Maximizing the benefit of pharmacotherapy in Parkinson's disease

Levodopa is one of the principal agents administered to treat patients with Parkinson's disease (PD). Several pharmacologic strategies can limit its side effects and enhance its activity. Although certain exceptions apply, dosage adjustments and drug changes should be instituted slowly. Levodopa is typically introduced in the form of carbidopa-levodopa, with upward dosage titration weekly until symptoms improve. A dopamine agonist may be added when the dosage of levodopa reaches 300-500 mg/day Dopamine agonists are used to control symptoms of PD, decrease or delay motor fluctuations, and allow lower dosages of levodopa to be administered. These agents are also being prescribed early in treatment before carbidopa-levodopa therapy is begun. Addition of a catechol-O-methyltransferase inhibitor can increase the duration of levodopa's effect and may prove especially valuable for patients who experience early wearing off of levodopa. Patients with PD require close monitoring for drug toxicity. Because most of them are treated with several agents to provide maximum improvement and also receive treatment for comorbid conditions, drug-drug interactions are possible. Frequently, clinically significant interactions are associated with agents that block D2 receptors or deplete dopamine stores in the brain.