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

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.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.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.