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

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

Exclusion criteria

• 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