Thousands of extra deaths among schizophrenics worldwide may have resulted due to the authorities' restrictions on the use of antipsychotic drug clozapine over safety concerns, says research.
Professor Jari Tiihonen, associated with the University of Kuopio and Niuvanniemi Hospital, Kuopio, Finland, says that the use of clozapine was found to lower mortality by 26 per cent when it and other antipsychotics were compared with the standard first generation antipsychotic perphenazine.
The researcher further revealed that long-term use of antipsychotics in general was associated with around 20 per cent lower mortality, compared with no antipsychotic use.
In the population-based study, the authors used national registers in Finland to compare the cause-specific mortality in some 67,000 patients versus the total population between 1996 and 2006, and to link these data with use of antipsychotic drugs.
They 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.
While the proportional use of second-generation antipsychotic drugs was found to rise from 13 to 64 per cent during follow-up, the gap in life expectancy from age 20 years between patients with schizophrenia and the general population did not widen between 1996 and 2006.
Compared with current use of perphenazine, the highest risk for overall mortality was recorded for quetiapine and the lowest for clozapine.
The authors say that long-term cumulative exposure (7-11 years) to any antipsychotic treatment was associated with around 20 per cent lower mortality than was no drug use.
In patients with one or more filled prescription for an antipsychotic drug, an inverse relation between mortality and duration of cumulative use was noted.
The authors say: "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. 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."
Based on their findings, the authors came to the conclusion that long-term treatment with antipsychotic drugs is associated with lower mortality compared with no antipsychotic use.
They say: "Restrictions on use of clozapine and thioridazine have not been based on any evidence for their overall ratio of risk to benefit. 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."
A research article on the study's findings have been published in the online edition of the journal The Lancet.