A Side Effect Of Antipsychotic Drugs: Obesity?

A new study last week found the annual number of children prescribed antipsychotic drugs jumped fivefold between 1995 and 2002, to an estimated 2.5 million children. The study is of concern to Dr. Marilyn Ader, Associate Professor of Physiology and Biophysics at the Keck School of Medicine of USC.



Ader and her colleague Dr. Richard Bergman, chair of her department at the Keck School, studied two of the six medications in this class of drugs. Their study, published in the February 2005 issue of the medical journal "Diabetes," noted that these drugs can have very serious side effects.



In their six-week study, animals given the antipsychotic drugs "virtually doubled their body fat, becoming obese in a very short period of time," said Ader. In addition, the researchers found the functioning of the pancreas was severely impaired.



"When obesity impairs the ability of insulin to lower the blood sugar ('insulin resistance"), a normal healthy pancreas will sense that the insulin isn't working, and then compensate by releasing more insulin. It's a very normal function, called compensatory hyperinsulinemia," said Ader. "When we looked at the animals that became obese and insulin resistant after receiving certain antipsychotic medications, we were surprised to find that they couldn't release more insulin. Their pancreatic secretory function was seriously impaired." Reduced secretory function of the pancreas presages Type 2 (adult-type) diabetes.



Ader and Bergman, renowned for their work on metabolism and diabetes, were asked to look at these drugs three years ago by a pharmaceutical company that wanted to understand why some patients were becoming obese or getting diabetes when taking the medication. "Not only were some patients on these drugs developing obesity or diabetes, but there were also scattered reports that patients were dying of diabetic ketoacidosis, which is a rare, but serious complication of Type 1 diabetes - the insulin-dependent form of the disease formerly known as juvenile diabetes. We found that antipsychotics may cause abnormalities linked to this dangerous complication in Type 2 diabetes- a usually rare occurrence."



Ader is quick to note that the drugs can reportedly be very effective in treating the devastating symptoms of schizophrenia, bipolar disorder and a number of very serious mental illnesses. "Patients who otherwise couldn't function are often able to perform very normal tasks, live more normal lives, with these medications," she said. "The reason this issue has become alarming is that these drugs are being used to treat more and more conditions, like dementia or anxiety or, as this recent study found, pediatric populations."



Ader and Bergman have been given a five-year grant from the National Institutes of Health to further study this group of antipsychotic drugs to help determine the risk factors critical in the development of these complications. They are also working to identify the mechanisms by which these drugs may cause increased fat mass and damage to pancreatic function. "We know antipsychotic drugs work on the brain, but when a patient develops obesity or a problem with pancreatic function, is that because the drugs are affecting the fat tissue or the pancreas, or is all of this mediated by some central mechanism of the brain?," she asks. "We need to answer these questions to figure out how to design a drug without the side effects, or to determine how you can block the bad effects with a different medication."



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