Effect of Miricorilant, a Selective Glucocorticoid Receptor Modulator, on Olanzapine-Associated Weight Gain in Healthy Subjects

Hunt, Hazel; Donaldson, Kirsteen; Strem, Mark; Tudor, Iulia Cristina; Sweet-Smith, Suzanne; Sidhu, Sharan

doi:10.1097/jcp.0000000000001470

Cited by 11 publications

(4 citation statements)

References 23 publications

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“…For example, antipsychotic medications, including olanzapine, are associated with considerable weight gain and metabolic disturbances. There are preliminary data showing that coadministration of miricorilant, a selective GR modulator, with olanzapine can ameliorate these effects [70].…”

Section: Beyond Affective Symptoms: Cognitive Dysfunction Metabolic D...mentioning

confidence: 99%

Increased Cortisol and Antiglucocorticoid Therapy in Mood Disorders: The Hippocampus as a Potential Drug Target

Gulyaeva

2024

Preprint

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The pathophysiology of many mood disorders is closely related with abnormal stress response associated with the dysfunction of the hypothalamic-pituitary-adrenal (HPA) axis and cortisol overproduction. The hippocampus, key structure of the limbic system responsible for both cognitive and emotional spheres, is selectively vulnerable to excess of glucocorticoids (GCs) inducing neuroinflammation and neurodegeneration. The antiGC therapy of psychiatric diseases, in particular depressive disorders, may be a useful additional treatment. Among other approaches, targeting glucocorticoid receptors, abounded in the hippocampus, is regarded as highly promising. However, though the preclinical data provide firm evidence to the concept of antiGC therapy for stress-related diseases, clinical studies still are at the proof-of-concept stage. Noteworthy, chronic GC excess is associated not only with mood diseases, but also with cognitive decline, metabolic disorders, diabetes. Potentially, antiGC (HPA axis modifying) therapy may alleviate affective symptoms, cognitive disturbances, GC and insulin resistance and adverse side effects of conventional drugs through beneficial effects on hippocampal dysfunction and neurodegeneration, neuroinflammation, and neurogenesis. Since stress/GC-associated neuroinflammation-mediated pathology of the limbic system and, specifically, the hippocampus, is a general feature typical for many brain diseases, the concept of antiGC therapy may be extended, tested and validated in a wider spectrum of cerebral pathologies.

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Section: Beyond Affective Symptoms: Cognitive Dysfunction Metabolic D...mentioning

confidence: 99%

Increased Cortisol and Antiglucocorticoid Therapy in Mood Disorders: The Hippocampus as a Potential Drug Target

Gulyaeva

2024

Preprint

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“…In this regard, a study on the effect of miricorilant, a selective glucocorticoid receptor modulator, on olanzapine-associated weight gain suggested that miricorilant could potentially be an option to mitigate the harmful effects of olanzapine. Still, research needs to be continued [ 21 ]. New research confirms that glucocorticoid therapy can cause several negative effects, including weight gain, dyslipidemia, and hyperglycemia [ 22 ].…”

Section: Drugs-induced Obesitymentioning

confidence: 99%

Pharmacological Treatments and Natural Biocompounds in Weight Management

et al. 2023

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The obesity pandemic is one of society’s most urgent public health concerns. One-third of the global adult population may fall under obese or overweight by 2025, suggesting a rising demand for medical care and an exorbitant cost of healthcare expenditure in the coming years. Generally, the treatment strategy for obese patients is largely patient-centric and needs dietary, behavioral, pharmacological, and sometimes even surgical interventions. Given that obesity cases are rising in adults and children and lifestyle modifications have failed to produce the desired results, the need for medical therapy adjunct to lifestyle modifications is vital for better managing obesity. Most existing or past drugs for obesity treatment target satiety or monoamine pathways and induce a feeling of fullness in patients, while drugs such as orlistat are targeted against intestinal lipases. However, many medications targeted against neurotransmitters showed adverse events in patients, thus being withdrawn from the market. Alternatively, the combination of some drugs has been successfully tested in obesity management. However, the demand for novel, safer, and more efficacious pharmaceutical medicines for weight management does exist. The present review elucidates the current understanding of the available anti-obesity medicines of synthetic and natural origin, their main mechanisms of action, and the shortcomings associated with current weight management drugs.

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“…Future studies need to replicate the previous results of fluvoxamine‐addition for AiWG in long‐term studies with Caucasian clozapine‐treated participants because of ethnical variation in CYP‐enzyme activity 61 . The efficacy of miricorilant, a selective glucocorticoid receptor modulator, for treatment of AiWG is currently being investigated 62 …”

mentioning

confidence: 98%

“…61 The efficacy of miricorilant, a selective glucocorticoid receptor modulator, for treatment of AiWG is currently being investigated. 62 In conclusion, amelioration of prevention and treatment interventions for AiWG is warranted. No pharmacological interventions are officially approved as adjunctive medication for treatment or prevention of AiWG.…”

mentioning

confidence: 99%