Age of onset for increased dose-adjusted serum concentrations of antidepressants and association with sex and genotype: An observational study of 34,777 individuals.
Eur J Clin Pharmacol
; 80(3): 435-444, 2024 Mar.
Article
em En
| MEDLINE
| ID: mdl-38197945
ABSTRACT
PURPOSE:
The aim of this study was to examine the age of onset for increased dose-adjusted serum concentrations (C/D ratio) of common antidepressant drugs and to explore the potential association with sex and CYP2C19/CYP2D6 genotype.METHODS:
Serum concentrations and prescribed daily doses for citalopram, escitalopram, sertraline, venlafaxine and mirtazapine, and CYP genotypes, were obtained from a therapeutic drug monitoring (TDM) service. Segmented linear regression analysis was used to examine the relationship between age and antidepressant log C/D ratio in (i) all individuals, (ii) men and women, and (iii) CYP2D6/CYP2C19 normal metabolizers (NMs) and CYP2D6/CYP2C19 intermediate or poor metabolizers (IMs/PMs).RESULTS:
A total of 34,777 individuals were included in the study; CYP genotype was available for 21.3%. An increase in C/D ratio started at 44â55 years of age. Thereafter, the increase progressed more rapidly for citalopram and escitalopram than for venlafaxine and mirtazapine. A doubled C/D ratio was estimated to occur at 79 (citalopram), 81 (escitalopram), 86 (venlafaxine), and 90 years (mirtazapine). For sertraline, only modest changes in C/D ratio were observed. For escitalopram and venlafaxine, the observed increase in C/D ratio started earlier in women than in men. The results regarding CYP genotype were inconclusive.CONCLUSION:
The age-related increase in C/D ratio starts in middle-aged adults and progresses up to more than twofold higher C/D ratio in the oldest old. Sertraline seems to be less prone to age-related changes in C/D ratio than the other antidepressants.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citalopram
/
Sertralina
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Eur J Clin Pharmacol
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
Noruega
País de publicação:
ALEMANHA
/
ALEMANIA
/
DE
/
DEUSTCHLAND
/
GERMANY