Abstract | OBJECTIVE: METHOD: Ten postmenopausal women (mean ± SD age: 62.8 ± 6.3 years; range, 53-69 years) with persistent depression despite adequate antidepressant treatment (current DSM-IV-TR major depressive episode per the Structured Clinical Interview for DSM-IV-TR, Montgomery-Asberg Depression Rating Scale [MADRS] score ≥ 16, and treated with an adequately dosed antidepressant for ≥ 6 weeks) were studied from December 2016 to April 2018. Open-label ganaxolone (225 mg twice daily, increased to 450 mg twice daily if tolerated) was administered for 8 weeks, followed by a 2-week taper. RESULTS: Mean ± SEM total MADRS score (primary endpoint) decreased by 8 weeks (24.4 ± 1.6 to 12.8 ± 2.9, P = .015), and the decrease persisted over the 2-week taper (P = .019); of the 9 subjects who completed the full 8-week treatment period, 44% (4/9) experienced response (MADRS score decrease ≥ 50%) and remission (final MADRS score < 10), which persisted in 100% and 50% of subjects at 10 weeks, respectively. Secondary endpoints showed significant improvement, including Inventory of Depressive Symptomatology-Self-Report score (P = .003), MADRS reduced sleep subscale score (P < .001), total Symptoms of Depression Questionnaire (SDQ) score (P = .012), and scores on SDQ subscales for disruptions in sleep quality (P = .003) and changes in appetite and weight (P = .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. CONCLUSIONS: In this open-label, uncontrolled pilot study, adjunctive 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. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02900092.
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Authors | Laura E Dichtel, Maren Nyer, Christina Dording, Lauren B Fisher, Cristina Cusin, Benjamin G Shapero, Paola Pedrelli, Allison S Kimball, Elizabeth M Rao, David Mischoulon, Maurizio Fava, Karen K Miller |
Journal | The Journal of clinical psychiatry
(J Clin Psychiatry)
Vol. 81
Issue 4
(06 09 2020)
ISSN: 1555-2101 [Electronic] United States |
PMID | 32558402
(Publication Type: Clinical Trial, Journal Article, Research Support, N.I.H., Extramural)
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Copyright | © Copyright 2020 Physicians Postgraduate Press, Inc. |
Chemical References |
- Antidepressive Agents
- GABA Modulators
- ganaxolone
- Pregnanolone
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Topics |
- Aged
- Antidepressive Agents
(therapeutic use)
- Depressive Disorder, Major
(drug therapy)
- Depressive Disorder, Treatment-Resistant
(drug therapy)
- Drug Therapy, Combination
- Female
- GABA Modulators
(therapeutic use)
- Humans
- Middle Aged
- Pilot Projects
- Postmenopause
- Pregnanolone
(analogs & derivatives, therapeutic use)
- Treatment Outcome
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