Antipsychotics Quickly Impair Metabolism
> 4/15/2008 2:46:57 PM

Alaska recently won a settlement against the manufacturers of an antipsychotic medication commonly prescribed to schizophrenics. The question at the heart of the case was not whether the medication works, but whether it causes side-effects that increase healthcare costs. Previous studies have confirmed that some antipsychotics do trigger weight gain and raise the risk of diabetes, but the precise mechanism and timing of these problematic effects was finally presented last week by Dr. Montserrat Victoriano at the annual meeting of the American Physiological Society.

Dr. Victoriano and his team were well prepared for this latest study because of prior work that they did to determine whether rats are good models for human weight gain. They discovered that male rats do gain weight to the same degree that human patients would if taking the same antipsychotics. Using this knowledge, they divided rats into three groups: a control group receiving nothing, a group receiving haloperidol, and a group receiving olanzapine. While haloperidol and olanzapine are both antipsychotics that control hallucinations and abnormal emotions, olanzapine is the only one of the two linked to weight gain.

As expected, rats given olanzapine eventually gained more weight than those in either of the other two groups. The interesting finding was that after only four weeks, while there were no changes in weight, significant metabolic differences were detected. Behavioral change could be ruled out as a mechanism, because there were no differences during these four weeks in eating or exercise habits. Tests did not detect elevated fat levels in the blood, but they did reveal that a higher proportion of fat was stored in the abdominal cavity of olanzapine rats. In addition, resting blood sugar levels quickly became less healthy, rising from 0.75 g/l  to 0.87 g/l. Not only was the blood sugar level elevated on average, but it also rose more sharply in response to meals, making it harder for the body to respond to the flood appropriately.

The two metabolic differences discovered by Dr. Victoriano should be valuable targets for other researchers. Fat accumulation in the abdominal cavity is the first step towards general weight gain, and early intervention might be able to stop the problem at this early stage. It is also important to address unbalanced blood sugar levels as early as possible, since such abnormalities often lead to metabolic syndrome, which increases the risk of heart attacks and diabetes. It is important to keep in mind that even antipsychotics that trigger metabolic changes can be valuable if these side-effects are handled promptly and vigilantly.

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