Abstract
The risk of suicide is a major factor in the morbidity and mortality of schizophrenia, accounting for approximately 10% of deaths in patients with this condition. Indicated risk factors include male gender, social isolation, depression, feelings of hopelessness, a history of suicide attempts, deteriorating health and, uniquely to patients with schizophrenia, young age in men and chronic schizophrenia with numerous exacerbations.
There is significant evidence suggesting that clozapine, the gold standard treatment for patients with treatment-resistant schizophrenia, reduces the suicide rate. Although the reasons for this are unknown, beneficial effects of clozapine that are thought to contribute to the reduced suicide rate include improved symptom control, reduced extrapyramidal symptoms, direct antidepressant action, improved cognitive function, and improved compliance. These improve self-perceived quality of life and hence lead to greater desire, and capacity, to survive. Reduced suicide attempts and completed suicide may also reflect the effect of weekly contact with mental health providers to obtain blood for white blood cell monitoring or cohort effects (i.e. time-dependent decrease in suicide attempt rates).
Data from a number of studies which have investigated the impact of clozapine on suicide rates in patients with schizophrenia demonstrate that the drug reduces the risk of suicide attempts by approximately 75 to 80%. It had a comparable effect in reducing the completed suicide rate in an epidemiological survey of all US patients in the Clozaril® National Registry.
A large scale prospective, randomised study comparing clozapine and olanzapine in patients with a recent history of suicidality is in process. The International Suicide Prevention Trial (InterSePT) will compare the effectiveness of clozapine (300 to 900 mg/day) with olanzapine (10 to 20 mg/day) in reducing suicide and suicide-related events in patients with schizophrenia and schizoaffective disor-der. An overview of the study methodology is provided in this review.
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References
Cohen LJ, Test MA, Brown RL. Suicide and schizophrenia: data from a prospective community treatment study. Am J Psychiatry 1990; 147: 602–7
Bleuler E (Translated by J. Zinkin). Dementia praecox of the group of schizophrenias (1911). New York: International Universities Press, 1950
Allebeck P. Schizophrenia: a life-shortening disease. Schizophr Bull 1989; 15: 81–9
Mortensen PB, Juel K. Mortality and causes of death in first admitted schizophrenic patients. Br J Psychiatry 1993; 163: 183–9
Carpenter WT, Buchanan RW. Schizophrenia. N Engl J Med 1994; 330: 681–90
Martin P. Medical economic impact of schizophrenia. Encephale 1995; 21: 67–73
Caldwell CB, Gottesman II. Schizophrenia — a high-risk factor for suicide: clues to risk reduction. Suicide Life Threat Behav 1992; 22: 479–93
Black DW. Mortality in schizophrenia — the Iowa Record-Linkage Study: a comparison with general population mortality. Psychosomatics 1988; 29: 55–60
Inskip HM, Harris EC, Barraclough B. Lifetime risk of suicide for affective disorder, alcoholism and schizophrenia. Br J Psychiatry 1998; 172: 35–7
Cooper PN, Milroy CM. The coroner’s system and under-reporting of suicide. Med Sci Law 1995; 35: 319–26
Ohberg A, Lonnqvist J. Suicides hidden among undetermined deaths. Acta Psychiatr Scand 1998; 98: 214–8
Niskanen P, Lonnqvist S, Achte K. Schizophrenia and suicide. Psychiatria Fennica 1973: 223-7
Planansky K, Johnston R. The occurrence and characteristics of suicidal preoccupation and acts in schizophrenia. Acta Psychiatr Scand 1971; 47: 473–83
Ettlinger R. Evaluation of suicide prevention after attempted suicide. Acta Psychiatr Scand Suppl. 1975; 260: 64–124
Meltzer HY. Suicidality and clozapine. J Clin Psychiatry 1996; 14: 13–5
Yarden P. Observations on suicide in chronic schizophrenics. Compr Psychiatry 1974; 15: 325–33
Axelsson R, Lagerkvist-Briggs M. Factors predicting suicide in psychotic patients. Eur Arch Psychiatry Clin Neurosci 1992; 241: 259–66
Caldwell CB, Gottesman II. Schizophrenics kill themselves too: a review of risk factors for suicide. Schizophr Bull 1990; 16: 571–89
Beck AT, Steer RA, Kovacs M, et al. Hopelessness and eventual suicide: a 10-year prospective study of patients hospitalized with suicidal ideation. Am J Psychiatry 1985; 142: 559–63
Black DW, Winokur G. Age, mortality and chronic schizophrenia. Schizophr Res 1988; 1: 267–72
Stephens JH, Richard P, McHugh PR. Suicide in patients hospitalized for schizophrenia: 1913–1940. J Nerv Ment Dis 1999; 187: 10–4
Drake RE, Cotton PG. Depression, hopelessness and suicide in chronic schizophrenia. Br J Psychiatry 1986; 148: 554–9
Krausz M, Müller-Thomsen T, Haasen C. Suicide among schizophrenic adolescents in the long-term course of illness. Psychopathology 1995; 28: 95–103
Heila H, Isometsa ET, Henriksson MM, et al. Suicide and schizophrenia: a nationwide psychological autopsy study on age- and sex-specific clinical characteristics of 92 suicide victims with schizophrenia. Am J Psychiatry 1997; 154: 1235–42
Steblaj A, Tavcar R, Dernovsek MZ. Predictors of suicide in psychiatric hospital. Acta Psychiatr Scand 1999; 100: 383–8
Gupta S, Black DW, Arndt S, et al. Factors associated with suicide attempts among patients with schizophrenia. Psychiatr Serv 1998; 49: 1353–5
Harkavy-Friedman JM, Restifo K, Malaspina D, et al. Suicidal behavior in schizophrenia: characteristics of individuals who had and had not attempted suicide. Am J Psychiatry 1999; 156: 1276–8
Meltzer HY, Okayli G. Reduction of suicidality during clozapine treatment of neuroleptic-resistant schizophrenia: impact on risk-benefit assessment. Am J Psychiatry 1995; 152: 183–90
Ciompi L. Late suicide in former mental patients. Psychiatr Clin (Basel) 1976; 9: 59–63
Winokur G, Tsuang M. The Iowa 500: Suicide in mania, depression and schizophrenia. Am J Psychiatry 1975; 132: 650–1
Drake RE, Ehrlich J. Suicide attempts associated with akathisia. Am J Psychiatry 1985; 142: 499–501
Shear MK, Frances A, Weiden P. Suicide associated with akathisia and depot fluphenazine treatment. Suicide 1983; 3: 235–6
Hamilton MS, Opler LA. Akathisia, suicidality and fluoxetine. J Clin Psychiatry 1992; 53: 401–6
Kerwin RW. The new atypical antipsychotics. A lack of extrapyramidal side-effects and new routes in schizophrenia research. Br J Psychiatry 1994; 164: 141–8
Claghorn J, Honifeld G, Abuzzahab FS, et al. The risks and benefits of clozapine versus chlorpromazine. J Clin Psychopharmacol 1987; 7: 377–84
Kane J, Honigfeld G, Singer J, et al. Clozapine for the treatment-resistant schizophrenic: a double-blind comparison with chlorpromazine. Arch Gen Psychiatry 1988; 45: 789–96
Meltzer HY. Treatment-resistant schizophrenia — the role of clozapine. Curr Med Res Opin 1997; 14: 1–20
Reid WH, Mason M, Hogan T. Suicide prevention effects associated with clozapine therapy in schizophrenia and schizo-affective disorder. Psychiatr Serv 1998; 49: 1029–33
Spivak B, Roitman S, Vered Y, et al. Diminished suicidal and aggressive behaviour high plasma norepinephrine levels and serum triglyceride levels in chronic neuroleptic-resistant schizophrenic patients maintained on clozapine. Clin Neuropharmacol 1998; 21: 245–50
Walker AM, Lanza LL, Arellano F, et al. Mortality in current and former users of clozapine. Epidemiology 1997; 8: 671–7
Altamura AC, Binotti S, Pioli R, et al. Suicidal behaviour in schizophrenia: a retrospective study. Eur Neuropsychopharmacol 1999; 9 Suppl. 5: S271
American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. 3rd rev. ed. Washington, DC: American Psychiatric Association, 1994
Data on file, Novartis US Clozaril® National Registry, 1998
Alvir JMJ, Lieberman JA, Safferman AZ, et al. Clozapine-induced agranulocytosis. Incidence and risk factors in the United States. N Engl J Med 1993; 329: 162–7
Conley RR. Optimizing treatment with clozapine. J Clin Psychiatry 1998; 59: 44–8
Asberg M. Neurotransmitters and suicidal behaviour. The evidence from cerebrospinal fluid studies. Ann NY Acad Sci 1997; 836: 158–81
Cooper SJ, Kelly CB, King DJ. 5-hydroxyindoleacetic acid in cerebrospinal fluid and prediction of suicidal behaviour in schizophrenia. Lancet 1992; 340: 940–1
Tuckwell HC, Koziol JA. On the concentration of 5-hydroxyindoleacetic acid in schizophrenia: a meta-analysis. Psychiatry Res 1996; 59: 239–44
Rao ML, Hawellek B, Papassotiropoulos A, et al. Upregulation of the platelet serotonin2A receptor and low blood serotonin in suicidal psychiatric patients. Neuropsychobiology 1998; 38: 84–9
Du L, Bakish D, Yvon D, et al. Association of polymorphism of serotonin 2A receptor gene with suicidal ideation in major depressive disorder. Am J Med Genet 2000; 96(1): 56–60
Wagstaff AJ, Bryson HM. Clozapine: a review of its pharmacological properties and therapeutic use in patients with schizophrenia who are unresponsive to or intolerant of classical antipsychotic agents. Drugs 1995; 4: 370–400
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Meltzer, H.Y., Anand, R. & Alphs, L. Reducing Suicide Risk in Schizophrenia. Mol Diag Ther 14, 355–365 (2000). https://doi.org/10.2165/00023210-200014050-00003
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DOI: https://doi.org/10.2165/00023210-200014050-00003