CYP1A2genetic polymorphisms are associated with early antidepressant escitalopram metabolism and adverse reactions

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Abstract

Aim:

The liver CYP1A2 enzyme may metabolize antidepressant escitalopram (S-CIT) to S-desmethylcitalopram (S-DCIT) and S-didesmethylcitalopram (S-DDCIT). This study tested whether genetic polymorphisms in the CYP1A2 gene are associated with the treatment responses to S-CIT.

Materials & methods:

Ten SNPs in CYP1A2 were selected and genotyped in 158 patients under S-CIT treatment. The serum levels of S-CIT and its metabolites were measured by HPLC.

Results:

CYP1A2 SNPs rs2069521, rs2069526, rs4646425 and rs4646427 are significantly associated with the metabolic ratios of S-DDCIT/S-DCIT (p = 0.002, 0.018, 0.008 and 0.004, respectively) at week 2 of treatment. Carriers of the allele types associated with higher S-DDCIT/S-DCIT ratios had more severe side effects.

Conclusion:

These results suggest that genetic variants in CYP1A2 may be indicators for S-CIT metabolism and that the fast metabolizers may experience more severe adverse reactions in the early stages of S-CIT treatment.

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