Current and emerging strategies in the management of Parkinson's disease: a critical reappraisal

ABSTRACT

The pharmacological treatment of Parkinson's disease [PD] can be subdivided into symptomatic treatment [e.g. levodopa combined with a peripheral decarboxylase inhibitor [PDI], direct-acting dopamine receptor agonists, amantadine, centrally-acting antimuscarinic drugs and catechol-0-methyltransferase [COMT] inhibitors] aimed at restoring striatal dopamine function and reversing functional disability, and neuroprotective treatment [e.g. monoamine oxidase-B [MAO-B] inhibitors] aimed at interfering either with the cause of the disease or pathophysiologic mechanism of substantia nigral cell death. Despite the controversy about the development of long-term side effects levodopa/PDI remains the gold standard for the symptomatic treatment of PD. Direct-acting dopamine receptor agonists are usually recommended as adjuvants to levodopa/PDI. There is no compelling evidence that newer generation dopamine receptor agonists have a greater therapeutic effect than existing ones. Amantadine has limited effectiveness and loss of its beneficial effect after several months seriously limits its usefulness. Centrally-acting antimuscarinic drugs all have low efficacy and high toxicity and should be restricted for young patients with tremor-predominant PD. COMT inhibitors improve the pharmacokinetic properties of levodopa, however data are still lacking about their long-term efficacy and safety. The neuroprotective effect claimed by MAO-B inhibitors can well be offset by the increased mortality reported in patients treated with these drugs. The clinical and pharmacokinetic properties of the current and emerging drugs used in the treatment of PD are reviewed and guidelines are provided for the management of early and advanced PD