Treatment initiation and utilization patterns of pharmacotherapies for early-onset idiopathic restless legs syndrome

Costales, Brianna; Vouri, Scott Martin; Brown, Joshua D.; Setlow, Barry; Goodin, Amie

doi:10.1016/j.sleep.2022.05.003

Cited by 4 publications

(2 citation statements)

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“…[1,3–8] Patients are usually forced to move the affected parts to alleviate their discomfort. [2,9] RLS can cause or coexist with cardiovascular, metabolic, sleep, and mental disorders (such as anxiety and depression) [1,2,10–12] and reduce quality of life. [5,11,13–16] The prevalence of RLS has been estimated to range from 4% to 29%, [11] and it has attracted wide attention in recent years.…”

Section: Introductionmentioning

confidence: 99%

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Uncovering the mechanism of Radix Paeoniae Alba in the treatment of restless legs syndrome based on network pharmacology and molecular docking

Liu

Hao³

et al. 2022

Medicine

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Restless legs syndrome (RLS) is a neurological motor disorder with a high prevalence. The treatment efficacy of RLS is unsatisfactory. Radix Paeoniae Alba (RPA) can effectively treat RLS symptoms such as the discomfort of the legs. RPA has great potential for the development of new medications for RLS. Hence, we explored the mechanism of RPA in the treatment of RLS using network pharmacology and molecular docking. The active components and targets of RPA were obtained from the Traditional Chinese Medicine System Pharmacology database and analysis platform and PharmMapper platform. The RLS-related targets were found in GeneCards, OMIM, DrugBank, and DisGeNET databases. The overlapping targets of RPA and RLS were then collected. The “active components-overlapping targets” network was built, and network topology analysis was performed. Furthermore, Cytoscape 3.9.1 software was used to screen the key components of RPA in the treatment of RLS. Protein-protein interaction was performed using the Search Tool for the Retrieval of Interacting Genes. The gene ontology functions and Kyoto Encyclopedia of Genes and Genomes signaling pathways were analyzed using ClusterProfiler, PathView, and other R packages to reveal the main mechanism of RPA in treating RLS. Component and protein structures were downloaded from the Traditional Chinese Medicine System Pharmacology and Protein Data Bank databases, respectively. The AutoDock 4.2.6 software was used for molecular docking. A total of 12 active components and 109 targets of RPA, as well as 2387 RLS-related targets, were collected. Following that, 47 overlapping targets were obtained. Furthermore, 5 key components and 12 core targets were screened. The results of gene ontology functions were as follows: 2368 biological processes, 264 molecular functions, and 164 cellular components. A total of 207 Kyoto Encyclopedia of Genes and Genomes signaling pathways were obtained, including the lipid and atherosclerosis pathway, the endocrine resistance pathway, the prolactin signaling pathway, and the IL-17 signaling pathway. The components and the core targets completed molecular docking stably. RPA has multi-component, multi-target, and multi-pathway characteristics in treating RLS, which could provide a basis for future research and improve clinical efficacy.

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Section: Introductionmentioning

confidence: 99%

“…However, their therapeutic effects are unsatisfactory. [5,12] In Traditional Chinese Medicine (TCM), RLS is classified as "arthralgia" and "tibial acid." In clinics, Radix Paeoniae Alba (RPA) can effectively relieve the discomfort of the legs and treat RLS.…”

Section: Introductionmentioning

confidence: 99%

Uncovering the mechanism of Radix Paeoniae Alba in the treatment of restless legs syndrome based on network pharmacology and molecular docking

Liu

Hao³

et al. 2022

Medicine

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Risk of Suicidal Ideation and Behavior Following Early‐Onset Idiopathic Restless Legs Syndrome Treatment

Costales,

Vouri,

Brown

et al. 2024

Pharmacoepidemiology and Drug

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PurposeTo estimate incidence rates of suicidal ideation and behavior following treatment initiation with gabapentinoids or dopamine agonists (DAs) in patients with newly diagnosed early‐onset idiopathic restless legs syndrome (RLS) and to examine suicidal behavior risk, comparing between those receiving gabapentinoids and DAs.MethodsA new user retrospective cohort study using MarketScan claims data from 2012 to 2019 was conducted. Exposures were monotherapy gabapentinoids or DAs initiated within 60 days of new RLS diagnosis. Three varying outcome measures of suicidality were examined and incidence rates were calculated for each. A log‐binomial regression model the estimated relative risk (RR) of the outcomes with gabapentinoids. Propensity score weighting adjusted for baseline covariates, including age, substance use disorders, hyperlipidemia, antipsychotic use, hypnotic/sedative use, and mood stabilizer use, which were most imbalanced before weighting.ResultsThe cohort included 6672 patients, with 4986 (74.7%) initiating a DA and 1686 (25.3%) initiating a gabapentinoid. Incidence rates for all outcome measures were higher in the gabapentinoid group (suicidality: 21.6 vs. 10.7 per 1000 person‐years; suicidality with self‐harm: 23.0 vs. 11.1 per 1000 person‐years; overdose‐ and suicide‐related events: 30.0 vs. 15.5 person‐years). Associated risk of suicidality (adjusted RR, 1.27 [95% CI, 0.86–1.88]); suicidality with self‐harm (adjusted RR, 1.30 [95% CI, 0.89–1.90]); or overdose‐ and suicide‐related events (adjusted RR, 1.30 [95% CI, 0.93–1.80]) was not significant with gabapentinoids.ConclusionsIncidence rates for suicidal ideation and behavior were higher among the gabapentinoid group, although increased risk was not detected after adjustment. A possible signal cannot be ruled out given limitations of the data and rarity of the outcome.

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Incident mental health episodes after initiation of gabapentinoids vs. dopamine agonists for early-onset idiopathic restless legs syndrome

Costales,

Vouri,

Brown

et al. 2023

Psychiatry Research

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Treatment initiation and utilization patterns of pharmacotherapies for early-onset idiopathic restless legs syndrome

Cited by 4 publications

References 36 publications

Uncovering the mechanism of Radix Paeoniae Alba in the treatment of restless legs syndrome based on network pharmacology and molecular docking

Uncovering the mechanism of Radix Paeoniae Alba in the treatment of restless legs syndrome based on network pharmacology and molecular docking

Risk of Suicidal Ideation and Behavior Following Early‐Onset Idiopathic Restless Legs Syndrome Treatment

Incident mental health episodes after initiation of gabapentinoids vs. dopamine agonists for early-onset idiopathic restless legs syndrome

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