Augmentation of Treatment-Resistant Depression With An Analog of the Neuroactive Steroid Allopregnanolone
| Status: | Completed |
|---|---|
| Conditions: | Depression, Depression, Major Depression Disorder (MDD) |
| Therapuetic Areas: | Psychiatry / Psychology, Pulmonary / Respiratory Diseases |
| Healthy: | No |
| Age Range: | 50 - 75 |
| Updated: | 2/20/2019 |
| Start Date: | November 2016 |
| End Date: | January 12, 2018 |
Treatment-Resistant Depression Augmentation Therapy With An Analog of the Neuroactive Steroid Allopregnanolone: A Pilot Study
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.
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.
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.
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.
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
We found this trial at
1
site
185 Cambridge Street
Boston, Massachusetts 02114
Boston, Massachusetts 02114
617-724-5200
Principal Investigator: Karen K Miller, MD
Phone: 617-726-3870
Click here to add this to my saved trials
