Investigation of Tibolone and Escitalopram in Perimenopausal Depression

This study has been terminated.
(Difficulty in recruiting)
Sponsor:
Information provided by (Responsible Party):
Jayashri Kulkarni, Professor, The Alfred
ClinicalTrials.gov Identifier:
NCT01368068
First received: June 3, 2011
Last updated: September 1, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Perimenopausal Depression
Drug: Tibolone
Drug: Escitalopram
Drug: Natvia
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Double-Blind Randomised Investigation of Tibolone or Escitalopram in First Onset Perimenopausal Depression

Resource links provided by NLM:


Further study details as provided by The Alfred:

Primary Outcome Measures:
  • Montgomery and Asberg Depression Rating Scale [ Time Frame: Baseline, then at weeks 2, 4, 8 and 12. ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Short Form-36 Health Survey (SF-36) [ Time Frame: Baseline and 12 ] [ Designated as safety issue: No ]
    A 36 item self report measure that assesses: physical health and bodily pain; vitality, social functioning; role limitations due to emotional problems; and mental health. This scale will be used to assess the changes to various domains of self-reported health from baseline compared to visits at baseline and week 12.

  • Pittsburgh Sleep Quality Index [ Time Frame: Baseline and 12. ] [ Designated as safety issue: No ]
    A valid and reliable 19-item self report index measuring sleep quality, latency, duration, disturbances, and daytime dysfunction. This scale will be used to measure different domains of sleep quality at visits occurring at week baseline and week 12 compared to initial baseline measurement.

  • Adverse Symptoms Checklist [ Time Frame: Weeks 2, 4, 8 and 12 ] [ Designated as safety issue: Yes ]
    A 22 item checklist of general adverse symptoms experienced. This scale will be used to measure adverse symptoms experienced by participants at weeks 2, 4, 8 and 12 compared to baseline.

  • Beck Depression Inventory Scale [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: Yes ]
    A subjective rating scale that compliments the MADRS and will be used at baseline and week 12 visits throughout the study.


Enrollment: 2
Study Start Date: July 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Tibolone
Subjects will take 2.5mg of oral Tibolone daily for the duration of the 12 week trial.
Drug: Tibolone
2.5mg/oral/daily
Other Name: Livial
Active Comparator: Escitalopram
10mg of escitalopram will be taken by participants daily for the duration of the 12 week trial period.
Drug: Escitalopram
10mg/oral/daily
Other Name: Lexapro
Placebo Comparator: Placebo
Placebo arm containing sweetener has been approved and will be used as placebo arm.
Drug: Natvia
serving size: 0.09g per tablet
Other Name: Natvia Natural Sweetener

Detailed Description:

All women experience menopause and a significant number suffer from ongoing, severe depression beginning with the major hormone fluctuations in this middle stage of life. The number of women experiencing menopause related major depression and the impact of this depression on the woman's life, work and her family are grossly underestimated. We propose to conduct a clinical trial of a new hormone treatment for women with severe depression related to menopause, compared with standard antidepressant medication.

Longitudinal epidemiological studies have shown that many women experience significant physical and psychological changes as they approach menopause and for a long time following. Vasomotor symptoms (such as hot flushes, night sweats), sleep disturbances and changes in libido are common, and impact significantly on the quality of life, social and personal well-being. However, the major reason that many women seek help from menopause clinics or their doctors, is for depression and anxiety symptoms.

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.

  Eligibility

Ages Eligible for Study:   45 Years to 55 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01368068

Locations
Australia, Victoria
The Alfred Hospital
Melbourne, Victoria, Australia, 3004
Sponsors and Collaborators
The Alfred
Investigators
Principal Investigator: Jayashri Kulkarni, PhD,FRANZP Monash Alfred Psychiatry Research Centre
  More Information

No publications provided

Responsible Party: Jayashri Kulkarni, Professor, Professor, The Alfred
ClinicalTrials.gov Identifier: NCT01368068     History of Changes
Other Study ID Numbers: 161/11
Study First Received: June 3, 2011
Last Updated: September 1, 2014
Health Authority: Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by The Alfred:
Perimenopause
Depression

Additional relevant MeSH terms:
Depression
Depressive Disorder
Behavioral Symptoms
Mental Disorders
Mood Disorders
Citalopram
Dexetimide
Tibolone
Anabolic Agents
Androgen Antagonists
Anti-Dyskinesia Agents
Antidepressive Agents
Antidepressive Agents, Second-Generation
Antihypertensive Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Antiparkinson Agents
Autonomic Agents
Cardiovascular Agents
Central Nervous System Agents
Cholinergic Agents
Cholinergic Antagonists
Estrogen Receptor Modulators
Hormone Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Muscarinic Antagonists
Neurotransmitter Agents
Neurotransmitter Uptake Inhibitors

ClinicalTrials.gov processed this record on October 23, 2014