Selegiline: a second look. Six years later: too risky in Parkinson's disease.

Prescrire international 2002 Aug

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1) The reference treatment for Parkinson's disease is levodopa plus a peripheral dopadecarboxylase inhibitor (benserazide or carbidopa). (2) In 1996, selegiline, a type B MAOI marketed in France since 1988, saw its indications extended to cover single-agent therapy of early-stage Parkinson's disease, and in combination with levodopa, before onset of complications of levodopa therapy. The initial clinical file failed to show that selegiline had any benefit in these indications. (3) Now, in 2002, new data from trials involving hundreds of untreated patients show that selegiline postpones the need for levodopa therapy for a few months but fails to substantially alter the progression of Parkinson's disease. (4) A clinical trial and a retrospective epidemiological study of patients with advanced Parkinson's disease showed excess mortality on selegiline. (5) The side effects of selegiline are similar to those of other antiparkinsonian drugs and amphetamine. Notable side effects include cardiovascular problems (postural hypotension, atrial fibrillation and arterial hypertension). (6) Selegiline can cause a serotoninergic syndrome and arterial hypertension, so must not be combined with pethidine, tramadol, bupropion, sumatriptan, zolmitriptan or naratriptan. Concurrent treatment with serotonin reuptake inhibitor antidepressants should also be avoided. (7) Given the only moderate effects of selegiline in Parkinson's disease, and the possibility of a slight increase in mortality, there is no justification for prescribing this medication in patients with Parkinson's disease. (8) Whatever the stage of Parkinson's disease, there is no justification for starting patients on selegiline. Patients who are already taking selegiline should only continue to take it if they feel a clear benefit and are free from risk factors for early mortality, especially cardiovascular disease.