Contact: Amy Gilliam

Jose de Leon

“This body of evidence is showing that doctors could select the best therapy sooner, help minimize the risks to the patient, and avoid unnecessary treatment costs by testing individual metabolic status before they write a prescription or set a dosing level,” he said.

-- Jose de Leon.
researcher and associate professor,
Department of Psychiatry,
UK College of Medicine

LEXINGTON, Ky. (Jan. 11, 2005) -- University of Kentucky researcher and associate professor in the UK College of Medicine, Department of Psychiatry, Dr. Jose de Leon has published novel findings that demonstrate adverse drug reactions may be caused, in part, by how individuals metabolize medications. de Leon’s findings were published in the January 2005 issue of Clinical Psychiatry.

de Leon and his team studied naturally occurring genetic variations which control production of an enzyme (Cytochrome P450 2D6), which plays a major role in drug metabolism. The genetic variations correlate with the frequency and severity of serious drug reactions, length of treatment, and cost of treatment for patients being treated for severe mental illness. UK conducted pilot studies which showed that individuals with genetic variations causing underproduction of the enzyme could have problems metabolizing certain drugs, suffer higher rates of serious adverse drug reactions and endure longer and more costly treatment cycles. Subjects whose genetic variations cause enzyme overproduction may require higher than usual doses of some medications to obtain therapeutic effects.

“Adverse drug reactions are the fourth to fifth leading cause of death in the United States, cause an additional 2.2 million hospitalizations, and cost the health care system $4 billion annually in direct treatment costs,” de Leon said.

“This body of evidence is showing that doctors could select the best therapy sooner, help minimize the risks to the patient, and avoid unnecessary treatment costs by testing individual metabolic status before they write a prescription or set a dosing level,” he said.

Promising new pharmacogenetic technologies, such as the recently FDA approved AmpliChip CYP450 test that provides CYP2D6 genetic variations, have been recognized by leading scientific journals as potentially viable methods for future genetic testing. Even science writers in magazines such as Time have predicted DNA chips or similar technologies will be used to tailor medications to each patient’s genetic makeup, also referred to as personalized prescriptions, by 2015.

“The AmpliChip CYP450 test may be used to help determine whether a standard dose of one of these drugs would be appropriate in a patient, whether it might cause serious adverse events, or even toxicities. However, on the opposite end of the spectrum, a drug might be cleared from the body so quickly that the patient does not achieve therapeutic levels.

“Adverse drug reactions remain a major complication for psychiatry in particular and medicine in general by limiting patient tolerance of what may otherwise be effective drugs,” he said.

De Leon’s research was conducted under a research-initiated grant from the Eli Lilly Research Foundation, a National Alliance for Research on Schizophrenia and Depression (NARSAD) Independent Award, internal funding, and by Roche Molecular Systems Inc. He and five other researchers co-authored the report, which tested more than 500 adults with psychiatric disorders from July 2000 to March 2003. Some of the patients were stabilized on their risperidone dose for at least five days. Other patients were studied after discontinuing risperidone, one of the most frequently used psychiatric drugs. In this naturalistic study, each patient’s treating physician prescribed risperidone. The majority of patients were taking other medications.

The research activities associated with this study were conducted at the Eastern State Hospital in Lexington, Ky., with support from the Bluegrass Regional Mental Health and Mental Retardation Board, which manages Eastern State Hospital. The Commonwealth of Kentucky Department of Mental Heath and Mental Retardation Services , which supervises the Kentucky State Hospitals, encouraged and supported this UK study.

Over the past two years, de Leon has received grant and research support from the NARSAD, Eli Lilly, and Roche Molecular Systems and has served on the speakers or advisory boards of Bristol-Myers Squibb, AstraZeneca, and Eli Lilly.