Atypical antipsychotics commonly used to treat children with aggression, bipolar disorder, and schizophrenia may trigger insulin resistance

Researchers from the Johns Hopkins Children's Center say a group of drugs known as "atypical antipsychotics" that are commonly used to treat children with aggression, bipolar disorder, and schizophrenia may trigger insulin resistance, a condition that increases the risk of developing Type 2 diabetes and heart disease later in life.

Results of the study linking insulin resistance to the use of these antipsychotics are scheduled for presentation October 20th during the annual meeting of the American Academy of Child and Adolescent Psychiatry in Washington, D.C. (October 19-24)

For the study, the Johns Hopkins team evaluated 11 children, some overweight and others obese, who gained significant amounts of weight (a 10 percent weight increase) while taking the new-generation, or atypical, antipsychotic drugs olanzpine, quetiapine, and risperidone. Considerable weight gain is a common side effect of atypical antipsychotic medications, and is also one of the many factors that can contribute to insulin resistance.

All six children on moderate or high doses of one of these drugs, and three of five children on low doses, had evidence of insulin resistance, a condition in which the body cannot properly use the insulin it produces. This evidence included hypertension, high levels of triglycerides, low levels of high density lipoprotein cholesterol ("good" cholesterol) and increased levels of protein in the urine.

"The insulin resistance seen in these children was greater than what would be expected from weight gain alone, suggesting there is a factor distinct from excess weight that directly induces insulin resistance," says the study's lead author, Mark A. Riddle, M.D., director of the division of child and adolescent psychiatry at the Children's Center.

In general, this group of new-generation antipsychotics creates fewer side effects than older drugs used to treat debilitating psychiatric conditions such as schizophrenia, Riddle says. The drugs, which balance certain chemicals in the brain and stabilize mood, have successfully treated countless numbers of children since being introduced in the 1990s, he notes.

"Treatments are always a matter of risk and benefit balance. Clearly these drugs are an important treatment option. But diabetes and heart disease are serious health issues, so it's important to further investigate this apparent relationship between atypical antipsychotics and insulin production and consumption," he adds. "We may need to reexamine how we are prescribing these drugs to see if dosage changes can be made to ensure children will continue to receive the benefits of these medications while not putting them at risk for developing other health problems in the future."

If the study's findings are confirmed by larger follow-up studies, Riddle says he would expect monitoring of metabolic side effects to become standard practice among clinicians prescribing atypical antipsychotics to children.

Insulin resistance occurs when muscle, fat, and liver cells do not properly use insulin, the hormone produced by the pancreas that helps cells absorb glucose and provides a source of energy to the body. The pancreas tries to keep up with the demand for insulin by producing more. Eventually, the pancreas cannot keep up with the body's need for insulin, and excess glucose builds up in the bloodstream. Excess weight, lack of exercise, and a family history of diabetes all contribute to insulin resistance. The condition is associated with an increased risk of developing Type 2 diabetes, heart disease, and stroke.

Study co-authors were David Cooke, M.D., and Helen Courvoisie, M.D., from the Johns Hopkins Children's Center.