London - Thousands of people with schizophrenia worldwide could have been saved if doctors had prescribed them the anti-psychotic drug clozapine, a new study says.
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.
  • On the Net: http://www.lancet.com
    - Sapa-AP

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  • Summary

    Background

    The introduction of second-generation antipsychotic drugs during the 1990s is widely believed to have adversely affected mortality of patients with schizophrenia. Our aim was to establish the long-term contribution of antipsychotic drugs to mortality in such patients.

    Methods

    Nationwide registers in Finland were used to compare the cause-specific mortality in 66 881 patients versus the total population (5·2 million) between 1996, and 2006, and to link these data with the use of antipsychotic drugs. We measured the all-cause mortality of patients with schizophrenia in outpatient care during current and cumulative exposure to any antipsychotic drug versus no use of these drugs, and exposure to the six most frequently used antipsychotic drugs compared with perphenazine use.

    Findings

    Although the proportional use of second-generation antipsychotic drugs rose from 13% to 64% during follow-up, the gap in life expectancy between patients with schizophrenia and the general population did not widen between 1996 (25 years), and 2006 (22·5 years). Compared with current use of perphenazine, the highest risk for overall mortality was recorded for quetiapine (adjusted hazard ratio [HR] 1·41, 95% CI 1·09–1·82), and the lowest risk for clozapine (0·74, 0·60–0·91; p=0·0045 for the difference between clozapine vs perphenazine, and p<0 0="" all="" an="" and="" antipsychotic="" any="" associated="" between="" cumulative="" drug="" drugs="" duration="" exposure="" filled="" for="" in="" inverse="" long-term="" lower="" more="" mortality="" no="" noted="" of="" one="" or="" other="" p="" patients="" per="" prescription="" relation="" than="" to="" treatment="" trend="" use="" was="" with="" year="" years="">

    Interpretation

    Long-term treatment with antipsychotic drugs is associated with lower mortality compared with no antipsychotic use. Second-generation drugs are a highly heterogeneous group, and clozapine seems to be associated with a substantially lower mortality than any other antipsychotics. Restrictions on the use of clozapine should be reassessed.

    Funding

    Annual EVO Financing (Special government subsidies from the Ministry of Health and Welfare, Finland).