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

Menopausal Depression Clinical Trial

Official title:

Double-Blind Randomised Investigation of Tibolone Alone or in Adjunct to Standard Antidepressant Treatment for Depression in Menopausal Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01470092
• Other study ID #: 485/11
• Status: Completed
• Phase: Phase 4
• Start date: July 2012
• Est. completion date: December 2017

Study information

• Verified date: January 2020
• Source: The Alfred
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 45 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Menopausal Depression

Intervention

Drug:
• 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.

Locations

Country	Name	City	State
Australia	The Alfred Hospital	Melbourne	Victoria

Sponsors (1)

Lead Sponsor	Collaborator
The Alfred

Country where clinical trial is conducted

Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Adverse Symptoms Checklist	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.	Weeks 2, 4, 8 and 12
Other	Pittsburgh Sleep Quality Index	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.	Baseline and week 12
Other	Short Form-36 Health Survey (SF-36)	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.	Baseline and week 12
Other	Menopause Specific Quality of Life Questionnaire	A menopause-specific quality of life questionnaire assessing the presence and severity of vasomotor, psychosocial, physical and sexual symptoms	baseline and week 12
Other	Menopause Specific Rating Scale for Depression	A 12-item rating scale used to detect depression in menopause.	baseline and week 12
Other	Hamilton Anxiety Scale	A 14-item scale used to assess the severity of anxiety symptoms.	Baseline and weeks 2,4,8 and 12
Other	Sexual Interest and Desire Inventory	A 13 item measure of the severity of symptoms related to hypoactive sexual desire	Baseline and week 12
Primary	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	The Beck Depression Inventory Second Edition	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.	Baseline and week 12