Risk of out-of-hospital cardiac arrest in antidepressant drug users
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Risk of out-of-hospital cardiac arrest in antidepressant drug users. / Eroglu, Talip E.; Barcella, Carlo A.; Gerds, Thomas A.; Kessing, Lars Vedel; Zylyftari, Nertila; Mohr, Grimur H.; Kragholm, Kristian; Polcwiartek, Christoffer; Wissenberg, Mads; Folke, Fredrik; Tan, Hanno L.; Torp-Pedersen, Christian; Gislason, Gunnar H.
I: British Journal of Clinical Pharmacology, Bind 88, Nr. 7, 2022, s. 3162-3171.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Risk of out-of-hospital cardiac arrest in antidepressant drug users
AU - Eroglu, Talip E.
AU - Barcella, Carlo A.
AU - Gerds, Thomas A.
AU - Kessing, Lars Vedel
AU - Zylyftari, Nertila
AU - Mohr, Grimur H.
AU - Kragholm, Kristian
AU - Polcwiartek, Christoffer
AU - Wissenberg, Mads
AU - Folke, Fredrik
AU - Tan, Hanno L.
AU - Torp-Pedersen, Christian
AU - Gislason, Gunnar H.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - antidepressants
KW - depolarization-blocking drugs
KW - sudden cardiac arrest
KW - NESTED CASE-CONTROL
KW - REGISTRY
KW - DEATH
U2 - 10.1111/bcp.15224
DO - 10.1111/bcp.15224
M3 - Journal article
C2 - 35001414
VL - 88
SP - 3162
EP - 3171
JO - British Journal of Clinical Pharmacology, Supplement
JF - British Journal of Clinical Pharmacology, Supplement
SN - 0264-3774
IS - 7
ER -
ID: 292140383