Comparison of Venlafaxine and Fluoxetine in the Treatment of Postmenopausal Women With Major Depression

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

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.

Study Overview

• Status: Completed
• Conditions: Major Depression
• Intervention / Treatment: Drug: venlafaxine; Drug: fluoxetine

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.

• Study Type: Interventional
• Enrollment (Actual): 189
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100088
      • Beijing Anding Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: venlafaxine; venlafaxine 75-225mg qd	Drug: venlafaxine; venlafaxine 75-225mg qd; Other Names: Efexor
Active Comparator: fluoxetine; fluoxetine 20-60mg qd	Drug: fluoxetine; fluoxetine 20-60mg qd; Other Names: Prozac

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Improvement	change of 24-item Hamilton Rating Scale for Depression total score	from baseline to endpoint(Week 8)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement of individual symptoms	the mean change of HAMD-24 subscale score in items 10, 11, 12, 13 (anxiety and somatizations) at endpoint	from baseline to endpoint(week 8)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain	the mean change of Pain visual analog scale (Pain VAS）	from baseline to endpoint
safety outcome	the proportion of patients who discontinue due to lack of efficacy or intolerability	From enrollment to endpoint (Week 8)

Collaborators and Investigators

• Sponsor: Capital Medical University
• Investigators: Principal Investigator: Gang Wang, M.D.,Ph.D, Beijing Anding Hospital, Capital Medical University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 7, 2013
• Primary Completion (Actual): March 16, 2017
• Study Completion (Actual): March 16, 2017

Study Registration Dates

• First Submitted: April 1, 2013
• First Submitted That Met QC Criteria: April 1, 2013
• First Posted (Estimate): April 4, 2013

Study Record Updates

• Last Update Posted (Actual): September 14, 2017
• Last Update Submitted That Met QC Criteria: September 12, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: major depressive disorder; postmenopause; fluoxetine; venlafaxine
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder; Depressive Disorder, Major; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Serotonin and Noradrenaline Reuptake Inhibitors; Cytochrome P-450 CYP2D6 Inhibitors; Venlafaxine Hydrochloride; Fluoxetine
• Other Study ID Numbers: VFPWMDD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No