Pharmacokinetic Pharmacogenetic Prescribing Guidelines for Antidepressants: A Template for Psychiatric Precision Medicine.
Antidepressants are commonly prescribed medications in the United States, and there is increasing interest in individualizing treatment selection for more than 20 US Food and Drug Administration-approved treatments for major depressive disorder. Providing greater precision to pharmacotherapeutic recommendations for individual patients beyond the large-scale clinical trials evidence base can potentially reduce adverse effect toxicity profiles and increase response rates and overall effectiveness. It is increasingly recognized that genetic variation may contribute to this differential risk to benefit ratio and thus provides a unique opportunity to develop pharmacogenetic guidelines for psychiatry. Key studies and concepts that review the rationale for cytochrome P450 2D6 (CYP2D6) and cytochrome P450 2C19 (CYP2C19) genetic testing can be delineated by serum levels, adverse events, and clinical outcome measures (eg, antidepressant response). In this article, we report the evidence that contributed to the implementation of pharmacokinetic pharmacogenetic guidelines for antidepressants primarily metabolized by CYP2D6 and CYP2C19.
Department of Psychiatry and Psychology and Mayo Clinic Depression Center, Mayo Clinic, Rochester, MN.
Malik
M
Nassan
Department of Anesthesiology, Mayo Clinic, Rochester, MN.
Wayne T
WT
Nicholson
Department of Internal Medicine, Division of Hematology, Mayo Clinic, Rochester, MN.
Michelle A
MA
Elliott
Center for Individualized Medicine, Mayo Clinic, Rochester, MN.
Carolyn R
CR
Rohrer Vitek
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.
John L
JL
Black
Department of Psychiatry and Psychology and Mayo Clinic Depression Center, Mayo Clinic, Rochester, MN. Electronic address: mfrye@mayo.edu.
Mark A
MA
Frye
D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D065607:Cytochrome P-450 Enzyme Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy* / Q000235:genetics; D005473:Fluoxetine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D017374:Paroxetine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D010597:Pharmacogenetics / Q000379:methods / Q000592:standards*; D017410:Practice Guidelines as Topic; D057285:Precision Medicine / Q000379:methods / Q000592:standards*; D055553:Prescription Drugs / Q000592:standards; D000069470:Venlafaxine Hydrochloride / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
D018687:Antidepressive Agents, Second-Generation; D065607:Cytochrome P-450 Enzyme Inhibitors; D055553:Prescription Drugs; D005473:Fluoxetine; D017374:Paroxetine; D000069470:Venlafaxine Hydrochloride; D019389:Cytochrome P-450 CYP2D6