High dose dopamine agonist treatment and combination of dopamine agonists

Abstract

Moving towards a more dopamine agonist based therapy is often an effective way to counteract motor fluctuations in patients with advanced Parkinson's disease. It is thereby an impression that higher doses of dopamine agonists than those normally recommended can lead to further improvements compared to treatment with dopamine agonists in the normal dose range. There are now a number of open-label clinical studies with different dopamine agonists confirming that this might be an effective strategy. There are also single studies indicating that combining different dopamine agonists might be a further treatment alternative with similar effects compared to high dose dopamine agonist treatment. In line with this we performed a study comparing the use of high doses of the dopamine agonist cabergoline with normal-dose treatment. Thirty-four patient with idiopathic Parkinson's disease were included in the study and 32 of these performed the whole study. Cabergoline was raised from a mean daily dosis of 6.4mg to a daily dosis of 13.7mg over a period of up to 20 weeks. The doses were then held constant for at least 6 weeks. Clinical evaluations were performed after 0, 1, 8, 16, 26 and 27 weeks. The time per day with dyskinesia and dystonia was shortened and the maximum dyskinesia/dystonia intensity was reduced with high dose cabergoline. Also part of the day with severe „off“ symptomatology and the symptomatology in „worst off“ improved. The mean L-dopa dose was reduced from 606 mh/day to 370mg/day. Evaluation with clinical global impression scales confirmed a clear improvement in a majority of the patients. Also the health related quality of life scale PDQ-39 showed an improvement regarding total score and all subscales appart from congnition. The most common side effect was hallucinations. There is now an urgent need for controlled studies and long-term studies, to investigate to what degree this treatment strategy shall be an option for Parkinson patients. Especially it will be important to further explore the risk for side effects. This concerns especially hallucinations and other psychotic symptoms. It also concerns cardiac valvular fibrosis, where it is still unclear which dopamine agonists that are at risk and if this side effect is dose-dependent. Until further information is available high dose dopamine agonist treatment and combination of dopamine agonists shall be handled by physicians with profound experience in Parkinson treatment and the patients shall regularly be monitored for the mentioned side effects. It seems clear that both these treatment options can be highly effective regarding improvement of motor symptomatology and can be considered especially in patients with motor fluctuations in spite of otherwise optimized p.o. therapy and low tendency to psychotic side effects.