Combination therapy with lisuride and L-dopa in the early stages of Parkinson's disease decreases and delays the development of motor fluctuations. Long-term study over 10 years in comparison with L-dopa monotherapy

A randomized, prospective study was carried out in order to investigate the efficacy of a dopamine agonist, lisuride, alone or in combination with levodopa, to minimize or postpone the development of motor fluctuations, compared with levodopa alone during 10 years' treatment of 90 patients with early Parkinson's disease. Only a small, and with time gradually decreasing number of patients obtained enough therapeutic benefit during long-term treatment with lisuride alone. Consequently, levodopa had to be added to the patients' regimen. During combined treatment with lisuride and levodopa the daily dose of levodopa needed for optimal therapeutic response was significantly lower than when using levodopa alone. The addition of levodopa to the lisuride regimen either from the beginning or at any time during long-term treatment according to clinical need, resulted in a therapeutic response in parkinsonian disability equal to that achieved with levodopa alone, but significantly decreased and postponed the development of motor fluctuations, end-of-dose failure and dyskinesias. Severe dopaminergic adverse events leading to withdrawal of the treatment were more frequent during treatment with lisuride and levodopa than with levodopa alone, but the lower mortality rate did not reach the level of statistical significance. In conclusion, according to the results obtained, it seems reasonable to consider a treatment strategy in early Parkinson's disease using a dopamine agonist, like lisuride, as the primary treatment and to delay the addition of levodopa until parkinsonian disability cannot be adequately controlled by a dopamine agonist.