Background
Tobacco smoking rates in depressive patients are higher compared with the general population. Smoking was demonstrated to accelerate the metabolism of different drugs metabolized by CYP1A2, but possibly also by CYP2C19 and CYP3A4. The principle aim of the present investigation from 2015 to 2018 was to determine the differences in the pharmacokinetics of escitalopram between smokers and nonsmokers.
Methods
A group of nonsmokers (n = 88) was compared with smokers (n = 36), both receiving escitalopram, using the Mann-Whitney U test. Linear regression analysis was used to account for the impact of escitalopram dose, age, and sex in addition to smoking on the steady-state serum concentration of escitalopram.
Results
Smokers received by mean 17.6% higher doses of escitalopram (P = 0.026) but showed 31.9% lower serum concentrations (P = 0.031). To control for confounders, linear regression analysis showed that dose (P < 0.001), sex (P = 0.03), and smoking tobacco (P = 0.027) did significantly influence serum concentrations of escitalopram with higher levels in women and nonsmokers.
Conclusions
Notwithstanding higher daily doses, smokers had significantly lower serum concentrations of escitalopram. In concordance with previous results, besides CYP1A2, a possible induction of CYP2C19 and CYP3A4 by tobacco smoke, resulting in lower serum concentrations of escitalopram in smokers than in nonsmokers, is suggested. Therefore, to provide personalized therapy, clinicians should consider smoking status and inform patients on the interactions of smoking and escitalopram metabolism.
Introduction Pharmacogenetic testing is proposed to minimize adverse
effects when considered in combination with pharmacological knowledge of the
drug. As yet, limited studies in clinical settings have investigated the
predictive value of pharmacokinetic (pk) gene variation on therapeutic drug
levels as a probable mechanism of adverse effects, nor considered the combined
effect of pk gene variation and drug level on antidepressant treatment
response.
Methods Two depression cohorts were investigated for the relationship
between pk gene variation and antidepressant serum concentrations of
amitriptyline, venlafaxine, mirtazapine and quetiapine, as well as treatment
response. For the analysis, 519 patients (49% females; 46.6±14.1
years) were included.
Results Serum concentration of amitriptyline was associated with
CYP2D6 (higher concentrations in poor metabolizers compared to normal
metabolizers), of venlafaxine with CYP2C19 (higher concentrations in
intermediate metabolizers compared to rapid/ultrarapid metabolizers) and
CYP2D6 (lower metabolite-to-parent ratio in poor compared to
intermediate and normal metabolizers, and intermediate compared to normal and
ultrarapid metabolizers). Pk gene variation did not affect treatment
response.
Discussion The present data support previous recommendations to reduce
starting doses of amitriptyline and to guide dose-adjustments via therapeutic
drug monitoring in CYP2D6 poor metabolizers. In addition, we propose including
CYP2C19 in routine testing in venlafaxine-treated patients to improve
therapy by raising awareness of the risk of low serum concentrations in CYP2C19
rapid/ultrarapid metabolizers. In summary, pk gene variation can predict
serum concentrations, and thus the combination of pharmacogenetic testing and
therapeutic drug monitoring is a useful tool in a personalized therapy approach
for depression.
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