Amantadine, Parkinson’s Treatment, Not Seen to Prevent COVID-19

Medication to ease dyskinesia and off episodes known to have antiviral activity

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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Using amantadine — a parkinsonian medication that has also antiviral activity — does not reduce the occurrence of COVID-19 or its severity among people with Parkinson’s disease, a Polish study found.

Rather, the researchers observed that COVID-19 was less common among people over age 50 age, and those with more advanced disease or a longer duration of Parkinson’s symptoms, possibly because they were less likely to be out and about.

The study, “Morbidity and severity of COVID-19 in patients with Parkinson’s disease treated with amantadine – A multicenter, retrospective, observational study,” was published in Parkinsonism & Related Disorders.

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Amantadine, sold as Gocovri for Parkinson’s in US, is antiviral of interest

Since the beginning of the COVID-19 pandemic, scientists have been searching for treatments that may narrow the chances of getting infected with SARS-CoV-2, the virus that causes COVID-19, or of becoming very sick from it.

Some of these treatments are known antiviral medications. Unlike vaccines, which may not be readily available during a pandemic’s start, existing antivirals can be used in its earliest phases.

Amantadine works by blocking M2, a channel protein that helps certain viruses enter host cells and use their machinery. Several studies suggested that the therapy could be effective also against SARS-CoV-2.

“However, these studies have significant limitations including: small number of patients (mostly case series reports), concurrent treatment with other therapies; no information on other medications, no endpoints predefined in the study methodology for the efficacy and safety of amantadine,” the researchers wrote.

With Parkinson’s, amantadine is used to treat disease symptoms and the motor complications that often arise with long-term levodopa treatment.

In the U.S., Supernus Pharmaceuticals’ Gocovri, an extended-release, long-lasting formulation of amantadine, is the only medication approved for both dyskinesia (irregular, uncontrolled movements) and “off” episodes in Parkinson’s patients who are on levodopa. Off episodes occur when symptoms return between levodopa doses.

The mechanisms behind amantadine’s beneficial effects in Parkinson’s are unclear, but the therapy is thought to help restore dopamine levels in the brain. Dopamine is the major chemical messenger in the brain that is progressively lost in people with Parkinson’s.

To find out if, and how well, regular amantadine use may protect people from COVID-19 or from a severe infection, researchers in Poland analyzed the health records of Parkinson’s patients who were taking amantadine as part of their parkinsonian treatment compared with those who were not.

A survey, conducted between Nov. 30, 2020, and Oct. 18, 2021, was completed by 552 people with Parkinson’s, mostly men (329 or 59.6%). Patients’ mean age was 64.8 years (range, 27–89), and their mean disease duration was 9.6 years.

Patients’ mean Hoehn and Yahr (H&Y) stage was 2.44. This scale, a measure of the functional disability associated with Parkinson’s, is divided into stages one to five, with higher stages indicating greater severity.

No major differences in infection rate or COVID-19 severity

A total of 104 (18.8%) patients tested positive for SARS-CoV-2. They were a mean five years younger than those who tested negative for the virus (60.8 vs. 65.8 years) — a difference that was statistically significant.

Consistent with this, patients older than 50 had a significantly lower rate of COVID-19 than younger patients (17% vs. 38%). This finding may be related to “less mobility and avoiding of social contacts during the pandemic in older PD [Parkinson’s disease] patients, and therefore lower exposure to infection,” the researchers wrote.

“Nevertheless, other factors have to be considered as well,” they added.

Infected patients also had a significantly shorter disease duration (8.4 vs. 9.9 years) and less severe disease (mean H&Y stage of 2.27 vs. 2.49).

Among all patients, 134 (24.3%) were fully vaccinated against COVID-19 during the study. However, a similar proportion of fully vaccinated patients did and did not test positive for the virus (24% vs. 24.3%).

Amantadine was taken by 219 patients (39.7%), with daily doses ranging from 100 mg to 400 mg.

The proportion of patients on amantadine who did or did not get infected also was not significantly different (46.2% vs. 38.2%). The mean daily dose of amantadine was also similar (237 vs. 257 mg).

A greater proportion of amantadine-treated patients had COVID-19 infection relative to those not taking the medication (22% vs. 17%), but this difference did not reach statistical significance.

Most SARS-CoV-2-infected patients developed mild COVID-19 symptoms, and the severity of symptoms was similar between those on amantadine and those who were not.

These findings highlighted that “amantadine did not affect the risk of developing COVID-19 or the severity of infection,” the researchers wrote.

“However, patients over 50 years old, slightly more advanced and with longer duration [Parkinson’s] had a lower incidence of SARS-CoV-2,” they added.

“Further studies on the effects of amantadine on COVID-19 should be continued, especially in terms of mortality,” the scientists concluded.