Penicillamine should not be used as initial therapy in Wilson's disease.

I feel honored to be asked by the Movement Disorders journal to contribute my thoughts to the controversy on how to treat patients with Wilson’s disease, particularly during the initial period. I am doubly honored to cross swords on this topic with Professor John Walshe, who has contributed so much to the treatment of Wilson’s disease. As I have said in other settings, a whole generation of patients with Wilson’s disease owe their lives to the pioneering work of Professor Walshe. But then was then and now is now, and the two are not the same. Drugs that do wonderful things in one era, along with some damage, tend to be replaced by drugs in another era, drugs that still do wonderful things but with much less damage. That is exactly the situation we have at present with penicillamine. Its era is over. It is far too toxic to use when we have drugs that are just as effective and much safer. One of the major problems with penicillamine occurs when it is used for the initial treatment of the patient presenting with neurologic disease. There is a major risk that the patient will be made permanently worse neurologically. Take the following case as an example of the disaster awaiting patient and physician when they use penicillamine in this situation. The patient was an attractive 27-year-old woman working on her master’s degree. She developed depression, a mild dysarthria, and mild tremor, and was diagnosed as having Wilson’s disease. She was started on 1.0 g penicillamine per day and over 4–8 weeks became much worse. Her dysarthria and tremor progressed, and she developed mild dystonia of the face, trunk, and limbs. Her dose of penicillamine was doubled. Over a 3–4-month period she worsened disastrously. Her dysarthria became severe, her posture changed because of the dystonia such that her back became continuously curved, and dystonia and tremor of her upper extremities worsened to the point where she was essentially unable to carry out even simple care tasks such as feeding herself. Her gait became distorted and uncomfortable, limiting her walking to very short stretches. Her face became grotesquely distorted with chronic drooling. Dysphagia developed and became severe enough to lead to frequent choking episodes, but the patient refused gastrostomy. This all happened 20 years ago, and despite many years of penicillamine therapy, bringing her copper status under good control, the patient has never recovered. She lives today crippled without hope of a meaningful social or working life. She has attempted suicide several times. Was this patient’s life destroyed by penicillamine? Some would argue that the real culprit was Wilson’s disease and the toxicity of copper, not the drug designed to get rid of that copper. However, I can almost guarantee, as close as anyone can ever come to guaranteeing anything in medicine, that if I had that patient to treat now at the beginning of her presentation, she would have been able to subsequently live a healthy, essentially normal life. This tragedy was unavoidable then. It is inexcusable now. Is penicillamine-induced worsening rare and this patient’s course an isolated occurrence? Unfortunately not. Along with Carol Terry, then President of the Wilson’s Disease Association, we did a retrospective survey of the Association members who had presented with neurologic symptoms and who had been treated with penicillamine. Of 27 respondents, 13 had shown initial deterioration, Received October 7, 1998. Accepted February 9, 1999. Address correspondence and reprint requests to George J. Brewer, MD, University of Michigan Medical School, 1301 Catherine St., Ann Arbor, MI 48109-0618, U.S.A. Movement Disorders Vol. 14, No. 4, 1999, pp. 551–554 © 1999 Movement Disorder Society