Increased Risk for New-Onset Psychiatric Adverse Events in Patients With Newly Diagnosed Primary Restless Legs Syndrome Who Initiate Treatment With Dopamine Agonists: A Large-Scale Retrospective Claims Matched-Cohort Analysis

Objective Several genetic variants have been found to increase the risk of restless legs syndrome (RLS). The aim of the present study was to determine if these genetic variants were also associated with the comorbidity of RLS and migraine in patients. Methods Thirteen single-nucleotide polymorphisms (SNPs) at six RLS risk loci ( MEIS1, BTBD9, MAP2K5, PTPRD, TOX3, and an intergenic region on chromosome 2p14) were genotyped in 211 migraine patients with RLS and 781 migraine patients without RLS. Association analyses were performed for the overall cohort, as well as for the subgroups of patients who experienced migraines with and without aura and episodic migraines (EMs) vs. chronic migraines (CMs). In order to verify which genetic markers were potentially related to the incidence of RLS in migraine patients, multivariate regression analyses were also performed. Results Among the six tested loci, only MEIS1 was significantly associated with RLS. The most significant SNP of MEIS1, rs2300478, increased the risk of RLS by 1.42-fold in the overall cohort ( p = 0.0047). In the subgroup analyses, MEIS1 augmented the risk of RLS only in the patients who experienced EMs (odds ratio (OR) = 1.99, p = 0.0004) and not those experiencing CMs. Multivariate regression analyses further showed that rs2300478 in MEIS1 (OR = 1.39, p = 0.018), a CM diagnosis (OR = 1.52, p = 0.022), and depression (OR = 1.86, p = 0.005) were independent predictors of RLS in migraine. Conclusions MEIS1 variants were associated with an increased risk of RLS in migraine patients. It is possible that an imbalance in iron homeostasis and the dopaminergic system may represent a link between RLS incidence and migraines.

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Newer Dopamine Agonists in the Treatment of Restless Legs Syndrome

Annals of Pharmacotherapy ◽

10.1345/aph.10271 ◽

2001 ◽

Vol 35 (5) ◽

pp. 627-630 ◽

Cited By ~ 12

Author(s):

Patti R Weimerskirch ◽

Michael E Ernst

Keyword(s):

Restless Legs Syndrome ◽

Dopamine Agonists ◽

Restless Legs

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An Exploratory Retrospective Evaluation of Ropinirole-Associated Psychotic Symptoms in an Outpatient Population Treated for Restless Legs Syndrome or Parkinson's Disease

Annals of Pharmacotherapy ◽

10.1345/aph.1m183 ◽

2009 ◽

Vol 43 (9) ◽

pp. 1426-1432 ◽

Cited By ~ 10

Author(s):

Steven C Stoner ◽

Megan M Dahmen ◽

Mignon Makos ◽

Jessica W Lea ◽

Lora J Carver ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Dopamine Receptors ◽

Restless Legs Syndrome ◽

Dopamine Agonists ◽

Dual Therapy ◽

Psychotic Symptoms ◽

Antipsychotic Treatment ◽

Restless Legs ◽

Psychotic Features

Background: Traditional treatment approaches for the management of restless legs syndrome (RLS) and Parkinson's disease (PD) include the use of medications that either directly or indirectly increase dopamine levels. In turn, a potential adverse event that could be expected is the development or exacerbation of psychiatric-related symptoms. Objective: To evaluate and describe the incidence of psychosis and associated behavioral features in patients taking ropinirole for RLS or PD. Methods: Patients were identified from a computerized database search of outpatients being treated with ropinirole for 1 of 2 medical conditions: PD or RLS. Data were collected in a retrospective manner from 95 patients who were tracked over the course of their therapy to determine whether psychosis or associated behavioral symptoms developed as a result and whether an intervention was needed to adjust ropinirole dosing or if additional medications had to be added to control features associated with psychosis. Results: A total of 284 patients being treated for RLS or PD were identified; of this group, 95 patients were identified as being treated for PD or RLS with ropinirole. Of the 95 patients being treated with ropinirole, 13 developed psychotic features that required therapeutic intervention with either the use of an antipsychotic or dose adjustment of ropinirole. PD patients included in this study were numerically more likely to develop psychotic features compared with RLS patients; however, the difference was not statistically significant (p = 0.122). The results do suggest that this risk is increased when ropinirole is used as part of a dual therapy approach with dopamine agonists in the treatment of either PD or RLS (p = 0.003). Discussion: Dopamine agonists have long been used as preferred treatment in the management of PD and RLS. When treating either PD or RLS in the psychiatric population, the concern arises that increased activity at dopamine receptors may induce or exacerbate psychiatric features. A potential clinical concern with the use of ropinirole is the potential for patients to develop psychiatric features, although there are few data available to demonstrate whether stimulation of targeted individual dopamine receptors is linked to the development or exacerbation of psychotic features. It is also undetermined whether concurrent antipsychotic treatment provides any protective benefit against psychosis, especially in patients already being treated for psychotic symptoms. Conclusions: Our findings suggest that ropinirole may play a role in inducing or exacerbating psychosis and its associated features, although a number of confounding variables prevent the determination of a clear association and suggest that further investigation is warranted in controlled clinical trials.

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P179 Glucocorticoid exposure and link to serious adverse events in patients with ANCA-associated vasculitis

Rheumatology ◽

10.1093/rheumatology/keaa111.174 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Philip Spearpoint ◽

Cormac Sammon ◽

Antonio Ramirez de ◽

Arellano Serna ◽

Peter Rutherford

Keyword(s):

Cardiovascular Disease ◽

Adverse Events ◽

Renal Disease ◽

Real World ◽

Low Dose ◽

Remission Induction ◽

High Dose ◽

Anca Associated Vasculitis ◽

Increased Risk ◽

New Onset

Abstract Background Remission induction in ANCA-associated vasculitis (AAV) is with high dose glucocorticoids (GC) and immunosuppressants. Patients are exposed to high GC dose and/or prolonged low dose. EULAR/EDTA guidelines target 7.5-10mg at 3 months but acknowledge this is often achieved later. This study used UK real world practice data to examine the scale of GC exposure and associated clinical risks in AAV. Methods The study utilised the Clinical Practice Research Datalink (CPRD) - Hospital Episode Statistics (HES) linked database. AAV patients were identified using specific READ and ICD codes and followed between 01/01/1997 and 01/01/2018. GP prescriptions were used to describe periods of continuous GC use, stop and restart and when high dose (> 30mg/day) and low dose (<30mg/day) was prescribed. Diagnostic codes indicative of infections and adverse events linked to GCs were used to estimate rates in the AAV population using a generalized linear model with a Poisson distribution. Results 450 AAV patients with at least one GC prescription were analysed. The median dose decreased to 9.3 mg (IQR 5.0 - 17.0) at 6 months and 5.1 mg (0.00 - 10.0) at 12 months,50% patients were taking > 10mg at 5 months and 25% were still > 10mg at 12 months. However, within 6 months of achieving 10mg/day, 50% relapse to needing dose >10mg, 75% within 2 years and 90% within 6 years. In adjusted Poisson model (age, gender, year of diagnosis before/after 2013) the rate of infection in AAV patients taking high dose was 2.59 times (CI95 1.95, 3.45) that of those on low dose and lower in those not taking GCs (IRR 0.27 (0.22-0.34)). Increased risk of new onset cardiovascular disease (IRR 2.55 (0.92, 7.04)) and new onset renal disease (IRR 3.4 (1.29-8.96)) were higher in patients receiving high dose. Conclusion AAV patients have significant exposure to high dose GCs and in real world practice, GC dose remains higher than recommended in current clinical guidelines. High dose GCs are associated with high risk of infection and new cardiovascular disease and renal disease. This creates a significant patient burden and has implications for healthcare resource use. Disclosures P. Spearpoint: Corporate appointments; Employee of Vifor Pharma. C. Sammon: Corporate appointments; Employee of PHMR. A. Ramirez de Arellano Serna: Corporate appointments; Employee of Vifor Pharma. P. Rutherford: Corporate appointments; Employee of Vifor Pharma. Shareholder/stock ownership; Vifor Pharma.

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SP439EXERCISE TRAINING AND DOPAMINE AGONISTS IN HEMODIALYSIS PATIENTS WITH RESTLESS LEGS SYNDROME. A RANDOMIZED DOUBLE-BLIND PLACEBO CONTROLLED STUDY

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfv194.03 ◽

2015 ◽

Vol 30 (suppl_3) ◽

pp. iii523-iii524

Author(s):

Giorgos Sakkas ◽

Christoforos Giannaki ◽

Christina Karatzaferi ◽

Georgios M. Hadjigeorgiou ◽

Ioannis Stefanidis

Keyword(s):

Restless Legs Syndrome ◽

Dopamine Agonists ◽

Hemodialysis Patients ◽

Controlled Study ◽

Double Blind ◽

Double Blind Placebo ◽

Restless Legs

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Neurology: Effect of Non-Ergot Dopamine Agonists on Health-Related Quality of Life of Patients with Restless Legs Syndrome

Annals of Pharmacotherapy ◽

10.1345/aph.1l673 ◽

2009 ◽

Vol 43 (5) ◽

pp. 813-821 ◽

Cited By ~ 6

Author(s):

Ripple Talati ◽

Olivia J Phung ◽

Jeffrey Mather ◽

Craig I Coleman

Keyword(s):

Quality Of Life ◽

Restless Legs Syndrome ◽

Dopamine Agonists ◽

Meta Analysis ◽

Health Related Quality ◽

Restless Legs ◽

Hrqol Data ◽

Related Quality ◽

Health Related

Background Non-ergot dopamine agonists (NEDAs) have become the gold-standard agents for the treatment of restless legs syndrome (RLS). While the efficacy and safety of these drugs have been widely studied, their effect on patients' health-related quality of life (HRQoL) has not been fully elucidated. Objective To better define the usefulness of NEDAs by assessing their impact on HRQoL. Methods We performed a meta-analysis of randomized, double-blind, placebo-controlled trials evaluating the use of NEDAs in patients with RLS. A systematic literature search of MEDLINE, EMBASE, and Cochrane CENTRAL was performed from the earliest possible date through July 2008. Trials were included in the analysis if they evaluated NEDAs for the treatment of RLS and reported HRQoL using any RLS disease-specific HRQoL instrument. HRQoL data were pooled and evaluated using an inverse variance weighting approach as standardized mean differences (SMDs) and 95% confidence interval (CI). For trials reporting HRQoL data obtained using the Johns Hopkins RLS-QoL Questionnaire, adjusted mean difference data were pooled to calculate the weighted mean difference (WMD) and 95% CI. Results Seven trials (N = 1483) met all inclusion criteria. Patients with RLS taking NEDAs had significantly improved overall effect on HRQoL compared with those taking placebo (SMD 0.20; 95% CI 0.10 to 0.30; degree of inconsistency across studies [I2] = 0%). When analyzing trials using the Johns Hopkins RLS-QoL questionnaire, the results also showed improvement with NEDAs compared with placebo (WMD 4.72; 95% CI 2.96 to 6.47; I2 = 0%). Study conclusions were unchanged upon sensitivity analysis. The number of trials for each NEDA was small, limiting the usefulness of between-agent comparisons. Conclusions In patients with RLS, use of NEDAs showed improved HRQoL compared with placebo. Since pooled effect sizes observed in this meta-analysis appear to surpass accepted values for minimally important clinical differences, these improvements may be clinically relevant for the average studied patient. However, future studies evaluating long-term treatment of RLS with NEDAs are necessary, as are head-to-head comparative trials and economic assessments.

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