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

✍ Scribed by Catherine A. M. Stedman; Evan J. Begg; Martin A. Kennedy; Rebecca Roberts; Timothy J. Wilkinson

• Book ID: 102263419
• Publisher: John Wiley and Sons
• Year: 2002
• Tongue: English
• Weight: 50 KB
• Volume: 17
• Category: Article
• ISSN: 0885-6222
• DOI: 10.1002/hup.394

✦ Synopsis

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.