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Incidence of diabetes due to atypical antipsychotic medication

Incidence of Newly Diagnosed Diabetes Attributable to Atypical Antipsychotic Medications

Douglas L. Leslie, Ph.D., and Robert A. Rosenheck, M.D.
Am J Psychiatry 161:1709-1711, September 2004

This is an article that attempts to clarify whether there is a direct relationship between diabetes and the use of atypical or second generation antipsychotics. Diabetes, which is a disease in which the body is unable to regulate the level of sugar in the blood, is important because it is a very strong risk factor for complications such as heart disease/heart attacks, blindness, kidney failure, limb amputations, and many other maladies. The prevailing wisdom, has been that while there is definitely a substantially higher proportion of people with schizophrenia who also have diabetes, there is apparently also a link between some of the newer antipsychotic medications and development diabetes irrespective of the already increased risk. It has been shown that particular antipsychotics have higher weight gain risk (clozapine, olanzapine and quetiapine) and this weight gain risk leads to increased risk of diabetes (or so the theory goes...) This is not terribly surprising because these medications share a common molecular ancestry that is different from the other antipsychotics. So, this paper seeks to clarify exactly what the risk of developing diabetes is by looking retrospectively at a large volume of data from the VA system (veteran�s affairs.)

The authors screened over 70,000 patients through the VA records and removed patients who either already had a diagnosis of diabetes or had demonstrated that they did not have adequate medical care (by not having had a recent primary care visit.) After removing those people, they had over 40,000 subjects left. They followed these subjects for a 3 month interval in which they determined the antipsychotic the patient was taking steadily. Of the patients that met that criterion, they followed them for an additional two years and counted up the number that developed diabetes in that time. The result was that over 4 percent of the patients developed diabetes which is nearly 10 times more than the general population. However, they were only barely able to note a statistical difference between medications in their liability towards causing diabetes. Only clozapine and olanzapine showed an increased risk of diabetes compared to the general group. The authors concluded that those medications did confer an increased risk, but a small one and attributed the overall increased risk of diabetes to other aspects of schizophrenia that have yet to be fully described but could be overall poor diet, poor medical care followup, low socioeconomic status and low exercise amounts.

It is important to note the limitations of the study. First, it was retrospective and therefore not as valuable as a study that seeks to answer a question with data that does not already exist. Also, the VA system does not necessarily represent the general population (higher amount of male patients, particular socioeconomic status, etc.) If someone was diagnosed with diabetes by an outside of the VA doctor, it would not necessarily have been reflected in their records. Also, there were a very large number of patients who were excluded from the study and so they may have already developed diabetes from their medication perhaps and we would not know. Lastly, the three month window that they used to determine which antipsychotic the patient was on may or may not have ultimately been the same as the medication they were on during the rest of the followup.

So, we know that diabetes is a large problem for people with schizophrenia. It may be that the medications are at least partially responsible, but we don�t know for sure. It is likely that olanzapine and clozapine confer at least a slightly increased risk compared to the other drugs. This goes along with their increased risk of weight gain. Future studies, which would be better if they were prospective (the question was asked before the data collected) and then we could get a better idea. However, this study does further add to the importance of having either the psychiatrist or primary care doctor follow a patient very closely to keep an eye out for the development of diabetes before they manifest the full blown illness.

Here is a link to the article on pubmed

Author: Jacob Ballon