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


Therapeutics

Deprenyl delayed the onset of disability in patients with early Parkinson disease

ACP J Club. 1993 May-June;118:71. doi:10.7326/ACPJC-1993-118-3-071


Source Citation

The Parkinson Study Group. Effects of tocopherol and deprenyl on the progression of disability in early Parkinson's disease. N Engl J Med. 1993 Jan 21;328:176-83.


Abstract

Objective

To evaluate the effectiveness of tocopherol and deprenyl, alone and in combination, in delaying the onset of disability requiring levodopa therapy in patients with early, untreated Parkinson disease.

Design

Randomized, placebo-controlled trial with a mean follow-up of 14 months.

Setting

Multicenter trial in North America.

Patients

800 untreated patients who had had Parkinson disease (stage I or II) for < 5 years. 57 patients (7%) withdrew from the study.

Intervention

Patients were randomly assigned to 1 of 4 treatment groups: 199 received placebo; 202 received tocopherol (2000 IU/d) and placebo; 202 received deprenyl (10 mg/d) and placebo; and 197 received deprenyl (10 mg/d) and tocopherol (2000 IU/d).

Main outcome measures

Time to the initiation of levodopa therapy. Patients were assessed for disability using the Unified Parkinson's Disease Rating Scale (UPDRS) and the Hamilton Depression Scale.

Main results

Tocopherol treatment, alone or in combination with deprenyl, did not delay the onset of disability requiring levodopa therapy (hazards ratio [HR] 0.91, 95% CI 0.74 to 1.12, P > 0.2). Deprenyl treatment, with placebo or tocopherol, did delay the onset of disability requiring levodopa therapy (HR 0.50, CI 0.41 to 0.62, P < 0.001). The median duration to the initiation of levodopa therapy was 719 days for patients receiving deprenyl and 454 days for patients receiving tocopherol or placebo, a difference of about 9 months. The beneficial effects of deprenyl therapy occurred largely during the first 12 months of treatment. The mean annual rate of decline in all UPDRS variables (mental, motor, and activities of daily living) was slower in patients receiving deprenyl (with placebo or tocopherol) (P < 0.001 for all comparisons). During the first 3 months of treatment with deprenyl, ratings for Parkinson disease on the UPDRS and the Hamilton Depression Scale improved (P < 0.001 and P = 0.007, respectively), and 2 months after the withdrawal of deprenyl, motor function worsened (P < 0.001).

Conclusions

Deprenyl (10 mg/d) delayed the onset of disability prompting the initiation of levodopa therapy in early, otherwise untreated Parkinson disease. The same benefit was not observed for tocopherol therapy (2000 IU/d).

Sources of funding: National Institute of Neurological Disorders and Stroke; National Institutes of Health; Parkinson's Disease Foundation at Columbia-Presbyterian Medical Center; National Parkinson Foundation; Parkinson Foundation of Canada; United Parkinson Foundation; American Parkinson's Disease Association; University of Rochester.

For article reprint: Dr. I. Shoulson, Box 673, Department of Neurology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. FAX 716-473-4678.


Commentary

Parkinson disease is a gradually progressive illness that is caused by degeneration of neurons in the substantia nigra. Previous studies suggest that the formation of free radicals from the action of monoamine oxidase causes damage to nigral neurons; however, the exact mechanism of the neuronal damage has been debated (1). The Parkinson Study Group has completed the first large, controlled study showing that deprenyl, a monoamine oxidase inhibitor, delays the onset of disability in early, untreated patients with Parkinson disease. These results suggest that deprenyl may have a protective effect by slowing nigral degeneration, but this assertion has not yet been established. This study failed, however, to show a beneficial effect of tocopherol, a substance that traps free radicals.

This study was well designed and carried out, but had no objective criteria for the major end point of the study. A subjective clinical judgment was made by the enrolling investigator about when a patient had reached a level of functional disability sufficient to warrant levodopa therapy. Also, the wash-out period may not have been long enough because deprenyl also showed mild symptomatic benefit. An important finding was the lack of serious side effects from deprenyl.

Considering that deprenyl has few side effects and may have a mild symptomatic benefit, clinicians should consider deprenyl in patients with early disease. Preliminary evidence in a small open trial has also shown that deprenyl may be useful as a supplement to levodopa therapy in patients with advanced Parkinson disease with symptom fluctuations (2). As yet, there is no evidence that deprenyl improves cognitive performance (3).

Barbara Scherokman, MD
Uniformed Services University of Health SciencesBethesda, Maryland, USA


References

1. Landau WM. Clinical neuromythology IX. Pyramid sale in the bucket shop: DATATOP bottoms out. Neurology. 1990;40:1337-9.

2. Golbe LI. Long-term efficacy and safety of deprenyl (selegiline) in advanced Parkinson's disease. Neurology. 1989;39:1109-11.

3. Kieburtz K, McDermott M, Como P, et al. The effect of deprenyl and tocopherol on cognitive performance in early untreated Parkinson's disease. Parkinson Study Group. Neurology. 1994;44:1756-9.