Patient Resources for
Postpartum Depression (PPD)
Postpartum Depression (PPD) can affect a mother’s ability to care for her child and may negatively affect a child’s cognitive development. PPD is thought to develop from rapid changes in the levels of endogenous neurosteroids during pregnancy.
Plasma levels of allopregnanolone, which is a metabolite of progesterone and GABA modulator, are known to increase throughout pregnancy and then precipitously drop after delivery. It is thought that these rapid hormonal changes are linked to triggering depression in women who are vulnerable to develop this condition.
The most common medications prescribed to women who seek treatment for PPD are SSRI’s and SNRI’s, which have limited evidence of efficacy. There are currently no approved therapies to treat PPD.
How does PPD affect the body?
PPD is a mood disorder that affects about 15% of women within the first year of childbirth. Women with PPD experience feelings of extreme sadness, hopelessness, suicidal ideation, anxiety, and fatigue. These symptoms mirror those of a major depressive episode with the additional criteria that the onset of depression occurs within 4 weeks of childbirth. PPD can affect a mother’s ability to care for her child and may negatively affect a child’s cognitive development.
Where can I find more information on PDD?
You can find additional educational and support resources on Postpartum Depression through the following foundations and patient advocacy groups:
Links to third party sites are provided for convenience purposes only. The information contained on these sites is not information provided, controlled or monitored by Marinus Pharmaceuticals in any way. Marinus Pharmaceuticals is not responsible in any way for the accuracy, completeness or fitness for any particular purpose of any content appearing on such sites.
Clinical Development of Ganaxolone in Postpartum Depression
The Magnolia study, a Phase 2 double-blind, placebo-controlled, multiple-dose escalation study, evaluated the safety, pharmacokinetics and efficacy of intravenous (IV) ganaxolone alone, or in combination with oral ganaxolone, in women with postpartum depression (PPD). The study consists of multiple cohorts of women with a Hamilton Depression Rating Scale (HAM-D17) score ≥26.. Patients randomized into the first part of the study underwent an infusion (IV) of either ganaxolone or placebo and were followed for 30 days. Data from the best performing cohort showed a clinically meaningful reduction in HAM-D17 compared to placebo at 48 hours that was durable through the last visit, day 34. 75% of patients were responders, as defined as having a ≥50% reduction from baseline, at day 34 and 67% were responders at 60 hours. 50% of patients achieved remission from depression, as determined by a HAM-D17 ≤7, at day 34 and 33% achieved remission at 60 hours.
Patients randomized into Part 2 of the study underwent an infusion of ganaxolone, followed by oral ganaxolone for 28 days, or received placebo. At the early time points of 6 hours and 24 hours post treatment, patients showed clinically meaningful reductions in HAM-D17, with 38% of patients defined as responders at 24 hours post treatment.
Ganaxolone was safe and well-tolerated in all dose groups. Consistent with previous ganaxolone studies, the most common reported adverse events were sedation and dizziness. There were no serious adverse events reported, no discontinuations due to a treatment related adverse event and importantly, there were no reports of syncope or loss of consciousness.
Together, Part 1 and 2 of the Magnolia Study consistently show that IV ganaxolone provides rapid and clinically meaningful reductions in HAM-D17 scores and was safe and well tolerated.
The Amaryllis study, a Phase 2 clinical trial, evaluated the safety, tolerability and efficacy of oral ganaxolone in women with PPD while determining the best oral dosing regimen for potential future studies. Data from the study show that ganaxolone oral alone was safe and well tolerated, with signs of rapid onset of clinical activity seen in the high dose cohort. As with IV, oral ganaxolone was generally safe and well-tolerated with no serious adverse events reported and no discontinuations due to treatment related adverse events. Data from the Amaryllis Study support continued use of the high dose in future clinical studies.
Liquid Suspension & Oral Dosing
Recent studies conducted in women with PPD showed that both oral and IV ganaxolone were safe, well-tolerated and effective in reducing PPD. The goal with developing multiple dose forms is to provide a dose regimen that is fast acting, durable and convenient, thereby eliminating an overnight hospital stay.