Login Register Cart 0
Systematic Review Article

The Association and Influencing Factors between Antipsychotics Exposure and the Risk of VTE and PE: A Systematic Review and Meta-analysis

Author(s): Luqi Dai, Qiunan Zuo, Fangying Chen, Lei Chen* and Yongchun Shen*

Volume 21, Issue 9, 2020

Page: [930 - 942] Pages: 13

DOI: 10.2174/1389450121666200422084414

Price: $65

Abstract

Background: Different clinical studies have given inconsistent results on whether the use of antipsychotics increases the risk of thromboembolism. In this paper, we reviewed all relevant literature to provide suggestions for clinical diagnosis and treatment.

Methods: PubMed, Web of Science, EMBASE, MEDLINE, Cochrane and Scopus databases were thoroughly searched up to June 2019. Two researchers independently searched the literature, extracted data. Data were analyzed by Stata 12.0 software.

Results: A total of 22 studies involving 31514226 subjects were included. This meta-analysis showed that patients taking the first- or second-generation antipsychotics had a higher risk of venous thromboembolism and pulmonary embolism than those who did not, and low potency first-generation agents increased the risk of venous thromboembolism more than high potency antipsychotics, and olanzapine, clozapine, haloperidol, perphenazine and risperidone also significantly increased the risk of it. The risk of venous thrombosis in obese people was higher than that in overweight people, patients not less than 65 years old had an increased risk compared with younger patients. In addition, women taking antipsychotics had a higher risk of pulmonary embolism than men.

Conclusion: The use of antipsychotics will increase the risk of venous thromboembolism and pulmonary embolism, which will be affected by the type of antipsychotics and patient characteristics.

Keywords: Antipsychotic drugs, venous thromboembolism, pulmonary embolism, systematic review, meta-analysis.

« Previous
Graphical Abstract

[1]
Alexopoulos GS, Streim J, Carpenter D, Docherty JP. Using antipsychotic agents in older patients. The Journal of clinical psychiatry 2004; 65(Suppl 2): 5-99 discussion 100-102; quiz 103-104
[2]
Kane JM, Leucht S, Carpenter D, Docherty JP. Expert Consensus Panel for Optimizing Pharmacologic Treatment of Psychotic Disorders. The expert consensus guideline series. Optimizing pharmacologic treatment of psychotic disorders. Introduction: methods, commentary, and summary. J Clin Psychiatry 2003; 64(Suppl. 12): 5-19.
[PMID: 14640142]
[3]
Stroup TS, Gray N. Management of common adverse effects of antipsychotic medications. World Psychiatry 2018; 17(3): 341-56.
[http://dx.doi.org/10.1002/wps.20567] [PMID: 30192094]
[4]
Lapeyre-Mestre M. A Review of Adverse Outcomes Associated with Psychoactive Drug Use in Nursing Home Residents with Dementia. Drugs Aging 2016; 33(12): 865-88.
[http://dx.doi.org/10.1007/s40266-016-0414-x] [PMID: 27812994]
[5]
Mahan CE, Borrego ME, Woersching AL, et al. Venous thromboembolism: annualised United States models for total, hospital-acquired and preventable costs utilising long-term attack rates. Thromb Haemost 2012; 108(2): 291-302.
[PMID: 22739656]
[6]
White RH. The epidemiology of venous thromboembolism. Circulation 2003; 107(23)(Suppl. 1): I4-8.
[PMID: 12814979]
[7]
Rosendaal FR. Venous thrombosis: a multicausal disease. Lancet 1999; 353(9159): 1167-73.
[http://dx.doi.org/10.1016/S0140-6736(98)10266-0] [PMID: 10209995]
[8]
Nielsen JD. The incidence of pulmonary embolism during deep vein thrombosis. Phlebology 2013; 28(Suppl. 1): 29-33.
[http://dx.doi.org/10.1177/0268355513477009] [PMID: 23482531]
[9]
Jackson JW, Schneeweiss S, VanderWeele TJ, Blacker D. Quantifying the role of adverse events in the mortality difference between first and second-generation antipsychotics in older adults: systematic review and meta-synthesis. PLoS One 2014; 9(8)e105376
[http://dx.doi.org/10.1371/journal.pone.0105376] [PMID: 25140533]
[10]
Keles E, Ulasli SS, Basaran NC, Babaoglu E, Koksal D. Acute massive pulmonary embolism associated with olanzapine. TheAmerican journal of emergency medicine 2017; 35(10): 1582. e1585
[http://dx.doi.org/10.1016/j.ajem.2017.07.026]
[11]
Gallerani M, Imberti D, Mari E, Marra A, Manfredini R. Risperidone and pulmonary embolism: a harmful association? Case series and review of the literature. Acta Neuropsychiatr 2012; 24(6): 361-8.
[http://dx.doi.org/10.1111/j.1601-5215.2012.00641.x] [PMID: 25287179]
[12]
Sarvaiya N, Lapitskaya Y, Dima L, Manu P. Clozapine-Associated Pulmonary Embolism: A High-Mortality, Dose-Independent and Early-Onset Adverse Effect. Am J Ther 2018; 25(4): e434-8.
[http://dx.doi.org/10.1097/MJT.0000000000000806] [PMID: 29985823]
[13]
Solmi M, Murru A, Pacchiarotti I, et al. Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review. Ther Clin Risk Manag 2017; 13: 757-77.
[http://dx.doi.org/10.2147/TCRM.S117321] [PMID: 28721057]
[14]
Dietrich-Muszalska A, Rabe-Jablonska J, Nowak P, Kontek B. The first- and second-generation antipsychotic drugs affect ADPinduced platelet aggregation. The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry 2010; 11(2 Pt 2): 268-75.
[15]
Wu CC, Tsai FM, Chen ML, et al. Antipsychotic Drugs Inhibit Platelet Aggregation via P2Y 1 and P2Y 12 Receptors. BioMed Res Int 2016; 20162532371
[PMID: 27069920]
[16]
Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315(7109): 629-34.
[http://dx.doi.org/10.1136/bmj.315.7109.629] [PMID: 9310563]
[17]
Zornberg GL, Jick H. Antipsychotic drug use and risk of first-time idiopathic venous thromboembolism: a case-control study. Lancet 2000; 356(9237): 1219-23.
[http://dx.doi.org/10.1016/S0140-6736(00)02784-7] [PMID: 11072939]
[18]
Thomassen R, Vandenbroucke JP, Rosendaal FR. Antipsychotic medication and venous thrombosis. Br J Psychiatry 2001; 179: 63-6.
[http://dx.doi.org/10.1192/bjp.179.1.63] [PMID: 11435271]
[19]
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): 205-9.
[PMID: 12195690]
[20]
Parkin L, Skegg DC, Herbison GP, Paul C. Psychotropic drugs and fatal pulmonary embolism. Pharmacoepidemiol Drug Saf 2003; 12(8): 647-52.
[http://dx.doi.org/10.1002/pds.841] [PMID: 14762980]
[21]
Hamanaka S, Kamijo Y, Nagai T, et al. Massive pulmonary thromboembolism demonstrated at necropsy in Japanese psychiatric patients treated with neuroleptics including atypical antipsychotics. Circulation journal : official journal of the Japanese Circulation Society 2004; 68(9): 850-2.
[http://dx.doi.org/10.1253/circj.68.850]
[22]
Liperoti R, Pedone C, Lapane KL, Mor V, Bernabei R, Gambassi G. Venous thromboembolism among elderly patients treated with atypical and conventional antipsychotic agents. Arch Intern Med 2005; 165(22): 2677-82.
[http://dx.doi.org/10.1001/archinte.165.22.2677] [PMID: 16344428]
[23]
Lacut K, Le Gal G, 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): 643-50.
[http://dx.doi.org/10.1111/j.1472-8206.2007.00515.x] [PMID: 18034665]
[24]
Masopust J, Malý R, Urban A, Hosák L, Cermáková E. Antipsychotic drugs as a risk factor for venous thromboembolism. Int J Psychiatry Clin Pract 2007; 11(3): 246-9.
[http://dx.doi.org/10.1080/13651500601017357] [PMID: 24941366]
[25]
Jönsson AK, Brudin L, Ahlner J, Hedenmalm K, Eriksson A, Hägg S. Antipsychotics associated with pulmonary embolism in a Swedish medicolegal autopsy series. Int Clin Psychopharmacol 2008; 23(5): 263-8.
[http://dx.doi.org/10.1097/YIC.0b013e3282fe9d44] [PMID: 18703935]
[26]
Jönsson AK, Horváth-Puhó E, Hägg S, Pedersen L, Sørensen HT. Antipsychotics and risk of venous thromboembolism: A population-based case-control study. Clin Epidemiol 2009; 1: 19-26.
[http://dx.doi.org/10.2147/CLEP.S4969] [PMID: 20865083]
[27]
Kleijer BC, Heerdink ER, Egberts TC, Jansen PA, van Marum RJ. Antipsychotic drug use and the risk of venous thromboembolism in elderly patients. J Clin Psychopharmacol 2010; 30(5): 526-30.
[http://dx.doi.org/10.1097/JCP.0b013e3181f0e87d] [PMID: 20814323]
[28]
Parker C, Coupland C, Hippisley-Cox J. Antipsychotic drugs and risk of venous thromboembolism: nested case-control study. BMJ 2010; 341: c4245.
[http://dx.doi.org/10.1136/bmj.c4245] [PMID: 20858909]
[29]
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.
[http://dx.doi.org/10.1136/bmj.d4656] [PMID: 21846713]
[30]
Allenet B, Schmidlin S, Genty C, Bosson JL. Antipsychotic drugs and risk of pulmonary embolism. Pharmacoepidemiol Drug Saf 2012; 21(1): 42-8.
[http://dx.doi.org/10.1002/pds.2210] [PMID: 22052683]
[31]
Schmedt N, Garbe E. Antipsychotic drug use and the risk of venous thromboembolism in elderly patients with dementia. J Clin Psychopharmacol 2013; 33(6): 753-8.
[http://dx.doi.org/10.1097/JCP.0b013e3182a412d5] [PMID: 24052055]
[32]
Wu CS, Lin CC, Chang CM, et al. Antipsychotic treatment and the occurrence of venous thromboembolism: a 10-year nationwide registry study. J Clin Psychiatry 2013; 74(9): 918-24.
[http://dx.doi.org/10.4088/JCP.12m08117] [PMID: 24107765]
[33]
Ishiguro C, Wang X, Li L, Jick S. Antipsychotic drugs and risk of idiopathic venous thromboembolism: a nested case-control study using the CPRD. Pharmacoepidemiol Drug Saf 2014; 23(11): 1168-75.
[http://dx.doi.org/10.1002/pds.3699] [PMID: 25195779]
[34]
Conti V, Venegoni M, Cocci A, Fortino I, Lora A, Barbui C. Antipsychotic drug exposure and risk of pulmonary embolism: a population-based, nested case-control study. BMC Psychiatry 2015; 15: 92.
[http://dx.doi.org/10.1186/s12888-015-0479-9] [PMID: 25924683]
[35]
Vigod SN, Gomes T, Wilton AS, Taylor VH, Ray JG. Antipsychotic drug use in pregnancy: high dimensional, propensity matched, population based cohort study. BMJ 2015; 350: h2298.
[http://dx.doi.org/10.1136/bmj.h2298] [PMID: 25972273]
[36]
Wang MT, Liou JT, Huang YW, et al. Use of antipsychotics and risk of venous thromboembolism in postmenopausal women. A population-based nested case-control study. Thromb Haemost 2016; 115(6): 1209-19.
[http://dx.doi.org/10.1160/TH15-11-0895] [PMID: 26941052]
[37]
Dennis M, Shine L, John A, et al. Risk of Adverse Outcomes for Older People with Dementia Prescribed Antipsychotic Medication: A Population Based e-Cohort Study. Neurol Ther 2017; 6(1): 57-77.
[http://dx.doi.org/10.1007/s40120-016-0060-6] [PMID: 28054240]
[38]
Ferraris A, Szmulewicz AG, Vazquez FJ, Vollmer WM, Angriman F. Antipsychotic Use Among Adult Outpatients and Venous Thromboembolic Disease: A Retrospective Cohort Study. J Clin Psychopharmacol 2017; 37(4): 405-11.
[http://dx.doi.org/10.1097/JCP.0000000000000738] [PMID: 28622161]
[39]
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.
[http://dx.doi.org/10.1007/s40264-013-0127-6] [PMID: 24403009]
[40]
Zhang R, Dong L, Shao F, Tan X, Ying K. Antipsychotics and venous thromboembolism risk: a meta-analysis. Pharmacopsychiatry 2011; 44(5): 183-8.
[http://dx.doi.org/10.1055/s-0031-1280814] [PMID: 21739416]
[41]
De Clerck F, Somers Y, Mannaert E, Greenspan A, Eerdekens M. In vitro effects of risperidone and 9-hydroxy-risperidone on human platelet function, plasma coagulation, and fibrinolysis. Clin Ther 2004; 26(8): 1261-73.
[http://dx.doi.org/10.1016/S0149-2918(04)80097-3] [PMID: 15476907]
[42]
Axelsson S, Hägg S, Eriksson AC, Lindahl TL, Whiss PA. In vitro effects of antipsychotics on human platelet adhesion and aggregation and plasma coagulation. Clin Exp Pharmacol Physiol 2007; 34(8): 775-80.
[http://dx.doi.org/10.1111/j.1440-1681.2007.04650.x] [PMID: 17600556]
[43]
Newcomer JW. Second-generation (atypical) antipsychotics and metabolic effects: a comprehensive literature review. CNS Drugs 2005; 19(Suppl. 1): 1-93.
[http://dx.doi.org/10.2165/00023210-200519001-00001] [PMID: 15998156]
[44]
Kemner C, Willemsen-Swinkels SH, de Jonge M, Tuynman-Qua H, van Engeland H. Open-label study of olanzapine in children with pervasive developmental disorder. J Clin Psychopharmacol 2002; 22(5): 455-60.
[http://dx.doi.org/10.1097/00004714-200210000-00003] [PMID: 12352267]
[45]
Lamberti JS, Bellnier T, Schwarzkopf SB. Weight gain among schizophrenic patients treated with clozapine. Am J Psychiatry 1992; 149(5): 689-90.
[http://dx.doi.org/10.1176/ajp.149.5.689] [PMID: 1349460]
[46]
Sikich L, Hamer RM, Bashford RA, Sheitman BB, Lieberman JA. A pilot study of risperidone, olanzapine, and haloperidol in psychotic youth: a double-blind, randomized, 8-week trial. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 2004; 29(1): 133-45.
[47]
Malý R, Masopust J, Hosák L, Konupcíková K. Assessment of risk of venous thromboembolism and its possible prevention in psychiatric patients. Psychiatry Clin Neurosci 2008; 62(1): 3-8.
[http://dx.doi.org/10.1111/j.1440-1819.2007.01773.x] [PMID: 18289135]
[48]
Scahill L, Leckman JF, Schultz RT, Katsovich L, Peterson BS. A placebo-controlled trial of risperidone in Tourette syndrome. Neurology 2003; 60(7): 1130-5.
[http://dx.doi.org/10.1212/01.WNL.0000055434.39968.67] [PMID: 12682319]
[49]
Arvanitis LA, Miller BG. Multiple fixed doses of “Seroquel” (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. The Seroquel Trial 13 Study Group. Biol Psychiatry 1997; 42(4): 233-46.
[http://dx.doi.org/10.1016/S0006-3223(97)00190-X] [PMID: 9270900]
[50]
Marder SR, McQuade RD, Stock E, et al. Aripiprazole in the treatment of schizophrenia: safety and tolerability in short-term, placebo-controlled trials. Schizophr Res 2003; 61(2-3): 123-36.
[http://dx.doi.org/10.1016/S0920-9964(03)00050-1] [PMID: 12729864]
[51]
Allison DB, Mentore JL, Heo M, et al. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry 1999; 156(11): 1686-96.
[PMID: 10553730]
[52]
Wang C, Xu J, Yang L, et al. China Pulmonary Health Study Group. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study. Lancet 2018; 391(10131): 1706-17.
[http://dx.doi.org/10.1016/S0140-6736(18)30841-9] [PMID: 29650248]

Rights & Permissions Print Cite
Article Metrics
35
3
© 2024 Bentham Science Publishers | Privacy Policy