Vortioxetine for Menopausal Depression

NCT02234362 | Completed Phase 4 Results

• 1 other identifier: 2014P001812
• Study Type: interventional
• Target: 47
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression; Menopause; Vasomotor Disturbance; Hot Flashes; Sleep

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Montgomery-Asberg Depression Rating Scale Score (MADRS) at Week 8 (Visit 5)

  The efficacy of vortioxetine for trea-ting depressive symptoms was measured by mean change in Montgomery-Asberg Depression Rating Scale (MADRS) depression score from Baseline (Visit 1) to Week 8 (Visit 5). The MADRS score was assessed at every study visit (Visits 1-5). Participants were considered to have responded to vortioxetine if their MADRS score was reduced by 50% or more from baseline to the end of treatment, and to be in remission if their final MADRS score was less than 10. Higher MADRS score indicates more severe depression. The overall MADRS score ranges from 0 to 60.

  Baseline and Week 8 (Visit 5)

Secondary Outcomes (13)

• Change From Baseline in Vasomotor Symptoms (VMS) Frequency During Daytime at Week 8 (Visit 5)

  Baseline and Week 8 (Visit 5)

• Change From Baseline in Vasomotor Symptoms (VMS) Severity During Daytime at Week 8 (Visit 5)

  Baseline and Week 8 (Visit 5)

• Change From Baseline in Vasomotor Symptoms (VMS) Frequency During Nighttime at Week 8 (Visit 5)

  Baseline and Week 8 (Visit 5)

• Change From Baseline in Vasomotor Symptoms (VMS) Severity During Nighttime at Week 8 (Visit 5)

  Baseline and Week 8 (Visit 5)

• Change From Baseline in Cognitive and Physical Functioning Questionnaire (CPFQ) Score at Week 8 (Visit 5)

  Baseline and Week 8 (Visit 5)

Study Arms (1)

open-label vortioxetine

EXPERIMENTAL

flexible-dose vortioxetine of 5-20 mg depending on tolerability

Drug: vortioxetine

Interventions

vortioxetine DRUG

Eligible subjects will initiate the treatment with 5 mg/day for two days and then 10 mg/day starting on Day 3. The dosage may be increased from 10 mg/day to 15 mg/day at Visit 2 or Visit 3. At Visit 4, the dosage may again be increased from 10 to 15 mg/day or from 15 to 20 mg/day, based on patient response and tolerability.

Also known as: Trintellix

open-label vortioxetine

Eligibility Criteria

• Age: 40 Years - 62 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Women aged 40-62 years who are perimenopausal or early postmenopausal (within 5 years of the last menstrual period if not surgically postmenopausal), including:
• Perimenopausal women who have experienced changes in menstrual cycle frequency or duration, and/or physical symptoms indicative of menopausal transition, as determined by clinician
• Women who are using the Mirena Intrauterine Device (IUD), with Follicle-stimulating hormone (FSH) level \> 20 milli-International unit/ml (mIU/mL)
• 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.)
• MADRS scores of at least 20 at baseline visit
• Women with significant menopause-related physical symptoms, indicated by any of the following criteria:
• Greene Climacteric Scale total scores \> 20;
• Greene Climacteric Scale sub-score for vasomotor symptoms \>3;
• or more bothersome hot flashes per week (self-reported).
• Signed informed consent.

You may not qualify if:

• Pregnancy (determined by urine pregnancy test), intending pregnancy, or breast feeding.
• 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.
• History of or current mania/hypomania, psychosis, or bipolar disorder
• Regular treatment with an Selective Serotonin Reuptake Inhibitor (SSRI) or Selective Norepinephrine Reuptake Inhibitors (SNRI) within 2 months prior to screening visit
• Serious suicidal ideation or intent
• Women who have used psychoactive or centrally acting medications within 2 weeks prior to study screening
• Women who have received hormonal intervention within 1 month prior to study entry
• Known hypersensitivity to vortioxetine or any of the inactive ingredients
• 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
• Treatment with linezolid or intravenous methylene blue
• Patients with severe hepatic impairment
• Uncontrolled hypertension (\>160/90 mmHg)
• Resting heart rate \>110/minute
• Any current severe or unstable medical illness
• Not using a medically approved method of birth control, if sexually active and not 12 or more months since last menstrual period

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Takeda Pharmaceuticals North America, Inc.: collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (5)

• Bang-Andersen B, Ruhland T, Jorgensen M, Smith G, Frederiksen K, Jensen KG, Zhong H, Nielsen SM, Hogg S, Mork A, Stensbol TB. Discovery of 1-[2-(2,4-dimethylphenylsulfanyl)phenyl]piperazine (Lu AA21004): a novel multimodal compound for the treatment of major depressive disorder. J Med Chem. 2011 May 12;54(9):3206-21. doi: 10.1021/jm101459g. Epub 2011 Apr 12.

  PMID: 21486038 BACKGROUND

• Bromberger JT, Assmann SF, Avis NE, Schocken M, Kravitz HM, Cordal A. Persistent mood symptoms in a multiethnic community cohort of pre- and perimenopausal women. Am J Epidemiol. 2003 Aug 15;158(4):347-56. doi: 10.1093/aje/kwg155.

  PMID: 12915500 BACKGROUND

• Loprinzi CL, Kugler JW, Sloan JA, Mailliard JA, LaVasseur BI, Barton DL, Novotny PJ, Dakhil SR, Rodger K, Rummans TA, Christensen BJ. Venlafaxine in management of hot flashes in survivors of breast cancer: a randomised controlled trial. Lancet. 2000 Dec 16;356(9247):2059-63. doi: 10.1016/S0140-6736(00)03403-6.

  PMID: 11145492 BACKGROUND

• Pehrson AL, Cremers T, Betry C, van der Hart MG, Jorgensen L, Madsen M, Haddjeri N, Ebert B, Sanchez C. Lu AA21004, a novel multimodal antidepressant, produces regionally selective increases of multiple neurotransmitters--a rat microdialysis and electrophysiology study. Eur Neuropsychopharmacol. 2013 Feb;23(2):133-45. doi: 10.1016/j.euroneuro.2012.04.006. Epub 2012 May 20.

  PMID: 22612991 BACKGROUND

• Pehrson AL, Sanchez C. Serotonergic modulation of glutamate neurotransmission as a strategy for treating depression and cognitive dysfunction. CNS Spectr. 2014 Apr;19(2):121-33. doi: 10.1017/S1092852913000540. Epub 2013 Aug 1.

  PMID: 23903233 BACKGROUND

MeSH Terms

Conditions

Depression; Hot Flashes

Interventions

Vortioxetine

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

* lack of control group (important given that previous VMS medication trials have indicated modest placebo response rates, and it is difficult to determine whether the side effects are associated with the medication) * small sample size

Results Point of Contact

• Title: Dr. Marlene Freeman
• Organization: MGH Center for Women's Mental Health

mfreeman@partners.org

617-723-6403

Study Officials

• Marlene P Freeman, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Director, Center for Women's Mental Health

Study Record Dates

• First Submitted: September 5, 2014
• First Posted: September 9, 2014
• Study Start: June 12, 2015
• Primary Completion: September 29, 2016
• Study Completion: September 29, 2016
• Last Updated: June 28, 2017
• Results First Posted: May 2, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)