Primary Combination Therapy of Early Parkinson’s Disease

The aim of this multicenter randomized prospective study in patients with early Parkinson’s disease is to differentiate over a 4-year period between levodopa/benserazide monotherapy and the corresponding combination with bromocriptine by the assessment of motorial side effects, therapeutical benefit and fine motorial skills. Although there is circumstantial evidence, that partial substitution of levodopa by bromocriptine carries benefit in preventing late levodopa-specific side effects and delaying the declining therapeutical benefit, so far no knowledge has been available how levodopa and the corresponding combination with bromocriptine would compare on a long-term basis. Such study appears all the more important since there are experimental findings consistent with a neurotoxic effect of levodopa on the one hand and some ‘protective’ impact of bromocriptine on the other. As to the practical procedure of the comparison, all patients were first treated with a levodopa monotherapy for 3 months. This was a platform for the consecutive randomized splitting of the patients into two groups receiving either continuing levodopa therapy or combination therapy, based upon at least 40 ± 10% substitution of levodopa by bromocriptine. The investigation methods included, besides the usual clinical rating scales (Webster, Zung, Hoehn and Yahr), an apparative test series, the so-called ‘MLS’, which allowed a sensitive and reliable assessment of fine motorial skills. The results of the first 3 months of treatment with levodopa monotherapy before the consecutive splitting into the two treatment regimens demonstrate that the randomization was successful and that there were no significant differences, that potentially might interfere with the drug-specific evaluation afterwards. The results of the substitution phase show that combined treatment permitted a mean reduction of the levodopa dosage by 40%, without deterioration of therapeutic response. In addition, feasibility of the overall approach based upon a sophisticated interplay between the practising neurologists (101) and the centers (27) was demonstrated.