Tibolone and Placebo in Adjunct to Antidepressant Medication for Women With Perimenopausal Depression

This study is currently recruiting participants.
Verified January 2014 by The Alfred
Sponsor:
Information provided by (Responsible Party):
Jayashri Kulkarni, Professor, The Alfred
ClinicalTrials.gov Identifier:
NCT01470092
First received: November 9, 2011
Last updated: January 13, 2014
Last verified: January 2014
  Purpose

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. As such, 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.

Newer therapies directly targeting the disrupted hormonal systems (in particular estrogen) through the administration of such compounds as tibolone, have shown significant potential to treat depression with the added benefit of fewer adverse side effects. With growing evidence supporting the use of tibolone as a viable and improved treatment for perimenopausal depression, the investigators propose to investigate the potential of tibolone, a selective Hormone Replacement Therapy (HRT), to ameliorate peri-menopausal depression in addition to treatment with Selective Serotonin Reuptake Inhibitors (SSRI). This will help to determine whether treatment with Tibolone aids the standard SSRI treatment approach for perimenopausal depression.


Condition Intervention Phase
Perimenopausal Depression
Drug: Tibolone
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Double-Blind Randomised Investigation of Tibolone in Adjunct to Standard Antidepressant Treatment for Relapsed and Persistent Depression in Peri and Post Menopausal Women

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:
  • The Beck Depression Inventory Second Edition [ Time Frame: Baseline and week 12 ] [ Designated as safety issue: No ]
    A subjective rating scale of depressive symptoms that compliments the MADRS to measure the change of subjective rating of depressive symptoms at week 12 compared to baseline.

  • Short Form-36 Health Survey (SF-36) [ Time Frame: Baseline and week 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 week 12.

  • Pittsburgh Sleep Quality Index [ Time Frame: Baseline and week 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 12 compared to initial baseline measurement.

  • Adverse Symptoms Checklist [ Time Frame: Baseline, 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


Estimated Enrollment: 30
Study Start Date: July 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Tibolone
Subjects will take 2.5mg of oral Tibolone daily for the duration of the 12 week trial in adjunct to currently prescribed anti-depressant medication.
Drug: Tibolone
Subjects will take 2.5mg of oral Tibolone daily for the duration of the 12 week trial in adjunct to currently prescribed antidepressant medication.
Other Name: Livial
No Intervention: Placebo
Subjects will take oral placebo tablets packaged daily for the duration of the 12 week trial in adjunct to currently prescribed antidepressant medication.

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. Many perimenopausal women experience severe mood symptoms for the first time in their life, with no past psychiatric history. The term "perimenopausal depression" denotes the onset of depression coinciding with the onset of reproductive hormone changes [1, 2] Many women with perimenopausal depression experience serious and long term debilitating symptoms.

Longitudinal epidemiological studies have shown that many women experience significant physical and psychological changes as they approach menopause and for a long time following [3]. 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 [4]. However, the major reason that many women seek help from menopause clinics or their doctors, is for depression and anxiety symptoms [5]. As such, 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 [6]. 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 [7].

Newer therapies directly targeting the disrupted hormonal systems (in particular estrogen) through the administration of such compounds as tibolone, have shown significant potential to treat depression with the added benefit of fewer adverse side effects [8]. With growing evidence supporting the use of tibolone as a viable and improved treatment for perimenopausal depression, the investigators propose to investigate the potential of tibolone, a selective Hormone Replacement Therapy (HRT), to ameliorate peri-menopausal depression in addition to treatment with Selective Serotonin Reuptake Inhibitors (SSRI). This will help to determine whether treatment with tibolone aids the standard SSRI treatment approach for depression.

Women with perimenopausal depression will be involved in a 12 week randomized controlled trial where they will randomised to either received tibolone (2.5mg oral/day) or with a placebo in addition to an SSRI prescribed by their primary treating clinician. Climateric symptoms, physical, psychological and sleep patterns will be assessed at baseline, at 2, 4, 8 and then again at 12 weeks. Analyses will assess whether the use of Tibolone in conjunction with SSRI aids treatment efficacy as compared to treatment with an SSRI and placebo.

  Eligibility

Ages Eligible for Study:   45 Years to 65 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Females who are currently physically well and between 45 and 65 years of age
  • Current DSM-IV diagnosis of depression disorder
  • Able to give informed consent
  • Perimenopausal as determined by standardized classification guidelines for female reproductive aging were proposed at the Stages of Reproductive (STRAW) -Aging Workshop and symptom profile on the STRAW and gonadal hormonal profile
  • Relapse depression during perimenopause
  • Currently taking an SSRI or SNRI
  • Evidence of a normal mammogram in the preceding 12 months.

Exclusion Criteria:

  • Patients with 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 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 or other nicotine products
  • illicit drug use
  • more than 3 standard drinks per day
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01470092

Contacts
Contact: Emmy Gavrilidis, BSc +613 9076 6913 emmy.gavrilidis@monash.edu
Contact: Tamsyn Van Rheenen, BSoCSci +613 9076 5031 tamsyn.van-rheenen@monash.edu.au

Locations
Australia, Victoria
The Alfred Hospital Recruiting
Melbourne, Victoria, Australia, 3181
Contact: Emmy Gavrilidis, Bsc    +613 9076 6913    emmy.gavrilidis@monash.edu   
Contact: Tamsyn Van Rheenen, BSocSci    +613 9076 5031    tamsyn.van-rheenen@monash.edu   
Principal Investigator: Jayashri Kulkarni, PhD,FRANZP         
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: NCT01470092     History of Changes
Other Study ID Numbers: 485/11
Study First Received: November 9, 2011
Last Updated: January 13, 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
Mood Disorders
Mental Disorders
Antidepressive Agents
Tibolone
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Androgen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antihypertensive Agents
Cardiovascular Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Modulators
Anabolic Agents
Hormones

ClinicalTrials.gov processed this record on April 17, 2014