Treatment of motor complications in advancing Parkinson's disease: Which drugs and when?

After several years of Parkinson's disease (PD), most levodopa-treated pati ents begin to experience motor complications, ie, clinical fluctuations and dyskinesias. The motor fluctuations relate to the development of short-dur ation levodopa responses, or "wearing-off" of the levodopa effect. This sho uld probably be treated initially with levodopa adjustment. Subsequently, a dopamine agonist (typically pergolide, pramipexole, or ropinirole) or the COMT inhibitor entacapone may be added. The advantage of entacapone is an i mmediate response, whereas the disadvantage is a greater likelihood of exac erbating dyskinesias. Another COMT inhibitor, tolcapone, is also efficaciou s but is a second-line drug because of its potential for serious, albeit ra re, hepatopathy. With each form of adjunctive therapy, further adjustment o f levodopa dosage is often necessary. Both classes of adjunctive therapy ma y be concomitantly employed. However, with increasing polypharmacy, psychos is or orthostatic hypotension is an occasional problem. Dyskinesias are bes t treated with levodopa dose reduction, as tolerated. Amantadine may be add ed in select refractory cases.