Withdrawing amantadine in dyskinetic patients with Parkinson disease
The AMANDYSK trial
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- Treatment of Motor Symptoms of Parkinson’s Disease, Neurologic Clinics, 43, 2, (341-363), (2025).https://doi.org/10.1016/j.ncl.2024.12.010
- Update on Treatments for Parkinson's Disease Motor Fluctuations – An International Parkinson and Movement Disorder Society Evidence‐Based Medicine Review, Movement Disorders, (2025).https://doi.org/10.1002/mds.30162
- Amantadine, The Movement Disorders Prescriber's Guide to Parkinson's Disease, (2-15), (2025).https://doi.org/10.1017/9781009222648.003
- Amantadine use in the French prospective NS-Park cohort, Journal of Neural Transmission, 131, 7, (799-811), (2024).https://doi.org/10.1007/s00702-024-02772-4
- Treatment of apathy in Parkinson's disease: A bayesian network meta-analysis of randomised controlled trials, Heliyon, 10, 4, (e26107), (2024).https://doi.org/10.1016/j.heliyon.2024.e26107
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- A Systematic Review of Pharmacological Interventions for Apathy in Aging Neurocognitive Disorders, Brain Sciences, 13, 7, (1061), (2023).https://doi.org/10.3390/brainsci13071061
- Investigation of the Long-Term Effects of Amantadine Use in Parkinson’s Disease, Journal of Movement Disorders, 16, 2, (224-226), (2023).https://doi.org/10.14802/jmd.23037
- Altered amantadine effects after repetitive treatment for l-dopa-induced involuntary movements in a rat model of Parkinson’s disease, Neuroscience Letters, 806, (137248), (2023).https://doi.org/10.1016/j.neulet.2023.137248
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We thank Dr. Friedman for his comments and agree that the differences observed in favor of amantadine in fatigue and apathy scores of the AMANDYSK trial are difficult to interpret and must be taken cautiously. [1] These measurements, although pre-specified, were only exploratory. The study was not powered to assess differences between such outcomes. The placebo and nocebo effects and the evolution of the scores in a wash-out design are still unclear. More patients dropped out prematurely because of the worsening of dyskinesia in the group switched to placebo versus those remaining on amantadine. Any interpretation is then quite speculative. In spite of these limitations, amantadine has been reported to have potentially positive effects on fatigue and apathy in other neurological disorders. [2,3] Further trials are needed to confirm or invalidate the hypothesis that amantadine could have such a potential beneficial effect in Parkinson disease.
1. Ory-Magne F, Corvol J-C, Azulay J-P, et al. Withdrawing amantadine in dyskinetic patients with Parkinson disease: The AMANDYSK trial. Neurology 2014; 82: 300-307.
2. Krupp LB, Coyle PK, Doscher C, et al. Fatigue therapy in multiple sclerosis: results of a double-blind, randomized, parallel trial of amantadine, pemoline, and placebo. Neurology 1995;45: 1956-1961.
3. Van Reekum R, Bayley M, Garner S, et al. N of 1 study: amantadine for the amotivational syndrome in a patient with traumatic brain injury. Brain Inj. 1995;9:49-53.
For disclosures, contact the editorial office at [email protected].
I applaud the authors of the AMANDYSK trial and agree that their placebo-controlled withdrawal design supports the anti-dyskinetic effect of amantadine for L-Dopa induced dyskinesias. [1] This design emulates clinical practice, where a drug is routinely tapered and stopped if the benefit is unclear. However, the authors??? deductions on the measured non-motor symptoms are dubious. They couched their interpretation in a "possible" effect of amantadine on fatigue, and state that the "observations should be interpreted cautiously," but a closer look actually underscores the importance of a placebo effect. Subjects whose amantadine was not altered reported an improvement in fatigue, while subjects whose amantadine was discontinued reported a decline. Similarly, the caregiver assessment of apathy worsened off amantadine and improved with its continuation. Even though the worsening could be a reflection of an effect of amantadine withdrawal, it is difficult to imagine either an anti-fatigue or an anti-apathy effect of simply continuing the drug.
1. Ory-Magne F, Corvol J-C, Azulay J-P, et al. Withdrawing amantadine in dyskinetic patients with Parkinson disease: The AMANDYSK trial. Neurology 2014; 82: 300-307.
For disclosures, please contact the editorial office at [email protected].