Practical aspects of prescribing antiparkinsonian drugs. The place of amantadines in the management of Parkinson’s disease

Abstract

Treatment of Parkinson’s disease (PD) includes the administration of dopaminergic and occasionally non-dopaminergic drugs, in mono- or in combination therapy. One of the key drug used to treat Parkinson’s disease is levodopa considered a gold standard. In addition levodopa can also be used as a challenge test to confirm the accuracy of diagnosis of PD known as the “Levodopa challenge test”. However many non levodopa class of drugs are also used and consist of dopamine agonists (ADRs), MAO-B and COMT inhibitors, as well as drugs working on glutamate such as a group of drug with NMDA receptor inhibitor activity (amantadines). The successful treatment of PD therefore depends on the correct choice of drugs to initiate treatment and sustainance of such therapy. The main parameters for personolised treatment include the patient’s age, severity and pattern of motor deficit, the state of cognitive function and lifestyle. Levodopa, although the most effective, is almost invariably associated with motor fluctuations and dyskinesias. Before prescribing levodopa, in addition to MAO-B inhibitors and ADRs, amantadines can be used as a monotherapy. Once replacement of therapy is required, then it is necessary to use a coefficient to calculate an equivalent dose of levodopa known as the levodopa equivalent dose. Progression of PD is inevitable inspite of adequate symptomatic therapy and at the advanced stage of PD approaches for the management of motor complications of levodopa need to be considered. For motor fluctuations these strategies require a change in the dosage regimen of levodopa (daily dose and frequency of intake), as well as the addition of an adjunct drug – ADRs, MAO-B inhibitor or COMT inhibitor. When dyskinesias arise, the management depends on correct identification of the type of dyskiensias. The commonest type of dyskinesia is peak dose dyskinesias related to peak plasma levodopa levels after intake. Amantadine provides a quick and long-lasting antidyskinetic effect which has been confirmed in open label as well as double-blind placebo-controlled studies. Compared to аmantadine chloride, amantadine sulfate has more stable pharmacokinetic parameters and a better safety profile. In addition, parenteral administration of amantadine sulfate can be utilized for severely ill patients with akinetic crisis in PD. Amantadine also has a broad spectrum effect and these may include improvement of fatigue and apathy. Some data also suggest that the use of amantadine in patients may increase life expectancy, improve survival and reduce the risk of dementia.