search
Back to results

Does Dual Therapy Hasten Antidepressant Response?

Primary Purpose

Major Depressive Disorder

Status
Completed
Phase
Phase 4
Locations
International
Study Type
Interventional
Intervention
escitalopram
bupropion extra long (XL)
escitalopram + bupropion
Sponsored by
New York State Psychiatric Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring depression, Major Depressive Disorder

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • New York State Psychiatric Institute
  • University of Ottawa, Institute of Mental Health Research

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Active Comparator

Arm Label

escitalopram + bupropion

escitalopram

bupropion

Arm Description

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)

escitalopram monotherapy

bupropion extra long (XL) monotherapy

Outcomes

Primary Outcome Measures

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
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.

Secondary Outcome Measures

Remission: Persistent Hamilton Rating Scale for Depression, 17 Items (HAM-D 17) <= 7, With no HAM-D 17 >7 Through Week 12
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.
Severity of Depressive Symptoms as Measured by Hamilton Rating Scale for Depression (HAM-D 17)
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
Functioning, as Measured by the Social Adjustment Scale (SAS) Summary Score
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
Quality of Life, as Measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Short Form (SF)
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.

Full Information

First Posted
August 20, 2007
Last Updated
September 5, 2017
Sponsor
New York State Psychiatric Institute
Collaborators
University of Ottawa, National Institute of Mental Health (NIMH)
search

1. Study Identification

Unique Protocol Identification Number
NCT00519428
Brief Title
Does Dual Therapy Hasten Antidepressant Response?
Official Title
Combining Antidepressants to Hasten Remission From Depression
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
July 2011 (Actual)
Study Completion Date
March 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
New York State Psychiatric Institute
Collaborators
University of Ottawa, National Institute of Mental Health (NIMH)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder
Keywords
depression, Major Depressive Disorder

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
245 (Actual)

8. Arms, Groups, and Interventions

Arm Title
escitalopram + bupropion
Arm Type
Experimental
Arm Description
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)
Arm Title
escitalopram
Arm Type
Active Comparator
Arm Description
escitalopram monotherapy
Arm Title
bupropion
Arm Type
Active Comparator
Arm Description
bupropion extra long (XL) monotherapy
Intervention Type
Drug
Intervention Name(s)
escitalopram
Other Intervention Name(s)
Lexapro
Intervention Description
10mg/d increasing by 10 mg/week to a maximum of 40 mg/d if tolerated and not remitted
Intervention Type
Drug
Intervention Name(s)
bupropion extra long (XL)
Other Intervention Name(s)
Wellbutrin extra long (XL)
Intervention Description
150mg/d increasing to 300 mg/d after 1 week and 450 mg/d after 3 weeks, all increases if tolerated and not remitted
Intervention Type
Drug
Intervention Name(s)
escitalopram + bupropion
Other Intervention Name(s)
Lexapro, Wellbutrin
Intervention Description
same dosing schedule as for monotherapy
Primary Outcome Measure Information:
Title
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
Description
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.
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Remission: Persistent Hamilton Rating Scale for Depression, 17 Items (HAM-D 17) <= 7, With no HAM-D 17 >7 Through Week 12
Description
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.
Time Frame
12 weeks
Title
Severity of Depressive Symptoms as Measured by Hamilton Rating Scale for Depression (HAM-D 17)
Description
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
Time Frame
12 weeks
Title
Functioning, as Measured by the Social Adjustment Scale (SAS) Summary Score
Description
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
Time Frame
12 weeks
Title
Quality of Life, as Measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Short Form (SF)
Description
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.
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Men and women ages 18-65 Major Depressive Disorder as primary diagnosis Physically healthy Signs informed consent Montgomery Asberg Depression Rating Scale (MADRS) >= 22 Exclusion Criteria: Bipolar Disorder (ie, Bipolar I, Bipolar II, Bipolar NOS) Life-time history of psychosis Current (ie, last 6 months) drug or alcohol abuse or dependence (except nicotine) Currently taking effective antidepressant medication 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 Most recent antidepressant was within 5 weeks for fluoxetine and 1 week for all others Currently taking a medication contraindicated with either study medication Life time history of anorexia or bulimia 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) 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 Unstable medical condition (ie, condition not adequately stabilized for >= 3 months) Prior intolerance to escitalopram (ESC) or bupropion (BUP) Inadequate understanding of English (for US site; Canadian site permits French fluency) Currently pregnant or breast-feeding; fecund women not using adequate contraceptive methods
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jonathan W. Stewart, M.D.
Organizational Affiliation
New York State Psychiatric Institute
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Pierre Blier, M.D.
Organizational Affiliation
University of Ottawa, Institute of Mental Health Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York State Psychiatric Institute
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Ottawa, Institute of Mental Health Research
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K1Z7K4
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
25615566
Citation
Weissman MM, Wickramaratne P, Pilowsky DJ, Poh E, Batten LA, Hernandez M, Flament MF, Stewart JA, McGrath P, Blier P, Stewart JW. Treatment of maternal depression in a medication clinical trial and its effect on children. Am J Psychiatry. 2015 May;172(5):450-9. doi: 10.1176/appi.ajp.2014.13121679. Epub 2015 Jan 23.
Results Reference
derived
PubMed Identifier
25295437
Citation
Gerra ML, Marchesi C, Amat JA, Blier P, Hellerstein DJ, Stewart JW. Does negative affectivity predict differential response to an SSRI versus a non-SSRI antidepressant? J Clin Psychiatry. 2014 Sep;75(9):e939-44. doi: 10.4088/JCP.14m09025.
Results Reference
derived
PubMed Identifier
24485847
Citation
Stewart JW, McGrath PJ, Blondeau C, Deliyannides DA, Hellerstein D, Norris S, Amat J, Pilowsky DJ, Tessier P, Laberge L, O'Shea D, Chen Y, Withers A, Bergeron R, Blier P. Combination antidepressant therapy for major depressive disorder: speed and probability of remission. J Psychiatr Res. 2014 May;52:7-14. doi: 10.1016/j.jpsychires.2013.12.001. Epub 2013 Dec 17.
Results Reference
derived
Links:
URL
http://depression-nyc.org/
Description
Depression Evaluation Service official website
URL
https://www.columbiapsychiatry.org/
Description
Columbia University Depart,ment of Psychiatry web page

Learn more about this trial

Does Dual Therapy Hasten Antidepressant Response?

We'll reach out to this number within 24 hrs