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CYP1A2 genetic polymorphisms are associated with early antidepressant escitalopram metabolism and adverse reactions
Hsiang-Wei Kuo1, Shu Chih Liu, Hsiao-Hui Tsou
1Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County 350, Taiwan.
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. Original submitted 27 December 2012; Revision submitted 15 May 2013.
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