Does Dual Therapy Hasten Antidepressant Response?

This study has been completed.
Sponsor:
Collaborators:
University of Ottawa
Information provided by (Responsible Party):
New York State Psychiatric Institute
ClinicalTrials.gov Identifier:
NCT00519428
First received: August 20, 2007
Last updated: June 26, 2012
Last verified: June 2012

August 20, 2007
June 26, 2012
August 2007
July 2011   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
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 ]
Complete list of historical versions of study NCT00519428 on ClinicalTrials.gov Archive Site
  • Remission: persistent HAM-D 17 <= 7, with no HAM-D 17 >7 through week 12 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Severity of depressive symptoms, measured by HAM-D 17, CGI, QIDS-SR 16 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Functioning, as measured by the SAS functioning summary score [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Quality of Life, as measured by the Q-LES-Q short form [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • 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 ]
Not Provided
Not Provided
 
Does Dual Therapy Hasten Antidepressant Response?
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.

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 DSM-IV Major Depressive Disorder 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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Major Depressive Disorder
  • 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 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: Welbutrin XL
  • Drug: escitalopram + bupropion
    same dosing schedule as for monotherapy
    Other Names:
    • Lexapro
    • Wellbutrin
  • Experimental: escitalopram + bupropion
    escitalopram plus bupropion XL
    Intervention: Drug: escitalopram + bupropion
  • Active Comparator: escitalopram
    escitalopram monotherapy
    Intervention: Drug: escitalopram
  • Active Comparator: bupropion
    bupropion XL monotherapy
    Intervention: Drug: bupropion XL
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
245
March 2012
July 2011   (final data collection date for primary outcome measure)

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 SSRI, BUP or BUP + SSRI ("adequate" is defined as >= 4 weeks taking >= 2/3 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 ESC or 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
Both
18 Years to 65 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Canada
 
NCT00519428
5476, 5R01MH076961-04
Yes
New York State Psychiatric Institute
New York State Psychiatric Institute
  • University of Ottawa
  • National Institute of Mental Health (NIMH)
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
New York State Psychiatric Institute
June 2012

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