Should dopamine agonists be given early or late? A review of nine years experience with bromocriptine.

Experience with bromocriptine in 106 patients treated over nine years was reviewed. Most of the patients were already being treated with levodopa (combined with a peripheral decarboxylase inhibitor). These patients, after having initially achieved a good response to levodopa, were no longer responding satisfactorily. Most of the patients were also experiencing diurnal oscillations in performance: "wearing off" and "on-off" phenomena. In these patients previous attempts at changing the dose (increasing or decreasing) or changing the scheduling of levodopa had been unsuccessful. Bromocriptine was added to levodopa beginning at a dose of 5 mg/day, and each week was increased by another 5 mg/day. At a dose of bromocriptine of at least 25 mg/day, there was a decrease in disability in the majority of patients with a decrease in the severity of the diurnal oscillations in performance (especially "wearing off" phenomena). In most patients, the addition of bromocriptine resulted in an approximately 10% reduction in the dose of levodopa. The majority of patients sustained their improvement at least one year. In some patients improvement was sustained for up to five years. The therapeutic efficacy of bromocriptine was limited in many patients by the occurrence of adverse effects including mental changes, dyskinesias, orthostatic hypotension, and nausea. These adverse effects could often be minimized by reducing the dose of bromocriptine or levodopa. All adverse effects were reversible upon stopping the drug. We have found bromocriptine to be a valuable adjunct in the treatment of these patients.

The antiparkinsonian efficacy of bromocriptine.

The antiparkinsonian activity of bromocriptine, a presumed dopaminergic receptor agonist, was investigated in monkeys with surgically induced tremor and in a group of parkinsonian patients. A single administration of bromocriptine resulted in a dose-dependent relief of tremor in monkeys. Repeated administration enhanced this effect. Only mild abnormal involuntary movements were observed and only after repeated administration. Eleven patients with Parkinson's disease were treated with bromocriptine (mean dose, 26.4 mg a day). Clinically obvious improvement was noted in one or more of the cardinal signs of the disease in six patients (responders). No obvious improvement in any of the cardinal signs was noted in the remaining five patients (nonresponders). Clinically, the responders were older and more severely affected and had been on a higher dose of levodopa. However, they had had the disease for a shorter period. It is suggested that failure to respond to bromocriptine may be related to a decrease in the sensitivity of postsynaptic dopaminergic receptors.