A new study is claiming that restrictions on first-line use of the antipsychotic clozapine has led to the premature deaths of thousands of schizophrenia patients.

A study, published in The Lancet looked at the mortality rates seen in some 67,000 schizophrenics in Finland between 1996 and 2006, Jari Tiihonen, of the University of Kuopio in Finland, and colleagues wrote that patients on clozapine, which has long been genericised but was developed by Novartis as Clozaril, demonstrated a lower risk of dying. The researchers noted that second-generation antipsychotics including AstraZeneca’s Seroquel (quetiapine), Eli Lillly’s Zyprexa (and Johnson & Johnson's Haldol (haloperidol) and Risperdal (risperidone) increased the risk by 41%, 13% and 34% respectively, when compared to the first-generation drug perphenazine.

In contrast, patients on clozapine, the first atypical antipsychotic, had a 26% lower chance of dying prematurely. However, clozapine is often regarded as a treatment of last resort due to its association with agranulocytosis, a potentially life-threatening condition involving the severe loss of white blood cells. Accordingly, it is available only through a restricted distribution system that requires regular blood tests.

The authors of the study say that the 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”. They add that 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 doctors and other hospital staff might therefore be reluctant to initiate treatment.

The authors write that “restrictions on use of clozapine…have not been based on any evidence for their overall ratio of risk to benefit” and “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”. They claim that such restrictions “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”.