title: Variation in the CYP2D6 gene is associated with a lower serum sodium concentration in patients on antidepressants.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Hospital Pharmacy, Erasmus Medical Centre, Rotterdam 3000 CA, The Netherlands.
authors.forename: Sonja
authors.initials: S
authors.lastname: Kwadijk-de Gijsel
authors.forename: Monique J
authors.initials: MJ
authors.lastname: Bijl
authors.forename: Loes E
authors.initials: LE
authors.lastname: Visser
authors.forename: Ron H N
authors.initials: RH
authors.lastname: van Schaik
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Arnold G
authors.initials: AG
authors.lastname: Vulto
authors.forename: Teun
authors.initials: T
authors.lastname: van Gelder
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Ch Stricker
mesh_terms: D000368:Aged; D000928:Antidepressive Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015331:Cohort Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D016903:Drug Monitoring; D005260:Female; D005838:Genotype; D006801:Humans; D007010:Hyponatremia / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D011110:Polymorphism, Genetic / Q000187:drug effects / Q000235:genetics
chemical_list: D000928:Antidepressive Agents; D019389:Cytochrome P-450 CYP2D6
references.citation: J Clin Psychopharmacol. 1984 Jun;4(3):146-7
references.pmid: 6429213
references.citation: Arq Neuropsiquiatr. 2006 Mar;64(1):142-5
references.pmid: 16622573
references.citation: N Engl J Med. 2000 May 25;342(21):1581-9
references.pmid: 10824078
references.citation: Mol Psychiatry. 2004 May;9(5):442-73
references.pmid: 15037866
references.citation: Br J Clin Pharmacol. 2008 Apr;65(4):558-64
references.pmid: 18070221
references.citation: Eur J Epidemiol. 2007;22(11):819-29
references.pmid: 17955331
references.citation: Am J Psychiatry. 1997 Apr;154(4):580
references.pmid: 9090354
references.citation: Am J Psychiatry. 1989 Jun;146(6):807
references.pmid: 2729439
references.citation: Eur J Epidemiol. 1991 Jul;7(4):403-22
references.pmid: 1833235
references.citation: Am J Med. 2006 Jan;119(1):71.e1-8
references.pmid: 16431193
references.citation: Hum Psychopharmacol. 2002 Jun;17(4):187-90
references.pmid: 12404686
references.citation: Eur J Clin Pharmacol. 2002 May;58(2):143-8
references.pmid: 12012148
references.citation: J Palliat Med. 2006 Apr;9(2):258-60
references.pmid: 16629552
references.citation: Nurse Pract. 2008 Feb;33(2):11-2
references.pmid: 18300778
references.citation: Am J Kidney Dis. 2006 Oct;48(4):e61-2
references.pmid: 16997047
references.citation: Pharmacogenomics. 2002 Mar;3(2):229-43
references.pmid: 11972444
references.citation: N Engl J Med. 2005 May 26;352(21):2211-21
references.pmid: 15917386
references.citation: Nephrol Dial Transplant. 2006 Jan;21(1):70-6
references.pmid: 16141458
references.citation: Ann Pharmacother. 2006 Sep;40(9):1618-22
references.pmid: 16896026