Retrospective single-center study of 132 Parkinson's patients treated up to 13 years with an amantadine + MAO-B inhibitor + dopamine agonist regimen (with low‑dose levodopa only if needed) reported a modest early UPDRS III improvement, persistently low rates of dyskinesia and OFF periods, and…

Clinically relevant, immediately actionable combination therapy using repurposed agents suggests a potential strategy to reduce levodopa exposure and limit dyskinesia, but the nonrandomized retrospective design means randomized controlled trials are required to validate efficacy and safety.

BACKGROUND: The standard therapy of Parkinson's disease consists in supplementing the depleted dopamine with oral levodopa. The disadvantages of the levodopa monotherapy - comparable to other dopaminergic substances - are the dose-dependent development of dyskinesia in ON-phases, and bradykinesia and akinesia in OFF-phases, the latter being a sign of dopaminergic deficiency with a recurrence of Parkinson's symptoms. AIM OF THE STUDY: In order to omit the side effects of levodopa, we devised a combination therapy consisting of amantadine, a monoamine oxidase type B-inhibitor and a dopamine agonist. Levodopa was added at a low dose, if necessary. METHODS: In a retrospective, monocenter study based on the patient records, we report the long-term results in 132 PD patients who had been treated with the amantadine-based therapy for up to 13 years in an outpatient Parkinson clinic. RESULTS: In 132 patients with the amantadine-based combination therapy, the mean UPDRS III score improved by 5.7 points from baseline during the first 2 years of treatment. Over the following 3 years it increased and remained at a plateau level slightly below baseline for the next 5 years. At no time did more than 20% of the patients suffer from Hoehn & Yahr stage 3 or higher. Only seven patients exhibited "OFF" periods and only seven (6 with additional levodopa) presented with dyskinesia at any time during therapy. The most important adverse effect was lower leg edema. CONCLUSION: The combination therapy of amantadine, a monoamine oxidase type B-inhibitor and a dopamine agonist is an alternate therapeutic approach that may be able to prevent dyskinesia and fluctuations by drug pharmacokinetics and synergistic effects, and may postpone or reduce the amount of levodopa. Prospective controlled studies are needed to compare the effects of the amantadine-based combination therapy with the standard levodopa therapy for Parkinson's disease.