New considerations in the medical management of early Parkinson's disease: impact of recent clinical trials on treatment strategy.

The best approach to medical management of early Parkinson's disease remains controversial. Recent studies suggest that early use of MAO-B inhibitors may improve long-term outcome. Long-term follow-up to a delayed-start rasagiline study indicated that patients who were treated with rasagiline from the start did better through 5.5-6 years of treatment (with all PD medications) than patients who began rasagiline after a delay of 6 months. In a long-term selegiline study, patients randomized to treatment with selegiline did better over 7 years than patients randomized to treatment with placebo. Dopamine agonists provide moderate symptomatic benefit, delay the need for levodopa, and delay the emergence of motor complications, especially dyskinesia. Long-term studies have not demonstrated a clear overall benefit to introducing a dopamine agonist prior to levodopa in general PD populations, but treatment regimens tend to become increasingly similar over time, most studies have had high drop-out rates, and there may be subsets of patients who experience greater benefit with this strategy. Levodopa remains the most efficacious oral medication for the treatment of motor signs of PD but is associated with the development of motor complications. Long-acting levodopa formulations are now under development and it will be important to determine whether they cause fewer motor complications than standard levodopa. The current approach to treatment of early PD depends in part on individual patient factors including age, severity of motor signs, presence of cognitive dysfunction, and other co-morbidities.