Does Dual Therapy Hasten Antidepressant Response?

NCT00519428 | Completed Phase 4 Results DMC

• 2 other identifiers: 54765R01MH076961-04
• Study Type: interventional
• Target: 245
• Locations: 2 countries
• Sites: 2

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.

Conditions

Major Depressive Disorder

Keywords

depression; Major Depressive Disorder

Outcome Measures

Primary Outcomes (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

  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

Secondary Outcomes (4)

• Remission: Persistent Hamilton Rating Scale for Depression, 17 Items (HAM-D 17) <= 7, With no HAM-D 17 >7 Through Week 12

  12 weeks

• Severity of Depressive Symptoms as Measured by Hamilton Rating Scale for Depression (HAM-D 17)

  12 weeks

• Functioning, as Measured by the Social Adjustment Scale (SAS) Summary Score

  12 weeks

• Quality of Life, as Measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Short Form (SF)

  12 weeks

Study Arms (3)

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)

Drug: escitalopram + bupropion

escitalopram

ACTIVE COMPARATOR

escitalopram monotherapy

Drug: escitalopram

bupropion

ACTIVE COMPARATOR

bupropion extra long (XL) monotherapy

Drug: bupropion extra long (XL)

Interventions

escitalopram DRUG

10mg/d increasing by 10 mg/week to a maximum of 40 mg/d if tolerated and not remitted

Also known as: Lexapro

escitalopram

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

Also known as: Wellbutrin extra long (XL)

bupropion

escitalopram + bupropion DRUG

same dosing schedule as for monotherapy

Also known as: Lexapro, Wellbutrin

escitalopram + bupropion

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women ages 18-65
• Major Depressive Disorder as primary diagnosis
• Physically healthy
• Signs informed consent
• Montgomery Asberg Depression Rating Scale (MADRS) \>= 22

You may not qualify if:

• Bipolar Disorder (ie, Bipolar I, Bipolar II, Bipolar NOS)
• Life-time history of psychosis
• Current (ie, last 6 months) drug or alcohol abuse or dependence (except nicotine)
• Currently taking effective antidepressant medication
• 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
• Most recent antidepressant was within 5 weeks for fluoxetine and 1 week for all others
• Currently taking a medication contraindicated with either study medication
• Life time history of anorexia or bulimia
• 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)
• 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
• Unstable medical condition (ie, condition not adequately stabilized for \>= 3 months)
• Prior intolerance to escitalopram (ESC) or bupropion (BUP)
• Inadequate understanding of English (for US site; Canadian site permits French fluency)
• Currently pregnant or breast-feeding; fecund women not using adequate contraceptive methods

Sponsors & Collaborators

• New York State Psychiatric Institute: lead
• University of Ottawa: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

University of Ottawa, Institute of Mental Health Research

Ottawa, Ontario, K1Z7K4, Canada

Location

Related Publications (4)

• 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.

  PMID: 38628260 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.

  PMID: 25615566 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.

  PMID: 25295437 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.

  PMID: 24485847 DERIVED

Related Links

• Depression Evaluation Service official website
• Columbia University Depart,ment of Psychiatry web page
• official website of the University of Ottawa's Institute of Mental Health Research

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Interventions

Escitalopram; Bupropion

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Propiophenones; Ketones

Limitations and Caveats

Sample size may have limited demonstration of differences.

Results Point of Contact

• Title: Jonathan W. Stewart, M.D.
• Organization: NYSPInstitute

jws6@columbia.edu

212-543-5745

Study Officials

• Jonathan W. Stewart, M.D.

  New York State Psychiatric Institute

  PRINCIPAL INVESTIGATOR

• Pierre Blier, M.D.

  University of Ottawa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2007
• First Posted: August 22, 2007
• Study Start: August 1, 2007
• Primary Completion: July 1, 2011
• Study Completion: March 1, 2012
• Last Updated: October 4, 2017
• Results First Posted: October 4, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); CA (1)