Clinical trial NCT02234362: Vortioxetine for Menopausal Depression
Official title: Vortioxetine for Menopausal Depression and Associated Symptoms
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Depression
Menopause
Vasomotor Disturbance
Hot Flashes
Sleep
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Takeda Pharmaceuticals North America, Inc.
First posted: 2014-09-09
Enrollment: 47
Sex: FEMALE
Minimum age (years): 40
Maximum age (years): 62
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The broad goal of this study was to examine the efficacy and tolerability of vortioxetine (flexible dose) for the treatment of major depressive disorder (MDD) in symptomatic women around the menopausal transition. We hypothesized that an eight-week treatment with vortioxetine would promote a significant improvement of depression symptoms and other menopause-related physical symptoms.

Detailed description: Forty-seven peri- and postmenopausal women were enrolled in this open-label study. This was an 8-week intervention using open-label vortioxetine with flexible dose between 5-20 mg, dependent on participant response and tolerability. In addition to assessment of depressive symptoms, improvement of menopause-related physical and emotional symptoms that occur with MDD, including vasomotor symptoms, cognition, fatigue, anxiety, sleep complaints, and quality of life, were also examined.

Eligibility criteria: Inclusion Criteria:

1. Women aged 40-62 years who are perimenopausal or early postmenopausal (within 5 years of the last menstrual period if not surgically postmenopausal), including:

   1. Perimenopausal women who have experienced changes in menstrual cycle frequency or duration, and/or physical symptoms indicative of menopausal transition, as determined by clinician
   2. Women who are using the Mirena Intrauterine Device (IUD), with Follicle-stimulating hormone (FSH) level \> 20 milli-International unit/ml (mIU/mL)
2. Women meeting Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV) criteria for major depression (assessed by the Mini International Neuropsychiatric Interview - M.I.N.I.)
3. MADRS scores of at least 20 at baseline visit
4. Women with significant menopause-related physical symptoms, indicated by any of the following criteria:

   1. Greene Climacteric Scale total scores \> 20;
   2. Greene Climacteric Scale sub-score for vasomotor symptoms \>3;
   3. 14 or more bothersome hot flashes per week (self-reported).
5. Signed informed consent.

Exclusion Criteria:

1. Pregnancy (determined by urine pregnancy test), intending pregnancy, or breast feeding.
2. Women whose primary diagnosis is Panic Disorder, Obsessive Compulsive Disorder (OCD), Generalized Anxiety Disorder (GAD), Seasonal Affective Disorder (SAD), or any other Axis I pathology active within 6 months prior to screening visit (except for specific phobias). Anxiety disorders are allowable if secondary to MDD as the primary diagnosis.
3. History of or current mania/hypomania, psychosis, or bipolar disorder
4. Regular treatment with an Selective Serotonin Reuptake Inhibitor (SSRI) or Selective Norepinephrine Reuptake Inhibitors (SNRI) within 2 months prior to screening visit
5. Serious suicidal ideation or intent
6. Women who have used psychoactive or centrally acting medications within 2 weeks prior to study screening
7. Women who have received hormonal intervention within 1 month prior to study entry
8. Known hypersensitivity to vortioxetine or any of the inactive ingredients
9. Treatment with a monoamine oxidase inhibitor (MAOI) within 14 days of randomization or potential need to use an MAOI during the study or within 21 days of discontinuation of study drug
10. Treatment with linezolid or intravenous methylene blue
11. Patients with severe hepatic impairment
12. Uncontrolled hypertension (\>160/90 mmHg)
13. Resting heart rate \>110/minute
14. Any current severe or unstable medical illness
15. Not using a medically approved method of birth control, if sexually active and not 12 or more months since last menstrual period
16. Drug or alcohol abuse in the past 1 year
17. Use of any disallowed medications (specified in the Excluded Concomitant Medication section below)
18. Concurrent enrollment in another clinical trial

Excluded Concomitant Medications:

* Selective estrogen-receptor modulators (SERMs)
* Hormone replacement therapy
* Hormonal contraceptives, excluding Mirena IUD
* Natural menopause supplements
* Episodic sleep medications (chronic, regular, stable-dose benzodiazepines are allowed)
* Antidepressants
* Phytoestrogens
* Soy-based medications
* Steroids
* Anorectics, appetite depressants

Primary outcomes:
measure: Change From Baseline in Montgomery-Asberg Depression Rating Scale Score (MADRS) at Week 8 (Visit 5)
timeFrame: Baseline and Week 8 (Visit 5)
Secondary outcomes:
measure: Change From Baseline in Vasomotor Symptoms (VMS) Frequency During Daytime at Week 8 (Visit 5)
timeFrame: Baseline and Week 8 (Visit 5)
measure: Change From Baseline in Vasomotor Symptoms (VMS) Severity During Daytime at Week 8 (Visit 5)
timeFrame: Baseline and Week 8 (Visit 5)
measure: Change From Baseline in Vasomotor Symptoms (VMS) Frequency During Nighttime at Week 8 (Visit 5)
timeFrame: Baseline and Week 8 (Visit 5)
measure: Change From Baseline in Vasomotor Symptoms (VMS) Severity During Nighttime at Week 8 (Visit 5)
timeFrame: Baseline and Week 8 (Visit 5)
measure: Change From Baseline in Cognitive and Physical Functioning Questionnaire (CPFQ) Score at Week 8 (Visit 5)
timeFrame: Baseline and Week 8 (Visit 5)
measure: Change From Baseline in Beck Anxiety Inventory (BAI) Score at Week 8 (Visit 5)
timeFrame: Baseline and Week 8 (Visit 5)
measure: Change From Baseline in Pittsburgh Sleep Quality Index (PSQI) Score at Week 8 (Visit 5)
timeFrame: Baseline and Week 8 (Visit 5)
measure: Change From Baseline in Menopause Specific Quality of Life (MENQOL) Score at Week 8 (Visit 5)
timeFrame: Baseline and Week 8 (Visit 5)
measure: Change From Baseline in Clinical Global Impression-Fatigue (CGI-F) Scale Score at Week 8 (Visit 5)
timeFrame: Baseline and Week 8 (Visit 5)
measure: Change From Baseline in Clinical Global Impression-Severity (CGI-S) Scale Score at Week 8 (Visit 5)
timeFrame: Baseline and Week 8 (Visit 5)
measure: Change From Baseline in Pain Assessment (PEG) Score at Week 8 (Visit 5)
timeFrame: Baseline and Week 8 (Visit 5)
measure: Change From Baseline in Greene Climacteric Scale (GCS) Score at Week 8 (Visit 5)
timeFrame: Baseline and Week 8 (Visit 5)
measure: Change From Baseline in Digit Symbol Substitution Test (DSST) Score at Week 8 (Visit 5)
timeFrame: Baseline and Week 8 (Visit 5)
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Marlene P Freeman, MD
role: PRINCIPAL_INVESTIGATOR
References:
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