Investigation of Tibolone and Escitalopram in Perimenopausal Depression

NCT01368068 | Terminated Phase 4 DMC

• 1 other identifier: 161/11
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Many perimenopausal women experience severe mood symptoms for the first time in their life, with no past psychiatric history. The importance of clearly identifying and treating a disorder that is increasingly referred to as "perimenopausal depression" is highlighted by the wide-reaching impact this can have on the lives of women suffering from it. This is not a minor or short term mood disturbance; it is a severe depressive illness, needing effective and early treatment. Relationships, employment, participation in social roles and individual well-being can all be disrupted by the combination of the mood, hormonal and physical changes associated with the transition to menopause. The term "perimenopausal depression" denotes the onset of depression coinciding with the onset of reproductive hormone changes. Many women with this type of depression experience serious and long term debilitating symptoms. Treatment commonly draws on traditional approaches for the management of major depression including the use of antidepressants such as selective serotonin reuptake inhibitors (SSRIs) as the first line response. However, standard treatment of perimenopausal depression using antidepressants has only shown small improvements at best and at worst, is associated with severe side effects. Some SSRIs have been shown to be less effective in postmenopausal women compared to child bearing age women. Hormone treatments directly targeting the fluctuating reproductive hormone systems (in particular estrogen) through the administration of compounds such as tibolone, have significant potential as a better overall treatment. To date, there is still a lack of clear clinical evidence about the best approach for the biological treatment of women with perimenopausal depression. The project we now propose to conduct is a 12-week randomised controlled trial (RCT) of 2.5 mg/day tibolone compared to 10mg/day of escitalopram (an SSRI that has targeted serotonin action)compared to placebo to discover the best treatment approach for a hitherto understudied depression that affects a large proportion of women in their late forties and fifties.

Conditions

Perimenopausal Depression

Keywords

Perimenopause; Depression

Outcome Measures

Primary Outcomes (1)

• Montgomery and Asberg Depression Rating Scale

  A 10-item clinician rated scale validated to be most strongly sensitive to change in depression associated with treatment. This scale will be used to measure change in depression associated with treatment at weeks 2, 4, 8 and 12 compared to baseline.

  Baseline, then at weeks 2, 4, 8 and 12.

Secondary Outcomes (4)

• Short Form-36 Health Survey (SF-36)

  Baseline and 12

• Pittsburgh Sleep Quality Index

  Baseline and 12.

• Adverse Symptoms Checklist

  Weeks 2, 4, 8 and 12

• Beck Depression Inventory Scale

  Baseline and week 12

Study Arms (3)

Tibolone

EXPERIMENTAL

Subjects will take 2.5mg of oral Tibolone daily for the duration of the 12 week trial.

Drug: Tibolone

Escitalopram

ACTIVE COMPARATOR

10mg of escitalopram will be taken by participants daily for the duration of the 12 week trial period.

Drug: Escitalopram

Placebo

PLACEBO COMPARATOR

Placebo arm containing sweetener has been approved and will be used as placebo arm.

Drug: Natvia

Interventions

Tibolone DRUG

2.5mg/oral/daily

Also known as: Livial

Tibolone

Escitalopram DRUG

10mg/oral/daily

Also known as: Lexapro

Escitalopram

Natvia DRUG

serving size: 0.09g per tablet

Also known as: Natvia Natural Sweetener

Placebo

Eligibility Criteria

• Age: 45 Years - 55 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Females who are currently physically well and between 45 and 55 years of age
• Current DSM-IV diagnosis of depression disorder
• Able to give informed consent
• Perimenopausal as determined by symptom profile on the Stages of Reproductive Aging Workshop and gonadal hormonal profile

You may not qualify if:

• Known abnormalities in the hypothalamic-pituitary gonadal axis, thyroid dysfunction, central nervous system tumours, active or past history of a venous thromboembolic event, breast pathology, undiagnosed vaginal bleeding or abnormal Pap smear results in the previous 2 years.
• Patients with any significant unstable medical illness such as epilepsy and diabetes or known active cardiac, renal or liver disease; or the presence of illness causing immobilisation.
• Patients receiving treatment for depression including antidepressant medications, electroconvulsive therapy (ECT) / Transcranial Magnetic Stimulation (TMS), formal psychotherapy or counselling, within the past 6 months
• Patients experiencing severe melancholia, neurovegetative symptoms or current suicidality necessitating acute hospitalisation or intensive psychiatric treatment.
• Patients with psychotic symptoms or past history of severe mental illness including schizophrenia, and bipolar disorder.
• Use of any form of estrogen, progestin or androgen as hormonal therapy, or antiandrogen including tibolone or use of phytoestrogen supplements as powder or tablet
• Pregnancy / Lactation
• Smoking cigarettes and other nicotine products.
• illicit drug use and more than 3 standard drinks per day

Sponsors & Collaborators

• The Alfred: lead

Study Sites (1)

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

MeSH Terms

Conditions

Depression

Interventions

tibolone; Escitalopram

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Jayashri Kulkarni, PhD,FRANZP

  Monash Alfred Psychiatry Research Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 3, 2011
• First Posted: June 7, 2011
• Study Start: July 1, 2012
• Primary Completion: July 1, 2012
• Study Completion: July 1, 2012
• Last Updated: March 31, 2015

Record last verified: 2015-03

Locations

AU (1)