Hostname: page-component-76fb5796d-vvkck Total loading time: 0 Render date: 2024-04-26T10:22:33.643Z Has data issue: false hasContentIssue false

Risperidone and pulmonary embolism: a harmful association? Case series and review of the literature

Published online by Cambridge University Press:  24 June 2014

Massimo Gallerani*
Affiliation:
Internal Medicine, Az. Ospedaliera Universitaria “St. Anna”, Ferrara, Italy
Davide Imberti
Affiliation:
Internal Medicine, Az. Ospedaliera Universitaria “St. Anna”, Ferrara, Italy
Elisa Mari
Affiliation:
Internal Medicine, Az. Ospedaliera Universitaria “St. Anna”, Ferrara, Italy
Anna Marra
Affiliation:
Pharmaceutical Department, Az. Ospedaliera Universitaria “St. Anna”, Ferrara, Italy
Roberto Manfredini
Affiliation:
Department of Clinical and Experimental Medicine, Clinica Medica and Vascular Diseases Center, University of Ferrara, Ferrara, Italy
*
Massimo Gallerani, MD, Division of Internal Medicine, Department of Medicine, Az. Ospedaliera, Universitaria “St. Anna”, Corso Giovecca 203, I-44100 Ferrara, Italy. Tel: +39532236294; Fax: +39532236294; E-mail: m.gallerani@ospfe.it

Extract

Gallerani M, Imberti D, Mari E, Marra A, Manfredini R. Risperidone and pulmonary embolism: a harmful association? Case series and review of the literature.

Objective: Risperidone is an atypical antipsychotic drug used to treat a number of psychiatric diseases, such as schizophrenia, schizoaffective and bipolar disorders and irritability in children with autism. Moreover, it is also often administered for short-term treatment of persistent aggression in people with moderate-to-severe Alzheimer's dementia. A possible association between risperidone and venous thromboembolism (VTE) has been described. We intended to verify the dimension of the problem in our hospital setting.

Methods: We considered all consecutive patients hospitalised in our Internal Medicine Department from January 2004 to December 2010, who were treated with risperidone and presented pulmonary embolism (PE).

Results: Four cases of patients, apparently free from the well-known major risk factors for VTE (i.e. cancer, prolonged immobilisation, acute cardiac and respiratory failure, infections), who presented PE associated with risperidone therapy, were reported in details.

Conclusions: A review of the available literature, discussing the possible different pathogenic reasons for this increased risk of VTE, is provided.

Type
Research Article
Copyright
Copyright © Cambridge University Press 2012

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Kopala, LC, Honer, WG.The use of risperidone in severely demented patients with persistent vocalizations. Int J Geriatr Psychiatry 1997;12:7377.3.0.CO;2-X>CrossRefGoogle ScholarPubMed
2.Workman, RH Jr, Orengo, CA, Bakey, AA, Molinari, VA, Kunik, ME.The use of risperidone for psychosis and agitation in demented patients with Parkinson's disease. J Neuropsychiatry Clin Neurosci 1997;9:594597.Google ScholarPubMed
3.Furmaga, KM, DeLeon, OA, Sinha, SB, Jobe, TH, Gaviria, M.Psychosis in medical conditions: response to risperidone. Gen Hosp Psychiatry 1997;19:223228.CrossRefGoogle ScholarPubMed
4.Katz, IR, Jeste, DV, Mintzer, JE, Clyde, C, Napolitano, J, Brecher, M.Comparison of risperidone and placebo for psychosis and behavioral disturbances associated with dementia: a randomized, double-blind trial. Risperidone Study Group. J Clin Psychiatry 1999;60:107115.CrossRefGoogle ScholarPubMed
5.Ballard, CG, Waite, J, Birks, J.Atypical antipsychotics for aggression and psychosis in Alzheimer's disease. Cochrane Database Syst Rev 2006: Art. No. CD003476. [E-pub ahead of print; DOI: 10.1002/14651858.CD003476.pub2]CrossRefGoogle ScholarPubMed
6.Prod Info Risperdal®. URL http://www.risperdal.com/sites/default/files/shared/pi/risperdal.pdf [accessed on 30 January 2011].Google Scholar
7.Ageno, W, Squizzato, A, Garcia, D, Imberti, D.Epidemiology and risk factors of venous thromboembolism. Semin Thromb Hemost 2006;32:651658.CrossRefGoogle ScholarPubMed
8.Manfredini, R, Portaluppi, F, Grandi, E, Fersini, C, Gallerani, M.Out-of-hospital sudden death referring to an emergency department. J Clin Epidemiol 1996;49:865868.CrossRefGoogle ScholarPubMed
9.Song, F.Risperidone in the treatment of schizophrenia: a meta-analysis of randomized controlled trials. J Psychopharmacol 1997;11:6571.CrossRefGoogle ScholarPubMed
10.Beck, NC, Greenfield, SR, Gotham, H, Menditto, AA, Stuve, P, Hemme, CA.Risperidone in the management of violent, treatment-resistant schizophrenics hospitalized in a maximum security forensic facility. J Am Acad Psychiatry Law 1997;25:461468.Google Scholar
11.Buckley, PF, Ibrahim, ZY, Singer, B, Orr, B, Donenwirth, K, Brar, PS.Aggression and schizophrenia: efficacy of risperidone. J Am Acad Psychiatry Law 1997;25: 173181.Google Scholar
12.Janicak, PG, Keck, PE Jr, Davis, JM et al. A double-blind, randomized, prospective evaluation of the efficacy and safety of risperidone versus haloperidol in the treatment of schizoaffective disorder. J Clin Psychopharmacol 2001;21:360368.CrossRefGoogle ScholarPubMed
13.Vieta, E, Herraiz, M, Fernández, A et al. Efficacy and safety of risperidone in the treatment of schizoaffective disorder: initial results from a large, multicenter surveillance study. Group for the Study of Risperidone in Affective Disorders (GSRAD). J Clin Psychiatry 2001;62:623630.CrossRefGoogle Scholar
14.Bai, YM, Yu, SC, Lin, CC.Risperidone for severe tardive dyskinesia: a 12-week randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2003;64:13421348.Google Scholar
15.Vieta, E, Goikolea, JM, Olivares, JM et al. 1-year follow-up of patients treated with risperidone and topiramate for a manic episode. J Clin Psychiatry 2003;64:834839.CrossRefGoogle ScholarPubMed
16.Wallaschofski, H, Eigenthaler, M, Kiefer, M et al. Hyperprolactinemia 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;23:479483.CrossRefGoogle ScholarPubMed
17.Zalsman, G, Carmon, E, Martin, A, Bensason, D, Weizman, A, Tyano, S.Effectiveness, safety, and tolerability of risperidone in adolescents with schizophrenia: an open-label study. J Child Adolesc Psychopharmacol 2003;13:319327.CrossRefGoogle ScholarPubMed
18.Addington, DE, Pantelis, C, Dineen, M, Benattia, I, Romano, SJ.Efficacy and tolerability of ziprasidone versus risperidone in patients with acute exacerbation of schizophrenia or schizoaffective disorder: an 8-week, double-blind, multicenter trial. J Clin Psychiatry 2004;65: 16241633.CrossRefGoogle ScholarPubMed
19.Bahk, WM, Yoon, JS, Kim, YH et al. Risperidone in combination with mood stabilizers for acute mania: a multicentre, open study. Int Clin Psychopharmacol 2004;19:299303.CrossRefGoogle Scholar
20.Hirschfeld, RM, Keck, PE Jr, Kramer, M et al. Rapid antimanic effect of risperidone monotherapy: a 3-week multicenter, double-blind, placebo-controlled trial. Am J Psychiatry 2004;161:10571065.CrossRefGoogle ScholarPubMed
21.Lasser, R, Bossie, CA, Gharabawi, G, Eerdekens, M, Nasrallah, HA.Efficacy and safety of long-acting risperidone in stable patients with schizoaffective disorder. J Affect Disord 2004;83:263275.Google Scholar
22.Lee, PE, Gill, SS, Freedman, M, Bronskill, SE, Hillmer, MP, Rochon, PA.Atypical antipsychotic drugs in the treatment of behavioural and psychological symptoms of dementia: systematic review. BMJ 2004;329:7578.CrossRefGoogle ScholarPubMed
23.Parellada, E, Baeza, I, de Pablo, J, Martínez, G.Risperidone in the treatment of patients with delirium. J Clin Psychiatry 2004;65:348353.CrossRefGoogle ScholarPubMed
24.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 2004;29:133145.CrossRefGoogle ScholarPubMed
25.Anil Yağcioğlu, AE, Kivircik Akdede, BB et al. A double-blind controlled study of adjunctive treatment with risperidone in schizophrenic patients partially responsive to clozapine: efficacy and safety. J Clin Psychiatry 2005;66:6372.CrossRefGoogle ScholarPubMed
26.Ciliberto, N, Bossie, CA, Urioste, R, Lasser, RA.Lack of impact of race on the efficacy and safety of long-acting risperidone versus placebo in patients with schizophrenia or schizoaffective disorder. Int Clin Psychopharmacol 2005;20:207212.CrossRefGoogle ScholarPubMed
27.Bai, YM, Chen, TT, Wu, B et al. A comparative efficacy and safety study of long-acting risperidone injection and risperidone oral tablets among hospitalized patients: 12-week randomized, single-blind study. Pharmacopsychiatry 2006;39:135141.CrossRefGoogle ScholarPubMed
28.Pandina, GJ, Bossie, CA, Youssef, E, Zhu, Y, Dunbar, F.Risperidone improves behavioral symptoms in children with autism in a randomized, double-blind, placebo-controlled trial. J Autism Dev Disord 2007;37:367373.Google Scholar
29.Yury, CA, Fisher, JE.Meta-analysis of the effectiveness of atypical antipsychotics for the treatment of behavioural problems in persons with dementia. Psychother Psychosom 2007;76:213218.Google Scholar
30.Pollock, BG, Mulsant, BH, Rosen, J et al. A double-blind comparison of citalopram and risperidone for the treatment of behavioral and psychotic symptoms associated with dementia. Am J Geriatr Psychiatry 2007;15:942952.Google Scholar
31.Amiri, A, Noorbala, AA, Nejatisafa, AA et al. Efficacy of selegiline add on therapy to risperidone in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled study. Hum Psychopharmacol 2008;23:7986.CrossRefGoogle Scholar
32.Gencer, O, Emiroglu, FN, Miral, S, Baykara, B, Baykara, A, Dirik, E.Comparison of long-term efficacy and safety of risperidone and haloperidol in children and adolescents with autistic disorder. An open label maintenance study. Eur Child Adolesc Psychiatry 2008;17: 217225.Google Scholar
33.Perez, V, Cañas, F, Tafalla, M; TESIS Study Group. A 12-month, open-label, comparative study of quetiapine and risperidone in the acute and long-term treatment of schizophrenia. Int Clin Psychopharmacol 2008;23:138149.CrossRefGoogle ScholarPubMed
34.Sacchetti, E, Valsecchi, P, Parrinello, G; QUERISOLA Group. A randomized, flexible-dose, quasi-naturalistic comparison of quetiapine, risperidone, and olanzapine in the short-term treatment of schizophrenia: the QUERISOLA trial. Schizophr Res 2008;98:5565.Google Scholar
35.Haas, M, Eerdekens, M, Kushner, S et al. Efficacy, safety and tolerability of two dosing regimens in adolescent schizophrenia: double-blind study. Br J Psychiatry 2009; 194:158164.CrossRefGoogle ScholarPubMed
36.Kane, JM, Correll, CU, Goff, DC et al. A multicenter, randomized, double-blind, placebo-controlled, 16-week study of adjunctive aripiprazole for schizophrenia or schizoaffective disorder inadequately treated with quetiapine or risperidone monotherapy. J Clin Psychiatry 2009;70:13481357.Google Scholar
37.Addington, DE, Labelle, A, Kulkarni, J, Johnson, G, Loebel, A, Mandel, FS.A comparison of ziprasidone and risperidone in the long-term treatment of schizophrenia: a 44-week, double-blind, continuation study. Can J Psychiatry 2009;54:4654.CrossRefGoogle ScholarPubMed
38.Sheehan, DV, McElroy, SL, Harnett-Sheehan, K et al. Randomized, placebo-controlled trial of risperidone for acute treatment of bipolar anxiety. J Affect Disord 2009;115:376385.CrossRefGoogle ScholarPubMed
39.Kim, JH, Ann, JH, Lee, J.Relationship between heart rate variability and the severity of psychiatric symptoms in schizophrenia. Acta Neuropsychiatrica 2011;23:161166.CrossRefGoogle ScholarPubMed
40.Chengappa, KNR, Turkin, SR, Schlicht, PJ et al. A pilot, 15-month, randomised effectiveness trial of risperidone long-acting injection (RLAI) versus oral atypical antipsychotic (AAP) in persons with bipolar disorder. Acta Neuropsychiatrica 2010;22:6880.Google Scholar
41.Nasrallah, H.A review of the effect of atypical antipsychotics on weight. Psychoneuroendocrinology 2003;28(Suppl. 1):8396.CrossRefGoogle ScholarPubMed
42.Yen, YC, Lung, FW, Chong, MY.Adverse effects of risperidone and haloperidol treatment in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2004;28:285290.CrossRefGoogle ScholarPubMed
43.Koga, M, Nakayama, K.Body weight gain induced by a newer antipsychotic agent. Acta Psychiatr Scand 2005;112:7576.CrossRefGoogle ScholarPubMed
44.Haupt, M, Cruz-Jentoft, A, Jeste, D.Mortality in elderly dementia patients treated with risperidone. J Clin Psychopharmacol 2006;26:566570.CrossRefGoogle ScholarPubMed
45.Raivio, MM, Laurila, JV, Strandberg, TE, Tilvis, RS, Pitkälä, KH.Neither atypical nor conventional antipsychotics increase mortality or hospital admissions among elderly patients with dementia: a two-year prospective study. Am J Geriatr Psychiatry 2007;15:416424.Google Scholar
46.BMJ Group. How safe are antipsychotics in dementia? Drug Ther Bull 2007;45:8185.CrossRefGoogle Scholar
47. Rete Nazionale di Farmacovigilanza, Italia. URL https://nsis.sanita.it/ACCN/accessportalnsis/ [accessed on 1 June 2011].Google Scholar
48.Grahmann, H, Suchenwirth, R.Thrombosis hazard in chlorpromazine and reserpine therapy of endogenous psychoses [in German]. Nervenarzt 1959;30:2245.Google Scholar
49.Haefner, H, Brehm, I.Thromboembolic complications in neuroleptic treatment. Compr Psychiatry 1965;58:2534.CrossRefGoogle Scholar
50.Varia, I, Krishnan, RR, Davidson, J.Deep-vein thrombosis with antipsychotic drugs. Psychosomatics 1983;24:10971098.CrossRefGoogle ScholarPubMed
51.Thorogood, M, Cowen, P, Mann, J, Murphy, M, Vessey, M.Fatal myocardial infarction and use of psychotropic drugs in young women. Lancet 1992;340:10671068.CrossRefGoogle ScholarPubMed
52.Zornberg, GL, Jick, H.Antipsychotic drug use and risk of first-time idiopathic venous thromboembolism: a case-control study. Lancet 2000;356:12191223.CrossRefGoogle ScholarPubMed
53.Hägg, S, Bate, A, Stahl, M, Spigset, O.Associations between venous thromboembolism and antipsychotics. A study of the WHO database of adverse drug reactions. Drug Saf 2008;31:685894.CrossRefGoogle ScholarPubMed
54.Parkin, L, Skegg, DC, Herbison, GP, Paul, C.Psychotropic drugs and fatal pulmonary embolism. Pharmacoepidemiol Drug Saf 2003;12:647652.CrossRefGoogle ScholarPubMed
55.Hägg, S, Spigset, O, Söderström, TG.Association of venous thromboembolism and clozapine. Lancet 2000;355:11551156.CrossRefGoogle ScholarPubMed
56.Hägg, S, Spigset, O.Antipsychotic-induced venous thromboembolism: a review of the evidence. CNS Drugs 2002;16:765766.Google ScholarPubMed
57.Kapur, S, Remington, G.Atypical antipsychotics. BMJ 2000;321:13601361.Google Scholar
58.Walker, AM, Lanza, LL, Arellano, F, Rothman, KJ.Mortality in current and former users of clozapine. Epidemiology 1997;8:671677.Google Scholar
59.Ihde-Scholl, T, Rolli, ML, Jefferson, JW.Clozapine and pulmonary embolus. Am J Psychiatry 2001;158:499500.CrossRefGoogle ScholarPubMed
60.Knudson, JF, Kortepeter, C, Dubitsky, GM, Ahmad, SR, Chen, M.Antipsychotic drugs and venous thromboembolism. Lancet 2000;356:252253.CrossRefGoogle ScholarPubMed
61.Hägg, S, Tatting, P, Spigset, O.Olanzapine and venous thromboembolism. Int Clin Psychopharmacol 2003;18:299300.CrossRefGoogle ScholarPubMed
62.Waage, IM, Gedde-Dahl, A.Pulmonary embolism possibly associated with olanzapine treatment. BMJ 2003;327:1384.Google Scholar
63.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;68:850852.CrossRefGoogle ScholarPubMed
64.Ray, JG, Mamdani, MM, Yeo, EL.Antipsychotic and antidepressant drug use in the elderly and the risk of venous thromboembolism. Thromb Haemost 2002;88:205209.Google ScholarPubMed
65.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;165:26772682.Google Scholar
66.Borras, L, Eytan, A, de Timary, P, Constant, EL, Huguelet, P, Hermans, C.Pulmonary thromboembolism associated with olanzapine and risperidone. J Emerg Med 2008;35:159161.Google Scholar
67.Ronco, R, Catalan, J, Salgado, C, Vogel, A.Syncope: a rare presentation of massive pulmonary embolism in a previously healthy girl. Pediatr Emerg Care 2010;26:287289.CrossRefGoogle Scholar
68.Medicines and Healthcare Products Regulatory Agency. URL http://www.mhra.gov.uk/index.htm [accessed on 31 May 2011].Google Scholar
69.Naranjo, CA, Busto, U, Sellers, EM et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239245.CrossRefGoogle ScholarPubMed
70.Boullin, DJ, Woods, HF, Grimes, RP, Grahame-smith, DG.Increased platelet aggregation responses to 5-hydroxytryptamine in patients taking chorpromazine. Br J Clin Pharmacol 1975;2:2935.CrossRefGoogle Scholar
71.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;26:12611273.CrossRefGoogle ScholarPubMed
72.Love, RC.Novel versus conventional antipsychotic drugs. Pharmacotherapy 1996;16:610.CrossRefGoogle ScholarPubMed
73.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;34:775780.CrossRefGoogle ScholarPubMed
74.Orr, MW, Boullin, DJ.The relationship between changes in 5-HT induced platelet aggregation and clinical state in patients treated with fluphenazine. Br J Clin Pharmacol 1976;3:925928.Google Scholar
75.Thorneycroft, IH, Goldzieher, JW.Venous thromboembolism. A review. J Reprod Med 2003;48:911920.Google Scholar
76.Canoso, RT, De Oliveira, RM, Nixon, RA.Neuroleptic-associated autoantibodies. A prevalence study. Biol Psychiatry 1990;27:863870.Google Scholar
77.Davis, S, Kern, HB, Asokan, R.Antiphospholipid antibodies associated with clozapine treatment. Am J Hematol 1994;46:166167.Google Scholar
78.Susser, E, Brown, AS, Klonowski, E, Allen, RH, Lindenbaum, J.Schizophrenia and impaired homocysteine metabolism: a possible association. Biol Psychiatry 1998; 44:141143.CrossRefGoogle ScholarPubMed
79.Applebaum, J, Shimon, H, Sela, BA, Belmaker, RH, Levine, J.Homocysteine levels in newly admitted schizop hrenic patients. J Psychiatr Res 2004;38:413416.Google Scholar
80.Doggen, CJ, Smith, NL, Lemaitre, RN, Heckbert, SR, Rosendaal, FR, Psaty, BM.Serum lipid levels and the risk of venous thrombosis. Arterioscler Thromb Vasc Biol 2004;24:19701975.CrossRefGoogle ScholarPubMed
81.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;21:643650.Google Scholar
82.Kamijo, Y, Soma, K.Nagai, T.Kurihara, K.Ohwada, T.Acute massive pulmonary thromboembolism associated with risperidone and conventional phenothiazincs. Circ J 2003;67:4648.Google Scholar