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March 2009 Issue

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Traditional Drugs May Affect Memory in Insulin Users

By Angela Koenig
Published March 2009

More than 200 million people worldwide take anti-psychotic medications to cope with psychiatric problems.

Within this population, the risk of diabetes is elevated as much as two-fold. Pair older generation anti-psychotic drugs with insulin-induced changes in brain chemistry and there may be potential for unnecessary memory impairment, theorizes an interdisciplinary team of researchers at UC’s College of Medicine and James L. Winkle College of Pharmacy.

The team, which includes associate professors of psychiatry Neil Richtand, MD, PhD, and Stephen Benoit, PhD, and pharmacy professor Gary Gudelsky, PhD, has received $425,000 from the National Institute of Mental Health to test its theory in an animal model.

Over the next two years, the researchers will measure what happens to memory when three individual drugs (haloperidol, quetiapine and aripiprazole) are coupled with insulin overdose. Insulin releases a brain chemical called glutamate which can kill neurons when it rises to abnormal levels.

The UC researchers have identified evidence that haloperidol will worsen the toxic effects of glutamate, while quetiapine and aripiprazole will be protective.

The study is especially relevant, says Richtand, because 35 million people worldwide could be affected by the combination of the two disease states—mental illness and diabetes—and the drug therapies involved to treat both conditions.

“We believe this particular side effect of older anti-psychotic drugs has been underappreciated. Fortunately, there are newer medications available which may provide protection against this problem, and are also better tolerated,” he says.

While other medications and clinical settings can also cause glutamate levels to rise, the focus is on insulin overdose because of the large population prescribed anti-psychotics and because, Richtand says, “persons with type l diabetes take too much insulin over 40 times a year, while patients with type 2 diabetes average more than one episode per month.”

Gudelsky’s role will be to measure the amounts of glutamate produced in the brain, while Benoit’s expertise is in learning and memory, and animal behavior models.

“We are very fortunate to have a team of investigators and labs able to study the different pieces of this puzzle,” says Richtand, who is principal investigator for the project.

The grant is funded through the National Institute of Mental Health Innovation Committee, which identifies projects with potential to shift paradigms or those involving high-risk, high-payoff research.

Richtand is a physician at the Cincinnati Department of Veterans Affairs Medical Center. He works as a paid speaker and consultant for the manufacturer of one of the study drugs and has been a consultant to another in the past.

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