Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 24 of 1013 for:    "Depressive Disorder" [DISEASE] AND Rating AND Major Depressive Disorder AND Antidepressive Agents

Does Dual Therapy Hasten Antidepressant Response?

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00519428
Recruitment Status : Completed
First Posted : August 22, 2007
Results First Posted : October 4, 2017
Last Update Posted : October 4, 2017
Sponsor:
Collaborators:
University of Ottawa
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
New York State Psychiatric Institute

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Major Depressive Disorder
Interventions Drug: escitalopram
Drug: bupropion extra long (XL)
Drug: escitalopram + bupropion
Enrollment 245
Recruitment Details Recruitment dates: August, 2007 to August 2011 Locations: 4 outpatient research clinics in two countries (US and Canada)
Pre-assignment Details All patients had to be psychoactive drug-free for at least two weeks (five weeks for fluoxetine) prior to randomization and had to continue to meet study entry criteria at point of randomization
Arm/Group Title Escitalopram + Bupropion Escitalopram Bupropion
Hide Arm/Group Description escitalopram plus bupropion escitalopram monotherapy bupropion monotherapy
Period Title: Overall Study
Started 78 84 83
Completed 57 69 58
Not Completed 21 15 25
Reason Not Completed
Adverse Event             5             2             10
Lost to Follow-up             7             7             6
Withdrawal by Subject             8             3             7
unstated             1             3             2
Arm/Group Title Escitalopram + Bupropion Escitalopram Bupropion Total
Hide Arm/Group Description escitalopram plus bupropion XL escitalopram monotherapy bupropion XL monotherapy Total of all reporting groups
Overall Number of Baseline Participants 78 84 83 245
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Age Number Analyzed 78 participants 84 participants 83 participants 245 participants
40  (10) 41  (11) 40  (11) 40  (11)
[1]
Measure Description: Patient's report of their age
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 78 participants 84 participants 83 participants 245 participants
Female
52
  66.7%
62
  73.8%
49
  59.0%
163
  66.5%
Male
26
  33.3%
22
  26.2%
34
  41.0%
82
  33.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 78 participants 84 participants 83 participants 245 participants
United States 37 42 41 120
Canada 41 42 42 125
1.Primary Outcome
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
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
age 18-65 with Major Depressive Disorder (MDD), non-bipolar, non-psychotic, non-substance abusing, without intolerance to study drugs or adequate selective serotonin re-uptake inhibitor (SSRI) and/or bupropion treatment in current episode; physically healthy without contraindications to bupropion or escitalopram.
Arm/Group Title Escitalopram + Bupropion Escitalopram Bupropion
Hide Arm/Group Description:
escitalopram plus bupropion XL
escitalopram monotherapy
bupropion XL monotherapy
Overall Number of Participants Analyzed 78 84 83
Mean (Standard Deviation)
Unit of Measure: weeks
8  (7) 9  (7) 10  (7)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Escitalopram + Bupropion, Escitalopram, Bupropion
Comments Hypothesis: Dual Treatment (escitalopram + bupropion) will result in greater improvement over 12 weeks than either monotherapy (i.e., two analyses: 1) dual treatment will outperform escitalopram monotherapy; 2) dual treatment will outperform bupropion monotherapy). Therefore each analysis will be done twice and it will be required that both analyses be significant to declare the over-all study significant.
Type of Statistical Test Superiority
Comments Hypothesis: Dual Treatment (escitalopram + bupropion) will result in greater improvement over 12 weeks than either monotherapy (i.e., two analyses: 1) dual treatment will outperform escitalopram monotherapy; 2) dual treatment will outperform bupropion monotherapy).
Statistical Test of Hypothesis P-Value .05
Comments Each individual test will require the calculated "p" to be < .0916 to declare that comparison to be significant. Since the hypothesis requires both comparisons to be significant, this produces an over-all alpha of .05.
Method Cochran-Mantel-Haenszel
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value .05
Parameter Dispersion
Type: Standard Deviation
Value: 4
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Remission: Persistent Hamilton Rating Scale for Depression, 17 Items (HAM-D 17) <= 7, With no HAM-D 17 >7 Through Week 12
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
age 18-65 with MDD, non-bipolar, non-psychotic, non-substance abusing, without intolerance to study drugs or adequate SSRI/bupropion treatment in current episode; physically healthy without contraindications to bupropion or escitalopram.
Arm/Group Title Escitalopram + Bupropion Escitalopram Bupropion
Hide Arm/Group Description:
escitalopram plus bupropion XL
escitalopram monotherapy
bupropion XL monotherapy
Overall Number of Participants Analyzed 78 84 83
Measure Type: Number
Unit of Measure: percentage of participants
52 46 34
3.Secondary Outcome
Title Severity of Depressive Symptoms as Measured by Hamilton Rating Scale for Depression (HAM-D 17)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
age 18-65 with MDD, non-bipolar, non-psychotic, non-substance abusing, without intolerance to study drugs or adequate SSRI/bupropion treatment in current episode; physically healthy without contraindications to bupropion or escitalopram.
Arm/Group Title Escitalopram + Bupropion Escitalopram Bupropion
Hide Arm/Group Description:
escitalopram plus bupropion XL
escitalopram monotherapy
bupropion XL monotherapy
Overall Number of Participants Analyzed 78 83 84
Mean (Standard Deviation)
Unit of Measure: units on Hamilton Rating Scale for Depre
10  (8) 9  (7) 12  (8)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Escitalopram + Bupropion, Escitalopram, Bupropion
Comments To test the hypothesis that escitalopram + bupropion would have superior efficacy relative to each monotherapy, the group receiving both medications was separately compared to each monotherapy group, covarying for baseline score and country
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0916
Comments escitalopram + bupropion vs. escitalopram: F(1,159) = 1.93, ns escitalopram + bupropion vs. bupropion: F (1,157) = 1.99, ns
Method ANCOVA
Comments adjusting for baseline score and country
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 10
Parameter Dispersion
Type: Standard Deviation
Value: 8
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Functioning, as Measured by the Social Adjustment Scale (SAS) Summary Score
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients; latest available Total SAS score used if week 12 score not available.
Arm/Group Title Escitalopram + Bupropion Escitalopram Bupropion
Hide Arm/Group Description:

escitalopram plus bupropion XL as dual treatment (i.e., this is not a SINGLE treatment arm; all patients assigned this arm received both medications)

escitalopram + bupropion: same dosing schedule as for monotherapy

escitalopram monotherapy

escitalopram: 10mg/d increasing by 10 mg/week to a maximum of 40 mg/d if tolerated and not remitted

bupropion XL monotherapy

bupropion 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

Overall Number of Participants Analyzed 78 83 84
Mean (Standard Deviation)
Unit of Measure: units on the SAS scale
2.65  (.69) 2.63  (.69) 2.74  (.71)
5.Secondary Outcome
Title Quality of Life, as Measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Short Form (SF)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
All Randomized Subjects
Arm/Group Title Escitalopram + Bupropion Escitalopram Bupropion
Hide Arm/Group Description:
escitalopram plus bupropion XL
escitalopram monotherapy
bupropion XL monotherapy
Overall Number of Participants Analyzed 78 83 84
Mean (Standard Deviation)
Unit of Measure: units on the Q-LES-Q scale
3.0  (.82) 3.0  (.76) 3.1  (.74)
Time Frame 12 weeks
Adverse Event Reporting Description A modified Systematic Assessment for Treatment Emergent Events (SAFTEE) at each visit specifically asked about 17 items (too much energy, muscle tightness, insomnia, tremor, poor concentration, word finding, spacy, dizzy, headache, dry mouth, decreased appetite, nausea, low energy, sleepy, sweating, decreased libido, anger/irritability) a pilot study showed occurred in at least 10% of patients treated with escitalopram plus bupropion. A General Inquiry then asked re additional symptoms.
 
Arm/Group Title Escitalopram + Bupropion Escitalopram Bupropion
Hide Arm/Group Description

escitalopram plus bupropion XL

escitalopram + bupropion: same dosing schedule as for monotherapy

escitalopram monotherapy

escitalopram: 10mg/d increasing by 10 mg/week to a maximum of 40 mg/d if tolerated and not remitted

bupropion XL monotherapy

bupropion 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

All-Cause Mortality
Escitalopram + Bupropion Escitalopram Bupropion
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Escitalopram + Bupropion Escitalopram Bupropion
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/78 (0.00%)      0/84 (0.00%)      0/83 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Escitalopram + Bupropion Escitalopram Bupropion
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   71/78 (91.03%)      80/84 (95.24%)      71/83 (85.54%)    
Cardiac disorders       
dizzy  8 [1]  19/78 (24.36%)  19 20/84 (23.81%)  20 19/83 (22.89%)  19
Gastrointestinal disorders       
dry mouth  10 [2]  27/78 (34.62%)  27 18/84 (21.43%)  18 28/83 (33.73%)  28
decreased appetite  11 [3]  17/78 (21.79%)  17 21/84 (25.00%)  21 21/83 (25.30%)  21
nausea, vomiting  12 [4]  25/78 (32.05%)  25 32/84 (38.10%)  32 28/83 (33.73%)  28
General disorders       
Too much energy  1 [5]  5/78 (6.41%)  5 4/84 (4.76%)  4 7/83 (8.43%)  7
insomnia  3 [6]  24/78 (30.77%)  24 27/84 (32.14%)  27 31/83 (37.35%)  31
lethargy  13 [7]  10/78 (12.82%)  10 15/84 (17.86%)  15 10/83 (12.05%)  10
sweating  15 [8]  19/78 (24.36%)  19 13/84 (15.48%)  13 5/83 (6.02%)  5
sexual dysfunction  16 [9]  20/78 (25.64%)  20 18/84 (21.43%)  28 9/83 (10.84%)  9
Musculoskeletal and connective tissue disorders       
muscle tightness  2 [10]  13/78 (16.67%)  13 14/84 (16.67%)  14 18/83 (21.69%)  18
Nervous system disorders       
tremor  4 [11]  23/78 (29.49%)  23 14/84 (16.67%)  14 18/83 (21.69%)  18
trouble thinking  5 [12]  12/78 (15.38%)  12 13/84 (15.48%)  13 5/83 (6.02%)  5
trouble finding words  6 [13]  5/78 (6.41%)  5 6/84 (7.14%)  6 7/83 (8.43%)  7
spacey  7 [14]  13/78 (16.67%)  13 12/84 (14.29%)  12 5/83 (6.02%)  5
headache  9 [15]  28/78 (35.90%)  28 28/84 (33.33%)  28 26/83 (31.33%)  26
daytime sleepiness  14 [16]  13/78 (16.67%)  13 17/84 (20.24%)  17 9/83 (10.84%)  9
Psychiatric disorders       
anger, irritability  17 [17]  4/78 (5.13%)  4 5/84 (5.95%)  5 14/83 (16.87%)  14
Indicates events were collected by systematic assessment
1
Term from vocabulary, Too much energy
2
Term from vocabulary, muscle tightness
3
Term from vocabulary, insomnia
4
Term from vocabulary, tremor
5
Term from vocabulary, cognitive disturbanc
6
Term from vocabulary, trouble finding word
7
Term from vocabulary, spacey
8
Term from vocabulary, dizzy
9
Term from vocabulary, headache
10
Term from vocabulary, dry mouth
11
Term from vocabulary, decreased appetite
12
Term from vocabulary, nausea, vomiting
13
Term from vocabulary, lethargy
14
Term from vocabulary, daytime sleepiness
15
Term from vocabulary, sweating
16
Term from vocabulary, sexual dysfunction
17
Term from vocabulary, anger, irritability
[1]
feeling dizzy, lightheaded or faint
[2]
dry mouth
[3]
anorexia
[4]
nausea, vomiting, queasy stomach
[5]
A feeling of being too "revved up"
[6]
trouble falling asleep, staying asleep or waking too early
[7]
low energy, lack of "get up and go"
[8]
sweating too much, excessive perspiration
[9]
delayed orgasm, anorgasmia, erectile dysfunction, poor libido, low sex drive
[10]
a feeling of tenseness or tightness in the muscles
[11]
involuntary shaking or trembling
[12]
trouble thinking or concentrating, cognitive disturbance
[13]
word finding difficulty
[14]
feeling "spacey", "out of it", "fuzzy headed", "cotton in my head"
[15]
pain inside the head
[16]
daytime sleepiness, feeling sleepy or groggy during the day
[17]
anger, irritability, feeling like "flying off the handle", too touchy
Sample size may have limited demonstration of differences.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Jonathan W. Stewart, M.D.
Organization: NYSPInstitute
Phone: 212-543-5745
EMail: jws6@columbia.edu
Layout table for additonal information
Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT00519428     History of Changes
Other Study ID Numbers: 5476
5R01MH076961-04 ( U.S. NIH Grant/Contract )
First Submitted: August 20, 2007
First Posted: August 22, 2007
Results First Submitted: October 6, 2016
Results First Posted: October 4, 2017
Last Update Posted: October 4, 2017