Effects of Open-Label, Adjunctive Ganaxolone on Persistent Depression Despite Adequate Antidepressant Treatment in Postmenopausal Women

Dichtel, Laura E.; Nyer, Maren; Dording, Christina; Fisher, Lauren; Cusin, Cristina; Shapero, Benjamin G.; Pedrelli, Paola; Kimball, Allison; Rao, Elizabeth; Mischoulon, David; Fava, Maurizio; Miller, Karen K.

doi:10.4088/jcp.19m12887

Cited by 33 publications

(21 citation statements)

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“…In an uncontrolled, open-label pilot study, this medication was administered for 8 weeks as an adjunct to an adequately dosed antidepressant to 10 postmenopausal women with persistent MDD. 16 Of the 9 women who completed the study, 4 (44%) improved significantly (P < .019) and the benefit was sustained for 2 additional weeks. 16 Adverse effects of ganaxolone included dizziness in 60% of participants, and sleepiness and fatigue in all of them with twice-daily dosing.…”

Section: Neurosteroidsmentioning

confidence: 91%

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Nontraditional therapies for treatment-resistant depression: Part 2

Dokucu¹

2021

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When patients with major depressive disorder (MDD) do not achieve optimal outcomes after FDA-approved first-line treatments and standard adjunctive strategies, clinicians look for additional approaches to alleviate their patients' symptoms. Recent research suggests that several "nontraditional" treatments used primarily as adjuncts to standard antidepressants have promise for treatment-resistant depression.In Part 1 of this article (Current Psychiatry, September 2021), we examined off-label medications. In Part 2, we will review other nontraditional approaches to treatmentresistant depression, including herbal/nutraceutical agents, anti-inflammatory/immune system therapies, device-based treatments, and other alternative approaches. Importantly, some treatments also demonstrate adverse effects (Table , 1-32 page 34). With a careful consideration of the risk/benefit balance, this article reviews some of the better-studied nontraditional treatment options for patients with treatmentresistant depression. Herbal/nutraceutical agentsThis category encompasses a variety of commonly available "natural" options patients often ask about and at times selfprescribe. Examples evaluated in clinical trials include:• vitamin D

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Section: Neurosteroidsmentioning

confidence: 91%

“…Transcranial direct current stimulation [18][19][20] Persistent skin lesions similar to burns; mania/hypomania; 1 reported seizure in a pediatric patient Ganaxolone 16 Dizziness, sleepiness, fatigue Statins 15 Headaches, myalgias (rarely rhabdomyolysis), dizziness, rash, liver toxicity St. John's Wort 9 Drug interactions:…”

Section: Medium Riskmentioning

confidence: 99%

Nontraditional therapies for treatment-resistant depression: Part 2

Dokucu¹

2021

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“…In these patients, a statistically significant decrease in symptoms measured by the Hamilton Depression Rating Scale was achieved in days 3, 8, 12, and 15 after treatment with SAGE-217 [ 69 ]. Additionally, recent results with ganaxolone, an allopregnanolone analogue, treatment-resistant depression of post-menopausal women, point out that it may be a useful adjunctive in patients with depression and insomnia [ 70 ].…”

Section: Allopregnanolone-based Therapeutics As a Treatment Option For Mdd And Ptsdmentioning

confidence: 99%

The Role of HPA Axis and Allopregnanolone on the Neurobiology of Major Depressive Disorders and PTSD

Almeida

Pinna

Barros

2021

IJMS

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Under stressful conditions, the hypothalamic-pituitary-adrenal (HPA) axis acts to promote transitory physiological adaptations that are often resolved after the stressful stimulus is no longer present. In addition to corticosteroids (e.g., cortisol), the neurosteroid allopregnanolone (3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one) participates in negative feedback mechanisms that restore homeostasis. Chronic, repeated exposure to stress impairs the responsivity of the HPA axis and dampens allopregnanolone levels, participating in the etiopathology of psychiatric disorders, such as major depressive disorder (MDD) and post-traumatic stress disorder (PTSD). MDD and PTSD patients present abnormalities in the HPA axis regulation, such as altered cortisol levels or failure to suppress cortisol release in the dexamethasone suppression test. Herein, we review the neurophysiological role of allopregnanolone both as a potent and positive GABAergic neuromodulator but also in its capacity of inhibiting the HPA axis. The allopregnanolone function in the mechanisms that recapitulate stress-induced pathophysiology, including MDD and PTSD, and its potential as both a treatment target and as a biomarker for these disorders is discussed.

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“…In one open label, pilot study in postmenopausal women, a significant decrease in MADRS score at week 8 ( n = 10). 34 There are also two active Phase-II studies that have completed, but not yet published official results: one study is a multiple-dose escalation design in individuals with severe PPD that is utilizing the orally bioavailable form of the drug (NCT03460756); the other study is being conducted in individuals with moderate PPD and is utilizing the intravenous form of the drug (Magnolia study; NCT03228394). Some study results have been shared through press releases but, to our knowledge, the primary outcome data of both studies are not yet reported.…”

Section: Agn-241751 (Allergan)mentioning

confidence: 99%

Emerging Therapeutics Based on the Amino Acid Neurotransmitter System: An Update on the Pharmaceutical Pipeline for Mood Disorders

Hecking

Davoudian

2021

Chronic Stress

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Mood disorders represent a pressing public health issue and significant source of disability throughout the world. The classical monoamine hypothesis, while useful in developing improved understanding and clinical treatments, has not fully captured the complex nature underlying mood disorders. Despite these shortcomings, the monoamine hypothesis continues to dominate the conceptual framework when approaching mood disorders. However, recent advances in basic and clinical research have led to a greater appreciation for the role that amino acid neurotransmitters play in the pathophysiology of mood disorders and as potential targets for novel therapies. In this article we review progress of compounds that focus on these systems. We cover both glutamate-targeting drugs such as: esketamine, AVP-786, REL-1017, AXS-05, rapastinel (GLYX-13), AV-101, NRX-101; as well as GABA-targeting drugs such as: brexanolone (SAGE-547), ganaxolone, zuranolone (SAGE-217), and PRAX-114. We focus the review on phase-II and phase-III clinical trials and evaluate the extant data and progress of these compounds.

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Effects of Open-Label, Adjunctive Ganaxolone on Persistent Depression Despite Adequate Antidepressant Treatment in Postmenopausal Women

Cited by 33 publications

References 0 publications

Nontraditional therapies for treatment-resistant depression: Part 2

Nontraditional therapies for treatment-resistant depression: Part 2

The Role of HPA Axis and Allopregnanolone on the Neurobiology of Major Depressive Disorders and PTSD

Emerging Therapeutics Based on the Amino Acid Neurotransmitter System: An Update on the Pharmaceutical Pipeline for Mood Disorders

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