title: Impact of age on serum concentrations of venlafaxine and escitalopram in different CYP2D6 and CYP2C19 genotype subgroups.
abstract: OBJECTIVE
  The aim of the present study was to investigate the effect of age on venlafaxine and escitalopram serum concentrations in various cytochrome P450 (CYP) 2D6 and CYP2C19 genotype subgroups.
  
  
  METHODS
  Serum concentration measurements from CYP-genotyped patients treated with venlafaxine (n = 255) or escitalopram (n = 541) were collected retrospectively from a therapeutic drug monitoring database. Patients were divided into three CYP2D6 (venlafaxine) or CYP2C19 (escitalopram) phenotype subgroups according to inherited genotype, i.e., poor metabolizers (PMs), heterozygous extensive metabolizers (HEMs), and extensive metabolizers (EMs), and subsequently distributed into three age groups, i.e., <40 (control), 40-65, and >65 years. The effect of age on dose-adjusted serum concentrations (i.e., nmol/L/mg/day) of venlafaxine and escitalopram in each of the phenotype subgroups was evaluated by separate multivariate mixed model analyses.
  
  
  RESULTS
  In CYP2D6 PMs, the mean dose-adjusted serum concentration of venlafaxine was 8-fold higher in patients >65 years compared with those <40 years (p < 0.001). In comparison, the respective age-related differences in mean dose-adjusted serum concentrations of venlafaxine were much less pronounced in CYP2D6 HEMs and EMs (<2-fold differences between age groups). A similar genotype-related effect of age was not observed for escitalopram (<1.5-fold age differences in all CYP2C19 subgroups).
  
  
  CONCLUSIONS
  This study suggests that the effect of age on serum concentration of venlafaxine is dependent on CYP genotype, in contrast to escitalopram. Thus, to prevent potential side effects, it might be particularly relevant to consider CYP2D6 genotyping prior to initiation of venlafaxine treatment in older patients.
authors.affiliation: Center for Psychopharmacology, Diakonhjemmet Hospital, PO Box 85 Vinderen, 0319, Oslo, Norway, ragnhild@waade.com.
authors.forename: Ragnhild Birkeland
authors.initials: RB
authors.lastname: Waade
authors.forename: Monica
authors.initials: M
authors.lastname: Hermann
authors.forename: Hanne Lewis
authors.initials: HL
authors.lastname: Moe
authors.forename: Espen
authors.initials: E
authors.lastname: Molden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D018687:Antidepressive Agents, Second-Generation / Q000097:blood / Q000493:pharmacokinetics; D015283:Citalopram / Q000097:blood* / Q000493:pharmacokinetics; D003511:Cyclohexanols / Q000097:blood* / Q000493:pharmacokinetics; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D017367:Selective Serotonin Reuptake Inhibitors / Q000097:blood / Q000493:pharmacokinetics; D000069470:Venlafaxine Hydrochloride; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D015283:Citalopram; D003511:Cyclohexanols; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D017367:Selective Serotonin Reuptake Inhibitors; D000069470:Venlafaxine Hydrochloride; C045793:CYP2C19 protein, human