All medicine-taking involves balancing potential benefits vs. real and possible risks. When drugs are used to treat life-threatening or major medical conditions, the willingness of patients to assume these risks becomes greater. Clozapine is an excellent example of a drug that is often effective for the treatment of schizophrenia in many patients who have failed to respond to other drugs. This same drug, however, can cause a potentially fatal blood disorder.
From the start, clozapine was different. It was synthesized in the early 1960s and found to have promising antischizophrenic effects. Unlike chlorpromazine (Thorazine) and all similar “typical” antipsychotic drugs then available, it did not cause tremors and rigidity, so-called extrapyramidal symptoms (EPS) that resemble Parkinson’s disease. Clozapine was the charter member of the “atypical” second-generation antipsychotic drug class.
Clozapine was first marketed in Europe in 1972, but three years later, it was withdrawn after causing agranulocytosis—a severe lack of infection-fighting white blood cells—and deaths in a number of patients. During the first months of treatment, agranulocytosis develops in 1 percent of clozapine-taking individuals—a risk that decreases over time. With the hindsight appreciation that it was effective when other drugs were not, clozapine (Clozaril) returned to the American and European markets in 1989. However, its use is accompanied by the caveat that blood tests must be conducted at very regular, specified intervals. These tests add considerably to the total cost of therapy.
Clozapine is arguably the most effective of all antischizophrenic drugs, but because of its potential dangers, its use has been greatly restricted. The drug is primarily given to “antipsychotic-resistant patients”—those 30–40 percent of individuals with chronic schizophrenia who are poorly controlled with other antipsychotic drugs. It is also approved for use in schizophrenics who are at high risk of suicidal behavior.
The effectiveness of clozapine has led to the development of newer second-generation drugs (such as Zyprexa) that are perhaps not as effective but are safer than clozapine. They are thought to produce their antischizophrenic effects by blocking both serotonin and dopamine receptors in the brain.
SEE ALSO Chlorpromazine (1952), Haldol (1958), Zyprexa (1996).
Don Quixote—the hero of what many authorities consider the greatest of all novels—suffered from delusions and hallucinations, which are classical symptoms of schizophrenia. But what would the world of literature be, had he been successfully treated with clozapine?