Mechanism identified for how antipsychotic drugs cause diabetes

Researchers have now identified the mechanism for how antipsychotic medications cause diabetes and obesity, according to Sanford-Burnham Medical Research Institute.

Researchers found that many antipsychotic drugs interfere with normal metabolism by activating a protein called SMAD3, an important part of the transforming growth factor beta (TGF?) pathway. This mechanism controls many cellular functions, including the production of insulin.

“We now believe that many antipsychotics cause obesity and diabetes because they trigger the TGF? pathway. Of all the drugs we tested, the only two that didn't activate the pathway were the ones that are known not to cause metabolic side effects,” said Fred Levine, MD, PhD, director of the Sanford Children's Health Research Center at Sanford-Burnham.

The scientific community has long associated antipsychotics with negative metabolic side effects, but the mechanism was unclear until now.

Antipsychotics are typically prescribed for bipolar disorder, schizophrenia and other behavior disorders. In 2008, roughly 14.3 million Americans were taking antipsychotics, according to Sanford-Burnham. These are among the most prescribed drugs in the US.

People who do not take antipsychotics also may experience dysfunction in the TGF? pathway and related health problems.

“It's known that people who have elevated TGF? levels are more prone to diabetes. So having a dysregulated TGF? pathway—whether caused by antipsychotics or through some other mechanism—is clearly a very bad thing,” said Levine.

“The fact that antipsychotics activate this pathway should be a big concern to pharmaceutical companies. We hope this new information will lead to the development of improved drugs,” he said.

Being overweight is a risk factor for developing diabetes. Other risk factors include family history, ethnicity, age, and physical inactivity.

The results of the research study were published on January 31 in the journal Molecular Psychiatry.

Source: Sanford-Burnham Medical Research Institute, National Institutes of Health