Menopausal DepressionPhase 4NCT01470092
Tibolone and Placebo in Adjunct to Antidepressant Medication for Women With Menopausal Depression
A Phase 4 study testing Tibolone in people with Menopausal Depression, run by The Alfred at 1 site in Australia.
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. Read more about this study
- Who is it for?
- Ages 45 to 65 years, women only
- Conditions the study is for
- Menopausal Depression
- What is being tested?
- Tibolone
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteAustralia
- Study dates
- Jul 2012to Dec 2017
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 65 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- Smoking cigarettes or other nicotine products
- Illicit drug use
- More than 3 standard drinks per day
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Double-Blind Randomised Investigation of Tibolone Alone or in Adjunct to Standard Antidepressant Treatment for Depression in Menopausal Women
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.
Read the 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
- Being tested
- Tibolone
- Keywords
- Menopause, Depression
- Medical subject headings
- Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TiboloneDrug
Also called Livial
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, then at weeks 2,4, 8 and 12
Secondary outcomes (1)
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.
Measured: Baseline and week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2011 (estimated)
- Study startJul 2012
- Primary completionDec 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Menopausal DepressionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Alfred
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Jayashri Kulkarni, Professor, The Alfred
- Investigators
- Jayashri Kulkarni, PhD,FRANZP, Principal investigator, Monash Alfred Psychiatry Research Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01470092
- Sponsor's protocol ID
- 485/11
- Status last verified
- Jan 2020
- First submitted
- 9 Nov 2011
- Last updated
- 9 Jan 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
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.
PubMed 29723767
Study at a glance
From the registry record, last updated by the sponsor on 9 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-Blind Randomised Investigation of Tibolone Alone or in Adjunct to Standard Antidepressant Treatment for Depression in Menopausal Women
- ClinicalTrials.gov ID
- NCT01470092
- Acronym / sponsor ID
- 485/11
- Conditions
- Menopausal Depression
- Keywords
- Menopause, Depression
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- The AlfredUniversity, hospital or other
- Study start
- Jul 2012
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 11 Nov 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Tibolone | Active comparator | Drug: TiboloneSubjects 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. |
| 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. |
Who may qualify
- Ages
- 45 to 65 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TiboloneAlso: LivialSubjects 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. | Drug | Tibolone |
Primary outcome
Montgomery and Asberg Depression Rating Scale
Time frame: Baseline, then at weeks 2,4, 8 and 12
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.
1 secondary outcome
The Beck Depression Inventory Second Edition
Time frame: Baseline and week 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jan 2020.
- Derived from this study: PubMed 29723767Kulkarni 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jayashri Kulkarni, PhD,FRANZP principal investigator
Monash Alfred Psychiatry Research Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tibolone in people with Menopausal Depression, run by The Alfred at 1 site in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Montgomery and Asberg Depression Rating Scale (time frame: Baseline, then at weeks 2,4, 8 and 12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01470092, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2020.