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Major Depressive DisorderPhase 4NCT00519428

Does Dual Therapy Hasten Antidepressant Response?

A Phase 4 study testing escitalopram, bupropion extra long (XL) and escitalopram + bupropion in people with Major Depressive Disorder, run by New York State Psychiatric Institute at 2 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Major Depressive Disorder
What is being tested?
escitalopram, bupropion extra long (XL) and escitalopram + bupropion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
245 participants
Where
2 sitesin 2 countries
Study dates
Aug 2007to Mar 2012
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • 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
Show all 14Show fewer
  • 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

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

United States1 site

  • New York State Psychiatric Institute

    New York, New York, 10032

Other trials in United States

Canada1 site

  • University of Ottawa, Institute of Mental Health Research

    Ottawa, Ontario, K1Z7K4

Other trials in Canada

About this study

Official title: Combining Antidepressants to Hasten Remission From Depression

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.

Read the 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.

Being tested
escitalopram, bupropion extra long (XL), escitalopram + bupropion
Keywords
depression, Major Depressive Disorder
Medical subject headings
Depressive Disorder, Major, Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • escitalopramDrug

    Also called Lexapro

    10mg/d increasing by 10 mg/week to a maximum of 40 mg/d if tolerated and not remitted

  • bupropion extra long (XL)Drug

    Also called Wellbutrin extra long (XL)

    150mg/d increasing to 300 mg/d after 1 week and 450 mg/d after 3 weeks, all increases if tolerated and not remitted

  • escitalopram + bupropionDrug

    Also called Lexapro, Wellbutrin

    same dosing schedule as for monotherapy

Study groups in NCT00519428
Study groupRoleWhat they receive
escitalopram + bupropionExperimentalescitalopram 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)
Receives: Drug: escitalopram + bupropion
escitalopramActive comparatorescitalopram monotherapy
Receives: Drug: escitalopram
bupropionActive comparatorbupropion extra long (XL) monotherapy
Receives: Drug: bupropion extra long (XL)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    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.

    Measured: 12 weeks

Secondary outcomes (4)

  1. Remission: Persistent Hamilton Rating Scale for Depression, 17 Items (HAM-D 17) <= 7, With no HAM-D 17 >7 Through Week 12

    Chi square comparison of rates of persistent remission (i.e., no subsequent Hamilton Rating Scale for Depression, 17 items [HAMD-D 17] > 7 once HAMD-D 17 <= 7); Dual rate vs. Escitalopram only rate and Dual rate vs. Bupropion only rate.

    Measured: 12 weeks

  2. Severity of Depressive Symptoms as Measured by Hamilton Rating Scale for Depression (HAM-D 17)

    Last summary score rating on the 17-item Hamilton Rating Scale for Depression Eight items are scored on a 5-point scale, ranging from 0 = not present to 4 = severe. Nine are scored from 0-2. Range 0-58.

    0-7 = Normal 8-13 = Mild Depression 14-18 = Moderate Depression 19-22 = Severe Depression

    ≥ 23 = Very Severe Depression

    Measured: 12 weeks

  3. Functioning, as Measured by the Social Adjustment Scale (SAS) Summary Score

    Social adjustment was measured using the Social Adjustment Scale (SAS). The SAS is a self-report scale that assesses depressive symptoms and functioning in nine social and work-related domains generating a total score that is indicative of a subject's overall level of social adjustment. Subjects rate their own social functioning over times on a 5-point scale on items covering work for pay, housework, extended family, parenting, marital status, social activity and leisure, family unit and student status (sub-scales). Mean values of all the sub-scales are used, with a range from 0-5. Higher score = worse outcome … worse functioning

    Measured: 12 weeks

  4. Quality of Life, as Measured by the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) Short Form (SF)

    The Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) intends to measure quality of life in 16 domains. A summary score is computed by adding the scores and dividing by 16 (or the number of answered items if some are not answered).

    The minimum raw score on the Q-LES-Q-SF is 14, and the maximum score is 70. Higher score means more satisfaction.

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Aug 2007 (estimated)
  2. Study startAug 2007
  3. Primary completionJul 2011
  4. Study completionMar 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
245 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00519428
Sponsor's protocol ID
5476
Other IDs
5R01MH076961-04
Status last verified
Sep 2017
First submitted
20 Aug 2007
Last updated
4 Oct 2017
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • van der Wijk G, Enkhbold Y, Cnudde K, Szostakiwskyj MW, Blier P, Knott V, Jaworska N, Protzner AB. One size does not fit all: notable individual variation in brain activity correlates of antidepressant treatment response. Front Psychiatry. 2024 Apr 2;15:1358018. doi: 10.3389/fpsyt.2024.1358018. eCollection 2024.

    PubMed 38628260

  • 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.

    PubMed 25615566

  • 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.

    PubMed 25295437

  • 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.

    PubMed 24485847

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing escitalopram, bupropion extra long (XL) and escitalopram + bupropion in people with Major Depressive Disorder, run by New York State Psychiatric Institute at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Oct 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Oct 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00519428, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2017.

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