There are several different classes of anti-Parkinson’s medication: L-dopa (e.g. Madopark, which contains L-dopa/beserazide; Sinemet, which contains L-dopa/carbidopa; Stalevo/Sastravi, which contains L-dopa/carbidopa/entacapone). Enzyme inhibitors: MAO-B inhibitors such as rasagiline (Xadago/safinamine), selegiline/Eldepryl, as well as COMT inhibitors such as entacapone/Comtess or as part of the combination tablets Stalevo/Sastravi, and tolcapone/Tasmar, opicapone/Ongentys; as well as dopamine agonists such as pramipexole/Sifrol, Mirapexin, Derinik, Opryema, rotigotine/Neupro, ropinirole/ReQuip, apomorphine and others.
These different medicines replace or increase dopamine levels, but the mechanisms by which they affect dopamine production and the effects vary between classes of medicines; the effects have different time profiles, but also different side-effect profiles.
It is beneficial to combine the different classes of medication to prevent treatment-related effects from arising over time, such as the development of dose gaps – for example, at night – or frequent dose gaps during the day accompanied by cramps and, in the long term, involuntary movements or other more severe fluctuations.
Medicines have different ‘half-lives’, i.e. how long the contents of a tablet remain in the blood, which is one of many measures of how a medicine works. L-dopa has the shortest half-life of all anti-Parkinson’s medicines, and there is a clear link between high single doses and a high total dose of L-dopa – particularly in younger patients – and the development of early fluctuations and, a little later on, severe hyperkinesia. Strict monotherapy with (short-acting) L-dopa in the form of various rapidly dissolving preparations, and at high doses, should be avoided over prolonged periods.
To achieve the best possible and most consistent treatment effect, the SweModis guidelines, amongst others, recommend combination therapy after a few years of treatment with medicines from different classes, to ensure that dopamine levels do not become too low or too high.
Dopamine agonists such as pramipexole have a place in the treatment arsenal and are among the most commonly used medicines for Parkinson’s disease; for many people, they have had a decisive, positive and long-lasting therapeutic effect. All medicines have side effects, and the decision on whether the benefits outweigh the drawbacks must be made on an individual basis. Not everyone is the same, and the range of responses to different medicines is vast and highly individual. It is impossible to predict how an individual patient will react to a particular drug or dose. It is therefore an advantage that there are different medicines within the various groups or classes of drugs. For example, if a patient develops intolerable side effects from a particular drug at a certain dose, they can try switching to another drug within the same group, depending on the severity of the symptoms and the nature of the side effects.
A distinction should be made between any side effects that occur shortly after starting a medication and those that may arise later on – this is where dopamine agonists and L-dopa differ, and this perspective needs to be taken into account when planning treatment. /Håkan Widner