In this issue of JAMA Neurology, Pahwa and colleagues1 report the results of the ADS-5102 Extended Release Capsules for the Treatment of Levodopa Induced Dyskinesia (EASE LID) Study. The authors investigated the safety and efficacy of extended-release amantadine as a treatment for the control of levodopa-induced dyskinesia (LID) in patients with Parkinson disease (PD). For over a half a century, levodopa has been the most effective gold standard therapy for PD symptomatic treatment. The major limitation of levodopa therapy has been the emergence of LID.2 Clinically, LID can manifest as purposeless, fidgety, or choreiform movements. There can also be writhing-type choreoathetoid, wild flinging ballistic movements, or dystonic posturing.3 Levodopa-induced dyskinesia is observed in more than 50% of patients who have received levodopa therapy for 4 to 6 years and in more than 90% of patients treated for 10 years.2 Besides the duration of levodopa therapy, the duration of the disease, the severity of the disease, and the age at onset are other important risk factors. Levodopa-induced dyskinesia is more frequent, more severe, and presents sooner in patients with PD who present with symptoms before 50 years of age.2 Severe LID significantly affects quality of life and is an important contributor to weight loss. The pathophysiology of LID is believed to be complex and multifactorial. Although nondopaminergic factors are known to contribute, progressive degeneration of the nigrostriatal tract (presynaptic), pulsatile stimulation of dopamine receptors, and postsynaptic modification of nuclear proteins are considered major factors in the development of LID.3
Wagle Shukla A. Extended-Release Amantadine—A Smart Pill for Treatment of Levodopa-Induced Dyskinesia but Does the Evidence Justify the Cost? JAMA Neurol. 2017;74(8):904–905. doi:10.1001/jamaneurol.2017.0954
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