Associations of antidepressants and antipsychotics with lipid parameters: Do CYP2C19/CYP2D6 genes play a role? A UK population-based study

Alvin Richards-Belle*, Isabelle Austin-Zimmerman, Baihan Wang, Eirini Zartaloudi, Marius Cotic, Caitlin Gracie, Noushin Saadullah Khani, Yanisa Wannasuphoprasit, Marta Wronska, Yogita Dawda, David PJ Osborn, Elvira Bramon

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

BACKGROUND: Dyslipidaemia is an important cardiovascular risk factor for people with severe mental illness, contributing to premature mortality. The link between antipsychotics and dyslipidaemia is well established, while evidence on antidepressants is mixed.

AIMS: To investigate if antidepressant/antipsychotic use was associated with lipid parameters in UK Biobank participants and if CYP2C19 and CYP2D6 genetic variation plays a role.

METHODS: Review of self-reported prescription medications identified participants taking antidepressants/antipsychotics. Total, low-, and high-density lipoprotein cholesterol (L/HDL-C) and triglycerides derived from blood samples. CYP2C19 and CYP2D6 metabolic phenotypes were assigned from genetic data. Linear regression investigated aims, adjusted for key covariates.

RESULTS: Of 469,739 participants, 36,043 took antidepressants (53% female, median age 58, 17% taking cholesterol-lowering medications) and 3255 took antipsychotics (58% female, median age 57, 27% taking cholesterol-lowering medications). Significant associations were found between use of each amitriptyline, fluoxetine, citalopram/escitalopram, sertraline, paroxetine and venlafaxine with higher total cholesterol, LDL-C, and triglycerides and lower HDL-C, compared to participants not taking each medication. Venlafaxine was associated with the worst lipid profile (total cholesterol, adjusted mean difference: 0.21 mmol/L, 95% confidence interval (CI): 0.17 to 0.26, p < 0.001). Antipsychotic use was significantly associated with lower HDL-C and higher triglycerides. In participants taking sertraline, CYP2C19 intermediate metabolisers had higher HDL-C (0.05 mmol/L, 95% CI: 0.01 to 0.09, p = 0.007) and lower triglycerides (-0.17 mmol/L, 95% CI: -0.29 to -0.05, p = 0.007), compared to normal metabolisers.

CONCLUSIONS: Antidepressants were significantly associated with adverse lipid profiles, potentially warranting baseline and regular monitoring. Further research should investigate the mechanistic pathways underlying the protective effects of the CYP2C19 intermediate metaboliser phenotype on HDL-C and triglycerides in people taking sertraline.

Original languageEnglish
Pages (from-to)396-407
Number of pages12
JournalJournal of Psychopharmacology
Volume37
Issue number4
Early online date11 Feb 2023
DOIs
Publication statusPublished - Apr 2023

Keywords

  • Female
  • Male
  • Animals
  • Cytochrome P-450 CYP2D6/genetics
  • Sertraline
  • Antipsychotic Agents
  • Venlafaxine Hydrochloride
  • Cytochrome P-450 CYP2C19
  • Antidepressive Agents/pharmacology
  • Triglycerides
  • Cholesterol
  • United Kingdom

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