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

NCT01470092 | Completed Phase 4 DMC

• 1 other identifier: 485/11
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

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) or Selective Norepinephrine Reuptake Inhibitors (SNRIs) as the first line response. However, standard treatment of menopausal 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 menopausal depression, the investigators propose to investigate the potential of tibolone, a selective Hormone Replacement Therapy (HRT), to ameliorate de-novo or first onset depression occurring in the menopausal period.

Conditions

Menopausal Depression

Keywords

Menopause; 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 (1)

• The Beck Depression Inventory Second Edition

  Baseline and week 12

Other Outcomes (7)

• Adverse Symptoms Checklist

  Weeks 2, 4, 8 and 12

• Pittsburgh Sleep Quality Index

  Baseline and week 12

• Short Form-36 Health Survey (SF-36)

  Baseline and week 12

Study Arms (2)

Tibolone

ACTIVE COMPARATOR

Subjects will take 2.5mg of oral Tibolone daily for the duration of the 12 week trial either alone or in adjunct to currently prescribed anti-depressant medication.

Drug: Tibolone

Placebo

NO INTERVENTION

Subjects will take oral placebo tablets packaged daily for the duration of the 12 week trial either alone or in adjunct to currently prescribed antidepressant medication.

Interventions

Tibolone DRUG

Subjects will take 2.5mg of oral Tibolone daily for the duration of the 12 week trial either alone or in adjunct to currently prescribed antidepressant medication.

Also known as: Livial

Tibolone

Eligibility Criteria

• Age: 45 Years - 65 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Menopausal 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
• First-onset or relapse depression during menopause
• Currently taking either an SSRI or SNRI, or no psychotropic medication at all
• Evidence of a normal mammogram in the preceding 12 months.

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• The Alfred: lead

Study Sites (1)

The Alfred Hospital

Melbourne, Victoria, 3181, Australia

Location

Related Publications (1)

• Kulkarni J, Gavrilidis E, Thomas N, Hudaib AR, Worsley R, Thew C, Bleeker C, Gurvich C. Tibolone improves depression in women through the menopause transition: A double-blind randomized controlled trial of adjunctive tibolone. J Affect Disord. 2018 Aug 15;236:88-92. doi: 10.1016/j.jad.2018.04.103. Epub 2018 Apr 24.

  PMID: 29723767 DERIVED

MeSH Terms

Conditions

Depression

Interventions

tibolone

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Study Officials

• Jayashri Kulkarni, PhD,FRANZP

  Monash Alfred Psychiatry Research Centre

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 9, 2011
• First Posted: November 11, 2011
• Study Start: July 1, 2012
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: January 9, 2020

Record last verified: 2020-01

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)