Genetic Determinants of Drug Response

CYP2D6 Gene Variants
1. Poor metabolizers (5-10%)
  1. No response (or reduced response) to Codeine, Tramadol
  2. Fluoxetine and Nortriptyline risk of toxicity
  3. Amitriptyline, Nortriptyline, Paroxetine risk of toxicity (reduce starting dose by 50%)
  4. Aripiprazole (Abilify) risk of toxicity (reduce starting dose)
  5. Atomoxetine (Strattera) risk of toxicity (reduce starting dose)
2. Ultra-metabolizers (1-2%)
  1. Codeine risk of toxicity (deaths have occurred)
  2. Amitriptyline, Nortriptyline, Paroxetine with reduced response (consider other agents)
CYP2C19 Gene Variants
1. Poor metabolizers (2-15%)
  1. Clopidogrel with reduced conversion to active form (higher risk for stent closure)
  2. Amitriptyline and Nortriptyline risk of toxicity (reduce starting dose by 50%)
  3. Citalopram, Escitalopram, Sertraline risk of toxicity (reduce starting dose by 50%)
2. Ultra-Metabolizers
  1. Citalopram, Escitalopram, Sertraline with reduced effect (consider alternative agents)
CYP2C9 Gene Variants
1. Poor metabolizers
  1. Reaching a steady-state INR on Coumadin requires >3 months
    1. Higher risk of toxicity and bleeding complications

HLA-B*1502
1. Carbamazepine induced Stevens–Johnson syndrome risk in asian patients (test before use)
HLA-B*5701
1. Abacavir (HIV agent) induced Hypersensitivity risk in HLA-B*5701 positive patients

TPMT Deficiency
1. Severe hematologic response to Azathioprine and Mercaptopurine
ADRB2 Variant
1. Asthma status worsens on Inhaled Beta Agonist (e.g. Albuterol)

Pharmacogenetic testing is indicated in specific cases
Broader screening for pharmacogenetic variation is not yet supported by the Medical Literature in 2015
1. Wang (2014) JAMA Intern Med 174(12):1938-44 +PMID:25317785 [PubMed]
No evidence of significant benefit in Antidepressant selection
1. Oslin (2022) JAMA 328(2): 151-61 [PubMed]