Major Depressive Disorder
Conditions
Keywords
postmenopausal, women, depression
Brief summary
Major depressive disorder (MDD) is highly prevalent and nearly 70% of individuals with MDD do not respond to standard antidepressant therapies despite adequate dosing. An effective and well-tolerated antidepressant augmentation therapy would have important clinical and public health implications. Neuroactive steroid hormones are known to directly activate neurotransmitter receptors in the brain, and thus are potential candidates for augmentation therapies to enhance the effect of traditional antidepressants. The investigators hypothesize that administration of an allopregnanolone analog in women with treatment-resistant depression will improve depressive symptoms.
Detailed description
Major depressive disorder (MDD) is highly prevalent and can have profoundly negative consequences on one's health, well-being and productivity. Women are twice as likely as men to experience depression during their lifetimes. In fact, it is reported that twelve million women in the U.S. each year will experience depression, and that one in eight women will experience a clinical depressive episode during their lifetimes. Additionally, nearly 70% of individuals with MDD do not respond to standard antidepressant therapies despite adequate dosing. Therefore, the identification of an effective and well tolerated antidepressant augmentation therapy would have important clinical and public health implications. Neuroactive steroid hormones are known to directly activate neurotransmitter receptors in the brain, and thus are potential candidates for augmentation therapies to enhance the effect of traditional antidepressants. Specifically, allopregnanolone, a steroid hormone derived from progesterone, is a potent positive modulator of GABA action at GABA-A receptors, which are known to have positive effects on mood symptoms. Data suggest that depression, chronic stress and posttraumatic stress disorder may be associated with low central nervous system allopregnanolone levels. The investigators propose to administer an oral allopregnanolone analog to 10 postmenopausal women with treatment-resistant depression as an add-on therapy to their current treatment for a period of 8 weeks followed by a 2-week taper. The investigators hypothesize that administration of the oral allopregnanolone analog in women with treatment-resistant depression will improve depressive symptoms.
Interventions
DRUGGanaxolone
Participants received ganaxolone
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
50 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Female, age 50-75 2. Postmenopausal 3. Major Depressive Disorder 4. Currently treated with SSRI or SNRI at adequate dose
Exclusion criteria
1. Serious suicide or homicide risk 2. Unstable medical illness 3. Substance use disorder 4. Psychosis 5. Use of hormones (estrogens, androgens or related hormones) 6. History of hormone responsive cancer 7. Receiving strong CYP3A4 inducers or inhibitors or who intend to consume grapefruit products regularly during the study 8. Alanine aminotransferase (ALT) or creatinine \> 3x upper limit of normal
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Montgomery-Asberg Depression Rating Scale (MADRS) | Week 8 | The MADRS is a diagnostic questionnaire that is used to measure the severity of depressive episodes in patients with mood disorders. The minimum and maximum values are 0 and 60, respectively, (higher scores are more severe). |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ganaxolone Treatment Arm Participants received ganaxolone | 10 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Ganaxolone Treatment Arm |
|---|---|
| Age, Continuous | 62.8 years STANDARD_DEVIATION 6.3 |
| Montgomery-Asberg Depression Rating Scale (MADRS) | 24.4 units on a scale STANDARD_DEVIATION 5.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 10 Participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 10 |
| other Total, other adverse events | 10 / 10 |
| serious Total, serious adverse events | 0 / 10 |
Outcome results
Primary
Montgomery-Asberg Depression Rating Scale (MADRS)
The MADRS is a diagnostic questionnaire that is used to measure the severity of depressive episodes in patients with mood disorders. The minimum and maximum values are 0 and 60, respectively, (higher scores are more severe).
Time frame: Week 8
Population: Ten subjects started the study. One subject dropped out (did not complete the 8-week study). Therefore, data from 9 subjects were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ganaxolone Treatment Arm | Montgomery-Asberg Depression Rating Scale (MADRS) | 12.8 units on a scale | Standard Deviation 2.9 |