Does Dual Therapy Hasten Antidepressant Response?

New York State Psychiatric Institute

Status and phase: Completed; Phase 4

Conditions: Major Depressive Disorder

Treatments: Drug: bupropion extra long (XL); Drug: escitalopram; Drug: escitalopram + bupropion

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00519428

5476

5R01MH076961-04 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 245 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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245 participants in 3 patient groups

escitalopram + bupropion

Experimental group

Description:

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)

Treatment:

Drug: escitalopram + bupropion

escitalopram

Active Comparator group

Description:

escitalopram monotherapy

Treatment:

Drug: escitalopram

bupropion

Active Comparator group

Description:

bupropion extra long (XL) monotherapy

Treatment:

Drug: bupropion extra long (XL)