July 13 (HealthDay News) -- Thousands of schizophrenia patients worldwide may have died because of safety restrictions on the use of the second-generation antipsychotic drug clozapine, a new study suggests.

Finnish researchers concluded that clozapine is associated with a lower death rate compared to other antipsychotics.

For this study, the researchers looked at the cause of death in about 67,000 schizophrenia patients in Finland between 1996 and 2006. They compared mortality rates associated with use of any psychotic drugs against no use of the drugs, and also compared mortality rates linked to the six most frequently used antipsychotic drugs with use of the first-generation antipsychotic perphenazine.

Although the use of second-generation antipsychotic drugs rose from 13 percent to 64 percent, the difference in life expectancy from age 20 between schizophrenia patients and the general population did not widen from 1996 (25 years) to 2006 (22.5 years).

Compared with current use of perphenazine, the highest risk for death was among patients taking quetiapine (41 percent higher) and the lowest was for clozapine (26 percent lower).

The study also found that long-term use (seven to 11 years) of antipsychotics in general is associated with about a 20 percent lower death rate than with no antipsychotic use.

The researchers said they were surprised that patients taking clozapine had the lowest death rate.

"Our results raise the issue of whether clozpaine 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," wrote Professor Jari Tiihonen, University of Kuopio and Niuvanniemi Hospital, and colleagues. "However, clozapine is inexpensive, and hence it is unprofitable for the pharmaceutical industry to market compared with other second-generation antipsychotic drugs. Additionally, monitoring schedules are a drawback that would be encountered with heightened use of clozapine, and physicians and other hospital staff might therefore be reluctant to initiate clozapine treatment."

The researchers suggest that restrictions on clozapine use were arbitrary. "Restrictions on use of clozapine and thioridazine have not been based on any evidence for their overall ratio of risk to benefit," Tiihonen wrote.

"Our results suggest that these instructions and recommendations [except for blood monitoring] might have caused thousands of premature deaths worldwide in patients who have been exposed to other antipsychotic drugs, which might be associated with increased mortality. In our opinion, such restrictions and recommendations should be based on solid scientific evidence for the safety of drugs. This example underscores the need for large nationwide databases to be used for surveillance of drug safety," they concluded.

The study appears online July 12 and in an upcoming print issue of The Lancet.

SOURCE: The Lancet, news release, July 12, 2009