Variation in the CYP2D6 gene is associated with a lower serum sodium concentration in patients on antidepressants

Br J Clin Pharmacol. 2009 Aug;68(2):221-5. doi: 10.1111/j.1365-2125.2009.03448.x.


Aim: To study the effect of the CYP2D6*4 polymorphism on serum sodium concentration in users of antidepressants [selective serotonin reuptake inhibitors and tricyclic antidepressants (TCAs)].

Methods: In this population-based cohort study, all subjects in the Rotterdam Study were included who used an antidepressant at baseline and from whom a blood sample was available in which CYP2D6 genotype and serum sodium concentration could be determined (n= 76). Multivariate linear regression was used to study the association between CYP2D6*4 and serum sodium concentration.

Results: CYP2D6 poor metabolizers (PMs) (*4/*4) had a significantly lower mean serum sodium concentration in comparison with CYP2D6 extensive metabolizers (EMs) (*1/*1) [difference -3.9 mmol l(-1); 95% confidence interval (CI) -0.86, -7.03; P= 0.013]. In CYP2D6*4 heterozygotes (*1/*4) serum sodium concentration was 1.7 mmol l(-1) (95% CI -3.48, 0.18) lower compared with CYP2D6 EMs, but this difference was not statistically significant (P= 0.077).

Conclusions: The serum sodium concentration in PMs was lower in users of an antidepressant, especially in TCA users. Therefore CYP2D6 PMs might be at increased risk of developing symptoms of hyponatraemia.

MeSH terms

  • Aged
  • Antidepressive Agents / pharmacokinetics*
  • Antidepressive Agents / therapeutic use
  • Cohort Studies
  • Cytochrome P-450 CYP2D6 / genetics*
  • Cytochrome P-450 CYP2D6 / metabolism
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Monitoring
  • Female
  • Genotype
  • Humans
  • Hyponatremia / chemically induced
  • Hyponatremia / metabolism*
  • Male
  • Polymorphism, Genetic / drug effects
  • Polymorphism, Genetic / genetics


  • Antidepressive Agents
  • Cytochrome P-450 CYP2D6