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Amantadine Revisited: A Contender for Initial Treatment in Parkinson’s Disease?


The best practice for the initiation of symptomatic motor treatment for Parkinson’s disease is an ongoing topic of debate. Fueled by interpretation of the results of the LEAP and MED Parkinson’s disease studies, many practitioners opt for early initiation of levodopa formulations, avoiding dopamine agonists to circumvent potential deleterious side effects, namely impulse control disorder. Compared with levodopa, monoamine oxidase inhibitors may lack necessary potency. Ignored in this academic debate is another therapeutic option for patients with Parkinson’s disease requiring treatment initiation: amantadine. Amantadine was first reported effective in the treatment of Parkinson’s disease in 1969 and several studies were published in the 1970s supporting its efficacy. Currently, amantadine is mainly utilized as an add-on therapy to mitigate levodopa-related dyskinesia and, more recently, new long-acting amantadine formulations have been developed, with new indications to treat motor fluctuations. Amantadine has not been reported to cause dyskinesia and is rarely implicated in impulse control disorder.

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Correspondence to Jason Margolesky.

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Conflicts of interest/competing interests

Sarah Marmol has no conflicts of interest to declare. Matthew Feldman has no conflicts of interest to declare. Carlos Singer has received grants from Pharma2B, Sunovion, Adamas, Revance, and Amneal, and honoraria from Abbvie and Mitsubishi. Jason Margolesky has no conflicts of interest to declare.

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SM performed the literature review, contributed significantly to the revised manuscript, and was co first author with MF. MF performed the literature review, contributed significantly to the revised manuscript, and was co first author with SM. CS conceptualized, designed, and provided revision to the manuscript. JM conceptualized, designed, and drafted the manuscript and performed the literature review. All authors approve the final version of the manuscript for submission and publication, and agree to be accountable for the work presented.

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Marmol, S., Feldman, M., Singer, C. et al. Amantadine Revisited: A Contender for Initial Treatment in Parkinson’s Disease?. CNS Drugs 35, 1141–1152 (2021).

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