Does Dual Therapy Hasten Antidepressant Response?

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.

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