Cytochrome P450 2D6 genotype does not predict SSRI (fluoxetine or paroxetine) induced hyponatraemia

Publisher Website
Google Scholar
Abstract
Aims The aims of this study were to determine if patients with SSRI‐related hyponatraemia were (1) genetically poor metabolizers of CYP2D6, and/or (2) had excessive plasma concentrations of the SSRI antidepressant. Methods Plasma DNA from 20 people with hyponatraemia attributable to fluoxetine or paroxetine was analysed for the CYP2D6 alleles *1–*16. Trough plasma concentrations of fluoxetine and norfluoxetine, or paroxetine were assayed in nine people who remained on the antidepressant. Results Genotype results were compared with those published in a large population study. The poor metabolizer PM/PM genotype was present in one subject only, or 5% of the study population, compared with 7.2% of a general population. The 95% Cl of this result was 0–21%, suggesting that it is most unlikely that hyponatremia is related to the PM/PM genotype. The intermediate IM/PM genotype was present in 5% compared with 19.7% of a general population. All differences were not statistically significant. Antidepressant concentrations of fluoxetine (n = 5, all EM) and paroxetine (n = 1 IM/PM and n = 3 EM) were all within the lower half of the reference range. Conclusions These results do not support the hypothesis that SSRI‐related hyponatraemia is linked to genetically poor metabolizers, or excessive drug concentrations. Copyright © 2002 John Wiley & Sons, Ltd.