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| ID | Type | Description | Link |
|---|---|---|---|
| 5R01MH076961-04 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| University of Ottawa | OTHER |
| National Institute of Mental Health (NIMH) | NIH |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| escitalopram + bupropion | Experimental | 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 | Active Comparator | escitalopram monotherapy |
|
| bupropion | Active Comparator | bupropion extra long (XL) monotherapy |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| escitalopram | Drug | 10mg/d increasing by 10 mg/week to a maximum of 40 mg/d if tolerated and not remitted |
|
| 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 | 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 |
| 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 | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jonathan W. Stewart, M.D. | New York State Psychiatric Institute | Principal Investigator |
| Pierre Blier, M.D. | University of Ottawa | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| New York State Psychiatric Institute | New York | New York | 10032 | United States | ||
| University of Ottawa, Institute of Mental Health Research |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38628260 | Derived | van der Wijk G, Enkhbold Y, Cnudde K, Szostakiwskyj MW, Blier P, Knott V, Jaworska N, Protzner AB. One size does not fit all: notable individual variation in brain activity correlates of antidepressant treatment response. Front Psychiatry. 2024 Apr 2;15:1358018. doi: 10.3389/fpsyt.2024.1358018. eCollection 2024. | |
| 25615566 | Derived | 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. |
| Label | URL |
|---|---|
| Depression Evaluation Service official website | View source |
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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
Recruitment dates: August, 2007 to August 2011 Locations: 4 outpatient research clinics in two countries (US and Canada)
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| ID | Title | Description |
|---|---|---|
| FG000 | Escitalopram + Bupropion | escitalopram plus bupropion |
| FG001 | Escitalopram | escitalopram monotherapy |
| FG002 | Bupropion | bupropion monotherapy |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Escitalopram + Bupropion | escitalopram plus bupropion XL |
| BG001 | Escitalopram | escitalopram monotherapy |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Patient's report of their age |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Mean | Standard Deviation | weeks | 12 weeks |
|
12 weeks
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Escitalopram + Bupropion | escitalopram plus bupropion XL escitalopram + bupropion: same dosing schedule as for monotherapy |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Too much energy | General disorders | Too much energy | Systematic Assessment | A feeling of being too "revved up" |
Sample size may have limited demonstration of differences.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Jonathan W. Stewart, M.D. | NYSPInstitute | 212-543-5745 | jws6@columbia.edu |
Not provided
| ID | Term |
|---|---|
| D003865 | Depressive Disorder, Major |
| D003863 | Depression |
| ID | Term |
|---|---|
| D003866 | Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D001526 | Behavioral Symptoms |
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| ID | Term |
|---|---|
| D000089983 | Escitalopram |
| D016642 | Bupropion |
| ID | Term |
|---|---|
| D011437 | Propylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
| D009570 | Nitriles |
| D001572 |
Not provided
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| bupropion extra long (XL) | Drug | 150mg/d increasing to 300 mg/d after 1 week and 450 mg/d after 3 weeks, all increases if tolerated and not remitted |
|
|
| escitalopram + bupropion | Drug | same dosing schedule as for monotherapy |
|
|
| 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 | 12 weeks |
| 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 | 12 weeks |
| 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. | 12 weeks |
| Ottawa |
| Ontario |
| K1Z7K4 |
| Canada |
| 25295437 | Derived | 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. |
| 24485847 | Derived | 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. |
| Columbia University Depart,ment of Psychiatry web page | View source |
| official website of the University of Ottawa's Institute of Mental Health Research | View source |
| Withdrawal by Subject |
|
| unstated |
|
| BG002 |
| Bupropion |
bupropion XL monotherapy |
| BG003 | Total | Total of all reporting groups |
| Mean |
| Standard Deviation |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
escitalopram plus bupropion XL |
| OG001 | Escitalopram | escitalopram monotherapy |
| OG002 | Bupropion | bupropion XL monotherapy |
|
|
|
| Secondary | 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. | 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. | Posted | Number | percentage of participants | 12 weeks |
|
|
|
| Secondary | 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 | 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. | Posted | Mean | Standard Deviation | units on Hamilton Rating Scale for Depre | 12 weeks |
|
|
|
|
| Secondary | 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 | All randomized patients; latest available Total SAS score used if week 12 score not available. | Posted | Mean | Standard Deviation | units on the SAS scale | 12 weeks |
|
|
|
| Secondary | 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. | All Randomized Subjects | Posted | Mean | Standard Deviation | units on the Q-LES-Q scale | 12 weeks |
|
|
|
| 0 |
| 78 |
| 71 |
| 78 |
| EG001 | Escitalopram | escitalopram monotherapy escitalopram: 10mg/d increasing by 10 mg/week to a maximum of 40 mg/d if tolerated and not remitted | 0 | 84 | 80 | 84 |
| EG002 | Bupropion | 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 | 0 | 83 | 71 | 83 |
|
| muscle tightness | Musculoskeletal and connective tissue disorders | muscle tightness | Systematic Assessment | a feeling of tenseness or tightness in the muscles |
|
| insomnia | General disorders | insomnia | Systematic Assessment | trouble falling asleep, staying asleep or waking too early |
|
| tremor | Nervous system disorders | tremor | Systematic Assessment | involuntary shaking or trembling |
|
| trouble thinking | Nervous system disorders | cognitive disturbanc | Systematic Assessment | trouble thinking or concentrating, cognitive disturbance |
|
| trouble finding words | Nervous system disorders | trouble finding word | Systematic Assessment | word finding difficulty |
|
| spacey | Nervous system disorders | spacey | Systematic Assessment | feeling "spacey", "out of it", "fuzzy headed", "cotton in my head" |
|
| dizzy | Cardiac disorders | dizzy | Systematic Assessment | feeling dizzy, lightheaded or faint |
|
| headache | Nervous system disorders | headache | Systematic Assessment | pain inside the head |
|
| dry mouth | Gastrointestinal disorders | dry mouth | Systematic Assessment | dry mouth |
|
| decreased appetite | Gastrointestinal disorders | decreased appetite | Systematic Assessment | anorexia |
|
| nausea, vomiting | Gastrointestinal disorders | nausea, vomiting | Systematic Assessment | nausea, vomiting, queasy stomach |
|
| lethargy | General disorders | lethargy | Systematic Assessment | low energy, lack of "get up and go" |
|
| daytime sleepiness | Nervous system disorders | daytime sleepiness | Systematic Assessment | daytime sleepiness, feeling sleepy or groggy during the day |
|
| sweating | General disorders | sweating | Systematic Assessment | sweating too much, excessive perspiration |
|
| sexual dysfunction | General disorders | sexual dysfunction | Systematic Assessment | delayed orgasm, anorgasmia, erectile dysfunction, poor libido, low sex drive |
|
| anger, irritability | Psychiatric disorders | anger, irritability | Systematic Assessment | anger, irritability, feeling like "flying off the handle", too touchy |
|
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| D001519 |
| Behavior |
| Benzofurans |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D011427 | Propiophenones |
| D007659 | Ketones |