Contact information
Type
Scientific
Primary contact
Prof Pierre Blier
ORCID ID
Contact details
1145 Carling Avenue
LG 2043
Ottawa
ON K1Z 7K4
Canada
+1 613 722 6521/6908
pblier@rohcg.on.ca
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Acronym
Study hypothesis
1. A six-week treatment with a daily dose 20 mg of fluoxetine by itself will produce a clinically significant antidepressant response
2. A six-week treatment with mirtazapine in combination with any of the following three antidepressant medications: fluoxetine, bupropion, or venlafaxine, by producing a sustained increase in 5-hydroxytryptamine (5-HT) synaptic availability in the presence of epinephrine (NE) reuptake blockade or increased NE release, will induce a more robust clinical response compared to those patients receiving only fluoxetine
3. A six-week treatment with a combination of mirtazapine and venlafaxine or with mirtazapine and bupropion, by producing initially a greater synaptic availability of NE than with mirtazapine alone, and by enhancing 5-HT neurotransmission rapidly as well, will induce a more rapid clinical response. Therefore, patients receiving a six-week treatment with these two combinations of antidepressant medications will demonstrate an earlier onset of their clinical response compared to those receiving only fluoxetine or fluoxetine plus mirtazapine.
Ethics approval
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Major depression
Intervention
This is a double-blind study comparing the effects of fluoxetine alone to those of mirtazapine plus fluoxetine, mirtazapine plus venlafaxine, and mirtazapine plus bupropion in patients presenting with major depression. At the end of the six-week trial, remitters that received either fluoxetine plus placebo or fluoxetine plus mirtazapine will be maintained on fluoxetine alone for six months and those that received either bupropion or venlafaxine will be maintained on mirtazapine alone for the same period of prolongation. Non-responders will be offered alternate treatment strategies by the principal investigator.
Intervention type
Drug
Phase
Not Specified
Drug names
1. Mirtazapine
2. Fluoxetine
3. Bupropion
4. Venlafaxine
Primary outcome measures
The primary efficacy variables are the total Hamilton Depression Rating Scale (HAM-D), total Montgomery-Asberg Depression Rating Scale (MADRS), Clinical Global Impression (CGI) improvement scale, CGI severity scale, the percentage of responders (i.e. improvement of 50% or more on the total MADRS), and the percentage of remitters (i.e. a score of 8 or less on the HAM-D)
Secondary outcome measures
The secondary variable is the depression subscale of the Symptom Checklist-90-R (SCL-90-R)
Overall trial start date
01/07/2001
Overall trial end date
31/12/2005
Reason abandoned
Eligibility
Participant inclusion criteria
1. Male or female patients between 18 and 65 years of age
2. Diagnosis of major depression according to the Diagnostic and Statistical Manual of Mental Disorders - fourth edition (DSM-IV) (American Psychiatric Association, 1994) using the Structural Clinical Interview for DSM-IV (SCID) (Spitzer and Williams, 1988)
3. Initial global score 18 on the first 17 items of the 24-item Hamilton Depression Rating Scale
4. Written informed consent signed by the patient
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
100
Participant exclusion criteria
1. Patients who have not participated in another clinical trial in the past 30 days
2. Evidence of suicidal tendencies
3. Evidence of significant physical illness contraindicating the use of fluoxetine, mirtazapine, venlafaxine or bupropion, found on physical or in the laboratory data obtained during the first week of the study
4. Mental retardation (Intelligence Quotient [IQ] lower than 80) rendering the response to investigators unreliable
5. Pregnancy, or absence of adequate contraceptive method in women with childbearing potential
6. Concurrent use of psychotropic medication such as neuroleptics, mood stabilizers or regular use of high doses of benzodiazepines
7. Lack of response to fluoxetine for the present episode
Recruitment start date
01/07/2001
Recruitment end date
31/12/2005
Locations
Countries of recruitment
United States of America
Trial participating centre
1145 Carling Avenue
Ottawa
ON K1Z 7K4
Canada
Funders
Funder type
Industry
Funder name
Organon International Inc (USA)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2010 results in http://www.ncbi.nlm.nih.gov/pubmed/20008946
Publication citations
-
Results
Blier P, Ward HE, Tremblay P, Laberge L, Hébert C, Bergeron R, Combination of antidepressant medications from treatment initiation for major depressive disorder: a double-blind randomized study., Am J Psychiatry, 2010, 167, 3, 281-288, doi: 10.1176/appi.ajp.2009.09020186.