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Cytochrome P450 2D6 genotype does not predict SSRI (fluoxetine or paroxetine) induced hyponatraemia
Catherine A M Stedman1, Evan J Begg, Martin A Kennedy
1Department of Clinical Pharmacology, Christchurch Hospital, Christchurch School of Medicine, Christchurch, New Zealand.
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.