Massive Pulmonary Thromboembolism Demonstrated at Necropsy in Japanese Psychiatric Patients Treated With Neuroleptics Including Atypical Antipsychotics
Background There may be an increased risk of pulmonary thromboembolism (PTE) with antipsychotic drugs, so this association was investigated in autopsy cases of sudden unexpected death determined by the Department of Legal Medicine of a Japanese university hospital. Methods and Results Records of 1,1...
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| Published in | Circulation Journal Vol. 68; no. 9; pp. 850 - 852 |
|---|---|
| Main Authors | , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Japan
The Japanese Circulation Society
01.09.2004
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1346-9843 1347-4820 |
| DOI | 10.1253/circj.68.850 |
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| Abstract | Background There may be an increased risk of pulmonary thromboembolism (PTE) with antipsychotic drugs, so this association was investigated in autopsy cases of sudden unexpected death determined by the Department of Legal Medicine of a Japanese university hospital. Methods and Results Records of 1,125 forensic autopsies (808 males, 317 females) performed during the study period for investigation of the cause of sudden unexpected death were reviewed and a logistic regression analysis was performed to explore whether age, gender, body mass index (BMI), and antipsychotic drug use were associated with fatal PTE. Among all records, 34 (3.0%; 14 males, 20 females) indicated the use of antipsychotic drugs and 28 (2.5%; 9 males, 19 females) indicated PTE as the cause of death. Of the 28 subjects who died from PTE, 8 had taken antipsychotic drugs (29%) and all were female. Female gender and antipsychotic drug use accounted for a significantly higher risk of PTE death with an odds ratio of 4.22 (95% confidence interval (CI), 1.82-9.78; p<0.01) and 10.49 (95% CI, 3.95-27.85; p<0.01), respectively. Conclusions Japanese women taking antipsychotic drugs may be at particular risk for PTE. (Circ J 2004; 68: 850 - 852) |
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| AbstractList | There may be an increased risk of pulmonary thromboembolism (PTE) with antipsychotic drugs, so this association was investigated in autopsy cases of sudden unexpected death determined by the Department of Legal Medicine of a Japanese university hospital.
Records of 1,125 forensic autopsies (808 males, 317 females) performed during the study period for investigation of the cause of sudden unexpected death were reviewed and a logistic regression analysis was performed to explore whether age, gender, body mass index (BMI), and antipsychotic drug use were associated with fatal PTE. Among all records, 34 (3.0%; 14 males, 20 females) indicated the use of antipsychotic drugs and 28 (2.5%; 9 males, 19 females) indicated PTE as the cause of death. Of the 28 subjects who died from PTE, 8 had taken antipsychotic drugs (29%) and all were female. Female gender and antipsychotic drug use accounted for a significantly higher risk of PTE death with an odds ratio of 4.22 (95% confidence interval (CI), 1.82-9.78; p<0.01) and 10.49 (95% CI, 3.95-27.85; p<0.01), respectively.
Japanese women taking antipsychotic drugs may be at particular risk for PTE. There may be an increased risk of pulmonary thromboembolism (PTE) with antipsychotic drugs, so this association was investigated in autopsy cases of sudden unexpected death determined by the Department of Legal Medicine of a Japanese university hospital.BACKGROUNDThere may be an increased risk of pulmonary thromboembolism (PTE) with antipsychotic drugs, so this association was investigated in autopsy cases of sudden unexpected death determined by the Department of Legal Medicine of a Japanese university hospital.Records of 1,125 forensic autopsies (808 males, 317 females) performed during the study period for investigation of the cause of sudden unexpected death were reviewed and a logistic regression analysis was performed to explore whether age, gender, body mass index (BMI), and antipsychotic drug use were associated with fatal PTE. Among all records, 34 (3.0%; 14 males, 20 females) indicated the use of antipsychotic drugs and 28 (2.5%; 9 males, 19 females) indicated PTE as the cause of death. Of the 28 subjects who died from PTE, 8 had taken antipsychotic drugs (29%) and all were female. Female gender and antipsychotic drug use accounted for a significantly higher risk of PTE death with an odds ratio of 4.22 (95% confidence interval (CI), 1.82-9.78; p<0.01) and 10.49 (95% CI, 3.95-27.85; p<0.01), respectively.METHODS AND RESULTSRecords of 1,125 forensic autopsies (808 males, 317 females) performed during the study period for investigation of the cause of sudden unexpected death were reviewed and a logistic regression analysis was performed to explore whether age, gender, body mass index (BMI), and antipsychotic drug use were associated with fatal PTE. Among all records, 34 (3.0%; 14 males, 20 females) indicated the use of antipsychotic drugs and 28 (2.5%; 9 males, 19 females) indicated PTE as the cause of death. Of the 28 subjects who died from PTE, 8 had taken antipsychotic drugs (29%) and all were female. Female gender and antipsychotic drug use accounted for a significantly higher risk of PTE death with an odds ratio of 4.22 (95% confidence interval (CI), 1.82-9.78; p<0.01) and 10.49 (95% CI, 3.95-27.85; p<0.01), respectively.Japanese women taking antipsychotic drugs may be at particular risk for PTE.CONCLUSIONSJapanese women taking antipsychotic drugs may be at particular risk for PTE. Background There may be an increased risk of pulmonary thromboembolism (PTE) with antipsychotic drugs, so this association was investigated in autopsy cases of sudden unexpected death determined by the Department of Legal Medicine of a Japanese university hospital. Methods and Results Records of 1,125 forensic autopsies (808 males, 317 females) performed during the study period for investigation of the cause of sudden unexpected death were reviewed and a logistic regression analysis was performed to explore whether age, gender, body mass index (BMI), and antipsychotic drug use were associated with fatal PTE. Among all records, 34 (3.0%; 14 males, 20 females) indicated the use of antipsychotic drugs and 28 (2.5%; 9 males, 19 females) indicated PTE as the cause of death. Of the 28 subjects who died from PTE, 8 had taken antipsychotic drugs (29%) and all were female. Female gender and antipsychotic drug use accounted for a significantly higher risk of PTE death with an odds ratio of 4.22 (95% confidence interval (CI), 1.82-9.78; p<0.01) and 10.49 (95% CI, 3.95-27.85; p<0.01), respectively. Conclusions Japanese women taking antipsychotic drugs may be at particular risk for PTE. (Circ J 2004; 68: 850 - 852) |
| Author | Hamanaka, Satoko Miyaoka, Hitoshi Nagai, Tomonori Kamijo, Yoshito Tanaka, Katsutoshi Soma, Kazui Kurihara, Katsuyoshi |
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| Cites_doi | 10.1192/bjp.179.1.63 10.1097/01.jcp.0000088914.24613.51 10.1055/s-0028-1106111 10.1055/s-2007-1019607 10.1097/00001648-199711000-00014 10.1253/circj.66.257 10.1055/s-0037-1614935 10.1002/ajh.2830270408 10.7134/phlebol.14-3-189 10.1253/circj.67.46 10.1016/S0140-6736(00)02066-3 10.1016/0165-1781(83)90004-5 10.1016/S0140-6736(00)02784-7 10.1002/ajh.2830460233 10.1016/S0010-440X(65)80005-0 |
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| References | 19. Kaiya H, Imai H, Muramatsu Y, Nozaki M, Fujimura H, Adachi S, et al. Platelet aggregation response in schizophrenia and prostaglandin E1. Psychiatry Res 1983; 9: 309-318. 1. Kumasaka N, Sakuma M, Shirato K. Incidence of pulmonary thromboembolism in Japan. Jpn Circ J 1999; 63: 825-827. 6. Hagg S, Spigset O, Soderstrom TG. Association of venous thromboembolism and clozapine. Lancet 2000; 355: 1155-1156. 12. Lacika S, Cooper JP. Pulmonary embolus possibly associated with clozapine treatment. Can J Psychiatry 1999; 44: 396-397. 8. Ungvari G. Neuroleptic-related sudden death (proven or a mere hypothesis?). Pharmacopsychiatry 1980; 13: 29-33. 18. Kinon BJ, Gilmore JA, Liu H, Halbreich UM. Prevalence of hyperprolactinemia in schizophrenic patients treated with conventional antipsychotic medications or risperidone. Psychoneuroendocrinology 2003; 28: 55-68. 13. Thomassen R, Vandenbroucke JP, Rosendaal FR. Antipsychotic medication and venous thrombosis. Br J Psychiatry 2001; 179: 63-66. 10. Zornberg GL, Jick H. Antipsychotic drug use and the risk of first-time idiopathic venous thromboembolism: A case-control study. Lancet 2000; 356: 1219-1223. 14. Davis S, Kern HB, Asokan R. Antiphospholipid antibodies associated with clozapine treatment. Am J Hematol 1994; 46: 166-167. 3. Tanifuji T, Kageyama N, Ro A, Hamamatsu A, Misawa S. A histo-pathological study of fatal pulmonary thromboembolism and deep vein thrombosis: In the study of deep vein thrombosis amoun forty patients with pulmonary thromboembolism Jpn J Phlebol 2003; 14: 189-195. 5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, edition IV. American Psychiatric Association, Washington D.C., 1994. 4. Kamijo Y, Soma K, Nagai T, Kurihara K, Ohwada T. Acute massive pulmonary thromboembolism associated with risperidone and conventional phenothiazines. Circ J 2003; 67: 46-48. 9. Haefner H, Brehm I. Thromboembolic complications in neuroleptic treatment. Compr Psychiatry 1965; 6: 25-34. 15. Canoso RT, Oliviera RM. Chlorpromazine-induced anticardiolipin antibodies and lupus anticoagulant: Absence of thrombosis. Am J Hematol 1998; 27: 272-275. 7. Vandenbroucke JP, Bertina RM, Holmes ZR, Spaargaren C, van Krieken JH, Menten B, et al. Factor V Leiden and fatal pulmonary embolism. Thromb Haemost 1998; 79: 511-516. 20. Grahmann H, Suchenwirth R. Thrombosis hazard in chlorpromazine and reserpine therapy of endogenous psychosis. Nervenarzt 1959; 30: 224-225. 16. Love RC. Novel versus conventional antipsychotic drugs. Pharmacotherapy 1996; 16: 6S-10S. 17. Wallaschofski H, Eigenthaler M, Kiefer M, Donne M, Hentschel B, Gertz HJ, et al. Hyperprolactinemina in patients on antipsychotic drugs causes ADP-stimulated platelet activation that might explain the increased risk for venous thromboembolism: Pilot study. J Clin Psychopharmacol 2003; 23: 479-483. 2. Nakamura M, Okada O, Sakuma M, Nakanishi N, Miyahara Y, Yamada N, et al. Incidence and clinical characteristics of chronic pulmonary thromboembolism in Japan compared with acute pulmonary thromboembolism: Results of a multicenter registry of the Japanese Society of Pulmonary Embolism Research. Circ J 2002; 66: 257-260. 11. Walker AM, Lanza LL, Arellano F, Rothman KJ. Mortality in current and former users of clozapine. Epidemiology 1997; 8: 671-677. 21. Meier-Ewert K, Baumgart HH, Friedenberg P. Thromboembolism complications in neuro- and thymoleptic therapy. Dtsch Med Wochenschr 1967; 92: 2174-2178. Tanifuji T, Kageyama N, Ro A, Hamam (3) 2003; 14 Canoso RT, Oliviera RM (15) 1998; 27 13 Vandenbroucke JP, Bertina RM, Holme (7) 1998; 79 Haefner H, Brehm I (9) 1965; 6 Lacika S, Cooper JP (12) 1999; 44 19 Ungvari G (8) 1980; 13 Davis S, Kern HB, Asokan R (14) 1994; 46 Wallaschofski H, Eigenthaler M, Kie (17) 2003; 23 Kinon BJ, Gilmore JA, Liu H, Halbre (18) 2003; 28 Grahmann H, Suchenwirth R (20) 1959; 30 5 Kamijo Y, Soma K, Nagai T, Kurihara (4) 2003; 67 6 Love RC (16) 1996; 16 HIROSE H (1) 1999; 63 Nakamura M, Okada O, Sakuma M, Naka (2) 2002; 66 Meier-Ewert K, Baumgart HH, Frieden (21) 1967; 92 Walker AM, Lanza LL, Arellano F, Ro (11) 1997; 8 10 |
| References_xml | – reference: 18. Kinon BJ, Gilmore JA, Liu H, Halbreich UM. Prevalence of hyperprolactinemia in schizophrenic patients treated with conventional antipsychotic medications or risperidone. Psychoneuroendocrinology 2003; 28: 55-68. – reference: 8. Ungvari G. Neuroleptic-related sudden death (proven or a mere hypothesis?). Pharmacopsychiatry 1980; 13: 29-33. – reference: 7. Vandenbroucke JP, Bertina RM, Holmes ZR, Spaargaren C, van Krieken JH, Menten B, et al. Factor V Leiden and fatal pulmonary embolism. Thromb Haemost 1998; 79: 511-516. – reference: 10. Zornberg GL, Jick H. Antipsychotic drug use and the risk of first-time idiopathic venous thromboembolism: A case-control study. Lancet 2000; 356: 1219-1223. – reference: 17. Wallaschofski H, Eigenthaler M, Kiefer M, Donne M, Hentschel B, Gertz HJ, et al. Hyperprolactinemina in patients on antipsychotic drugs causes ADP-stimulated platelet activation that might explain the increased risk for venous thromboembolism: Pilot study. J Clin Psychopharmacol 2003; 23: 479-483. – reference: 9. Haefner H, Brehm I. Thromboembolic complications in neuroleptic treatment. Compr Psychiatry 1965; 6: 25-34. – reference: 11. Walker AM, Lanza LL, Arellano F, Rothman KJ. Mortality in current and former users of clozapine. Epidemiology 1997; 8: 671-677. – reference: 14. Davis S, Kern HB, Asokan R. Antiphospholipid antibodies associated with clozapine treatment. Am J Hematol 1994; 46: 166-167. – reference: 20. Grahmann H, Suchenwirth R. Thrombosis hazard in chlorpromazine and reserpine therapy of endogenous psychosis. Nervenarzt 1959; 30: 224-225. – reference: 15. Canoso RT, Oliviera RM. Chlorpromazine-induced anticardiolipin antibodies and lupus anticoagulant: Absence of thrombosis. Am J Hematol 1998; 27: 272-275. – reference: 5. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, edition IV. American Psychiatric Association, Washington D.C., 1994. – reference: 12. Lacika S, Cooper JP. Pulmonary embolus possibly associated with clozapine treatment. Can J Psychiatry 1999; 44: 396-397. – reference: 13. Thomassen R, Vandenbroucke JP, Rosendaal FR. Antipsychotic medication and venous thrombosis. Br J Psychiatry 2001; 179: 63-66. – reference: 16. Love RC. Novel versus conventional antipsychotic drugs. Pharmacotherapy 1996; 16: 6S-10S. – reference: 6. Hagg S, Spigset O, Soderstrom TG. Association of venous thromboembolism and clozapine. Lancet 2000; 355: 1155-1156. – reference: 21. Meier-Ewert K, Baumgart HH, Friedenberg P. Thromboembolism complications in neuro- and thymoleptic therapy. Dtsch Med Wochenschr 1967; 92: 2174-2178. – reference: 2. Nakamura M, Okada O, Sakuma M, Nakanishi N, Miyahara Y, Yamada N, et al. Incidence and clinical characteristics of chronic pulmonary thromboembolism in Japan compared with acute pulmonary thromboembolism: Results of a multicenter registry of the Japanese Society of Pulmonary Embolism Research. Circ J 2002; 66: 257-260. – reference: 1. Kumasaka N, Sakuma M, Shirato K. Incidence of pulmonary thromboembolism in Japan. Jpn Circ J 1999; 63: 825-827. – reference: 3. Tanifuji T, Kageyama N, Ro A, Hamamatsu A, Misawa S. A histo-pathological study of fatal pulmonary thromboembolism and deep vein thrombosis: In the study of deep vein thrombosis amoun forty patients with pulmonary thromboembolism Jpn J Phlebol 2003; 14: 189-195. – reference: 4. Kamijo Y, Soma K, Nagai T, Kurihara K, Ohwada T. Acute massive pulmonary thromboembolism associated with risperidone and conventional phenothiazines. Circ J 2003; 67: 46-48. – reference: 19. Kaiya H, Imai H, Muramatsu Y, Nozaki M, Fujimura H, Adachi S, et al. Platelet aggregation response in schizophrenia and prostaglandin E1. 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| Snippet | Background There may be an increased risk of pulmonary thromboembolism (PTE) with antipsychotic drugs, so this association was investigated in autopsy cases of... There may be an increased risk of pulmonary thromboembolism (PTE) with antipsychotic drugs, so this association was investigated in autopsy cases of sudden... |
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| SubjectTerms | Aged Antidepressive Agents, Second-Generation - adverse effects Antiphospholipid antibodies Antipsychotic Agents - adverse effects Atypical antipsychotic drugs Autopsy Death, Sudden Female Humans Japan Male Medical Records Middle Aged Phenothiazines Psychotic Disorders - drug therapy Pulmonary Embolism - chemically induced Pulmonary Embolism - mortality Pulmonary thromboembolism |
| Title | Massive Pulmonary Thromboembolism Demonstrated at Necropsy in Japanese Psychiatric Patients Treated With Neuroleptics Including Atypical Antipsychotics |
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