Risk of out-of-hospital cardiac arrest in antidepressant drug users.

Talip E Eroglu, Carlo A Barcella, Thomas A Gerds, Lars Vedel Kessing, Nertila Zylyftari, Grimur H Mohr, Kristian Kragholm, Christoffer Polcwiartek, Mads Wissenberg, Fredrik Folke, Hanno L Tan, Christian Torp-Pedersen, Gunnar H Gislason

Journal: British journal of clinical pharmacology 2022;88(7):3162-3171

PMID: 35001414

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Abstract

UNLABELLED

Conflicting results have been reported regarding the association between antidepressant use and out-of-hospital cardiac arrest (OHCA) risk. We investigated whether the use of antidepressants is associated with OHCA.

METHODS

We conducted a nationwide nested case-control study to assess the association of individual antidepressant drugs within drug classes with the hazard of OHCA. Cases were defined as OHCA from presumed cardiac causes. Cox regression with time-dependent exposure and time-dependent covariates was conducted to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs) overall and in subgroups defined by established cardiac disease and cardiovascular risk factors. Also, we studied antidepressants with and without sodium channel blocking or potassium channel blocking properties separately.

RESULTS

During the study period from 2001 to 2015 we observed 10 987 OHCA cases, and found increased OHCA rate for high-dose citalopram (>20 mg) and high-dose escitalopram (>10 mg; HR:1.46 [95% CI:1.27-1.69], HR:1.43 [95% CI:1.16-1.75], respectively) among selective serotonin reuptake inhibitors (reference drug sertraline), and for high-dose mirtazapine (>30; HR:1.59 [95% CI:1.18-2.14]) among the serotonin-norepinephrine reuptake inhibitors or noradrenergic and specific serotonergic antidepressants (reference drug duloxetine). Among tricyclic antidepressants (reference drug amitriptyline), no drug was associated with significantly increased OHCA rate. Increased OHCA rate was found for antidepressants with known potassium channel blocking properties (HR:1.14 [95% CI:1.05-1.23]), but for not those with sodium channel blocking properties. Citalopram, although not statistically significant, and mirtazapine were associated with increased OHCA rate in patients without cardiac disease and cardiovascular risk factors.

CONCLUSION

Our findings indicate that careful titration of citalopram, escitalopram and mirtazapine dose may have to be considered due to drug safety issues.

Address: Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark.; Department of Experimental and Clinical Cardiology, Heart Centre, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.; Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark.; The Danish Heart Foundation, Copenhagen, Denmark.; Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.; Copenhagen Affective Disorder research Center (CADIC), Psychiatric Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.; Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark.; Department of Cardiology, Nordsjaellands Hospital, Hillerød, Denmark.; Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark.; Mental Health Centre Glostrup, Copenhagen University Hospital, Copenhagen, Denmark.; Copenhagen Affective Disorder research Center (CADIC), Psychiatric Center Copenhagen, Copenhagen University Hospital, Copenhagen, Denmark.; Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark.; Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.; Copenhagen University Hospital - Copenhagen Emergency Medical Services, Copenhagen, Denmark.; Department of Experimental and Clinical Cardiology, Heart Centre, Amsterdam Cardiovascular Sciences, Amsterdam UMC, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.; Netherlands Heart Institute, Utrecht, The Netherlands.; Department of Cardiology, Nordsjaellands Hospital, Hillerød, Denmark.; Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.; Department of Cardiology, Copenhagen University Hospital - Herlev and Gentofte, Copenhagen, Denmark.; Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.

DOI: 10.1111/bcp.15224

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MeSH Terms: Antidepressive Agents, Case-Control Studies, Citalopram, Humans, Mirtazapine, Norepinephrine, Out-of-Hospital Cardiac Arrest, Potassium Channels, Selective Serotonin Reuptake Inhibitors