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Volume 15 No. 09
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Accepted Papers

Scientific Investigations

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

Cheryl Hankin, PhD1; Daniel Lee, MD2; Diego Garcia-Borreguero, MD, PhD3; Zhaohui Wang, MS1
1BioMedEcon, LLC, Moss Beach, California; 2Baptist Health Medical Group, Richmond, Kentucky; 3Sleep Research Institute, Madrid, Spain

Study Objectives:

Published literature documents increased risk for psychiatric adverse events (P-AEs) following dopamine agonist (DA) initiation for treatment of primary restless legs syndrome (RLS). We examined the association between DA initiation and subsequent new-onset P-AEs among patients with a new diagnosis of RLS who had no history of psychiatric disorder or DA use.


Selected were adults (age 18 years or older) enrolled through United States employer-sponsored plans and Medicare Advantage from 7/1/2008–12/31/2014, with ≥ 2 years of claims data preceding their first RLS diagnosis (“preindex period”). Excluded were those with psychiatric diagnoses (International Classification of Diseases, Ninth Revision [ICD-9] 290-319) or DA use during the preindex period, and those with possible secondary RLS. Patients who initiated (DA+) versus did not initiate (DA−) DAs were matched 1:1 on age at index RLS diagnosis, sex, geographic region, and employment status, and preindex period comorbid illness burden and number of non-DA drug fills. Using a validated ICD-9-based severity-of-illness psychiatric disorder classification system, we compared likelihoods of new-onset P-AEs between matched pairs during parallel follow-up periods.


Identified were 889 matched pairs. Compared with their DA− counterparts, DA+ patients were nearly two times more likely to experience development of any P-AE (odds ratio [OR] 1.71, 95% confidence interval [CI] 1.31–2.24, P < .0001); and similarly more likely to experience the development of a severe (OR 1.68, 95% CI 1.03–2.86, P = .04), moderately severe (OR 1.63, 95% CI 1.17–2.29, P = .004), or mild (OR 1.72, 95% CI 1.12–2.65, P = .01) P-AE.


Compared to DA− matched control patients, patients in whom RLS was newly diagnosed and who initiated de novo DAs demonstrated significantly increased risk for subsequent development of P-AEs of any severity.


Hankin C, Lee D, Garcia-Borreguero D, Wang Z. 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. J Clin Sleep Med. 2019;15(9): 1225–1232.

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