In their review, the investigators identified 289 cases of diabetes in patients who had been given olanzapine. Of the 289 cases of diabetes linked to the use of olanzapine, 225 were newly diagnosed cases. Ketosis was reported in 100 patients and pancreatitis in 22 patients. There were 23 deaths, including that of a 15-year-old adolescent who died of necrotizing pancreatitis. Most cases (71 percent) occurred within six months of starting the drug, and many cases were associated with moderate weight gain.

Other atypical antipsychotic agents include clozapine, risperidone, quetiapine, and ziprasidone.

"While our report does not prove a causal relationship between the drug and diabetes, doctors should be aware of such potentially adverse effects," said P. Murali Doraiswamy, M.D., a coauthor of the study. "We've found cases where patients had some very serious problems associated with olanzapine, and at least 23 of them died."

"The average age of adults showing signs of diabetes after taking olanzapine was about 10 years younger than what is generally seen in the community," said Doraiswamy. "The younger age at onset plus the number of serious complications and the improvements reported when the drug was stopped all suggest a link to the disease. However, until we know if there are risk differences among drugs in this class, it is important for physicians to watch all patients receiving this medication for signs of diabetes so that it can be detected quickly and managed."

The study merely suggests an association between the drug and diabetes, said Doraiswamy. Further studies are needed to offer more conclusive evidence of a direct causal relationship. If future studies confirm the findings, he said that perhaps the authorities should consider including a stronger warning label for these drugs.

"The numbers are still sketchy since many adverse reactions are not reported to the Food and Drug Administration and we don't have a good handle on how many people have actually received these drugs," he cautioned. "Atypical antipsychotics can be life saving medications, but we need to learn more about their long-term side-effects. I think this should be a high priority for investigation."

Doraiswamy was part of a team from Duke University that first reported a link between the antipsychotic drug clozapine and the development of diabetes in a 1994 issue of the American Journal of Psychiatry. Last year, Elizabeth A. Koller, M.D., lead author of the study, reported in the American Journal of Medicine that the Food and Drug Administration had received 384 reports of diabetes associated with the drug clozapine. According to the researchers, many cases of diabetes have also been reported with other antipsychotic drugs.