Does Dual Therapy Hasten Antidepressant Response?

Phase 4

Completed

• Conditions: Major Depressive Disorder
• Interventions: Drug: escitalopram + bupropion; Drug: bupropion extra long (XL); Drug: escitalopram

• Registration Number: NCT00519428
• Lead Sponsor: New York State Psychiatric Institute

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 Timeline

• Study Start: 2007-08
• Study First Submitted: 2007-08-20
• Study First Submitted QC: 2007-08-20
• Study First Posted: 2007-08-22
• Primary Completion: 2011-07
• Study Completion: 2012-03
• Results First Submitted: 2016-10-06
• Status Verified: 2017-09
• Results First Submitted QC: 2017-09-05
• Last Update Submitted: 2017-09-05
• Results First Posted: 2017-10-04
• Last Update Posted: 2017-10-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 245

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
escitalopram + bupropion	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)
bupropion	bupropion extra long (XL)	bupropion extra long (XL) monotherapy
escitalopram	escitalopram	escitalopram monotherapy

Primary Outcome Measures

Name	Time	Method
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	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

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

Trial Locations

Locations (2)

University of Ottawa, Institute of Mental Health Research; 🇨🇦 Ottawa, Ontario, Canada

New York State Psychiatric Institute; 🇺🇸 New York, New York, United States