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

NCT ID: NCT01470092

Last Updated: 2020-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2017-12-31

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.

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. 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.

Indeed, many menopausal women with no past psychiatric history experience severe mood symptoms during menopause for the first time in their life, and this has serious and debilitating long term consequences. Treatment for such depression 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 women of child bearing age.

Newer therapies directly targeting the fluctuations in reproductive hormonal hormone systems (in particular estrogen, progesterone and testosterone) 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 relapsing depression occurring in the menopausal period.

Women with menopausal depression either currently using or not using an SSRI or SNRI medication will be involved in a 12 week randomized control trial in which they may be randomised to one of two groups: i) Tibolone (2.5mg oral/day) or ii) placebo.

It is hypothesized that women receiving Tibolone in adjunct to standard antidepressant medication, will have the same as or a significantly greater improvement in depressive symptoms compared with women receiving placebo in adjunct to standard antidepressant medication and women not using any psychotropic/hormone treatment.

Conditions

Menopausal Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Tibolone

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.

Group Type: ACTIVE_COMPARATOR

Tibolone

Intervention Type: 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.

Placebo

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

Tibolone

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.

Intervention Type: DRUG

Other Intervention Names

Livial

Eligibility 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
• 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.

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.
• 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

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

The Alfred

OTHER

Sponsor Role: lead

Responsible Party

Jayashri Kulkarni, Professor

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jayashri Kulkarni, PhD,FRANZP

Role: PRINCIPAL_INVESTIGATOR

Monash Alfred Psychiatry Research Centre

Locations

The Alfred Hospital

Melbourne, Victoria, Australia

Countries

Australia

References

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.

Reference Type: DERIVED

PMID: 29723767 (View on PubMed)

Other Identifiers

485/11

Identifier Type: -

Identifier Source: org_study_id