Cytochrome P450 2D6 genotype does not predict SSRI (fluoxetine or paroxetine) induced hyponatraemia.
OBJECTIVE
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.
Stedman
Catherine A M
CA
Department of Clinical Pharmacology, Christchurch Hospital, Christchurch School of Medicine, Christchurch, New Zealand.
Begg
Evan J
EJ
Kennedy
Martin A
MA
Roberts
Rebecca
R
Wilkinson
Timothy J
TJ
D000368:Aged; D000369:Aged, 80 and over; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D003866:Depressive Disorder / Q000188:drug therapy; D005260:Female; D005473:Fluoxetine / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D005838:Genotype; D006801:Humans; D007010:Hyponatremia / Q000139:chemically induced / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D017374:Paroxetine / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics*; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics*
D019389:Cytochrome P-450 CYP2D6; D005473:Fluoxetine; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors