Genetic variation is an important factor for the variation in psychiatric drug response. The meta-analysis conducted by Kirchheiner et al. showed that of 36 commonly used antidepressants, for 20 of those, data on polymorphic CYP2D6 or CYP2C19 were found and that in 14 drugs such genetic variation would require at least doubling of the dose in extensive metabolizers in comparison to poor metabolizers. They also showed that out of 38 antipsychotics, CYP2D6 and CYP2C19 genotype was of relevant in 13 drugs. Amitriptyline has relatively narrow therapeutic range and high toxicity at increased concentrations, leading to severe adverse effects. The main CYPs involved in amitriptyline metabolism are CYP2C19. Genetic variation of these enzymes has been shown to correlate with the serum concentrations of amitriptyline, as well as with the occurrence of side-effects related to amitriptyline therapy.
Sunday 10 February 2019
Expected inter-patient variability with respect to neurodisorder drug response
Genetic variation is an important factor for the variation in psychiatric drug response. The meta-analysis conducted by Kirchheiner et al. showed that of 36 commonly used antidepressants, for 20 of those, data on polymorphic CYP2D6 or CYP2C19 were found and that in 14 drugs such genetic variation would require at least doubling of the dose in extensive metabolizers in comparison to poor metabolizers. They also showed that out of 38 antipsychotics, CYP2D6 and CYP2C19 genotype was of relevant in 13 drugs. Amitriptyline has relatively narrow therapeutic range and high toxicity at increased concentrations, leading to severe adverse effects. The main CYPs involved in amitriptyline metabolism are CYP2C19. Genetic variation of these enzymes has been shown to correlate with the serum concentrations of amitriptyline, as well as with the occurrence of side-effects related to amitriptyline therapy.
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