I was interested to see the spirited controversy about levodopa "toxicity" in the March issue of the ARCHIVES— glad to see the care with which arguments were marshaled on both sides, glad, above all, to see the matter out in the open.
When I started giving levodopa to my own patients more than 30 years ago, it became clear that pathological sensitivities and imbalances of all sorts could develop very rapidly—this was especially so in patients with postencephalitic parkinsonism, but they also developed, if more slowly, in patients with idiopathic Parkinson disease. When I tried to draw attention to these effects—commonly dismissed as "side effects"—and to sound a cautious note, there were only reactions of violent disagreement.1 It seemed that rational discussion was scarcely possible at the time. Since the neurological complexities of long-term levodopa treatment are now widely conceded—complexities that may be attenuated but not prevented by concurrent therapy with dopamine receptor agonists, COMT inhibitors, etc—the problems of decision have become sharpened and focused.
Sacks O. Weighing the Neurological Complexities of Long-term Levodopa Use. Arch Neurol. 2000;57(10):1531. doi: