CLOZAPINA nu scurteaza viata

Restrictions on Clozapine Should Be Reassessed: Report

NEW YORK (Reuters Health) Jul 13 - Restrictions on the use of the second-generation antipsychotic drug clozapine, instituted during the 1990s due to safety concerns, may have caused "thousands" of premature deaths worldwide in patients who were treated with other, potentially more harmful, antipsychotic drugs, Finnish investigators reported online today in The Lancet.

In a population-based study of schizophrenics, Dr. Jari Tiihonen of University of Kuopio and colleagues found that clozapine users had a lower mortality than users of other antipsychotic drugs.

"Our results raise the issue of whether clozapine should be used as a first-line treatment, because it seems to be the safest antipsychotic in terms of mortality and it is also the most effective," the investigators say.

"The introduction of second-generation antipsychotic drugs during the 1990s is widely believed to have adversely affected mortality of patients with schizophrenia," the investigators explain, "especially because of the raised risk of death from cardiovascular disease."

To establish the long-term contribution of antipsychotic drugs to mortality in schizophrenia patients, Dr. Tiihonen's team used national registers in Finland to compare death rates between 1996 and 2006 in 66,881 patients with schizophrenia with the rates in the general Finnish population. They focused on some of the most frequently used antipsychotic drugs including risperidone, clozapine, quetiapine, haloperidol and olanzapine, which were compared with perphenazine use.

Compared with current use of the first-generation antipsychotic perphenazine, the use of quetiapine, haloperidol, and risperidone was associated with an increase in mortality (adjusted hazard ratio 1.41, 1.37, and 1.34, respectively), the authors report.

On the other hand, the use of clozapine was associated with a 26% lower risk of death (adjusted HR, 0.74).

The analysis also showed that cumulative exposure to any antipsychotic treatment over 7 to 11 years was associated with about 20% lower mortality compared with no drug treatment. "In patients with one or more filled prescription for an antipsychotic drug, an inverse relation between mortality and duration of cumulative use was noted," they report.

In addition, the researchers found that clozapine and olanzapine were associated with "a slightly lower total mortality and deaths due to ischemic heart disease than were other antipsychotic drugs at the 7-11 year interval of cumulative exposure."

"Restrictions on the use of clozapine should be reassessed," Dr. Tiihonen and colleagues conclude.

In an editorial, Dr. Lydia A. Chwastiak and Dr. Cenk Tek from Yale School of Medicine, New Haven, Connecticut, point out that "clozapine is the only second-generation drug shown to have an increased effectiveness in treatment-resistant schizophrenia."

Based on the current study, they add, "the risk to benefit ratio of clozapine seems somewhat more favorable than of other second-generation drugs."

Lancet 2009