Miller reports receiving study medication at no cost and assay support from Marinus Pharmaceuticals for this study. Please see the study for all other authors’ relevant financial disclosures.
Adjunctive ganaxolone appeared to reduce persistent depression among postmenopausal women, according to results of an open-label, uncontrolled pilot study published in Journal of Clinical Psychiatry.
Karen K. Miller
The drug may also produce sedation, which could benefit patients with depression and insomnia.
“Resistance to antidepressants occurs among more than 50% of patients with major depressive disorder,” Karen K. Miller, MD, professor of medicine at Harvard Medical School in Boston, told Healio Psychiatry. “Therefore, most patients treated have significant symptoms of depression despite taking antidepressant medications. In addition, there are few effective augmentation therapies available to such patients. We hypothesized that ganaxolone (Marinus Pharmaceuticals), an oral allopregnanolone analog and positive GABAA allosteric modulator, might be an effective augmentation therapy for postmenopausal women, as menopause is characterized by low allopregnanolone levels.”
To test this hypothesis, Miller and colleagues collected data from December 2016 to April 2018 of 10 postmenopausal women aged 53 years to 69 years with persistent depression despite adequate antidepressant treatment. Participants received 225 mg of open-label ganaxolone twice daily, which was increased to 450 mg twice daily if tolerated, for 8 weeks, followed by a 2-week taper.
Results showed a decrease in total Montgomery-Asberg Depression Rating Scale (MADRS) score by 8 weeks. The decrease was sustained over the 2-week taper (P = .019). Four of nine (44%) participants who completed the full 8-week treatment period exhibited response and remission, which persisted among 100% and 50% of participants at 10 weeks, respectively. The researchers observed significant improvement according to secondary endpoints, including Inventory of Depressive Symptomatology-Self-Report score (P = .003), MADRS reduce sleep subscale score (P < .001), total Symptoms of Depression Questionnaire (SDQ) score (P = .012) and scores on SDQ subscales for changes in appetite and weight (P = .009) and disruptions in sleep quality (P = .003) across 8 weeks. They observed no significant effects on sexual function or quality of life, sleepiness and fatigue among all participants and dizziness among 60% of participants.
“Further controlled studies are needed to determine whether ganaxolone is a potential augmentation strategy for postmenopausal women with MDD among whom antidepressants are not adequate treatment and who suffer with insomnia, a common comorbid condition,” Miller told Healio Psychiatry.