The clinical questions are not well answered, and probably never will be

Parkinson's disease is the second most common neurodegenerative disorder, after dementia. About 1.4% of people aged 55 years or over have Parkinson's disease,1 and because of the aging of Western populations the absolute number of patients is rapidly increasing. Until now, treatment has been mainly symptomatic, but much effort is being put into developing neuroprotective agents that may stop progression or even cure the disease. Clearly, unrecognised adverse effects of such treatments may potentially affect large numbers of patients and any suggestion of such effects needs thorough investigation.

Selegiline has probably become the most controversial drug in Parkinson's disease during the past decade. Its presumed efficacy was initially ascribed to neuroprotection due to inhibition of monoamine oxidase-B, then to a symptomatic effect, and more recently again to neuroprotection, this time due to inhibition of apoptosis. The greatest controversy, however, occurred because selegiline caused the early termination of the intervention arms of two large multicentre studies—for completely different reasons. In the DATATOP study of the US Parkinson Study Group subjects randomised to receive selegiline did better than those randomised to placebo or tocopherol in that they reached the endpoint (start of levodopa treatment) significantly later.2 In …