Early Combination of Selegiline and Low-Dose Levodopa as Initial Symptomatic Therapy in Parkinson's Disease: Experience in 26 Patients Receiving Combined Therapy for 26 Months

Thirty-eight patients newly diagnosed as having Parkinson's disease (mean age, 57.3 years; mean Parkinson's disease duration, 2.7 years) in the earlier phase of the disease (mean Hoehn/Yahr stage, 2; mean motor scores, 11.4) were given selegiline (Deprenyl), 10mg daily, and maintained on this drug alone until significant clinical worsening warranted the addition of low-dose levodopa (Sinemet, 25/100 three to four doses per day). Five of these patients were not yet receiving additional levodopa despite some worsening of motor scores. Of the 33 patients now taking combined therapy, seven have been followed up for 6 months or less. Twenty-four (92%) of the 26 patients taking combined therapy for a mean of 26 months (8.5 to 99 months) who have had Parkinson's disease for 6 years showed a dramatic improvement in their parkinsonism shortly after the addition of levodopa, with significant decreases in their rated motor scores, such improvement being maintained at their latest neurologic evaluation. Eighteen (75%) of these 24 patients responded to the combined selegiline/levodopa therapy with degrees of improvement equal to or greater than 50%, compared with their motor status at the start of combined therapy just before the addition of levodopa. This degree of “reversal” of parkinsonism on addition of levodopa (mean carbidopa/levodopa dose, 98/389 mg) was not observed in any of these same patients receiving selegiline alone for an average of 13.8 months. Four patients taking combined therapy developed mild, transient, abnormal involuntary movements, and end-of-dose pattern of response after more than 2 years of combined therapy (24.75 and 33.5 months, respectively). Our results on combined selegiline/levodopa therapy reemphasize the continuing dominant role of levodopa as the primary drug for the symptomatic treatment of Parkinson's disease. A possible synergistic role of selegiline with levodopa in the early cases is suggested by the sustained therapeutic effectiveness of even low doses of the latter for a period of 26 months, with a delay in the appearance of relatively minor side effects developing only after more than 2 years of combined therapy. At an average disease duration of 6 years, no patient has had a major functional disability. A concurrently studied control group of patients treated with low-dose levodopa alone, or one treated with a combination of low-dose levodopa and a dopamine agonist like bromocriptine or pergolide, may have clarified further the role of selegiline, but such control subjects were not available to us at this time. We suggest the early combination of a selective monoamine oxidase type B inhibitor like selegiline, and the original dopamine replacement drug, levodopa (as low-dose Sinemet), as initial symptomatic therapy in newly diagnosed cases of Parkinson's disease.