The right drug at the right dose at the right time. Faithful readers of the Center for Individualized Medicine blog already know we’re talking again about pharmacogenomics, or PGx. As we’ve explored in previous posts, these “right” goals drive pharmacogenomics — how genetics influence a person's response to medications.

But can pharmacogenomics and precision medicine improve our treatment of mental health? A group of researchers at Mayo Clinic, working with the support of the Center for Individualized Medicine, think so. In the current issue of Mayo Clinic Proceedings, they are highlighting the potential merits of using pharmacogenomics and precision medicine in prescribing antidepressants.

Dr. Wayne Nicholson

“This approach reveals a unique opportunity to apply precision medicine to psychiatry. The Pharmacogenomics Task Force has developed important educational resources that are delivered to physicians at the point-of-care. These resources will assist them in prescribing the most effective drug to meet the individual needs of the patient,” says Wayne Nicholson, M.D., Pharm.D., chair, Pharmacogenomics Task Force.

In a recent population-based drug prescription study of 142,377 Olmsted County, Minnesota, residents from the Rochester Epidemiology Project, antidepressants were identified as the second most commonly prescribed drug class. And if you’ve lived through a few Minnesota winters, you would understand why people turn to Prozac for a little help.

Prozac, as the drug fluoxetine is more commonly known, has improved the lives of millions of people — and not just in Minnesota.  Eleven percent of Americans 12 years and older have been prescribed antidepressant medication, according to the Centers for Disease Control and Prevention.

But fluoxetine and other similar drugs are metabolized, at least in part, by the cytochrome P450 (CYP) isoenzyme 2D6 (CYP2D6). People with multiple copies of the CYP2D6 gene may be rapid metabolizers of some drugs and may not receive the desired benefits at the usual drug dose. Conversely, some people have few functional CYP2D6 genes.  They may be slow metabolizers, causing drug levels to exceed the therapeutic range.

Dr. Mark Frye

Mark Frye, M.D., department chair of Psychiatry and Psychology at Mayo Clinic, recognizes there is increasing interest in individualizing treatment selection for more than 20 treatments approved by the U.S. Food and Drug Administration (FDA) for major depressive disorders. By doing so, physicians may be able to provide greater precision to pharmacotherapy recommendations for individual patients beyond the large-scale, clinical trials evidence base.

“The medical community continues to recognize that genetic variation may contribute to disparate patient reactions to drugs,” Dr. Frye says. “For example, some may experience adverse side effects, while others respond positively to the same drug.”

He says the different responses to pharmacotherapy provide a unique opportunity to develop pharmacogenetic guidelines for psychiatry.

The Pharmacogenomics Task Force at Mayo Clinic has implemented decision-support guidelines to provide clinicians with up-to-date information on a patient's genotype and subsequent recommendations. For example, when prescribing fluoxetine — remember that’s Prozac — paroxetine, or venlafaxine to a patient who is a known poor metabolizer of CYP2D6 or prescribing citalopram or escitalopram to a patient who is a known poor metabolizer of CYP2C19, another gene with enzymes that metabolize selective serotonin reuptake inhibitors, an alert will appear on the computerized physician order entry system.

The drug-gene alert will inform the clinician that, in the absence of clear FDA guidelines for dose adjustment, an alternative medication that is metabolized by another enzyme should be considered.

The Center for Individualized Medicine’s Education Program has also worked at linking the decision-support guidelines to the web-based Ask Mayo Expert. There, educational material is provided to the clinician to provide further information about specific genotypes, drugs, or decision-support tools.

Dr. Frye explains that using the electronic health record along with genetic testing results has the potential to further enable prescribers the ability to individualize treatment for their patients taking antidepressants.

Dr. Mark Frye, a professor of Psychiatry at Mayo Clinic in Rochester, Minn., provides clinicians with an insight for the real and potential benefits of precision medicine in patients with psychiatric conditions.

Other authors of this study, all of Mayo Clinic, include:

• Malik Nassan, M.B.B.S.
• Wayne Nicholson, M.D., Pharm.D.
• Michelle Elliott, M.D.
• Carolyn Rohrer Vitek
• John Black, M.D.

Tags: antidepressants, center for individualized medicine, CYP2D6, depression, Dr. Mark Frye, Dr. Wayne Nicholson, genome, mental health, pharmacogenomics, Precision Medicine, Prozac, Psychiatry, Uncategorized