine. Ann Gen Psychiatry. 2010 Feb 26;9:10. doi: 10.1186/1744-859X-9-10.
PubMed 20187924
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prozac Treatment of Major Depression: Discontinuation Study
- ClinicalTrials.gov ID
- NCT00427128
- Acronym / sponsor ID
- 4099R
- Conditions
- Major Depression
- Keywords
- Major Depression, "true drug" response, "placebo response" pattern, continuation treatment outcomes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 627 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Collaborators
- Massachusetts General Hospital
- Study start
- Nov 1995
- Study completion
- Mar 2003 (actual)
- First posted
- 26 Jan 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- men and women ages 18-65
- meets criteria for DSM IV Major Depression
- signs informed consent and able to comply with study
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| fluoxetineAlso: Prozac10mg/day increased over 12 weeks to 20-80 mg/day; 20-80 mg/day maintained from week 13-36. | Drug | – |
| placeboWeek 13-36. | Drug | – |
Primary outcome
MDD section of Mood Disorders Module of Structured Clinical Interview for DSM-IV (SCID)
Time frame: up to 9 mos.
Ham-D
Time frame: up to 9 mos.
CGI
Time frame: up to 9 mos.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2011.
- Results publication: PubMed 16946178McGrath 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. doi: 10.1176/ajp.2006.163.9.1542.
- Derived from this study: PubMed 21672502Posternak MA, Baer L, Nierenberg AA, Fava M. Response rates to fluoxetine in subjects who initially show no improvement. J Clin Psychiatry. 2011 Jul;72(7):949-54. doi: 10.4088/JCP.10m06098. Epub 2011 May 31.
- Derived from this study: PubMed 20187924Yang H, Sinicropi-Yao L, Chuzi S, Youn SJ, Clain A, Baer L, Chen Y, McGrath PJ, Fava M, Papakostas GI. Residual sleep disturbance and risk of relapse during the continuation/maintenance phase treatment of major depressive disorder with the selective serotonin reuptake inhibitor fluoxetine. Ann Gen Psychiatry. 2010 Feb 26;9:10. doi: 10.1186/1744-859X-9-10.
- official site of Depression Evaluation ServiceLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patrick J McGrath, MD principal investigator
New York State Psychiatric Institute
Maurizio Fava, MD principal investigator
Massachussets General Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing fluoxetine in people with Major Depression, run by New York State Psychiatric Institute at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Dec 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MDD section of Mood Disorders Module of Structured Clinical Interview for DSM-IV (SCID) (time frame: up to 9 mos.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00427128, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2011.