If fluoxetine is prescribed to a patient known to be a poor metabolizer of CYP2D6, should the dose be reduced or an alternative medication prescribed?

The answer: In the absence of clear US Food and Drug Administration (FDA) dose adjustment guidelines for antidepressants in the treatment of major depressive disorders (MDD), “an alternative medication that is metabolized by another enzyme should be considered.”

That’s the conclusion of the Clinical Pharmacogenetics Implementation Consortium (CPIC), which recently released guidelines for CYP2D6/CYP2C19 genotypes and dosing of selective serotonin reuptake inhibitors, or SSRIs. Established as a joint effort between the National Institutes of Health’s Pharmacogenomics Research Network and the Pharmacogenomics Knowledge Base (PharmGKB), CPIC has the “provisional goal of more precise medical practice in psychiatry.”1 The Consortium is tasked with providing “peer-reviewed, updated, evidence-based, freely accessible guidelines for gene/drug pairs.”2

This effort is designed “to address clinical translational barriers to implementation of pharmacogenomics tests into practice,” reported Mark A. Frye, MD, from the Department of Psychiatry and Psychology and Mayo Clinic Depression Center, Mayo Clinic, Rochester, Minnesota, and colleagues in Mayo Clinic Proceedings.

More than 20 antidepressants are FDA-approved for major depressive disorder (MDD), and “interest in individualized treatment selection” is escalating, according to the study authors. A study of residents from the Rochester Epidemiology Project in Olmsted County, Minnesota, identified antidepressants as the second most commonly prescribed drug class, with depression having “a peak prevalence rate of 26% in women aged 50 to 64 years.”

However, “the adverse effect toxicity profile of antidepressants and their effectiveness for major depression and anxiety disorders vary among patients, and it is increasingly recognized that genetic variation may contribute to this differential risk to benefit ratio,” Dr. Frye noted.