Does Dual Therapy Hasten Antidepressant Response?

September 5, 2017 updated by: New York State Psychiatric Institute

Combining Antidepressants to Hasten Remission From Depression

This study will utilize a randomized double-blind design to evaluate whether initial treatment with two anti-depressant medications (escitalopram and bupropion) results in more rapid remission and greater over-all remission rates than either monotherapy in 240 depressed subjects.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Depression is a major public health problem due to its prevalence and accompanying dysfunction and costs. Depression is undertreated, but even when treatment is adequate and effective, sources of delay in current pharmacologic strategies include: mechanistic delays, those related to the physiologic and behavioral effects of antidepressants; dosing delays in identifying the effective dose; and programmatic delays in identifying an effective agent using sequential monotherapy. This study will randomize 240 patients with Diagnostic and Statistical Manual, 4th Edition (DSM-IV) Major Depressive Disorder (MDD) to 12 week double blind treatment with combined escitalopram and bupropion or each antidepressant administered alone to evaluate whether combined escitalopram and bupropion result in more rapid remission and greater over-all remission than monotherapy. Preclinical and clinical studies suggest that bupropion might prevent one mechanistic delay inherent in escitalopram monotherapy. Rapid dose escalation may counter dosing delays. The simultaneous use of two known antidepressant medications may alleviate programmatic delays inherent in usual sequential monotherapy. Six months follow up and careful assessment of adverse events will address tolerability, acceptability, sustainability, and pharmacoeconomic concerns. If successful, this study might have a significant impact on clinical practice, public health, and depression's cost consequences.

Study Type

Interventional

Enrollment (Actual)

245

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Ottawa, Ontario, Canada, K1Z7K4
        • University of Ottawa, Institute of Mental Health Research
  • United States
    • New York
      • New York, New York, United States, 10032
        • New York State Psychiatric Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Men and women ages 18-65
  2. Major Depressive Disorder as primary diagnosis
  3. Physically healthy
  4. Signs informed consent
  5. Montgomery Asberg Depression Rating Scale (MADRS) >= 22

Exclusion Criteria:

  1. Bipolar Disorder (ie, Bipolar I, Bipolar II, Bipolar NOS)
  2. Life-time history of psychosis
  3. Current (ie, last 6 months) drug or alcohol abuse or dependence (except nicotine)
  4. Currently taking effective antidepressant medication
  5. Prior adequate treatment in current depressive episode with a selective serotonin re-uptake inhibitor (SSRI), bupropion (BUP) or bupropion (BUP) + a selective serotonin re-uptake inhibitor (SSRI) ("adequate" is defined as >= 4 weeks taking >= 2/3 Physician's Desk Reference (PDR) maximal dose
  6. Most recent antidepressant was within 5 weeks for fluoxetine and 1 week for all others
  7. Currently taking a medication contraindicated with either study medication
  8. Life time history of anorexia or bulimia
  9. Life time history of seizure or known increased seizure risk (e.g., history of significant brain trauma, taking pro-convulsant medication, known anatomical brain lesion)
  10. Currently taking psychoactive medication deemed to be necessary (including but not limited anticonvulsants, antidepressants, antipsychotics, steroids, and B-blockers); occasional use of hypnotics (ie, less than three times per week) will be allowed
  11. Unstable medical condition (ie, condition not adequately stabilized for >= 3 months)
  12. Prior intolerance to escitalopram (ESC) or bupropion (BUP)
  13. Inadequate understanding of English (for US site; Canadian site permits French fluency)
  14. Currently pregnant or breast-feeding; fecund women not using adequate contraceptive methods

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: escitalopram + bupropion
escitalopram plus bupropion extra long (XL) as dual treatment (i.e., this is not a SINGLE treatment arm; all patients assigned this arm received both medications)
Drug: escitalopram + bupropion
same dosing schedule as for monotherapy
Other Names:
  • Wellbutrin
  • Lexapro
ACTIVE_COMPARATOR: escitalopram
escitalopram monotherapy
Drug: escitalopram
10mg/d increasing by 10 mg/week to a maximum of 40 mg/d if tolerated and not remitted
Other Names:
  • Lexapro
ACTIVE_COMPARATOR: bupropion
bupropion extra long (XL) monotherapy
Drug: bupropion extra long (XL)
150mg/d increasing to 300 mg/d after 1 week and 450 mg/d after 3 weeks, all increases if tolerated and not remitted
Other Names:
  • Wellbutrin extra long (XL)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to Remission, Defined by the Week of Onset of Persistent Hamilton Rating Scale for Depression (HAM-D 17) <= 7, With no Subsequent HAM-D 17 > 7
Time Frame: 12 weeks
Life Table Survival Analysis run twice, once comparing Dual Therapy (i.e., Bupropion + Escitalopram) to Bupropion alone (i.e., Bupropion + Placebo) and once comparing Dual Therapy to Escitalopram alone (i.e., Escitalopram + Placebo). Because both analyses must significantly favor Dual Therapy, each individual analysis must reach a critical alpha = .0916 in order to reach an over-all alpha = .05.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Remission: Persistent Hamilton Rating Scale for Depression, 17 Items (HAM-D 17) <= 7, With no HAM-D 17 >7 Through Week 12
Time Frame: 12 weeks
Chi square comparison of rates of persistent remission (i.e., no subsequent Hamilton Rating Scale for Depression, 17 items [HAMD-D 17] > 7 once HAMD-D 17 <= 7); Dual rate vs. Escitalopram only rate and Dual rate vs. Bupropion only rate.
12 weeks
Severity of Depressive Symptoms as Measured by Hamilton Rating Scale for Depression (HAM-D 17)
Time Frame: 12 weeks

Last summary score rating on the 17-item Hamilton Rating Scale for Depression Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2. Range 0-58.

0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression

≥ 23 = Very Severe Depression
12 weeks
Functioning, as Measured by the Social Adjustment Scale (SAS) Summary Score
Time Frame: 12 weeks
Social adjustment was measured using the Social Adjustment Scale (SAS). The SAS is a self-report scale that assesses depressive symptoms and functioning in nine social and work-related domains generating a total score that is indicative of a subject's overall level of social adjustment. Subjects rate their own social functioning over times on a 5-point scale on items covering work for pay, housework, extended family, parenting, marital status, social activity and leisure, family unit and student status (sub-scales). Mean values of all the sub-scales are used, with a range from 0-5. Higher score = worse outcome … worse functioning
12 weeks
Quality of Life, as Measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Short Form (SF)
Time Frame: 12 weeks

The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) intends to measure quality of life in 16 domains. A summary score is computed by adding the scores and dividing by 16 (or the number of answered items if some are not answered).

The minimum raw score on the Q-LES-Q-SF is 14, and the maximum score is 70. Higher score means more satisfaction.
12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

New York State Psychiatric Institute

Collaborators

National Institute of Mental Health (NIMH)
University of Ottawa

Investigators

  • Principal Investigator: Pierre Blier, M.D., University of Ottawa, Institute of Mental Health Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2007

Primary Completion (ACTUAL)

July 1, 2011

Study Completion (ACTUAL)

March 1, 2012

Study Registration Dates

First Submitted

August 20, 2007

First Submitted That Met QC Criteria

August 20, 2007

First Posted (ESTIMATE)

August 22, 2007

Study Record Updates

Last Update Posted (ACTUAL)

October 4, 2017

Last Update Submitted That Met QC Criteria

September 5, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 5476
  • 5R01MH076961-04 (NIH)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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