Clinical News & Knowledge: Schizophrenia
April 15, 2008
Psychiatric Times.
No. 5
Can Atypical Antipsychotics Reduce Suicide Risk in Patients With Schizophrenia?
An Evidence-Based Analysis
Eduardo J. Aguilar, MD, PhD, Samuel G. Siris, MD, and Carmen Leal, MD, PhD
Dr Aguilar is a psychiatrist at the Clinic University Hospital in Valencia, Spain. Dr Siris is affiliated with the Zucker-Hillside Hospital of the North Shore, Long Island Jewish Health System, in Glen Oaks, NY, and is professor of psychiatry at Albert Einstein College of Medicine. Dr Leal is chair of the psychiatric unit and a member of the faculty of medicine at Valencia University, and head of Psychiatric Services at Clinic University Hospital, Valencia, Spain. The authors report no conflicts of interest concerning the subject matter of this article.
There is a similar level of evidence for risperidone, but there have been more studies of this medication. Double-blind, randomized studies that compared this drug with olanzapine have found superiority of olanzapine,44 nonsignificant differences,45 and superiority of risperidone.46 Peuskens and colleagues47 analyzed pooled data (N = 1294) from 6 double-blind trials and found risperidone to be superior in comparison to haloperidol or placebo in reducing the Positive and Negative Syndrome Scale anxious/depressive factor. Myers and Thase48 reviewed 7 randomized, controlled trials of risperidone (vs haloperidol, olanzapine, and clozapine) in patients with schizophrenia or schizoaffective disorders and concluded that risperidone was efficacious in the treatment of depressive symptoms in these pathologies; the greatest support came from the haloperidol studies. More recently, a study that reanalyzed data from the North American risperidone trial showed similar results.49
Examining the only long-acting atypical antipsychotics (risperidone microspheres) is relevant at this point, since poor adherence to treatment has also been linked with suicidal risk.28 Several open-label, uncontrolled studies have demonstrated that long-acting risperidone improves anxiety and depression symptoms in stable patients with schizophrenia and/or schizoaffective disorder.50,51
Amisulpride also has a fairly good level of evidence for treating depressive symptoms in schizophrenia. Peuskens and colleagues52 compiled data from 3 short-term, double-blind, randomized studies. They found a greater improvement in the anx- ious/depressive factor for amisulpride compared with haloperidol and risperidone in patients with acute exacerbations of schizophrenia. Eighty-five adults fulfilling DSM-IV criteria for schizophrenia and presenting with a depressive episode were randomized to amisulpride or olanzapine for 8 weeks. There were no significant differences in depressive symptom improvements between the 2 drugs.53 A multicenter, double-blind, randomized study that evaluated patients with chronic schizophrenia (DSM-IV) showed that amisulpride was not inferior to risperidone in improving symptoms of depression.54 Finally, findings from an open-label, 12-week study of patients who were initially treated with risperidone and were randomized to a risperidone-continuation group or an amisulpride-switch group showed that improvements in depressive symptoms were significantly greater in the amisulpride-switch group than in the risperidone-continuation group.55
Quetiapine is superior to placebo in reducing anxiety, depression, and hostility56 but, to the best of our knowledge, it has not yet been compared with another atypical antipsychotic for its antidepressant effect in schizophrenia. This efficacy for treatment of affective symptoms is maintained in long-term treatment.57 Additional evidence comes from a multicenter, double-blind, randomized trial of quetiapine compared with high doses of haloperidol (20 mg/d). The study demonstrated superiority of quetiapine in reducing depressive symptoms in patients with refractory schizophrenia.58 Haloperidol dosage is a strong limitation of this study, since higher doses of antipsychotics could be associated with worsening of depressive symptoms.
Somewhat surprisingly, scarce attention has been paid to the effect of clozapine on depressive symptoms. Indirect data come from the study by Meltzer and colleagues.12 These investigators reported that patients who received clozapine required less concomitant treatment with antidepressants than the patients who were treated with olanzapine.
For the rest of the compounds, the highest level of evidence corresponds to flupentixol and ziprasidone, although very little information is available. In a randomized, double-blind, multicenter study of patients with predominant negative symptoms, flupenthixol demonstrated noninferiority compared with risperidone.59 Similarly, in a 6-week, multicenter, double-blind, parallel-design, flexible-dose trial, ziprasidone and olanzapine showed comparable efficacy in reducing depressive symptoms of acutely ill inpatients with schizophrenia or schizoaffective disorder.60
Aripiprazole is also a potentially good choice for treating depressive symptoms in patients with schizophrenia, but there are no comparisons with other atypical antipsychotics. Relevant indirect data come from a recent study of aripiprazole augmentation in a group of outpatients who had chronic schizophrenia and were treated with clozapine. The researchers found that the augmentation led to a substantial improvement in depressive symptoms.61 Furthermore, analysis of data from 2 randomized, double-blind, multicenter studies of 1294 patients with chronic schizophrenia in acute relapse who had previously responded to antipsychotic medications suggests that aripiprazole is superior to haloperidol in improving depressive symptoms.62
Conclusion
Although clozapine is the only strictly evidence-based treatment for reducing the risk of suicide in schizophrenia, several other atypical anti- psychotics may be reasonable options when treating specific symptoms associated with suicide risk, such as depressive symptoms. Olanzapine, risperidone, and amisulpride also may be helpful. These and the other atypical antipsychotics need to be compared in head-to-head randomized and, preferably, independent studies. Further reviews and meta-analyses will confirm the steps for preventing suicide through evidence-based use of these drugs.
• Hennen J, Baldessarini RJ. Suicidal risk during treatment with clozapine: a meta-analysis. Schizophr Res. 2005;73:139-145.
• Mamo DC. Managing suicidality in schizophrenia. Can J Psychiatry. 2007;52(6 suppl 1):59S-70S.
References
1. Siris SG. Suicide and schizophrenia. J Psychopharmacol. 2001;15:127-135.
2. Palmer BA, Pankratz S, Bostwick JM. The lifetime risk of suicide in schizophrenia: a re-examination. Arch Gen Psychiatry. 2005;62:247-253.
3. Harris EC, Barraclough B. Suicide as an outcome for mental disorders. A meta-analysis. Br J Psychiatry. 1997;170:205-228.
4. Ernst CL, Goldberg JF. Antisuicide properties of psychotropic drugs: a critical review. Harv Rev Psychiatry. 2004;12:14-41.
5. Winokur G, Tsuang M. The Iowa 500: suicide in mania, depression, and schizophrenia. Am J Psychiatry. 1975;132:650-651.
6. Healy D, Harris M, Tranter R, et al. Lifetime suicide rates in treated schizophrenia: 1875-1924 and 1994-1998 cohorts compared. Br J Psychiatry. 2006;188: 223-228.
7. Aguilar EJ, Siris SG. Do antipsychotic drugs influence suicidal behavior in schizophrenia? Psychopharmacol Bull. 2007;40:128-142.
8. Khan A, Khan SR, Leventhal RM, Brown WA. Symptom reduction and suicide risk among patients treated with placebo in antipsychotic clinical trials: an analysis of the Food and Drug Administration database. Am J Psychiatry. 2001;158:1449-1454.
9. Stosorum JG, van Zwieten BJ, Wohlfarth T, et al. Suicide risk in placebo vs active treatment in placebo-controlled trials for schizophrenia. Arch Gen Psychiatry. 2003;60:365-368.
10. Heres S, Davis J, Maino K, et al. Why olanzapine beats risperidone, risperidone beats quetiapine, and quetiapine beats olanzapine: an exploratory analysis of head-to-head comparison studies of second-generation antipsychotics. Am J Psychiatry. 2006;163: 185-194.
11. Hennen J, Baldessarini RJ. Suicidal risk during treatment with clozapine: a meta-analysis. Schizophr Res. 2005;73:139-145.
12. Meltzer HY, Alphs L, Green AI, et al. Clozapine treatment for suicidality in schizophrenia. Arch Gen Psychiatry. 2003;60:82-91.
13. Clozaril approved for reducing risk of suicide. FDA Consum. 2003;37:5.
14. Moore TA, Buchanan RW, Buckley PF, et al. The Texas Medication Algorithm Project antipsychotic algorithm for schizophrenia: 2006 update. J Clin Psychiatry. 2007;68:1751-1762.
15. Herings RM, Erkens JA. Increased suicide attempt rate among patients interrupting use of atypical antipsychotics. Pharmacoepidemiol Drug Saf. 2003;12: 423-424.
16. Ward A, Ishak K, Proskorovsky I, Caro J. Compliance with refilling prescriptions for atypical antipsychotic agents and its association with the risks for hospitalization, suicide, and death in patients with schizophrenia in Quebec and Saskatchewan: a retrospective database study. Clin Ther. 2006;28:1912-1921.
17. Capel MM, Colbridge MG, Henry JA. Overdose profiles of new antipsychotic agents. Int J Neuropsychopharmacol. 2000;3:51-54.
18. Griffiths C, Flanagan RJ. Fatal poisoning with antipsychotic drugs, England and Wales 1993-2002. J Psychopharmacol. 2005;19:667-674.
19. Altamura AC, Bassetti R, Bignotti S, et al. Clinical variables related to suicide attempts in schizophrenic patients: a retrospective study. Schizophr Res. 2003;60:47-55.
20. Barak Y, Mirecki I, Knobler HY, et al. Suicidality and second generation antipsychotics in schizophrenia patients: a case-controlled retrospective study during a 5-year period. Psychopharmacology. 2004;175: 215-219.
21. Kissling W, Glue P, Medori R, Simpson S. Long-term safety and efficacy of long-acting risperidone in elderly psychotic patients. Hum Psychopharmacol. 2007;22:505-513.
22. Glazer WM. Formulary decisions and health economics. J Clin Psychiatry. 1998;59:23-29.
23. Tran PV, Hamilton SH, Kuntz AJ, et al. Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders. J Clin Psychopharmacol. 1997;17:407-418.
24. Tandon R. Improvement without impairment: a review of clinical data for quetiapine in the treatment of schizophrenia. J Clin Psychopharmacol. 2003;23: 15-20.
25. Peuskens J, Moore N, Azorin JM, et al. The European sertindole safety and exposure survey: a follow-up study of 8600 patients. Pharmacoepidemiol Drug Saf. 2007;16:804-811.
26. Holzer L, Eap CB. Aripiprazole and suicidality. Int Clin Psychopharmacol. 2006;21:125-126.
27. Carstairs SD, Williams SR. Overdose of aripiprazole, a new type of antipsychotic. J Emerg Med. 2005; 28:311-313.
28. Hawton K, Sutton L, Haw C, et al. Schizophrenia and suicide: systematic review of risk factors. Br J Psychiatry. 2005;187:9-20.
29. Acosta FJ, Aguilar EJ, Cejas MR, et al. Are there subtypes of suicidal schizophrenia? A prospective study. Schizophr Res. 2006;86:215-220.
30. Mizrahi R, Rusjan P, Agid O, et al. Adverse subjective experience with antipsychotics and its relationship to striatal and extrastriatal D2 receptors: a PET study in schizophrenia. Am J Psychiatry. 2007; 164: 630-637.
31. Rachid F, Bertschy G, Bondolfi G, Aubry JM. Possible induction of mania or hypomania by atypical antipsychotics: an updated review of reported cases. J Clin Psychiatry. 2004;65:1537-1545.
32. Kaptsan A, Dwolatzky T, Lerner V. Ziprasidone-associated depressive state in schizophrenic patients. Clin Neuropharmacol. 2007;30:357-361.
33. Mergui J, Jaworowski S, Lerner V. Quetiapine-associated depression in a patient with schizophrenia. Clin Neuropharmacol. 2005;28:133-135.
34. Aguilar EJ, Leal C, Acosta FJ, et al. A psychopathological study of a group of schizophrenic patients after attempting suicide. Are there two different clinical subtypes? Eur Psychiatry. 2003;18:190-192.
35. McGirr A, Tousignant M, Routhier D, et al. Risk factors for completed suicide in schizophrenia and other chronic psychotic disorders: a case-control study. Schizophr Res. 2006;84:132-143.
36. American Psychiatric Association. Practice Guideline for the Treatment of Patients With Schizophrenia. 2nd ed. Arlington, Va: American Psychiatric Association; 2004.
37. McGirr A, Turecki G. The relationship of impulsive aggressiveness to suicidality and other depression-linked behaviors. Curr Psychiatry Rep. 2007;9:460-466.
38. Citrome L, Volavka J, Czobor P, et al. Effects of clozapine, olanzapine, risperidone, and haloperidol on hostility among patients with schizophrenia. Psychiatr Serv. 2001;52:1510-1514.
39. Potkin SG, Alphs L, Hsu Ch, et al. Predicting suicidal risk in schizophrenic and schizoaffective patients in a prospective two-year trial. Biol Psychiatry. 2003;54:444-452.
40. Hansen L, Jones RM, Kingdon D. No association between akathisia or parkinsonism and suicidality in treatment-resistant schizophrenia. J Psychopharmacol. 2004;18:384-387.
41. Hansen L. A critical review of akathisia, and its possible association with suicidal behaviour. Hum Psychopharmacol. 2001;16:495-505.
42. Tollefson GD, Sanger TM, Lu Y, et al. Depressive signs and symptoms in schizophrenia: a prospective blinded trial of olanzapine and haloperidol. Arch Gen Psychiatry. 1998;55:250-258.
43. Kinon BJ, Lipkovich I, Edwards SB, et al. A 24-week randomized study of olanzapine versus ziprasidone in the treatment of schizophrenia or schizoaffective disorder in patients with prominent depressive symptoms. J Clin Psychopharmacol. 2006;26:157-162.
44. Tollefson GD, Andersen SW, Tran PV. The course of depressive symptoms in predicting relapse in schizophrenia: a double-blind, randomized comparison of olanzapine and risperidone. Biol Psychiatry. 1999;46: 365-373.
45. Dollfus S, Olivier V, Chabot B, et al. Olanzapine versus risperidone in the treatment of post-psychotic depression in schizophrenic patients. Schizophr Res. 2005;78:157-159.
46. Conley RR, Mahmoud R. A randomized double-blind study of risperidone and olanzapine in the treatment of schizophrenia or schizoaffective disorder. Am J Psychiatry. 2001;158:765-774.
47. Peuskens J, Van Baelen B, De Smedt, Lemmens P. Effects of risperidone on affective symptoms in patients with schizophrenia. Int Clin Psychopharmacol. 2000;15:343-349.
48. Myers JE, Thase ME. Risperidone: review of its therapeutic utility in depression. Psychopharmacol Bull. 2001;35:109-129.
49. Davis JM, Chen N. Clinical profile of an atypical antipsychotic: risperidone. Schizophr Bull. 2002;28: 43-61.
50. Canuso C, Bossie C A, Zhu Y, et al. Long-acting risperidone reduces symptoms of depression and anxiety in patients with schizophrenia and schizoaffective disorder. Bipolar Disord. 2003;5:38.
51. Mohl A, Westlye K, Opjordsmoen S, et al. Long-acting risperidone in stable patients with schizoaffective disorder. J Psychopharmacol. 2005;19:22-31.
52. Peuskens J, Möller HJ, Puech A. Amisulpride improves depressive symptoms in acute exacerbations of schizophrenia: comparison with haloperidol and risperidone. Eur Neuropsychopharmacol. 2002;12: 305-310.
53. Vanelle JM, Douki S. A double-blind randomised comparative trial of amisulpride versus olanzapine for 2 months in the treatment of subjects with schizophrenia and comorbid depression. Eur Psychiatry. 2006;21:523-530.
54. Sechter D, Peuskens J, Fleurot O, et al. Amisulpride vs risperidone in chronic schizophrenia: results of a 6-month double-blind study. Neuropsychopharmacology. 2002;27:1071-1081.
55. Kim SW, Shin IS, Kim JM, et al. Amisulpride versus risperidone in the treatment of depression in patients with schizophrenia: a randomized, open-label, controlled trial. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31:1504-1509.
56. Buckley PF. Efficacy of quetiapine for the treatment of schizophrenia: a combined analysis of three placebo-controlled trials. Curr Med Res Opin. 2004; 20:1357-1363.
57. Kasper S. Quetiapine is effective against anxiety and depressive symptoms in long-term treatment of patients with schizophrenia. Depress Anxiety. 2004; 20:44-47.
58. Emsley RA, Buckley P, Jones AM, Greenwood MR. Differential effect of quetiapine on depressive symptoms in patients with partially responsive schizophrenia. J Psychopharmacol. 2003;7:254-257.
59. Ruhrmann S, Kissling W, Lesch OM, et al. Efficacy of flupentixol and risperidone in chronic schizophrenia with predominantly negative symptoms. Prog Neuropsychopharmacol Biol Psychiatry. 2007;31: 1012-1022.
60. Simpson GM, Glick ID, Weiden PJ, et al. Randomized, controlled, double-blind multicenter comparison of the efficacy and tolerability of ziprasidone and olanzapine in acutely ill inpatients with schizophrenia or schizoaffective disorder. Am J Psychiatry. 2004;161: 1837-1847.
61. Mitsonis CI, Dimopoulos NP, Mitropoulos PA, et al. Aripiprazole augmentation in the management of residual symptoms in clozapine-treated outpatients with chronic schizophrenia: an open-label pilot study. Prog Neuropsychopharmacol Biol Psychiatry. 2007; 31:373-377.
62. Kasper S, Lerman MN, McQuade RD, et al. Efficacy and safety of aripiprazole vs. haloperidol for long-term maintenance treatment following acute relapse of schizophrenia. Int J Neuropsychopharmacol. 2003;6:325-337.
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