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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

Study Description
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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.

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: escitalopram Drug: bupropion extra long (XL) Drug: escitalopram + bupropion Phase 4

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 Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 245 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Combining Antidepressants to Hasten Remission From Depression
Study Start Date : August 2007
Actual Primary Completion Date : July 2011
Actual Study Completion Date : March 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Antidepressants

Arms and Interventions
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Arm Intervention/treatment
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)
 Drug: escitalopram + bupropion
same dosing schedule as for monotherapy
Other Names:
  • Lexapro
  • Wellbutrin
Active Comparator: escitalopram
escitalopram monotherapy
 Drug: escitalopram
10mg/d increasing by 10 mg/week to a maximum of 40 mg/d if tolerated and not remitted
Other Name: Lexapro
Active Comparator: bupropion
bupropion extra long (XL) monotherapy
 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)


Outcome Measures
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Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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


  3. 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

  4. 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.



Eligibility Criteria
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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00519428


Locations
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United States, New York
New York State Psychiatric Institute
New York, New York, United States, 10032
Canada, Ontario
University of Ottawa, Institute of Mental Health Research
Ottawa, Ontario, Canada, K1Z7K4
Sponsors and Collaborators
New York State Psychiatric Institute
University of Ottawa
National Institute of Mental Health (NIMH)
Investigators
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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
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT00519428    
Other Study ID Numbers: 5476
5R01MH076961-04 ( U.S. NIH Grant/Contract )
First Posted: August 22, 2007    Key Record Dates
Results First Posted: October 4, 2017
Last Update Posted: October 4, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by New York State Psychiatric Institute:
depression
Major Depressive Disorder
Additional relevant MeSH terms:
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Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
Dexetimide
Citalopram
Bupropion
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
 Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Dopamine Uptake Inhibitors
Dopamine Agents
Cytochrome P-450 CYP2D6 Inhibitors