Less is more: pathophysiology of dopaminergic-therapy-related augmentation in restless legs syndrome.
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.
Paulus
Walter
W
Department of Clinical Neurophysiology, University of Göttingen, Göttingen, Germany. wpaulus@med.uni-goettingen.de
Trenkwalder
Claudia
C
D002940:Circadian Rhythm / Q000502:physiology; D004298:Dopamine / Q000172:deficiency; D015259:Dopamine Agents / Q000627:therapeutic use*; D018491:Dopamine Agonists / Q000627:therapeutic use; D006801:Humans; D007501:Iron / Q000502:physiology; D007980:Levodopa / Q000627:therapeutic use; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D012148:Restless Legs Syndrome / Q000188:drug therapy* / Q000503:physiopathology*
D015259:Dopamine Agents; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D007980:Levodopa; D007501:Iron; D004298:Dopamine