Amitriptyline or Not, That Is the Question Identifies….pdfVIP

Clinical Chemistry 51:2 376–385 (2005) Drug Monitoring and Toxicology Amitriptyline or Not, That Is the Question: Pharmacogenetic Testing of CYP2D6 and CYP2C19 Identifies Patients with Low or High Risk for Side Effects in Amitriptyline Therapy Werner Steimer,1* Konstanze Zo¨ pf,1 Silvia von Amelunxen,2 Herbert Pfeiffer,3 Julia Bachofer,1 Johannes Popp,1 Barbara Messner,1 Werner Kissling,2 and Stefan Leucht2 Background: Amitriptyline has been replaced in many significantly lower risk of side effects than carriers of countries by alternative and more expensive drugs only one functional allele (12.1% vs 76.5%; P 0.00001). based on claims of improved tolerability and toxicity The lowest risk was observed for carriers of two func- and despite slightly reduced efficacy. Preliminary stud- tional CYP2D6 alleles combined with only one func- ies indicate that adverse effects could be linked to tional CYP2C19 allele [0 of 13 (0%) vs 9 of 11 (81.8%) for polymorphisms of drug-metabolizing enzymes, but in- the high-risk group; P 0.00004]. We found no correla- formation on their clinical impact remains scanty and tions between drug concentrations or genotypes and includes mainly case reports. We conducted a prospec- therapeutic response. tive blinded two-center study seeking correlations be- Conclusions: Combined pharmacogenetic testing for tween CYP2C19 and CYP2D6 genotypes, drug concentra- CYP2D6 and CYP2C19 iden