Does Dual Therapy Hasten Antidepressant Response?

Major Depressive Disorder Clinical Trial

Official title:

Combining Antidepressants to Hasten Remission From Depression

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00519428
• Other study ID #: 5476
• Secondary ID: 5R01MH076961-04
• Status: Completed
• Phase: Phase 4
• First received: August 20, 2007
• Last updated: September 5, 2017
• Start date: August 2007
• Est. completion date: March 2012

Study information

• Verified date: September 2017
• Source: New York State Psychiatric Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 245
• Est. completion date: March 2012
• Est. primary completion date: July 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• escitalopram
10mg/d increasing by 10 mg/week to a maximum of 40 mg/d if tolerated and not remitted
• 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
• escitalopram + bupropion
same dosing schedule as for monotherapy

Locations

Country	Name	City	State
Canada	University of Ottawa, Institute of Mental Health Research	Ottawa	Ontario
United States	New York State Psychiatric Institute	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
New York State Psychiatric Institute	National Institute of Mental Health (NIMH), University of Ottawa

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Remission: Persistent Hamilton Rating Scale for Depression, 17 Items (HAM-D 17) <= 7, With no HAM-D 17 >7 Through Week 12	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.	12 weeks
Secondary	Severity of Depressive Symptoms as Measured by Hamilton Rating Scale for Depression (HAM-D 17)	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	12 weeks
Secondary	Functioning, as Measured by the Social Adjustment Scale (SAS) Summary Score	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	12 weeks
Secondary	Quality of Life, as Measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Short Form (SF)	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.	12 weeks

External Links

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