Adjuvant therapies for Parkinson’s disease: critical evaluation of safinamide

Abstract

Safinamide (SAF) is a new drug developed for the treatment of Parkinson’s disease (PD). It is a benzylamino derivative with multiple mechanisms of action and antiparkinsonian, anticonvulsant, and neuroprotective properties. SAF inhibits monoamine oxidase B and dopamine reuptake and glutamate release, blocks voltage-dependent sodium channels, and modulates calcium channels. Although the antiparkinsonian effect can be ascribed in part to the inhibition of the monoamine oxidase B, which is complete at 50 mg, the enhanced benefit seen at the 100 mg dose is probably due to nondopaminergic mechanisms. SAF will represent an important option for patients with both early and advanced PD. In early PD patients, the addition of SAF to dopamine agonists may be an effective treatment strategy to improve motor function, prolong the use of dopamine agonists, and/or delay the introduction of levodopa. In advanced parkinsonian patients, SAF has been demonstrated to significantly increase on time with no, or nontroublesome dyskinesias. All studies performed have demonstrated its efficacy in benefiting both short-term and long-term quality-of-life outcomes in both early and advanced PD patients. SAF has been investigated in long-term (24 months), double-blind, placebo-controlled studies, where it showed a very good safety profile. SAF has not been studied in de novo PD patients, and its potential positive effect on dyskinesia deserves further dedicated studies.

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Keywords:

• safinamide
• Parkinson’s disease
• add-on
• dopamine agonist
• l-dopa
• motor fluctuations
• dyskinesia
• a-aminoamide

Disclosure

The first author has been a consultant to TEVA, Novartis, GSK, Lundbeck, Merck Serono, MSD, UCB, Chiesi Pharma, IMPAX, Newron, Zambon, and Britannia. He has also received research funding from Novartis and GlaxoSmithKline as well as received honoraria for educational symposia and consultancy to GlaxoSmithKline. The second author reports no conflict of interest in this work.