Depression, antidepressant use, and risk of venous thromboembolism: systematic review and meta-analysis of published observational evidence

PURPOSE: Evidence on the association between depression, antidepressant use and venous thromboembolism (VTE) risk is conflicting. We conducted a systematic review and meta-analysis of published observational studies evaluating the associations of depression and antidepressant use with VTE risk. DESIGN: Eligible studies were identified in a literature search of MEDLINE, Embase, Web of Science and reference list of relevant studies up to April 2018. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were aggregated using random effects models. RESULTS: Eight observational studies with data on 960 113 nonoverlapping participants and 9027 VTE cases were included. The pooled RR (95% CI) for VTE comparing antidepressant use with no antidepressant use was 1.27 (1.06-1.51). Tricyclic antidepressants, selective serotonin reuptake inhibitors and other antidepressants were each associated with an increased VTE risk; 1.16 (1.06-1.27), 1.12 (1.02-1.23), and 1.59 (1.21-2.09), respectively. In pooled analysis of three studies that compared patients with depression versus individuals without depression, the RR for VTE was 1.31 (1.13-1.53). CONCLUSIONS: Pooled observational evidence suggests that depression and use of antidepressants are each associated with an increased VTE risk. The effect of antidepressant drugs on VTE may be a class effect. The mechanistic pathways underlying these associations deserve further evaluation. Systematic review registration: PROSPERO 2018: CRD42018095595 Key messages Emerging evidence suggests that depression and antidepressant use may be associated with venous thromboembolism (VTE) risk, but the evidence is conflicting. This first systematic review and meta-analysis of observational studies shows that depression and use of antidepressants are each associated with an increased risk of VTE. There may be a class effect of antidepressant drugs on VTE.