Menopausal and Postmenopausal Disorders, Moderate Depression
Conditions
Keywords
Depression, Perimenopause, Postmenopause, Homeopathy
Brief summary
The aim of this study was to determine whether individualized homeopathic treatment and fluoxetine are more efficient than placebo for moderate to severe depression in peri- and postmenopausal women.
Detailed description
Perimenopausal period is characterized by an increased risk of depressive symptoms. Major depression is one of the most disabling medical conditions worldwide. At present, it is becoming more difficult to prove that antidepressants actually work better than placebo in clinical trials.Use of homeopathy to treat depression is widespread, but there is a lack of clinical trails about its efficacy in depression in peri- and postmenopausal women. Previous trials suggest that individualized homeopathic treatments improve depression in general population. The purpose of this study was to determine whether individualized homeopathic treatment and fluoxetine are more efficient than placebo for moderate depression in peri- and postmenopausal women.
Interventions
DRUGIndividualized homeopathic treatment
A single dose of the individualized homeopathic remedy in C-potency was dissolved in a 60 ml bottle of 30% alcohol-distilled water:15 drops PO two times per day following agitation plus fluoxetine-dummy loaded PO daily during 6 weeks. The homeopathic remedy could be changed at every follow-up (week 4) according to patient´s symptoms.
DRUGFluoxetine
20 mg per day PO during 6 weeks plus individualized homeopathic dummy-loaded (60 bottle of 30% alcohol-distilled water: 15 drops PO two times per day following agitation). The individualized homeopathic dummy-loaded was repeated at week 4.
DRUGPlacebo
Fluoxetine placebo (capsules containing sucrose microgranules) PO daily during 6 weeks plus individualized homeopathic placebo (60 ml bottle of 30% alcohol-distilled water: 15 drops PO two times per day following agitation). The individualized homeopathic placebo was repeated at week 4.
Sponsors
Hospital Juarez de Mexico
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Major depression according to DSM-IV * Moderate to severe depression according to 17-item Hamilton Rating Scale for Depression (14-24 score) * No current use of homeopathic treatment for depression or antidepressants or anxiolytic drugs 3 months prior to study entry * Not be currently taking psychotherapy for at least 3 months before study entry * Early transition to menopause defined by a change in cycle length of 7 days or longer in either direction from the participant´s own baseline for at least 2 cycles * Late transition to menopause defined as 3 to 11 months of amenorrhea * Postmenopausal stage defined by 12 months or more of amenorrhea * Capability and willingness to give informed consent and to comply with the study procedures
Exclusion criteria
* Pregnancy or breastfeeding * Other psychiatric disorders different from moderate to severe depression (severe depression, schizophrenia, psychotic disorders, bipolar affective disorders, suicide attempt) * Alcohol or other substance abuse * Known allergy to fluoxetine * Cancer or hepatic diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 17-item Hamilton Rating Scale for Depression at 6 Weeks. | Baseline and 6 weeks | 17-item Hamilton Rating Scale for Depression (HRSD) is a well-known standardized scale used worldwide to assess severity of depression. Score ranges from 0 (no depression) up to 52 (maximum depression severity). A total score in HRSD was assessed at baseline and after six weeks of treatment. For this study the change was calculated as the later time point (total score in 17- HRSD at 6 weeks) minus the earlier time point (total score at baseline). A score \< or = 7 is considered normal, 7 - 13 (mild depression), 14 - 24 (moderate to severe depression), \> 24 (severe depression). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Beck Depression Inventory at 6 Weeks. | Baseline and 6 weeks | Beck Depression Inventory (BDI) is a 21-question multiple-choice self-report inventory that assess severity of depression. A total score range was assessed at baseline and after six weeks of treatment. A score 0 (without depression) up to 63 (most severe depression). For this study the change was calculated as the later time point (total score in BDI at 6 weeks) minus the earlier time point (total score in BDI at baseline). A score 0 - 8 is considered normal, 9 - 18 (mild to moderate depression), 19 - 28 (moderate to severe depression), \> 29 (severe depression). |
| Responder Rates at 6 Weeks. | 6 weeks | 17-item Hamilton Rating Scale for Depression is a well-known standardized scale used worldwide to assess severity of depression. Score ranges from 0 (no depression) up to 52 (maximum depression severity). A total score in 17-item Hamilton Scale for Depression was assessed for this study. It ranges from 0 (no depression) up to 52 (most severe depression). A score \< or = 7 is considered normal, 7 - 13 (mild depression), 14 - 24 (moderate to severe depression), \> 24 (severe depression). Responder rate definition: a decrease of 50% or more from baseline score using 17-item Hamilton Rating Scale for Depression after six weeks treatment. |
| Change From Baseline in Greene´s Scale at 6 Weeks. | Baseline and 6 weeks | Greene Climacteric Scale (GS) is intended to be a standard measure of core climacteric symptoms. For this study a total range was assessed at baseline and after six weeks of treatment. A total score 0 (without climacteric symptoms) up to 63 (most severe climacteric symptoms). The change was calculated as the later time point (total score in GS at 6 weeks) minus the earlier time point (total score at baseline).The scale measures four separate sub-scales (anxiety, depression, somatic symptoms and sexual function). The score of the four sub-scales was summed. A total score of 0 -10 is considered without symptoms, 11 - 29 (mild symptoms), 30 - 49 (moderate symptoms) and \> 50 (severe symptoms). |
| Remission Rates at 6 Weeks | 6 weeks | 17-item Hamilton Rating Scale for Depression is a well-known standardized scale used worldwide to assess severity of depression. Score ranges from 0 (no depression) up to 52 (maximum depression severity). A total score in 17-item Hamilton Scale for Depression was assessed for this study. It ranges from 0 (no depression) up to 52 (most severe depression). A score \< or = 7 is considered normal, 7 - 13 (mild depression), 14 - 24 (moderate to severe depression), \> 24 (severe depression). Remission rate definition: 17-item Hamilton Rating Scale for Depression score \< 7 points after 6 weeks of treatment. |
Countries
Mexico
Participant flow
Recruitment details
The study was conducted in a public, academic and research hospital in Mexico City. Participants were recruited since March 2012 until December 2013. The recruitment methods included advertisements through internet, community groups,liaisons with health professionals, posters and brochures distributed among hospital population.
Pre-assignment details
Five hundred thirty-four women seeking medical care for menopausal complaints were interviewed and screened. Four hundred and one women did not meet inclusion criteria and were excluded: no depression (44), mild depression (150), severe depression and/or attempt of suicide (43), did not meet other inclusion criteria (164).
Participants by arm
| Arm | Count |
|---|---|
| Individualized Homeopathic Treatment Selection of the individualized homeopathic remedy based on Hahnemann´s methodology after the case history of each patient.
Individualized homeopathic treatment: A single dose of the individualized homeopathic remedy in C-potency was dissolved in a 60 ml bottle of 30% alcohol-distilled water:15 drops PO two times per day following agitation plus fluoxetine-dummy loaded PO daily during 6 weeks. The homeopathic remedy could be changed at every follow-up (week 4) according to patient´s symptoms. | 44 |
| Fluoxetine Selective serotonin reuptake inhibitor.
Fluoxetine: 20 mg per day PO during 6 weeks plus individualized homeopathic dummy-loaded (60 bottle of 30% alcohol-distilled water: 15 drops PO two times per day following agitation). The individualized homeopathic dummy-loaded was repeated at week 4. | 46 |
| Placebo Fluoxetine placebo plus individualized homeopathic placebo
Placebo: Fluoxetine placebo (capsules containing sucrose microgranules) PO daily during 6 weeks plus individualized homeopathic placebo (60 ml bottle of 30% alcohol-distilled water: 15 drops PO two times per day following agitation). The individualized homeopathic placebo was repeated at week 4. | 43 |
| Total | 133 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 7 | 6 |
Baseline characteristics
| Characteristic | Individualized Homeopathic Treatment | Fluoxetine | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 49 years STANDARD_DEVIATION 6.4 | 49.2 years STANDARD_DEVIATION 5.3 | 48.8 years STANDARD_DEVIATION 5.8 | 49 years STANDARD_DEVIATION 5.8 |
| Baseline score in 17-item Hamilton Rating Scale for Depression | 21.2 Units in Hamilton Scale STANDARD_DEVIATION 2.7 | 20.6 Units in Hamilton Scale STANDARD_DEVIATION 2.9 | 20.7 Units in Hamilton Scale STANDARD_DEVIATION 3.1 | 20.8 Units in Hamilton Scale STANDARD_DEVIATION 2.9 |
| Baseline score in Beck Depression Inventory | 26.3 Units in Beck Depression Inventory STANDARD_DEVIATION 7.2 | 25.0 Units in Beck Depression Inventory STANDARD_DEVIATION 7.8 | 27.0 Units in Beck Depression Inventory STANDARD_DEVIATION 9 | 26.1 Units in Beck Depression Inventory STANDARD_DEVIATION 8 |
| Baseline score in Greene Climacteric Scale | 35.3 Units in Greene Climacteric Scale STANDARD_DEVIATION 8.5 | 33.5 Units in Greene Climacteric Scale STANDARD_DEVIATION 10.1 | 37.9 Units in Greene Climacteric Scale STANDARD_DEVIATION 11.5 | 35.5 Units in Greene Climacteric Scale STANDARD_DEVIATION 10.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 44 Participants | 46 Participants | 43 Participants | 133 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Mexico | 44 participants | 46 participants | 43 participants | 133 participants |
| Sex: Female, Male Female | 44 Participants | 46 Participants | 43 Participants | 133 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 19 / 44 | 24 / 46 | 16 / 43 |
| serious Total, serious adverse events | 0 / 44 | 0 / 46 | 0 / 43 |
Outcome results
Primary
Change From Baseline in 17-item Hamilton Rating Scale for Depression at 6 Weeks.
17-item Hamilton Rating Scale for Depression (HRSD) is a well-known standardized scale used worldwide to assess severity of depression. Score ranges from 0 (no depression) up to 52 (maximum depression severity). A total score in HRSD was assessed at baseline and after six weeks of treatment. For this study the change was calculated as the later time point (total score in 17- HRSD at 6 weeks) minus the earlier time point (total score at baseline). A score \< or = 7 is considered normal, 7 - 13 (mild depression), 14 - 24 (moderate to severe depression), \> 24 (severe depression).
Time frame: Baseline and 6 weeks
Population: All patients under randomization were included in the primary efficacy population (intention-to-treat population), regardless whether or not they adhered to the treatment protocol or provided complete data sets.The mean and SD presented in outcome measure data table are the final scores in Hamilton Scale after 6 weeks of treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Individualized Homeopathic Treatment | Change From Baseline in 17-item Hamilton Rating Scale for Depression at 6 Weeks. | 9.9 Units in Hamilton Scale | Standard Deviation 3 |
| Fluoxetine | Change From Baseline in 17-item Hamilton Rating Scale for Depression at 6 Weeks. | 11.7 Units in Hamilton Scale | Standard Deviation 3.7 |
| Placebo | Change From Baseline in 17-item Hamilton Rating Scale for Depression at 6 Weeks. | 15 Units in Hamilton Scale | Standard Deviation 3.7 |
p-value: <0.0595% CI: [3.1, 7]ANOVA
p-value: <0.0595% CI: [1.31, 5.25]ANOVA
Secondary
Change From Baseline in Beck Depression Inventory at 6 Weeks.
Beck Depression Inventory (BDI) is a 21-question multiple-choice self-report inventory that assess severity of depression. A total score range was assessed at baseline and after six weeks of treatment. A score 0 (without depression) up to 63 (most severe depression). For this study the change was calculated as the later time point (total score in BDI at 6 weeks) minus the earlier time point (total score in BDI at baseline). A score 0 - 8 is considered normal, 9 - 18 (mild to moderate depression), 19 - 28 (moderate to severe depression), \> 29 (severe depression).
Time frame: Baseline and 6 weeks
Population: All patients under randomization were included in the primary efficacy population (intention-to-treat population) regardless whether or not they adhered to the treatment protocol or provided complete data sets. The mean and SD presented here in the Outcome measure data table are the final scores after 6 weeks treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Individualized Homeopathic Treatment | Change From Baseline in Beck Depression Inventory at 6 Weeks. | 12 Units in Beck Depression Inventory | Standard Deviation 6.1 |
| Fluoxetine | Change From Baseline in Beck Depression Inventory at 6 Weeks. | 14.2 Units in Beck Depression Inventory | Standard Deviation 7.8 |
| Placebo | Change From Baseline in Beck Depression Inventory at 6 Weeks. | 15.5 Units in Beck Depression Inventory | Standard Deviation 8.8 |
p-value: 0.1495% CI: [-0.73, 7.61]ANOVA
p-value: 0.9995% CI: [-2.93, 5.5]ANOVA
Secondary
Change From Baseline in Greene´s Scale at 6 Weeks.
Greene Climacteric Scale (GS) is intended to be a standard measure of core climacteric symptoms. For this study a total range was assessed at baseline and after six weeks of treatment. A total score 0 (without climacteric symptoms) up to 63 (most severe climacteric symptoms). The change was calculated as the later time point (total score in GS at 6 weeks) minus the earlier time point (total score at baseline).The scale measures four separate sub-scales (anxiety, depression, somatic symptoms and sexual function). The score of the four sub-scales was summed. A total score of 0 -10 is considered without symptoms, 11 - 29 (mild symptoms), 30 - 49 (moderate symptoms) and \> 50 (severe symptoms).
Time frame: Baseline and 6 weeks
Population: All patients under randomization were included in the primary efficacy population (intention-to-treat population) regardless whether or not they adhered to the treatment protocol or provided complete data sets.The mean and SD presented here in the Outcome measure data table are the final scores after 6 weeks treatment.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Individualized Homeopathic Treatment | Change From Baseline in Greene´s Scale at 6 Weeks. | 18.1 Units in Green Scale | Standard Deviation 7.8 |
| Fluoxetine | Change From Baseline in Greene´s Scale at 6 Weeks. | 23.1 Units in Green Scale | Standard Deviation 12.3 |
| Placebo | Change From Baseline in Greene´s Scale at 6 Weeks. | 26.8 Units in Green Scale | Standard Deviation 11.7 |
p-value: 0.00295% CI: [2.72, 14.52]ANOVA
p-value: 0.42495% CI: [-2.33, 9.6]ANOVA
Secondary
Remission Rates at 6 Weeks
17-item Hamilton Rating Scale for Depression is a well-known standardized scale used worldwide to assess severity of depression. Score ranges from 0 (no depression) up to 52 (maximum depression severity). A total score in 17-item Hamilton Scale for Depression was assessed for this study. It ranges from 0 (no depression) up to 52 (most severe depression). A score \< or = 7 is considered normal, 7 - 13 (mild depression), 14 - 24 (moderate to severe depression), \> 24 (severe depression). Remission rate definition: 17-item Hamilton Rating Scale for Depression score \< 7 points after 6 weeks of treatment.
Time frame: 6 weeks
Population: All patients under randomization were included in the primary efficacy population (intention-to-treat population) regardless whether or not they adhered to the treatment protocol or provided complete data sets.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Individualized Homeopathic Treatment | Remission Rates at 6 Weeks | 7 participants with a score of < 7 in HS |
| Fluoxetine | Remission Rates at 6 Weeks | 7 participants with a score of < 7 in HS |
| Placebo | Remission Rates at 6 Weeks | 2 participants with a score of < 7 in HS |
p-value: 0.195% CI: [0.05, 1.32]Chi-squared
p-value: 0.1195% CI: [0.05, 1.39]Chi-squared
Secondary
Responder Rates at 6 Weeks.
17-item Hamilton Rating Scale for Depression is a well-known standardized scale used worldwide to assess severity of depression. Score ranges from 0 (no depression) up to 52 (maximum depression severity). A total score in 17-item Hamilton Scale for Depression was assessed for this study. It ranges from 0 (no depression) up to 52 (most severe depression). A score \< or = 7 is considered normal, 7 - 13 (mild depression), 14 - 24 (moderate to severe depression), \> 24 (severe depression). Responder rate definition: a decrease of 50% or more from baseline score using 17-item Hamilton Rating Scale for Depression after six weeks treatment.
Time frame: 6 weeks
Population: All patients under randomization were included in the primary efficacy population (intention-to-treat population) regardless whether or not they adhered to the treatment protocol or provided complete data sets.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Individualized Homeopathic Treatment | Responder Rates at 6 Weeks. | 24 participants with a decrease >50% in HS |
| Fluoxetine | Responder Rates at 6 Weeks. | 19 participants with a decrease >50% in HS |
| Placebo | Responder Rates at 6 Weeks. | 5 participants with a decrease >50% in HS |
p-value: <0.0595% CI: [0.03, 0.34]Chi-squared
p-value: <0.0595% CI: [0.06, 0.56]Chi-squared