Weight gain has long been an unwanted side effect of medicines commonly used to treat psychiatric conditions such as bipolar disorder or schizophrenia. 

Some patients may quit their meds to avoid piling on pounds. Or if they stick to their meds and weight gain continues, they face higher risks for diabetes and liver disease. 

However, research in mice is pinpointing how this drug-linked weight gain happens in the first place — and how to stop it.

The answer may lie in a hormone called leptin, explain researchers at the University of Texas Southwestern Medical Center in Dallas.

According to the Cleveland Clinic, leptin is a hormone that’s emitted by fat cells and is involved in hunger and weight maintenance.

Prior research has shown that patients who start taking common psychiatric meds such as olanzapine (used against bipolar disorder) and risperidone (used to treat schizophrenia) typically experience an uptick in their leptin levels before a surge in weight gain.

The new study was conducted in mice. It might explain how a drug-induced rise in leptin is linked to added pounds. 

“While it was historically viewed as a ‘passenger’ to obesity – meaning [leptin] levels go up as we gain weight – our data strongly suggest that it is a ‘driver’ for drug-induced obesity,” said study lead author Philipp Scherer. He’s professor of internal medicine and director of the Touchstone Center for Diabetes Research at UT Southwestern.

“Weight gain affects most patients who start taking these antipsychotic drugs and is a well-established side effect of these interventions,” he said in a UT Southwestern news release. “As a result, many individuals become insulin resistant and diabetic. The study implicates leptin as a key driver of these negative metabolic consequences.”

Of course, studies in mice do not always pan out in humans. But the research did offer a hint as to how patients taking olanzapine or risperidone might avoid gaining weight.

Treating the mice with an antibody that neutralized leptin appeared to shortcircuit the weight gain, blood sugar issues and inflammation that otherwise came with higher leptin levels, the Texas group said. 

“We are working hard to take the leptin-neutralizing antibodies that we have used here into a clinical setting to find out whether the mechanisms defined in rodents also apply to individuals who embark on an antipsychotic treatment regimen,” Scherer said.

The findings were published recently in Science Translational Medicine.

More information

Find out more about bipolar disorder treatment at the Mayo Clinic.

SOURCE: UT Southwestern Medical Center, news release, Jan. 9, 2024