Antipsychotic drug exposure and risk of venous thromboembolism and pulmonary embolism: a meta-analysis_Chinese Journal of Evidence-Based Medicine

Authors：

CHEN Hong ¹ ,  FENG Jian ²

1. Department of Internal Medicine, the Fourth People Hospital of Nantong, Nantong, 226005, P.R.China;
2. Department of Respiratory Medicine, the Affiliated Hospital of Nantong University, Nantong, 226001, P.R.China;

Corresponding author：

FENG Jian, Email: 363969667@qq.com

Keywords：

Antipsychotic drugs; Venous thromboembolism; Pulmonary embolism; Meta-analysis

DOI：

10.7507/1672-2531.201610069

Video：

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Objective To investigate whether antipsychotic drugs will increase the risk of venous thromboembolism (VTE) and pulmonary embolism (PE), and to provide evidence for the prevention of VTE and PE in patients with APs exposure. Methods Databases including PubMed, Web of Science, CNKI, VIP and Elsevier were searched from inception to July 2016 to collect case-control studies and cohort studies on the association between APs exposure and the risk of VTE and PE. The literature were screened according to the inclusion and exclusion criteria, the data were extracted and the bias risk of the included studies were evaluated by two reviewers independently. The Meta-analysis was performed by using Stata 12 software. Results Nineteen studies were included. The results of meta-analysis showed that APs exposure was associated with VTE (OR=1.50, 95%CI 1.30 to 1.74,P<0.001). Exposure to low-potency FGA (OR=2.28, 95%CI 1.02 to 5.10,P=0.045), high-potency FGA (OR=1.68, 95%CI 1.37 to 2.05,P<0.001) and SGA (OR=1.74, 95%CI 1.24 to 2.44,P=0.001) revealed an increased risk of VTE. Exposure to APs also signi?cantly increase the risk of PE (OR=3.69, 95%CI 1.23 to 11.07,P=0.02), especially exposure to FGA (OR=2.54, 95%CI 1.22 to 5.32,P=0.013), but exposure to SGA could not revealed an increased risk of PE. Conclusion FGA and SGA exposure maybe associated with an increase in the risk of developing VTE. And exposure to the FGA could increase the risk of PE. The occurrence of VTE and PE should be monitored when taking Aps.

Citation： CHENHong, FENGJian. Antipsychotic drug exposure and risk of venous thromboembolism and pulmonary embolism: a meta-analysis. Chinese Journal of Evidence-Based Medicine, 2017, 17(2): 162-171. doi: 10.7507/1672-2531.201610069 Copy

1.	Rojo LE, Gaspar PA, Silva H,et al. Metabolic syndrome and obesity among users of second generation antipsychotics: a global challenge for modern psychopharmacology. Pharmacol Res, 2015, 101: 74-85.
2.	Jesus C, Jesus I, Agius M. A review of the evidence for the use of metformin in the treatment of metabolic syndrome caused by antipsychotics. Psychiatr Danub, 2015, 27(Suppl 1): 489-491.
3.	Kyrle PA, Eichinger S. Deep vein thrombosis. Lancet, 2005, 365(9465): 1163-1174.
4.	Cohen AT, Dobromiski M, Gurwith MM. Managing pulmonary embolism from presentation to extended treatment. Thromb Res, 2014, 133(2): 139-148.
5.	Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet, 2012, 379(9828): 1835-1846.
6.	Maurice H. Des complications phlepitiques au cours des traitements par les neuroleptiques. Encephale, 1956, 45(4): 797-801.
7.	Grahmann H, Suchenwirth R. Thrombose hazard in chlorpromazine and reserpine therapy of endogenous psychosis. Nervenazt, 1959, 30(5): 224-225.
8.	Mahmodian M. Ursachen der lungenembolie bei psychisch und neurologisch Kranken. Rrch Psichiatr Nervenkr, 1963, 204: 229-244.
9.	Meier-Ewert K, Baumgart H, Friedenberg P. Thromboembolism complications in neuro- and thymoleptic therapy. Dtsch Med Wochenschr, 1967, 92(47): 2174-2178.
10.	Walker AM, Lanza LL, Arellano F,et al. Mortality in current and former users of clozapine. Epidemiology, 1997, 8(6): 671-677.
11.	Hägg S, Spigset O, Söderström TG. Association of venous thromboembolism and clozapine. Lancet, 2000, 355(9210): S1155-S1156.
12.	王建秋, 刘广敬, 路以荣. 精神分裂症合并肺栓塞一例. 中华精神科杂志, 2006, 39(3): 140.
13.	刘人申, 汪作为, 张少平. 氯氮平致肺栓塞 1 例. 临床精神医学杂志, 2007, 17(1): 64.
14.	Zhang R, Dong L, Shao F,et al. Antipsychotics and venous thromboembolism risk: a meta-analysis. Pharmacopsychiatry, 2011, 44(5): 183-188.
15.	Barbui C, Conti V, Cipriani A. Antipsychotic drug exposure and risk of venous thromboembolism: a systematic review and meta-analysis of observational studies. Drug Saf, 2014, 37(2): 79-90.
16.	Greenland S. Quantitative methods in the review of epidemiologic literature. Epidemiol Rev, 1987, 9(1): 1-30.
17.	Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med, 2002, 21(11): 1539-1558.
18.	Wu CS, Lin CC, Chang CM,et al. Antipsychotic treatment and the occurrence of venous thromboembolism: a 10-year nationwide registry study. J Chin Psychiatry, 2013, 74(9): 918-924.
19.	Schmedt N, Garbe E. Antipsychotic drug use and the risk of venous thromboembolism in elderly patients with dementia. J Clin Psychopharmacol, 2013, 33(6): 753-758.
20.	Ishiguro C, Wang X, Li L,et al. Antipsychotic drugs and risk of idiopathic venous thromboembolism: a nested case-control study using the CPRD. Pharmacoepidemiol Drug Saf, 2014, 23(11): 1168-1175.
21.	Wang MT, Liou JT, Huang YW ,et al. Use of antipsychotics and risk of venous thromboembolism in postmenopausal women. Thromb Haemost, 2016, 115(6): 1209-1219.
22.	Masopust J, Maly R, Urban A,et al. Antipsychotic drugs as a risk factor for venous thromboembolism. Int J Psych Clin Pract, 2007, 11(3): 246-249.
23.	Zornberg GL, Jick H. Antipsychotic drug use and risk of first-time idiopathic venous thromboembolism: a case-control study. Lancet, 2000, 356(9237): 1219-1223.
24.	Thomassen R, Vandenbroucke JP, Rosendaal FR. Antipsychotic medication and venous thrombosis. Br J Psychiatry, 2001, 179: 63-66.
25.	Liperoti R, Pedone C, Lapane KL,et al. Venous thromboembolism among elderly patients treated with atypical and conventional antipsychotic agents. Arch Intern Med, 2005, 165(22): 2677-2682.
26.	Lacut K, Le GG, Couturaud F,et al. Association between antipsychotic drugs, antidepressant drugs and venous thromboembolism: results from the EDITH case-control study. Fundam Clin Pharmacol, 2007, 21(6): 643-650.
27.	Parker C, Coupland C, Hippisley-Cox J. Antipsychotic drugs and risk of venous thromboembolism: nested case–control study. BMJ, 2010, 341: c4245.
28.	Hippisley-Cox J, Coupland C. Development and validation of risk prediction algorithm (QThrombosis) to estimate future risk of venous thromboembolism: prospective cohort study. BMJ, 2011, 343: d4656.
29.	Jonsson AK, Horvath-Puho E, Hagg S,et al. Antipsychotics and risk of venous thromboembolism: a population-based case-control study. Clin Epidemiol, 2009, 1(9): 19-26.
30.	Ray JG, Mamdani MM, Yeo EL. Antipsychotic and antidepressant drug use in the elderly and the risk of venous thromboembolism. Thromb Haemost, 2002, 88(2): 205-209.
31.	Kleijer BC, Heerdink ER, Egberts TC,et al. Antipsychotic drug use and the risk of venous thromboembolism in elderly patients. J Clin Psychopharmacol, 2010, 30(5): 526-530.
32.	Allenet B, Schmidlin S, Genty C,et al. Antipsychotic drugs and risk of pulmonary embolism. Pharmacoepidemiol Drug Saf, 2012, 21(1): 42-48.
33.	Conti Valentino, Venegoni Manro, Cocci Alfredo,et al. Antipsychotic drug exposure and risk of pulmonary embolism: a population-based, nested case-control study. BMC Psychiatry, 2015, 1592.
34.	Hamanaka S, Kamijo Y, Nagai T,et al. Massive pulmonary thromboembolism demonstrated at necropsy in Japanese psychiatric patients treated with neuroleptics including atypical antipsychotics. Circ J, 2004, 68(9): 850-852.
35.	Parkin L, Skegg DC, Herbison GP,et al. Psychotropic drugs and fatal pulmonary embolism. Pharmacoepidemiol Drug Saf, 2003, 12(8): 647-652.
36.	Jonsson AK, Brudin L, Ahlner J,et al. Antipsychotics associated with pulmonary embolism in a Swedish medicolegal autopsy series. Int Clin Psychopharmacol, 2008, 23(5): 263-268.
37.	Kamijo Y, Soma K, Nagai T,et al. Acute massive pulmonary thromboembolism associated with risperidone and conventional phenothiazines. Circ J, 2003, 67(4): 46-48.
38.	Skokou M, Gourzis P. Pulmonary embolism related to amisulpride treatment: a case report. Case Rep Psychiatry, 2013, 2013: 718950.
39.	Jönsson AK, Spigset O, Hagg S. Venous thromboembolism in recipients of antipsychotics: incidence, mechanisms and management. CNS Drugs, 2012, 26(8): 649-662.
40.	Hagg S, Jonsson AK, Spigset O. Risk of venous thromboembolism due to antipsychotic drug therapy. Drug Saf, 2009, 8(5): 537-547.
41.	Hagg S, Spigset O. Antipsychotic-induced venous thromboembolism: a review of the evidence. CNS Drugs, 2002, 16(11): 765-776.

1. Rojo LE, Gaspar PA, Silva H,et al. Metabolic syndrome and obesity among users of second generation antipsychotics: a global challenge for modern psychopharmacology. Pharmacol Res, 2015, 101: 74-85.
2. Jesus C, Jesus I, Agius M. A review of the evidence for the use of metformin in the treatment of metabolic syndrome caused by antipsychotics. Psychiatr Danub, 2015, 27(Suppl 1): 489-491.
3. Kyrle PA, Eichinger S. Deep vein thrombosis. Lancet, 2005, 365(9465): 1163-1174.
4. Cohen AT, Dobromiski M, Gurwith MM. Managing pulmonary embolism from presentation to extended treatment. Thromb Res, 2014, 133(2): 139-148.
5. Goldhaber SZ, Bounameaux H. Pulmonary embolism and deep vein thrombosis. Lancet, 2012, 379(9828): 1835-1846.
6. Maurice H. Des complications phlepitiques au cours des traitements par les neuroleptiques. Encephale, 1956, 45(4): 797-801.
7. Grahmann H, Suchenwirth R. Thrombose hazard in chlorpromazine and reserpine therapy of endogenous psychosis. Nervenazt, 1959, 30(5): 224-225.
8. Mahmodian M. Ursachen der lungenembolie bei psychisch und neurologisch Kranken. Rrch Psichiatr Nervenkr, 1963, 204: 229-244.
9. Meier-Ewert K, Baumgart H, Friedenberg P. Thromboembolism complications in neuro- and thymoleptic therapy. Dtsch Med Wochenschr, 1967, 92(47): 2174-2178.
10. Walker AM, Lanza LL, Arellano F,et al. Mortality in current and former users of clozapine. Epidemiology, 1997, 8(6): 671-677.
11. Hägg S, Spigset O, Söderström TG. Association of venous thromboembolism and clozapine. Lancet, 2000, 355(9210): S1155-S1156.
12. 王建秋, 刘广敬, 路以荣. 精神分裂症合并肺栓塞一例. 中华精神科杂志, 2006, 39(3): 140.
13. 刘人申, 汪作为, 张少平. 氯氮平致肺栓塞 1 例. 临床精神医学杂志, 2007, 17(1): 64.
14. Zhang R, Dong L, Shao F,et al. Antipsychotics and venous thromboembolism risk: a meta-analysis. Pharmacopsychiatry, 2011, 44(5): 183-188.
15. Barbui C, Conti V, Cipriani A. Antipsychotic drug exposure and risk of venous thromboembolism: a systematic review and meta-analysis of observational studies. Drug Saf, 2014, 37(2): 79-90.
16. Greenland S. Quantitative methods in the review of epidemiologic literature. Epidemiol Rev, 1987, 9(1): 1-30.
17. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med, 2002, 21(11): 1539-1558.
18. Wu CS, Lin CC, Chang CM,et al. Antipsychotic treatment and the occurrence of venous thromboembolism: a 10-year nationwide registry study. J Chin Psychiatry, 2013, 74(9): 918-924.
19. Schmedt N, Garbe E. Antipsychotic drug use and the risk of venous thromboembolism in elderly patients with dementia. J Clin Psychopharmacol, 2013, 33(6): 753-758.
20. Ishiguro C, Wang X, Li L,et al. Antipsychotic drugs and risk of idiopathic venous thromboembolism: a nested case-control study using the CPRD. Pharmacoepidemiol Drug Saf, 2014, 23(11): 1168-1175.
21. Wang MT, Liou JT, Huang YW ,et al. Use of antipsychotics and risk of venous thromboembolism in postmenopausal women. Thromb Haemost, 2016, 115(6): 1209-1219.
22. Masopust J, Maly R, Urban A,et al. Antipsychotic drugs as a risk factor for venous thromboembolism. Int J Psych Clin Pract, 2007, 11(3): 246-249.
23. Zornberg GL, Jick H. Antipsychotic drug use and risk of first-time idiopathic venous thromboembolism: a case-control study. Lancet, 2000, 356(9237): 1219-1223.
24. Thomassen R, Vandenbroucke JP, Rosendaal FR. Antipsychotic medication and venous thrombosis. Br J Psychiatry, 2001, 179: 63-66.
25. Liperoti R, Pedone C, Lapane KL,et al. Venous thromboembolism among elderly patients treated with atypical and conventional antipsychotic agents. Arch Intern Med, 2005, 165(22): 2677-2682.
26. Lacut K, Le GG, Couturaud F,et al. Association between antipsychotic drugs, antidepressant drugs and venous thromboembolism: results from the EDITH case-control study. Fundam Clin Pharmacol, 2007, 21(6): 643-650.
27. Parker C, Coupland C, Hippisley-Cox J. Antipsychotic drugs and risk of venous thromboembolism: nested case–control study. BMJ, 2010, 341: c4245.
28. Hippisley-Cox J, Coupland C. Development and validation of risk prediction algorithm (QThrombosis) to estimate future risk of venous thromboembolism: prospective cohort study. BMJ, 2011, 343: d4656.
29. Jonsson AK, Horvath-Puho E, Hagg S,et al. Antipsychotics and risk of venous thromboembolism: a population-based case-control study. Clin Epidemiol, 2009, 1(9): 19-26.
30. Ray JG, Mamdani MM, Yeo EL. Antipsychotic and antidepressant drug use in the elderly and the risk of venous thromboembolism. Thromb Haemost, 2002, 88(2): 205-209.
31. Kleijer BC, Heerdink ER, Egberts TC,et al. Antipsychotic drug use and the risk of venous thromboembolism in elderly patients. J Clin Psychopharmacol, 2010, 30(5): 526-530.
32. Allenet B, Schmidlin S, Genty C,et al. Antipsychotic drugs and risk of pulmonary embolism. Pharmacoepidemiol Drug Saf, 2012, 21(1): 42-48.
33. Conti Valentino, Venegoni Manro, Cocci Alfredo,et al. Antipsychotic drug exposure and risk of pulmonary embolism: a population-based, nested case-control study. BMC Psychiatry, 2015, 1592.
34. Hamanaka S, Kamijo Y, Nagai T,et al. Massive pulmonary thromboembolism demonstrated at necropsy in Japanese psychiatric patients treated with neuroleptics including atypical antipsychotics. Circ J, 2004, 68(9): 850-852.
35. Parkin L, Skegg DC, Herbison GP,et al. Psychotropic drugs and fatal pulmonary embolism. Pharmacoepidemiol Drug Saf, 2003, 12(8): 647-652.
36. Jonsson AK, Brudin L, Ahlner J,et al. Antipsychotics associated with pulmonary embolism in a Swedish medicolegal autopsy series. Int Clin Psychopharmacol, 2008, 23(5): 263-268.
37. Kamijo Y, Soma K, Nagai T,et al. Acute massive pulmonary thromboembolism associated with risperidone and conventional phenothiazines. Circ J, 2003, 67(4): 46-48.
38. Skokou M, Gourzis P. Pulmonary embolism related to amisulpride treatment: a case report. Case Rep Psychiatry, 2013, 2013: 718950.
39. Jönsson AK, Spigset O, Hagg S. Venous thromboembolism in recipients of antipsychotics: incidence, mechanisms and management. CNS Drugs, 2012, 26(8): 649-662.
40. Hagg S, Jonsson AK, Spigset O. Risk of venous thromboembolism due to antipsychotic drug therapy. Drug Saf, 2009, 8(5): 537-547.
41. Hagg S, Spigset O. Antipsychotic-induced venous thromboembolism: a review of the evidence. CNS Drugs, 2002, 16(11): 765-776.

Chinese Journal of Evidence-Based Medicine

Antipsychotic drug exposure and risk of venous thromboembolism and pulmonary embolism: a meta-analysis

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