Clinical trial NCT02900092: Augmentation of Treatment-Resistant Depression With An Analog of the Neuroactive Steroid Allopregnanolone
Official title: Treatment-Resistant Depression Augmentation Therapy With An Analog of the Neuroactive Steroid Allopregnanolone: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Major Depressive Disorder
Keywords: postmenopausal
women
depression
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
First posted: 2016-09-14
Enrollment: 10
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: Week 8
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Karen K Miller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dichtel LE, Nyer M, Dording C, Fisher LB, Cusin C, Shapero BG, Pedrelli P, Kimball AS, Rao EM, Mischoulon D, Fava M, Miller KK. Effects of Open-Label, Adjunctive Ganaxolone on Persistent Depression Despite Adequate Antidepressant Treatment in Postmenopausal Women: A Pilot Study. J Clin Psychiatry. 2020 Jun 9;81(4):19m12887. doi: 10.4088/JCP.19m12887.