restless legs syndrome and impusive control disorders

Last edited 09/2019

Restless legs syndrome (RLS) is a common sleep related movement disorder associated with mood and cognitive disorders (1,2)

Non-ergot-derived dopamine agonists (DA) such as ropinirole, pramipexole, and rotigotine are the first-line treatment of RLS with rapid efficacy, generally at low doses.

• however, dopamine agonists may cause side effects such as impulse control disorders such as binge eating, compulsive shopping, gambling disorder or compulsive sexual behavior
• DA used in RLS have high selective affinity for the D2/D3 receptor subtypes, which are expressed predominantly in the brain limbic areas, regions that are implicated in addiction and impulse control disorders (ICDs) (3)
• unclear why some RLS patients develop these complications while others do not
• DA dose does not correlate with the incidence of ICDs in RLS patients (8)

Abnormal reward-mediated processing is frequently observed in human disorders

• in Parkinson disease (PD), use of the D2/ D3 selective receptor agonists is associated with an increased risk of ICD including pathological gambling, compulsive buying, compulsive sexual behavior, and binge or compulsive eating
  • prevalence rates of ICDs in DA-treated patients with PD is 13.6%, compared to 0.5-1% in the general population (4,5)

As opposed to PD, the relationship between ICDs and DA in RLS is not as well established, with prevalence estimates for ICDs and/or addictive behaviors ranging from 5-17% (6,7)

• however Heim B et al noted, albeit via a retrospective case-control study, that patients with RLS with augmentation with DA therapy have an almost 6-fold increased risk of exhibiting ICD symptoms (8)

Reference:

• Pearson VE, Allen RP, Dean T, Gamaldo CE, Lesage SR, Earley CJ. Cognitive deficits associated with restless legs syndrome (RLS). Sleep Med 2006;7:25-30.
• Gamaldo CE, Benbrook AR, Allen RP, Oguntimein O, Earley CJ. A further evaluation of the cognitive deficits associated with restless legs syndrome (RLS). Sleep Med 2008;9:500-5.
• Manconi M, Ferri R, Zucconi M, et al. Preferential D2 or preferential D3 dopamine agonists in restless legs syndrome. Neurology 2011;77:110-7.
• Petry NM, Stinson FS, Grant BF. Comorbidity of DSM-IV pathological gambling and other psychiatric disorders: results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry 2005;66:564-74.
• Weintraub D, Koester J, Potenza MN, et al. Impulse control disorders in Parkinson disease: a cross-sectional study of 3090 patients. Arch Neurol 2010;67:589-95
• Dang D, Cunnington D, Swieca J. The emergence of devastating impulse control disorders during dopamine agonist therapy of the restless legs syndrome. Clin Neuropharmacol 2011;34:66-70.
• Voon V, Schoerling A, Wenzel S, et al. Frequency of impulse control behaviours associated with dopaminergic therapy in restless legs syndrome. BMC Neurol 2011;11:117
• Heim B et al. Augmentation and impulsive behaviors in restless legs syndrome: Coexistence or association?Neurology. 2016 Jul 5;87(1):36-40