Drug-Induced Dyskinesia, Part 1: Treatment of Levodopa-Induced Dyskinesia

Dyskinesias encompass a variety of different hyperkinetic phenomenologies, particularly chorea, dystonia, stereotypies, and akathisia. Levodopa-induced dyskinesia (LID) is one of the main types of drug-induced dyskinesia, occurring in patients with Parkinson’s disease (PD) who have been treated with levodopa for long time, but this side effect may be encountered even within a few weeks or months after initiation of levodopa therapy. Based on the temporal pattern in relationship to levodopa dosing, LIDs are divided into “peak-dose dyskinesia,” “diphasic dyskinesia,” and “wearing off” or “off-period” dyskinesia, of which peak-dose dyskinesia is the most common, followed by off-period, and then diphasic dyskinesia. Treatment strategy includes identifying the kind of dyskinesia and tailoring treatment accordingly. Peak-dose dyskinesia is treated mainly by reducing individual doses of levodopa and adding amantadine and dopamine agonists, whereas off-period dystonia often responds to baclofen and botulinum toxin injections. Diphasic dyskinesias, occurring particularly in patients with young-onset PD, are the most difficult to treat. While fractionation of levodopa dosage is the most frequently utilized strategy, many patients require deep brain stimulation to control their troublesome motor fluctuations and LIDs. A variety of emerging (experimental) drugs currently in development promise to provide better control of LIDs and other levodopa-related complications in the near future.