Study: Clozapine may have saved schizophrenics

Clozapine was introduced in the 1970s, but was banned for about a decade because of a rare but potentially deadly side effect: up to 2 percent of patients lose their white blood cells while taking the drug.

It was brought back to the market in the 1980s with warnings about its use, and is sold generically as Clozaril, Leponex, Denzapine, Fazaclo, among other names.

In most developed countries, guidelines recommend clozapine only as a last resort, if patients have already tried two other drugs but still aren't better.

In a study examining the death rates of about 67,000 schizophrenic patients in Finland versus those of the general population between 1996 and 2006, Jari Tiihonen, of the University of Kuopio in Finland, and colleagues found that patients on clozapine had the lowest risk of dying, compared to other patients with schizophrenia. The study was published online Monday in the medical journal, Lancet.

James MacCabe, a consultant psychiatrist at the National Psychosis Unit at South London and Maudsley Hospital, called the research "striking and shocking." He was not linked to the study.

"There is now a case to be made for revising the guidelines to make clozapine available to a much larger proportion of patients," he said.

Tiihonen and colleagues found that even though the use of anti-psychotic medications has jumped in the last decade, people with schizophrenia in Finland still die about two decades earlier than other people.

The researchers concluded that newer drugs including quetiapine, haloperidol and risperidone increased the death risk by 41 percent, 37 percent and 34 percent respectively, when compared to older drugs. In contrast, patients on clozapine had a 26 percent lower chance of dying. The study was paid for by Finland's Ministry of Health and Welfare.

Experts said the Finnish findings could be extrapolated to most other developed countries. MacCabe suggested doctors might give their schizophrenic patients clozapine after trying one other drug, as opposed to two.

MacCabe said clozapine is particularly effective in reducing suicidal tendencies in schizophrenic patients, in whom suicides account for about 40 percent of unexpected deaths.

"We should find ways to get more people on this medicine," said Lydia Chwastiak of the department of psychiatry at Yale University, who was not connected to the research. A study at the University of Maryland found that African-American patients in particular are treated less often with clozapine.

"If this drug can help people live longer, we need to look seriously at the barriers to using it," she said.

Tiihonen said the pharmaceutical industry is partly to blame for why clozapine has often been overlooked. "Clozapine's patent expired long ago, so there's no big money to be made from marketing it," he said.

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