Effects of supra-threshold levodopa doses on dyskinesias in advanced Parkinson's disease

The levodopa (LD) dose-antiparkinsonian response relationship becomes progressively steeper with advancing Parkinson's disease (PD). To establish the dose-response profile for the dyskinesiogenic effect of LD, we administered intravenous LD over a wide dose range to 25 patients with advanced PD. As expected in these patients with nonexistent therapeutic windows, the threshold doses (TD) for both motor effects were similar. Just around the TD, the relationship between LD dose and the magnitude of antiparkinsonian and dyskinesiogenic responses inclined steeply, reaching a plateau above 1.5 x TD. Response duration, however, continued to increase. The findings suggest that attempts to ameliorate dyskinesias in advanced PD patients by giving smaller, more frequent LD doses may be counter-productive due to shorter motor responses, more "off" time, and dose failures, while some may, in fact, benefit from higher LD doses to assure a full response and prolong its duration.