- Design
- Systematic review and meta-analysis of cohort and case-control studies
- Population
- 12 studies, about 9.6 million participants
- Primary outcome
- Ventricular arrhythmia or sudden cardiac death; atrial fibrillation
- Effect
- VA/SCD OR 1.34 (95% CI 1.15 to 1.55); AF OR 1.75 (0.84 to 3.62)
A systematic review and meta-analysis in the European Journal of Clinical Pharmacology (24 September 2026) pooled 12 cohort and case-control studies with about 9.6 million participants comparing antidepressant users with non-users.
Antidepressant use was associated with ventricular arrhythmia or sudden cardiac death (nine studies, OR 1.34, 95% CI 1.15 to 1.55), for both SSRIs and tricyclics. For atrial fibrillation the pooled estimate was not significant (OR 1.75, 0.84 to 3.62) and depended on one influential study.
Heterogeneity was extreme (I² 90-98%), and depression itself raises cardiac risk, so confounding by indication is the main alternative explanation. Read alongside the randomised BMJ analysis in this edition, which found no early excess of cardiovascular events, the observational signal is best treated as a prompt to manage modifiable risk rather than to withhold treatment.
- Take an ECG before starting an antidepressant in patients with structural heart disease or a long QT history
- Check potassium and magnesium in cardiac patients starting a tricyclic or SSRI
- Remember that untreated depression carries its own cardiac risk
- Avoid tricyclics in patients after MI or with conduction disease
Why it matters
It keeps alive a sudden-death signal that randomised trials, too short and too selected, are poorly placed to rule out.
Don't overread it
These are observational associations with extreme heterogeneity; depression itself may explain much of the excess.
The statistics, in plain English
An OR of 1.34 means about a third higher odds, but I² of 90.5% means the studies disagree far more than chance would explain, so the pooled number is an average of quite different estimates. The AF result's interval (0.84 to 3.62) crosses 1 and cannot be relied on.
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