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: CRD42018095595Key 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.

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.