[Bromocriptin in the treatment of progressive stages of Parkinson's disease (author's transl)]. Adjunctive therapy with bromocriptine in Parkinson's disease. Low dosages of bromocriptine added to levodopa in Parkinson's disease. Effects of bromocriptine on parkinsonism. A nation-wide collaborative double-blind study. Treatment of the on-off syndrome in Parkinsonism with low dose bromocriptine in combination with levodopa. Bromocriptine versus placebo in levodopa treated patients with Parkinson's disease.
Forty patients with severe Parkinson's disease (23 men, 17 women) who had been treated for six years with L-dopa-decarboxylase inhibitor, were part of a placebo-controlled double-blind trial to test the effectiveness of bromocriptin. In all patients the effectiveness of L-dopa had been decreasing, 34 patients had L-dopa-induced dyskinesias, 35 "on-off" symptoms. Bromocriptin dosage was gradually increased to a total dose of 30 - 40 mg daily. This led to a 25% reduction in L-dopa requirements. The symptoms of Parkinson's disease were favourably influenced, with rigor, tremor and also walking disturbances responding better than bradykinesia of the hands. At the same time, there was a marked prolongation of the periods of good mobility ("on" time) from 7 to 10.8 hours without influence on other "on-off" symptoms such as paradoxical akinesia. Two patients had to be excluded from the trial because the treatment caused side effects (orthostatic hypotension, exogenous psychotic symptoms). Other side effects, such as nausea and mild forms of collapse, could be controlled by drugs. Patients with moderately severe Parkinson's disease complicated by the adverse effects of chronic levodopa use benefited from the addition of bromocriptine (Parlodel; Sandoz) in doses up to 26 mg daily, which allowed an approximate 30% reduction of levodopa dose. This resulted in a significant decrease in the amount of levodopa side-effects while maintaining or improving the original parkinsonian clinical stage. Increased effectiveness in these patients was not associated with increased dosage beyond 25-30 mg daily. When the doses of bromocriptine were increased slowly, the adverse reactions were minor and usually transient. Thirty-six patients with Parkinson's disease, on levodopa, were admitted to a double-blind, parallel, 40-week study of adjunct bromocriptine in dosages increased by 2.5 mg every 4 weeks. A 37% improvement of the mean neurologic deficit score was obtained at the maximal daily dosage of 20 mg. Improvement was greatest in patients with mild disease. The wearing-off effect, off-dose abnormal involuntary movements, and leg pains, associated with levodopa, improved in over 70% of patients at an average dosage of 13 mg. Only 15% of patients had adverse reactions severe enough to necessitate discontinuance of the drug. Abnormalities of mental state were less severe than expected, but two patients had exacerbations of angina pectoris. The effects of bromocriptine in patients with Parkinson's disease manifesting various problems in levodopa therapy were tested in a double-blind manner with the collaboration of 59 institutions. The slow and low principle was in part adopted. Either bromocriptine or placebo was added to levodopa. Twenty-nine % of the bromocriptine-treated patients (n = 108), in contrast to 14.8% of the placebo-treated (n = 108), showed either marked or moderate improvement (P less than 0.05). Twenty to 37% improvement was noted in most of the symptoms studied in those treated with bromocriptine. The significant superiority of bromocriptine was also noted in the effects on wearing-off phenomena and frozen gait. No irreversible side effects were noted. It is concluded that bromocriptine is useful in patients who are manifesting various difficulties in levodopa therapy. Our results are comparable to those using higher maintenance doses. Dopamine antagonistic actions were not observed. This is unlike the case with experimental animals. The addition of bromocriptine, given in divided doses up to 30 mg per day, to conventional anti-Parkinsonism therapy has been studied in a double-blind placebo controlled clinical trial in 11 patients with Parkinsonism with the "on-off" syndrome. Four patients withdrew because of side effects. Of the seven remaining, three had clinical benefit from bromocriptine with reduction in severity and frequency of fluctuations. There was, however, no statistically significant benefit of bromocriptine when the group as a whole was assessed in terms of severity or frequency of fluctuations measured by three different methods. The mean frequency of major fluctuations on placebo was 2.9/day and on bromocriptine 1.8/day (P less than 0.1 greater than 0.05). There appears to be a limited role for bromocriptine as additional therapy in the management of some patients with the on-off syndrome. Twenty patients with idiopathic parkinsonism who had been on optimal levodopa therapy for at least 3 months prior to the investigation and where effect of the treatment was decreasing or side effects were increasing, were treated with bromocriptine in a double-blind crossover trial during a 12 + 12 weeks period. Reduction in disability scores was found significant. Hyperkinesia was more frequent in the bromocriptine period than in the placebo period, but reduction of dose in six patients for this reason was not followed by deterioration. Both hyperkinesia and other side effects disappeared after dose reduction. Doses were 2.5 mg-40 mg. Bromocriptine seems a valuable supplement to previous therapy in these patients.
This review highlights major methodological problems and sources of heterogeneity that not only hamper the comparability of trials but also preclude a conclusion on the efficacy of BR in the adjunct treatment of PD patients with motor complications.