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ELDEPRYL (Selegiline)- The Truth! The stubborn transatlantic scientific debate over use of Eldepryl (Deprenyl, selegiline) continues with a new volley from the UK side in the British Medical Journal for 18 April 1998. The principal adversaries are the (U.S.) Parkinson Study Group, headed by the eminent authorities C. Olanow, S. Fahn, and J. Langston; and the Parkinson's Disease Research Group of the United Kingdom, led by eminent authorities A. Lees, Y. Ben-Shlomo, and A. Churchyard. About 1985, when selegiline, a selective inhibitor of the free radical monoamine oxidase-B (MAO-B), was hailed as the first drug that could slow the progression of Parkinson's Disease (PD) rather than merely relieve its symptoms, the U.S. group launched an ambitious trial of some 800 PD patients from hospitals and clinics all over the country. Pursuing the notion that "oxidative stress" by free radicals kills the neurons whose loss leads to PD, they arranged a carefully randomized and blind test of selegiline and the powerful antioxidant tocopherol (Vitamin E), both singly and together. Subjects of the DATATOP (Deprenyl And Tocopherol As Treatment Of Parkinson's) study are still tracked for long-term effects. The U.K. group began its own study of about 624 subjects, comparing the effects on PD of selegiline, selegiline plus levodopa (Sinemet in the U.S.), and levodopa plus the dopamine agonist bromocriptine (Parlodel), with similar long-term follow-up. Late in 1996 the U.K. group announced not only that selegiline was useless, but also that its recipients in the study seemed to be dying 60 percent more often than average. They quit giving it to the assigned subjects, provoking near panic among other prescribers and users, and a response by the U.S. group that their DATATOP showed no such mortality excess, but in fact a slight increase in average longevity. Furthermore, the DATATOP results seem to show that selegiline is indeed protective, and somewhat relieves PD symptoms as well. The debate continued with attacks by each side on the statistical data treatment and conclusions of the other. The U.K. group is specially scornful of the oxidative-stress hypothesis, and of Dr. W. Birkmayer, head of a private Swiss research lab that was the original promoter of selegiline. On the other hand, Dr. Birkmayer is respected for his co-discovery of levodopa/carbidopa (now Sinemet) as the most effective PD drug yet found. Extracting a simple, broad, unequivocal conclusion from the complicated data of any big study is a tough job. For example, the severity or progression of PD symptoms is not an objective measurement, but a personal judgement by one among hundreds of clinical raters, and the patient himself. Raw mortality data don't mean much if the proximal cause of death is reported by some rural doctor as "Parkinson's" instead of something unambiguous such as stroke, heart failure, injury from a fall, etc. And there is no way to account for the multiplicity of other drugs and/or treatment that different subjects of the study group may be taking. In their latest shot (see above), the U.K. group insists that there is too a premature-mortality effect, and no significant symptomatic benefit, of selegiline. The same issue of the BMJ carries a long editorial by a Netherlands pharmacology authority, mildly critical of the article and advising caution before making a rash decision. I think it was Mark Twain who once said, "There are lies, damned lies, and statistics!" Cheers, Joe J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013