Safety review of current pharmacotherapies for levodopa-treated patients with Parkinson's disease.

INTRODUCTION: Levodopa remains the gold standard for treatment of Parkinson's disease (PD). Patients develop complications with disease progression, necessitating adjunctive therapy to control fluctuations in motor and non-motor symptoms and dyskinesia. Knowledge of medication safety and tolerability is critical to ascertain the benefit-risk ratio and select an adjunctive therapy that provides the highest chance for medication adherence. Posing a challenge are the sheer abundance of options, stemming from the development of several new drugs in recent years, as well as differences in commercial drug availability worldwide.

AREAS COVERED: This review evaluates the efficacy, safety, and tolerability of current US FDA-approved pharmacotherapies for levodopa-treated PD patients, including dopamine agonists, monoamine oxidase type-B inhibitors, catechol-O-methyltransferase inhibitors, the N-methyl-D-aspartate receptor antagonist amantadine, and the adenosine receptor antagonist istradefylline. Data were taken from pivotal phase III randomized controlled and post-surveillance studies, when available, that directly led to FDA-approval.

EXPERT OPINION: No strong evidence exists to support use of a specific adjunctive treatment for improving Off time. Only one medication has demonstrated improvement in dyskinesia in levodopa-treated PD patients; however, every patient cannot tolerate it and therefore adjunctive therapy should be tailored to an individual's symptoms and risk for specific adverse effects.