Table 1

 Possible therapeutic options in the management of long term motor complications of levodopa therapy

Therapeutic strategyComments
NMDA, N-methyl-D-aspartate.
Taking levodopa before mealsShould be tried in the initial stages before adding other drug; helps to achieve better absorption of levodopa. Limited use in late stages
Low protein dietAbsorption of levodopa is reduced by amino acids in the diet. Diet low in protein may help in early fluctuations
COMT inhibitors (entacapone, tolcapone)Attractive theoretical basis, shown to be effective in randomised trials. Useful in motor fluctuations by increasing duration of on time. Possible worsening of dyskinesia reported. Tolcapone has potentially life threatening hepatotoxicity
Dopamine agonistsShown in several studies to be effective in prevention and treatment of motor complications. Probably should be the initial drug of choice in young and biologically fit older patients. Possible neuroprotection. Common short term side effects lead to frequent dropouts
Amantidine and other NMDA antagonistsIn some trials, shown to be useful against motor complications; consistent with theory of upregulation of NMDA receptors. Evidence insufficient
Controlled release preparations of levodopaMay be effective in simple end of dose deterioration. Not effective in severe fluctuations and dyskinesia
Continuous intraduodenal/intravenous levodopa infusionShown to be effective in preventing and treating motor complications. Practicalities limit routine use
Liquid levodopa preparations, in frequent dosageFast and predictable response, effective against motor complications. Small sized trials, cumbersome method
Neurosurgical approaches (thalamotomy, pallidotomy, deep brain stimulation)Small studies have shown benefit. Limitations of patient selection, postoperative complications and invasiveness