LONDON (Reuters) - Schizophrenia patients given a cheap older drug are less likely to die prematurely than people on newer treatments, despite the older product’s well-known adverse side effects, Finnish researchers said on Monday.
A woman places her hands over her ears in a file image. REUTERS/File
The finding may lead to wider use of clozapine -- sold by Novartis as Clozaril, but also available as a generic -- instead of newer drugs like AstraZeneca’s Seroquel, the current market leader.
Clozapine was the first of a new generation of schizophrenia drugs, known as atypical antipsychotics, but its use has been restricted by health authorities because of safety concerns, and patients taking it require regular blood tests.
Despite this, an analysis of 10 years’ records for 67,000 patients in Finland found that, compared with treatment with the first-generation drug perphenazine, the risk of early death for patients on clozapine was reduced by 26 percent.
By contrast, mortality risk was 41 percent higher for those on Seroquel, known chemically as quetiapine; 34 percent higher with Johnson & Johnson’s Risperdal, or resperidone; and 13 percent higher with Eli Lilly’s Zyprexa, or olanzapine.
“We know that clozapine has the highest efficacy of all the antipsychotics and it is now clear, after all, that it is not that risky or dangerous a treatment,” study leader Jari Tiihonen of the University of Kuopio said in a telephone interview.
“We should consider whether clozapine should be used as a first-line treatment option.”
THOUSANDS OF PREMATURE DEATHS
Tiihonen estimates clozapine is given to around one fifth of Finnish schizophrenia patients, but less than 5 percent in the United States.
Clozapine’s side effects include agranulocytosis, a potentially fatal decline in white blood cells, and current rules stipulate the drug can only be used after two unsuccessful trials with other antipsychotics.
Tiihonen and colleagues wrote in the Lancet medical journal that these restrictions should be reassessed in the light of their findings, since not using the drug may have caused thousands of premature deaths worldwide.
But Les Iversen, a professor of pharmacology at the University of Oxford in Britain, who wasn’t involved in the study, said the risk of agranulocytosis was serious and should not be under estimated.
“For this reason, clozapine has become a drug of last resort -- and will probably remain so,” he said.
Seroquel, Zyprexa and Risperdal are among the world’s top-selling drugs, with combined sales of $12.5 billion in 2008, though Risperdal now faces generic competition.
Worries about the safety profile of all the atypical antipsychotics have loomed large since 2002, however, following evidence of increased rates of diabetes and cardiovascular disease.
The Finnish study found no pronounced differences in heart deaths between the different atypicals, but patients on clozapine had a substantially lower risk of suicide, while those on Seroquel were more likely to kill themselves.
An AstraZeneca spokeswoman said the Anglo-Swedish company was comfortable that Seroquel was safe, effective and an important treatment for mental illness.
Schizophrenia is a severe psychiatric disorder in which patients experience distorted thinking, hallucinations and abnormal emotions.
Editing by Jon Loades-Carter/Will Waterman
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Banned drug may have saved schizophrenics
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.
- Sapa-AP
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11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study)
Prof Jari Tiihonen, MD
Correspondence information about the author Prof Jari Tiihonen
Email the author Prof Jari Tiihonen
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Correspondence information about the author Prof Jari TiihonenEmail the author Prof Jari Tiihonen
Published: 13 July 2009
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