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Using genetic information to guide prescribing antidepressant medications.

July 16, 2015

Genetic testing of drug metabolism genes may help personalize the selection of antidepressant medication. While not quite coming out to recommend the testing itself, an expert panel has recommended the use of such test results if they exist.

An expert panel has just released guidelines on how to use genetic information when prescribing the most widely used class of drug for the treatment of depression and anxiety, the “Selective Serotonin Reuptake Inhibitors” (SSRIs). The Clinical Pharmacogenetics Implementation Consortium (CPIC) analyzed the published literature from genetic studies and provided dosing recommendations for drugs such as citalopram (Celexa® or Cipramil®) or sertraline (Zoloft®) based on a patient’s drug metabolism genes.

Drug metabolism genes such as the cytochrome P450 genes have long been known to influence the activity of drugs as well as potential side effects. Depending on the particular types of these genes an individual has inherited, and the particular metabolic pathway each drug undergoes, different drugs may be under- or over-active, or even potentially harmful. However the use of such genetic (or what is called “pharmacogenetic”) information to guide drug selection and drug dosing has not yet entered routine clinical use. This is despite the fact that, according to the Personalized Medicine Coalition, SSRI anti-depressants are ineffective for an average of 38% of the people they are first prescribed for, resulting in a lengthy trial and error process to find the most effective option for each patient.

The CPIC panel’s recommendations are an important but cautious step towards the routine use of pharmacogenetic information for the care of mental health patients – important in the release of guidance about how to use such genetic information if it exists, but cautious in that the panel did not have sufficient validation and cost-effectiveness studies to make recommendations about whether clinicians should order the genetic testing itself.

An important study is underway at the Center for Addiction and Mental Health (CAMH) that may help provide such evidence. Patients participating in the IMPACT Study (Individualized Medicine: Pharmacogenetic Assessment & Clinical Treatment) are offered a saliva-based genetic test to identify which antidepressant or antipsychotic medications will work best for them. Clinicians receive an easy-to-interpret report listing drugs in three categories (Green – use as recommended, Yellow – use with caution, Red – avoid) to help determine which drug, and which dose, is most likely to be most effective. So far over 3000 patients have been enrolled. Studies such as this will help contribute to real world cost-effectiveness data that a future CPIC panel could use when considering recommendations for the pharmacogenetic testing itself of patients.

By: Kathryn Deuchars, Director, Ontario Personalized Medicine Networ