Association Between Antidepressant Use and Risk of Venous Thromboembolism: A Systematic Review and Meta-Analysis
Abstract
1. Introduction
2. Materials and Methods
2.1. Search Strategy and Databases
2.2. Study Inclusion and Exclusion Criteria
2.3. Data Extraction and Quality Assessment
2.4. Statistical Analysis
3. Results
3.1. Study Selection and Characteristics
3.2. Association Between Antidepressants and VTE
3.3. Subgroup Analysis
3.4. Sensitivity Analysis and Publication Bias
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AF | atrial fibrillation |
ASA | acetylsalicylic acid (aspirin) |
BMI | body mass index |
BP | blood pressure |
BZD | benzodiazepine |
CHD | coronary heart disease |
CHF | congestive heart failure |
CVA | cerebrovascular accident |
DM | diabetes mellitus |
DVT | deep vein thrombosis |
GPRD | general practice research database |
HF | heart failure |
HRT | hormone replacement therapy |
HTN | hypertension |
IBD | inflammatory bowel disease |
LD | liver disease |
MAOI | monoamine oxidase inhibitor |
MI | myocardial infarction |
NDRI | norepinephrine-dopamine reuptake inhibitor |
NSAIDs | nonsteroidal anti-inflammatory drugs |
OC | oral contraceptive |
PE | pulmonary embolism |
PVD | peripheral vascular disease |
SNRI | serotonin-norepinephrine reuptake inhibitor |
SSRI | selective serotonin reuptake inhibitor |
TCA | tricyclic antidepressant |
UK | United Kingdom |
USA | United States of America |
UTI | urinary tract infection |
VTE | venous thromboembolism. |
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Study | Country | Study Design | No. of Patients | Female (%) | Age | Types of Antidepressants | NOS | Covariate |
---|---|---|---|---|---|---|---|---|
Aune et al. (2024) [31] | Norway, Sweden | case-crossover | 48,192 | 53.2 | ≥30 | Antidepressant (sertraline, escitalopram, mianserin, and mirtazapine) | 8 | No covariate adjusted |
Bouyer et al. (2018) [32] | France | cohort | 323,737 | 48.6 | ≥18 | Not Classified | 8 | Age, obesity, active cancer, previous thromboembolism, severe paralysis, renal disease, psychiatric disease, and use of OC |
Bruun et al. (2018) [28] | Denmark | prospective cohort | 68,487 | 71.2 | ≥18 | SSRI | 8 | Age, gender, marital status, operation year, MI, CHF, PVD, dementia, chronic pulmonary disease, connective tissue disease, ulcer disease, LD, DM, hemiplegia, moderate to severe renal disease, cancer, NSAIDs, corticosteroids, anticoagulants, statins, non-SSRI antidepressants, antipsychotics, and clustering by unit setting |
Eckert et al. (2024) [33] | Denmark | nested case control study | 15,193 | 100 | ≥45 | SSRI, TCA | 8 | Age at cohort entry, income quartiles, ischemic heart disease, atrial fibrillation, valvular disease, history of cancer, osteoporosis, diabetes, chronic obstructive pulmonary disease, history of lung cancer, loop diuretic use, systemic corticosteroids, SSRI, TCA, antipsychotics, opioids, statins, ASA, vitamin K antagonists, novel oral anticoagulants, insulin therapy, diuretics, renin-angiotensin inhibitors, and systemic HRT |
Fu et al. (2022) [34] | USA | retrospective cohort study | 13,831 | 53.2 | <60 | Not Classified | 8 | Age, sex, geographic region, insurance type, year at index, index VTE type, time from index VTE to treatment, comorbid conditions, concomitant medications, and procedures |
Jick et al. (2008) [30] | UK | nested case control study | 3867 | 65.2 | ≥18 | SSRI, TCA, others | 8 | Smoking, BMI, OC, HRT, and antipsychotic agents |
Lacut et al. (2007) [35] | France | case control study | 1354 | 56.7 | 50–64 | Not Classified | 7 | Age, gender, BMI, factor V Leiden, and prothrombin G20210A gene variation |
Lee et al. (2015) [26] | Taiwan | retrospective cohort | 105,822 | 61.6 | 15–59 | SSRI, non-SSRI | 8 | Age, sex, AF, HTN, DM, CVA, HF, lower leg fracture or operations, and cancers |
Marchena et al. (2020) [36] | Spain | retrospective cohort | 49,007 | 49.5 | 63 | Not Classified | 8 | Gender, chronic lung disease, anemia, cancer, transient risk factors for VTE, prior VTE, and initial VTE presentation (PE vs. DVT) |
Parkin et al. (2003) [37] | New Zealand | case control study | 375 | 68 | ≥65 | Not Classified | 9 | Age, sex, weight, OC, and HRT |
Parkin et al. (2017) [27] | UK | prospective cohort | 734,092 | 100 | ≥65 | SSRI, TCA, others | 9 | Age, BMI, smoking, alcohol consumption, frequency of strenuous physical activity, HTN, DM, high BP, and socioeconomic status, and stratified by recruitment region |
Ray et al. (2002) [38] | Canada | retrospective cohort | 131,196 | 63.5 | ≤70 | SSRI, TCA | 7 | Sex, hospitalization, current residence within a long-term care facility, newly diagnosed cancer or concurrent prescription of either lithium or estrogen, and aspirin or warfarin |
Schink et al. (2022) [39] | German | nested case control study | 12,826 | 100 | 10–19 | Not Classified | 9 | Age, other comorbidities, potential other (off-label) indications, lifestyle factors, and co-medication |
Stuijver et al. (2013) [40] | Netherlands | population based case control study | 21,297 | 57 | 17–73 | Not Classified | 8 | Age, sex, hospitalizations (for malignancy, pregnancy, trauma, surgery, IBD, inflammatory arthritis, chronic respiratory failure), use of anticoagulants, drugs for respiratory diseases, antibiotics, antidepressants, and HRT and OC within 90 days prior to the index date |
Svendsen et al. (2021) [41] | Denmark | case control study | 68,696 | 100 | ≥55 | Not Classified | 8 | Age, frequency of recurrent UTI, obesity, venous insufficiency, medication to treat cardiovascular disease, and history of VTE |
Wu et al. (2013a) [29] | Taiwan | nested case control study | 13,110 | 52.3 | ≥20 | TCA, SSRI, SNRI, MAOI, NDRI, multiple users | 8 | Age, sex, and disease risk score |
Wu et al. (2013b) [42] | Taiwan | case control study | 15,128 | 51.8 | ≥16 | Not Classified | 9 | CHD, HF, PVD, mood/psychotic disorders, hormones, lipid agents, mood stabilizers, antithrombotics, BZD, and clinic visits and hospitalizations prior 1 year |
Zornberg et al. (2000) [43] | UK | population based nested case control study | 214 | 76 | ≥18 | Not Classified | 8 | Age, sex, general practice, index date, years of recorded history in the GPRD before the index date, BMI, smoking status, HTN, and estrogen use |
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Uh, M.; Rhee, H.Y.; Rhew, K. Association Between Antidepressant Use and Risk of Venous Thromboembolism: A Systematic Review and Meta-Analysis. J. Clin. Med. 2025, 14, 5512. https://doi.org/10.3390/jcm14155512
Uh M, Rhee HY, Rhew K. Association Between Antidepressant Use and Risk of Venous Thromboembolism: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine. 2025; 14(15):5512. https://doi.org/10.3390/jcm14155512
Chicago/Turabian StyleUh, Minyoung, Hey Young Rhee, and Kiyon Rhew. 2025. "Association Between Antidepressant Use and Risk of Venous Thromboembolism: A Systematic Review and Meta-Analysis" Journal of Clinical Medicine 14, no. 15: 5512. https://doi.org/10.3390/jcm14155512
APA StyleUh, M., Rhee, H. Y., & Rhew, K. (2025). Association Between Antidepressant Use and Risk of Venous Thromboembolism: A Systematic Review and Meta-Analysis. Journal of Clinical Medicine, 14(15), 5512. https://doi.org/10.3390/jcm14155512