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
  Purpose

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 Intervention Phase
Major Depressive Disorder
Drug: escitalopram
Drug: bupropion XL
Drug: escitalopram + bupropion
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Combining Antidepressants to Hasten Remission From Depression

Resource links provided by NLM:


Further study details as provided by New York State Psychiatric Institute:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 245
Study Start Date: August 2007
Study Completion Date: March 2012
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: escitalopram + bupropion
escitalopram plus bupropion XL
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 XL monotherapy
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

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 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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00519428

Locations
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
Investigators
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

Additional Information:
No publications provided by New York State Psychiatric Institute

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: New York State Psychiatric Institute
ClinicalTrials.gov Identifier: NCT00519428     History of Changes
Other Study ID Numbers: 5476, 5R01MH076961-04
Study First Received: August 20, 2007
Last Updated: June 26, 2012
Health Authority: United States: Institutional Review Board
Canada: Canadian Institutes of Health Research
Canada: Ethics Review Committee
Canada: Health Canada

Keywords provided by New York State Psychiatric Institute:
depression
MDD
Major Depressive Disorder

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
Antidepressive Agents
Citalopram
Bupropion
Dexetimide
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Antiparkinson Agents
Anti-Dyskinesia Agents
Parasympatholytics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Muscarinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Serotonin Agents
Antidepressive Agents, Second-Generation
Dopamine Uptake Inhibitors

ClinicalTrials.gov processed this record on August 19, 2014