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Does Dual Therapy Hasten Antidepressant Response?

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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

Tracking Information
First Submitted Date  ICMJE August 20, 2007
First Posted Date  ICMJE August 22, 2007
Results First Submitted Date  ICMJE October 6, 2016
Results First Posted Date  ICMJE October 4, 2017
Last Update Posted Date October 4, 2017
Study Start Date  ICMJE August 2007
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 5, 2017)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 20, 2007)
Time to remission, defined by the week of onset of persistent HAM-D 17 <= 7, with no subsequent HAM-D 17 > 7 [ Time Frame: 12 weeks ]
Change History Complete list of historical versions of study NCT00519428 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 5, 2017)
  • 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.
  • 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
  • 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
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2007)
  • Remission: persistent HAM-D 17 <= 7, with no HAM-D 17 >7 through week 12 [ Time Frame: 12 weeks ]
  • Severity of depressive symptoms, measured by HAM-D 17, CGI, QIDS-SR 16 [ Time Frame: 12 weeks ]
  • Functioning, as measured by the SAS functioning summary score [ Time Frame: 12 weeks ]
  • Quality of Life, as measured by the Q-LES-Q short form [ Time Frame: 12 weeks ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Does Dual Therapy Hasten Antidepressant Response?
Official Title  ICMJE Combining Antidepressants to Hasten Remission From Depression
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Major Depressive Disorder
Intervention  ICMJE
  • Drug: escitalopram
    10mg/d increasing by 10 mg/week to a maximum of 40 mg/d if tolerated and not remitted
    Other Name: Lexapro
  • 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 Name: Wellbutrin extra long (XL)
  • Drug: escitalopram + bupropion
    same dosing schedule as for monotherapy
    Other Names:
    • Lexapro
    • Wellbutrin
Study Arms  ICMJE
  • 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)
    Intervention: Drug: escitalopram + bupropion
  • Active Comparator: escitalopram
    escitalopram monotherapy
    Intervention: Drug: escitalopram
  • Active Comparator: bupropion
    bupropion extra long (XL) monotherapy
    Intervention: Drug: bupropion extra long (XL)
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: June 26, 2012)
245
Original Estimated Enrollment  ICMJE
 (submitted: August 20, 2007)
240
Actual Study Completion Date  ICMJE March 2012
Actual Primary Completion Date July 2011   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00519428
Other Study ID Numbers  ICMJE 5476
5R01MH076961-04 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party New York State Psychiatric Institute
Study Sponsor  ICMJE New York State Psychiatric Institute
Collaborators  ICMJE
  • University of Ottawa
  • National Institute of Mental Health (NIMH)
Investigators  ICMJE
Principal Investigator: Jonathan W. Stewart, M.D. New York State Psychiatric Institute
Principal Investigator: Pierre Blier, M.D. University of Ottawa, Institute of Mental Health Research
PRS Account New York State Psychiatric Institute
Verification Date September 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP