Combining Antidepressants to Hasten Remission From Depression
Overview
- Phase
- Phase 4
- Intervention
- escitalopram + bupropion
- Conditions
- Major Depressive Disorder
- Sponsor
- New York State Psychiatric Institute
- Enrollment
- 245
- Locations
- 2
- Primary Endpoint
- 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
- Status
- Completed
- Last Updated
- 8 years ago
Overview
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.
Investigators
Eligibility Criteria
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
Arms & Interventions
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)
Intervention: escitalopram + bupropion
escitalopram
escitalopram monotherapy
Intervention: escitalopram
bupropion
bupropion extra long (XL) monotherapy
Intervention: bupropion extra long (XL)
Outcomes
Primary Outcomes
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
Time Frame: 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 Outcomes
- Remission: Persistent Hamilton Rating Scale for Depression, 17 Items (HAM-D 17) <= 7, With no HAM-D 17 >7 Through Week 12(12 weeks)
- Severity of Depressive Symptoms as Measured by Hamilton Rating Scale for Depression (HAM-D 17)(12 weeks)
- Functioning, as Measured by the Social Adjustment Scale (SAS) Summary Score(12 weeks)
- Quality of Life, as Measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Short Form (SF)(12 weeks)