Clinical trial NCT00519428: Does Dual Therapy Hasten Antidepressant Response?
Official title: Combining Antidepressants to Hasten Remission From Depression
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Major Depressive Disorder
Keywords: depression
Major Depressive Disorder
Lead sponsor: New York State Psychiatric Institute
Sponsor class: OTHER
Collaborators: name: University of Ottawa
name: National Institute of Mental Health (NIMH)
First posted: 2007-08-22
Enrollment: 245
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: 12 weeks
Secondary outcomes:
measure: Remission: Persistent Hamilton Rating Scale for Depression, 17 Items (HAM-D 17) <= 7, With no HAM-D 17 >7 Through Week 12
timeFrame: 12 weeks
measure: Severity of Depressive Symptoms as Measured by Hamilton Rating Scale for Depression (HAM-D 17)
timeFrame: 12 weeks
measure: Functioning, as Measured by the Social Adjustment Scale (SAS) Summary Score
timeFrame: 12 weeks
measure: Quality of Life, as Measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Short Form (SF)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: New York
country: United States
facility: New York State Psychiatric Institute
state: New York
city: Ottawa
country: Canada
facility: University of Ottawa, Institute of Mental Health Research
state: Ontario
Study officials:
affiliation: New York State Psychiatric Institute
name: Jonathan W. Stewart, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Ottawa
name: Pierre Blier, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Weissman MM, Wickramaratne P, Pilowsky DJ, Poh E, Batten LA, Hernandez M, Flament MF, Stewart JA, McGrath P, Blier P, Stewart JW. Treatment of maternal depression in a medication clinical trial and its effect on children. Am J Psychiatry. 2015 May;172(5):450-9. doi: 10.1176/appi.ajp.2014.13121679. Epub 2015 Jan 23.
citation: Gerra ML, Marchesi C, Amat JA, Blier P, Hellerstein DJ, Stewart JW. Does negative affectivity predict differential response to an SSRI versus a non-SSRI antidepressant? J Clin Psychiatry. 2014 Sep;75(9):e939-44. doi: 10.4088/JCP.14m09025.
citation: Stewart JW, McGrath PJ, Blondeau C, Deliyannides DA, Hellerstein D, Norris S, Amat J, Pilowsky DJ, Tessier P, Laberge L, O'Shea D, Chen Y, Withers A, Bergeron R, Blier P. Combination antidepressant therapy for major depressive disorder: speed and probability of remission. J Psychiatr Res. 2014 May;52:7-14. doi: 10.1016/j.jpsychires.2013.12.001. Epub 2013 Dec 17.