Clinical trial NCT01824433: Comparison of Venlafaxine and Fluoxetine in the Treatment of Postmenopausal Women With Major Depression
Official title: A 8-week, Rater-blind, Active-controlled, Randomized Study to Compare the Effectiveness of Venlafaxine With Fluoxetine in the Treatment of Postmenopausal Women With Major Depressive Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Major Depression
Keywords: venlafaxine
fluoxetine
postmenopause
major depressive disorder
Lead sponsor: Capital Medical University
Sponsor class: OTHER
First posted: 2013-04-04
Enrollment: 189
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Women are more prone to depression at certain points of the life cycle, although the etiologic and therapeutic implications remain largely unknown1,2. It is reported that pre- and postmenopausal women have a significant difference in response to some antidepressants, within a large clinical trial data set3, 4. A growing number of researches indicate that a woman's hormonal status may influence response to different forms of antidepressant medication. Specifically, younger women appeared to respond better to monoamine oxidase inhibitors (MAOIs) and selective serotonin reuptake inhibitor (SSRIs), whereas men and older women have tended to have relatively better responses to tricyclic antidepressants (TCAs) 1-5. One difference between these classes of antidepressants is that the SSRIs are strongly serotoninergic, whereas TCAs have predominantly noradrenergic effects. One pooled analysis 6 suggests that older women (age ≥ 50) tend to respond poorer to SSRI, while this phenomenen was not observed with venlafaxine.

The antidepressive mechanism of venlafaxine that has both noradrenergic and serotonergic effects is superior to SSRIs. As a noradrenergic and serotonergic antidepressant, venlafaxinee has been demonstrated of significant advantages in response and remission rates compared with various SSRIs. As mentioned above, older women tend to have relatively better responses to TCAs which is predominantly noradrenergic antidepressant. Postmenopausal women with depression also would be predicted to respond better to an SSRI if administered along with hormone replacement therapy 6. This could be critical to understanding age difference in antidepressant responses across the life cycle because circulating estrogen levels may modulate central serotoninergic pathways. Therefore, it is presumed that antidepressants which enhance both serotonergic and noradrenergic neurotransmission, as venlafaxine, may be more effective than SSRIs for postmenopausal women with major depressive disorder.

Detailed description: The study is designed as a multicenter, rater-blind, parallel-group, active-controlled, flexible dose, randomized trial in postmenopausal women who are recently experiencing major depressive disorder.

Patients will be female, aged 55 or older, outpatient or inpatient status, with diagnosis of major depressive episode (single or recurrent) by DSM-IV, the current depressive episode within 1 years. The patients should also have HAMD-24 total score≥20,a HAMD-24 Item 1 (depressed mood) score≥2 at screening and baseline.

The eligible subjects will be randomly assigned to 1 of 2 treatment groups with 1:1 allocation ratio: venlafaxine 75\~225mg/d or fluoxetine 20\~60mg/d. Treatment and observational duration will be 56 days (8 weeks).

Primary efficacy measure will be assessed based on the decrease of HAMD-24 from baseline to endpoint. The secondary efficacy measures are change from baseline to endpoint in CGI-S, CGI-I, and Pain VAS et al.

The safety in this study will be assessed by adverse event reporting, clinical laboratory measurements and physical examinations.

Eligibility criteria: Inclusion Criteria:

* Female, aged 50 or older, memopausal.
* Meet DSM-IV criteria for current unipolar major depressive disorder.
* The total score of the HAMD-24 is at least 20 at screening and baseline.
* The current depressive episode within 1 year.
* If recurrent depression, the remission of previous episode is at least 5 years from the current episode.
* Providing informed consent form to participate in the study by patients or their legal representatives.

Exclusion Criteria:

* Current Axis I primary psychiatric diagnosis other than major depressive disorder.
* Substance abuse or dependence.
* Patients were also excluded if they had any medical condition that would contraindicate the use of venlafaxine or fluoxetine.
* Organic mental disease, including mental retardation.
* History of clinically significant disease, including any cardiovascular, hepatic, renal, respiratory, hematologic, endocrinologic, or neurologic disease, or clinically significant laboratory abnormality that is not stabilized or is anticipated to require treatment during the study.
* Use of psychiatric agents within 5 days prior to randomization.
* Have proved no response to venlafaxin or fluoxetine by previous treatment.
* Participation in another clinical study within 4 weeks (or longer time according to the local requirement)
* Has received ECT or MECT within 3 months prior to randomization.
* Significant risk of suicidal and/or self-harm behaviors.

Primary outcomes:
measure: Overall Improvement
timeFrame: from baseline to endpoint(Week 8)
Secondary outcomes:
measure: Improvement of individual symptoms
timeFrame: from baseline to endpoint(week 8)
Other outcomes:
measure: Pain
timeFrame: from baseline to endpoint
measure: safety outcome
timeFrame: From enrollment to endpoint (Week 8)
Locations:
city: Beijing
country: China
facility: Beijing Anding Hospital
state: Beijing
Study officials:
affiliation: Beijing Anding Hospital, Capital Medical University
name: Gang Wang, M.D.,Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zhou J, Wang X, Feng L, Xiao L, Yang R, Zhu X, Shi H, Hu Y, Chen R, Boyce P, Wang G. Venlafaxine vs. fluoxetine in postmenopausal women with major depressive disorder: an 8-week, randomized, single-blind, active-controlled study. BMC Psychiatry. 2021 May 19;21(1):260. doi: 10.1186/s12888-021-03253-8.