Popular antidepressants linked to heart risks in major long-term study
Anticholinergic antidepressants—among the most widely prescribed psychiatric drugs globally—carry measurable cardiovascular risks compared to alternatives, according to a large UK analysis spanning 15 years. The finding could reshape treatment guidelines and force pharmaceutical companies to reconsider marketing strategies for aging populations most vulnerable to heart complications.
Originaltitel: Long-Term Cardiovascular Risks of Anticholinergic Versus Non-Anticholinergic Antidepressants: A Target Trial Emulation With Negative Control Correction.
Anticholinerga antidepressiva ökar risken för kardiovaskulära händelser jämfört med alternativ utan denna egenskap — en upptäckt som bör påverka ordinationsrutiner inom primärvården. Forskarna analyserade 24 547 användare av anticholinerga antidepressiva mot 20 519 användare av icke-anticholinerga preparat i UK Biobank mellan 2006–2021. Efter matchning på propensity-score följdes patienterna i median 9,1 år. Huvudutfallet var hospitalisering eller död från kardiovaskulär sjukdom. Med avancerad metodologi (proximal causal inference och negative control outcome calibration) fann gruppen ökad kardiovaskulär risk vid anticholinerg exponering. Peking University ledde studien med stöd från Karolinska institutet och University of North Carolina. Resultaten har betydelse för inköpsval och farmakoterapeutiska riktlinjer inom regionvården: chefsläkare bör prioritera antidepressiva med låg anticholinerg börda, särskilt för äldre patienter och dem med befintlig hjärtsjukdom. Ordinationsstandarden kräver granskning.
PURPOSE: Antidepressants remain widely prescribed worldwide, and the potential cardiovascular risks associated with their anticholinergic properties are poorly understood. METHODS: We employed an active-comparator new-user design to emulate a target trial spanning 2006-2021 in UK Biobank. Participants aged ≥ 40 years with linked primary care records who newly initiated an anticholinergic vs. a non-anticholinergic antidepressant were included. The primary outcome was hospitalization or death from cardiovascular events. To adjust for measured and unmeasured confounding, we applied propensity score matching (PSM) with proximal causal inference (PCI) and negative control outcome calibration (NCOC) to estimate the intention-to-treat hazard difference (HD). Subgroup analyses were conducted by age, sex, socioeconomic status, lifestyle factors, apolipoprotein E genotype, and major comorbidities. Sensitivity analyses included data-driven negative control selection, alternative anticholinergic burden scale, comparisons across different anticholinergic burden levels, complete-case analysis, a 6-month induction period, and a 2-year washout period. RESULTS: The study included 24 547 anticholinergic antidepressant users and 20 519 non-anticholinergic users. Measured covariates were balanced among 32 588 PS-matched participants with a median follow-up of 9.1 years. Negative control correction revealed anticholinergic antidepressant use was associated with increased risk of cardiovascular events (HD CONCLUSIONS: Anticholinergic antidepressants may increase the risk of cardiovascular events compared with non-anticholinergic antidepressants. These findings underscore prioritizing therapeutic options with a lower anticholinergic burden in clinical practice.