Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Selegiline was effective in patients with early Parkinson disease

ACP J Club. 1992 July-Aug;117:10. doi:10.7326/ACPJC-1992-117-1-010


Source Citation

Myllylä VV, Sotaniemi KA, Vuorinen JA, Heinonen EH. Selegiline as initial treatment in de novo parkinsonian patients. Neurology. 1992 Feb;42:339-43.


Abstract

Objective

To determine if selegiline will reduce disability and delay the initiation of levodopa in patients with early Parkinson disease.

Design

Randomized, placebo-controlled trial with ≥ 24 months of follow-up.

Setting

Ambulatory care clinic in a Finnish university medical center.

Patients

52 patients (27 women; mean age, 61 y) with idiopathic Parkinson disease were enrolled if they had taken anticholinergic drugs for ≤ 3 months and had never taken any other antiparkinsonian medication. Patients were excluded if they had any concomitant disease that might have influenced drug absorption or excretion or interfered with evaluation of function.

Intervention

27 patients received selegiline, a selective monoamine oxidase (MAO) type B inhibitor, 10 mg each morning. 25 patients received matching placebo. Anticholinergic treatment was allowed for tremor after 4 months. Study medication was continued until it became necessary to start levodopa therapy because of functional deterioration.

Main outcome measures

The median number of days until initiation of levodopa. Patients were assessed for disability at baseline; 3 weeks; 2, 4, 8, and 12 months; and then every 4 months using 3 Parkinson disease rating scales (Hoehn and Yahr staging, Webster Rating Scale [WRS], and the Columbia University Rating Scale [CURS]). The Northwestern University Disability Scale (NUDS) measured activities of daily living.

Main results

3 patients withdrew and 2 died. Available data from these 5 were included. The median number of days before starting levodopa was 545 days (95% CI 386 to 845 d) after randomization for patients in the selegiline group and 372 days (CI 253 to 464 d) for patients in the placebo group (P = 0.03). Parkinson symptoms initially improved in both groups. Percentages of patients with reductions in total scores were 56% and 32% (WRS); 44% and 12% (NUDS); and 63% and 48% (CURS) for selegiline and control groups, respectively. Scores were significantly better in actively treated patients up to 1 year. At 2 years, when most patients in both groups were taking levodopa, the groups did not differ. Selegiline was well tolerated with no major side effects. 4 patients in the selegiline group had insomnia; 3 patients in the control group had dry mouth and 3 had nausea.

Conclusion

Selegiline given to patients with early Parkinson disease delayed initiation of levodopa treatment and improves functional status for up to 12 months.

Source of funding: Not stated.

Address for article reprint: Dr. V.V. Myllylä, Department of Neurology, Oulu University Central Hospital, SF-90220 Oulu, Finland.


Commentary

The progressive loss of substantia nigra neurons that underlies Parkinson disease may relate to the oxidative stresses caused by metabolism of dopamine by MAO (1). Selegiline is an MAO type B inhibitor that has been investigated in several studies of patients with early Parkinson disease including this study by Myllylä and colleagues (2, 3). These studies have concluded that selegiline treatment delays the need to start therapy with levodopa, produces mild but important improvement in parkinsonian symptoms, and may slow the progression of Parkinson disease. There is no method, independent of signs and symptoms, of measuring disease progression. Delay in starting levodopa therapy will result from any treatment that produces a symptomatic benefit, even if it has no effect on the progression of the underlying disease. Because the differences in functional status that emerged in the 4 months of therapy had been reduced by 12 months, the benefits of selegiline may be restricted to temporary improvement of symptoms and delay in the need for levodopa therapy.

Most experts in the field of movement disorders use selegiline, 10 mg daily taken in 2 divided doses, as initial or early therapy in patients with early Parkinson disease. For patients with more advanced disease, selegiline may be a useful adjunct to levodopa, but its effects on disease progression in these patients has not yet been studied.

Kathleen M. Shannon, MD
Rush-Presbyterian-St. Luke's Medical CenterChicago, Illinois, USA


References

1. Cohen G. Oxidative stress in the nervous system. In: Sies H; ed. Oxidative Stress. London: Academic Press; 1985:383-402.

2. Tetrud JW, Langston JW. The effect of deprenyl (selegiline) on the natural history of Parkinson's disease. Science. 1989;245:519-22.

3. The Parkinson Study Group. Effect of deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med. 1989;321:1364-71.