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

TY - JOUR

T1 - Associations of antidepressants and antipsychotics with lipid parameters

T2 - Do CYP2C19/CYP2D6 genes play a role? A UK population-based study

AU - Richards-Belle, Alvin

AU - Austin-Zimmerman, Isabelle

AU - Wang, Baihan

AU - Zartaloudi, Eirini

AU - Cotic, Marius

AU - Gracie, Caitlin

AU - Saadullah Khani, Noushin

AU - Wannasuphoprasit, Yanisa

AU - Wronska, Marta

AU - Dawda, Yogita

AU - Osborn, David PJ

AU - Bramon, Elvira

PY - 2023/4

Y1 - 2023/4

N2 - 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.

AB - 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.

KW - Female

KW - Male

KW - Animals

KW - Cytochrome P-450 CYP2D6/genetics

KW - Sertraline

KW - Antipsychotic Agents

KW - Venlafaxine Hydrochloride

KW - Cytochrome P-450 CYP2C19

KW - Antidepressive Agents/pharmacology

KW - Triglycerides

KW - Cholesterol

KW - United Kingdom

U2 - 10.1177/02698811231152748

DO - 10.1177/02698811231152748

M3 - Article

C2 - 36772859

SN - 0269-8811

VL - 37

SP - 396

EP - 407

JO - Journal of Psychopharmacology

JF - Journal of Psychopharmacology

IS - 4

ER -