Use of antidepressant serotoninergic medications and cardiac valvulopathy: a nested case–control study in the health improvement network (THIN) database


Dr Francesco Lapi PharmD PhD, Department of Preclinical and Clinical Pharmacology, University of Florence, Viale G. Pieraccini 6, 50139 Florence, Italy. Tel.: +39 055 427 1270. Fax: +39 055 427 1280. E-mail:



• Some medications can induce cardiac valvulopathy by acting on 5-HT2B receptors.

• Antidepressant serotoninergic medications may activate 5-HT2B receptors via a direct or an indirect mechanism.


• These data do not appear to support an association between exposure to antidepressant serotoninergic medications and an increased risk of cardiac valvulopathy.

AIMS To quantify the risk of cardiac valvulopathy (CV) associated with the use of antidepressant serotoninergic medications (SMs).

METHODS We conducted a case–control study nested in a cohort of users of antidepressant SMs selected from The Health Improvement Network database. Patients who experienced a CV event during follow-up were cases. Cases were ascertained in a random sample of them. Up to 10 controls were matched to each case by sex, age, month and year of the study entry. Use of antidepressant SMs during follow-up was defined as current (the last prescription for antidepressant SMs occurred in the 2 months before the CV event), recent (in the 2–12 months before the CV event) and past (>12 months before the CV event). We fitted a conditional regression model to estimate the association between use of antidepressant SMs and the risk of CV by means of odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Sensitivity analyses were conducted to test the robustness of our results.

RESULTS The study cohort included 752 945 subjects aged 18–89 years. Throughout follow-up, 1663 cases (incidence rate: 3.4 per 10 000 person-years) of CV were detected and were matched to 16 566 controls. The adjusted OR (95% CI) for current and recent users compared with past users of antidepressant SMs were 1.16 (0.96–1.40) and 1.06 (0.93–1.22), respectively. Consistent effect estimates were obtained when considering cumulative exposure to antidepressant SMs during follow-up.

CONCLUSIONS These results would suggest that exposure to antidepressant SMs is not associated with an increased risk of CV.