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Antidepressants and the risk of sudden cardiac death and ventricular arrhythmia.

ABSTRACT: To examine the association between exposure to antidepressants and emergency department or inpatient admission for sudden cardiac death and ventricular arrhythmia (SD/VA), and to examine the impact of dose and cytochrome P-450 inhibition.A cohort study was conducted using 1999-2003 Medicaid claims data from beneficiaries of five large states, supplemented with Medicare claims for dually eligible individuals. Exposures were prescription claims for antidepressants of interest or a reference antidepressant. Outcomes were incident first-listed emergency department or principal inpatient diagnoses indicative of SD/VA originating in the outpatient setting, an outcome previously found to have a positive predictive value of 85%.In 1.3 million person-years of antidepressant exposure, we identified 4222 SD/VA outcomes for a rate of 3.3/1000 person-years (95%CI, 3.2-3.4). Compared with paroxetine (a referent with a putatively favorable cardiovascular risk profile), adjusted hazard ratios (HRs) were 0.80 (0.67-0.95) for bupropion, 1.24 (0.93-1.65) for doxepin, 0.79 (0.55-1.15) for lithium, and 1.26 (1.11-1.42) for mirtazapine. HRs for amitriptyline, citalopram, fluoxetine, nefazodone, nortriptyline, sertraline, trazodone, and venlafaxine were near unity. For antidepressants having nonnull risks (bupropion and mirtazapine), we observed no relationship with antidepressant dose and some relationships with concomitant cytochrome P-450 inhibition.Of antidepressants studied, only mirtazapine had a statistically significantly greater SD/VA risk versus paroxetine. However, baseline differences between these users suggest that this finding may be attributable to residual confounding. Eleven other antidepressants had SD/VA risks no greater than that of paroxetine, thereby providing reassurance regarding the comparative cardiovascular safety of antidepressants.

SUBMITTER: Leonard CE

PROVIDER: S-EPMC3217297 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Antidepressants and the risk of sudden cardiac death and ventricular arrhythmia.

Leonard Charles E CE Bilker Warren B WB Newcomb Craig C Kimmel Stephen E SE Hennessy Sean S

Pharmacoepidemiology and drug safety 20110728 9

<h4>Purpose</h4>To examine the association between exposure to antidepressants and emergency department or inpatient admission for sudden cardiac death and ventricular arrhythmia (SD/VA), and to examine the impact of dose and cytochrome P-450 inhibition.<h4>Methods</h4>A cohort study was conducted using 1999-2003 Medicaid claims data from beneficiaries of five large states, supplemented with Medicare claims for dually eligible individuals. Exposures were prescription claims for antidepressants o ...[more]

PMID: 21796718

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Project description:ImportanceThe combination of ceftriaxone and lansoprazole has been shown to prolong the corrected QT interval on electrocardiogram. However, it is unknown whether this translates to clinically important patient outcomes.ObjectiveTo compare lansoprazole with another proton pump inhibitor (PPI) during ceftriaxone treatment in terms of risk for ventricular arrhythmia, cardiac arrest, and in-hospital mortality.Design, setting, and participantsA retrospective cohort study including adult medical inpatients receiving ceftriaxone with lansoprazole or another PPI in 13 hospitals in Ontario, Canada, was conducted from January 1, 2015, to December 31, 2021.ExposureLansoprazole during ceftriaxone treatment vs other PPIs during ceftriaxone treatment.Main outcomes and measuresThe primary outcome was a composite of ventricular arrhythmia or cardiac arrest that occurred after hospital admission. The secondary outcome was all-cause in-hospital mortality. Propensity-score weighting was used to adjust for covariates including hospital site, demographic characteristics, comorbidities, risk factors for ventricular arrhythmia, illness severity, admitting diagnoses, and concomitant medications.ResultsOf the 31 152 patients hospitalized on internal medicine wards who were treated with ceftriaxone while receiving a PPI, 16 135 patients (51.8%) were male, and the mean (SD) age was 71.7 (16.0) years. The study included 3747 patients in the lansoprazole group and 27 405 patients in the other PPI group. Ventricular arrhythmia or cardiac arrest occurred in 126 patients (3.4%) within the lansoprazole group and 319 patients (1.2%) within the other PPI group. In-hospital mortality occurred in 746 patients (19.9%) within the lansoprazole group and 2762 patients (10.1%) in the other PPI group. After weighting using propensity scores, the adjusted risk difference for the lansoprazole group minus other PPI group was 1.7% (95% CI, 1.1%-2.3%) for ventricular arrhythmia or cardiac arrest and 7.4% (95% CI, 6.1%-8.8%) for in-hospital mortality.Conclusions and relevanceThe findings of this cohort study suggest that combination therapy with lansoprazole and ceftriaxone should be avoided. More studies are needed to determine whether these findings could be replicated in other populations and settings.

Dataset Information

Antidepressants and the risk of sudden cardiac death and ventricular arrhythmia.

Publications

Antidepressants and the risk of sudden cardiac death and ventricular arrhythmia.

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