Less is more: pathophysiology of dopaminergic-therapy-related augmentation in restless legs syndrome

• Published in: Lancet neurology Vol. 5; no. 10; pp. 878 - 886
• Main Authors: Paulus, Walter, Trenkwalder, Claudia
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2006; Elsevier Limited
• Subjects: Catecholamines; Circadian Rhythm - physiology; Dopamine; Dopamine - deficiency; Dopamine Agents - therapeutic use; Dopamine Agonists - therapeutic use; Genes; Humans; Iron - physiology; Levodopa - therapeutic use; Neurosciences; Parkinson's disease; Pathophysiology; Receptors, Dopamine D2 - drug effects; Restless legs syndrome; Restless Legs Syndrome - drug therapy; Restless Legs Syndrome - physiopathology; Spinal cord
• ISSN: 1474-4422; 1474-4465
• DOI: 10.1016/S1474-4422(06)70576-2

Therapy-related augmentation of the symptoms of restless legs syndrome (RLS) is an important clinical problem reported in up to 60% of patients treated with levodopa and, to a lesser extent, with dopamine agonists. The efficacy of low-dose dopaminergic drugs for RLS has been established, but the mode of action is unknown. Here, we review the existing data and conclude that augmentation is a syndrome characterised by a severely increased dopamine concentration in the CNS; overstimulation of the dopamine D1 receptors compared with D2 receptors in the spinal cord may lead to D1-related pain and generate periodic limb movements; iron deficiency may be a main predisposing factor of augmentation, probably caused by a reduced function of the dopamine transporter; therapy with levodopa or dopamine agonists should remain at low doses and; iron supplementation and opiates are the therapy of choice to counter augmentation.