Effects of Open-Label, Adjunctive Ganaxolone on Persistent Depression Despite Adequate Antidepressant Treatment in Postmenopausal Women
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Miller, Karen K.
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CitationDichtel, Laura E., Maren Nyer, Christina Dording, Lauren B. Fisher, Cristina Cusin, Benjamin G. Shapero, Paola Pedrelli, et al. 2020. “Effects of Open-Label, Adjunctive Ganaxolone on Persistent Depression Despite Adequate Antidepressant Treatment in Postmenopausal Women: A Pilot Study.” The Journal of Clinical Psychiatry 81 (4).
Objective: The neuroactive steroid metabolite of progesterone, allopregnanolone, is a positive allosteric modulator of GABAA receptors and a putative treatment for mood disorders. We performed a pilot study to determine whether an oral allopregnanolone analog (ganaxolone) may be effective for treatment-resistant depression in postmenopausal women.
Methods: Ten post-menopausal women (age 62.8±6.3 years, range 53-69) with treatment-resistant depression [current DSM-IV major depressive episode per the Structured Clinical Interview for DSM-IV (SCID), Montgomery-Asberg Depression Rating Scale (MADRS) 16, and treated with an adequately dosed antidepressant for ≥6 weeks] were studied from 12/2016 to 4/2018. Open-label ganaxolone (225 mg BID, increased to 450 mg BID if tolerated) was administered for 8 weeks, followed by a 2-week taper.
Results: Mean total MADRS score (primary endpoint) decreased by 8 weeks [24.4±1.6 (SEM) to 12.8±2.9, p=0.015] and persisted over the two-week taper (p=0.019); 44% of subjects experienced response (score decrease ≥50%) and remission (final score <10), which persisted in 100% and 50% of subjects at 10 weeks, respectively. Secondary endpoints showed significant improvement, including the Inventory of Depressive Symptomatology-Self-Report (IDS-SR; p=0.003), MADRS Reduced Sleep subscale (p<0.001), Symptoms of Depression Questionnaire (SDQ) total score (p=0.012), and SDQ subscales for disruptions in sleep quality (p=0.003) and changes in appetite and weight (p=0.009) over 8 weeks. No significant effects were observed on quality-of-life or sexual function. All subjects experienced sleepiness and fatigue; 60% experienced dizziness.
Conclusion: In this open-label, uncontrolled pilot study, ganaxolone appears to exert antidepressant effects but produces sedation with twice-daily dosing. Ganaxolone may also improve sleep, which may be useful in patients with depression and insomnia.
Citable link to this pagehttps://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37375032
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