CNS Drugs

, Volume 17, Issue 4, pp 273–280 | Cite as


In Prevention of Suicide in Patients with Schizophrenia or Schizoaffective Disorder
  • Antona J. Wagstaff
  • Caroline M. Perry
Adis Drug Profile


▴ The atypical antipsychotic agent clozapine is associated with a lower propensity for extrapyramidal symptoms than classical antipsychotic agents.

▴ The pharmacokinetics of clozapine are affected by wide interpatient variability and a potential for drug interactions. Some studies have shown a relationship between plasma concentrations, duration of treatment and antipsychotic clinical response.

▴ Clozapine (mean 274.2 mg/day; n = 490) had a greater preventive effect on suicidality among patients with schizophrenia or schizoaffective disorder at high risk for suicide than olanzapine (mean 16.6 mg/day; n = 490) in a randomised, rater-blinded, multicentre study (p < 0.05; a 22–24% improvement).

▴ Other prospective noncomparative trials of the effects of clozapine on suicidal ideation or attempts endorsed these results, while results from retrospective trials are equivocal.

▴ Clozapine is commonly associated with sedation, hypersalivation, tachycardia, dizziness, constipation and orthostatic hypotension. Agranulocytosis, diabetes mellitus and weight gain may also occur.


Schizophrenia Clozapine Olanzapine Suicide Attempt Suicidal Behaviour 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Raymont V. Suicide in schizophrenia: how can research influence training and clinical practice? Psychiatric Bull 2001; 25(2): 46–50CrossRefGoogle Scholar
  2. 2.
    Meltzer HY. Suicidality in schizophrenia: a review of the evidence for risk factors and treatment options. Curr Psychiatry Rep 2002 Aug; 4(4): 279–83PubMedCrossRefGoogle Scholar
  3. 3.
    Allebeck P. Schizophrenia: a life-shortening disease. Schizophr Bull 1989; 15(1): 81–9PubMedCrossRefGoogle Scholar
  4. 4.
    Siris SG. Suicide and schizophrenia. J Psychopharmacol 2001 Jun; 15(2): 127–35PubMedCrossRefGoogle Scholar
  5. 5.
    Meltzer HY. Suicide in schizophrenia: risk factors and clozapine treatment. J Clin Psychiatry 1998; 59 Suppl. 3: 15–20Google Scholar
  6. 6.
    Heilä H, Isometsä ET, Henriksson MM, et al. Suicide victims with schizophrenia in different treatment phases and adequacy of antipsychotic medication. J Clin Psychiatry 1999; 60(3): 200–8PubMedCrossRefGoogle Scholar
  7. 7.
    Meltzer HY, Alphs L, Green AI, et al. Clozapine treatment for suicidality in schizophrenia: international suicide prevention trial (InterSePT). Arch Gen Psychiatry 2003; 60: 82–91PubMedCrossRefGoogle Scholar
  8. 8.
    FDA. FDA approves Clozaril to reduce the risk of suicidal behavior in patients with schizophrenia or schizoaffective disorder [online]. Available from URL: [Accessed 2002 Dec 20]
  9. 9.
    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. CNS Drugs 1995; 4(5): 370–400CrossRefGoogle Scholar
  10. 10.
    Fitton A, Benfield P. Clozapine: an appraisal of its pharmacoeconomic benefits in the treatment of schizophrenia. Pharmacoeconomics 1993; 4(2): 131–56PubMedCrossRefGoogle Scholar
  11. 11.
    Josselyn SA, Miller R, Beninger RJ. Behavioral effects of clozapine and dopamine receptor subtypes. Neurosci Biobehav Rev 1997 Sep; 21(5): 531–58PubMedCrossRefGoogle Scholar
  12. 12.
    Meltzer HY, Anand R, Alphs L. Reducing suicide risk in schizophrenia: focus on the role of clozapine. CNS Drugs 2000; 14(5): 355–65CrossRefGoogle Scholar
  13. 13.
    Spivak B, Lamschtein C, Talmon Y, et al. The impact of clozapine treatment on serum lipids in chronic schizophrenic patients. Clin Neuropharmacol 1999 Mar; 22(2): 98–101PubMedCrossRefGoogle Scholar
  14. 14.
    Margolese HC, Chouinard G, Beauclair L. Relationship between akathisia and tardive dyskinesia and suicidality in schizophrenia: impact of clozapine, olanzapine and risperidone [abstract no. P.01.008]. Int J Neuropsychopharmacol 2000 Jul; 3Suppl. 1: S94Google Scholar
  15. 15.
    Atbaşo EC, Schultz SK, Andreasen NC. The relationship of akathisia with suicidality and depersonalization among patients with schizophrenia. J Neuropsychiatry Clin Neurosci 2001; 13(3): 336–41CrossRefGoogle Scholar
  16. 16.
    Roggenbach J, Müller-Oerlinghausen B, Franke L. Suicidality, impulsivity and aggression: is there a link to 5HIAA concentration in the cerebrospinal fluid? Psychiatry Res 2002 Dec 15: 113 (1–2): 193-206Google Scholar
  17. 17.
    Hu RJ, Malhotra AK, Pickar D. Predicting response to clozapine: status of current research. CNS Drugs 1999 Apr; 11(4): 317–26CrossRefGoogle Scholar
  18. 18.
    Spivak B, Roitman S, Vered Y, et al. Diminished suicidal and aggressive behavior, high plasma norepinephrine levels, and serum triglyceride levels in chronic neuroleptic-resistant schizophrenic patients maintained on clozapine. Clin Neuropharmacol 1998 Jul; 21(4): 245–50PubMedGoogle Scholar
  19. 19.
    Mantel-Teeuwisse AK, Kloosterman JME, Maitland-van der Zee AH, et al. Drug-induced lipid changes: a review of the unintended effects of some commonly used drugs on serum lipid levels. Drug Saf 2001; 24(6): 443–56PubMedCrossRefGoogle Scholar
  20. 20.
    Henderson DC. Clozapine: diabetes mellitus, weight gain, and lipid abnormalities. J Clin Psychiatry 2001; 62 Suppl. 23: 39–44Google Scholar
  21. 21.
    Mancama D, Arranz MJ, Kerwin RW. Genetic predictors of therapeutic response to clozapine: current status of research. CNS Drugs 2002; 16(5): 317–24PubMedCrossRefGoogle Scholar
  22. 22.
    Fontaine KR, Heo M, Harrigan EP, et al. Estimating the consequences of anti-psychotic induced weight gain on health and mortality rate. Psychiatry Res 2001 Apr 15; 101(3): 277–88PubMedCrossRefGoogle Scholar
  23. 23.
    Masellis M, Basile VS, Özdemir V, et al. Pharmacogenetics of antipsychotic treatment: lessons learned from clozapine. Biol Psychiatry 2000 Feb 1; 47(3): 252–66PubMedCrossRefGoogle Scholar
  24. 24.
    Cheng YF, Lundberg T, Bondesson U, et al. Clinical pharmacokinetics of clozapine in chronic schizophrenic patients. Eur J Clin Pharmacol 1988; 34: 445–9PubMedCrossRefGoogle Scholar
  25. 25.
    Byerly MJ, DeVane CL. Pharmacokinetics of clozapine and risperidone: a review of recent literature. J Clin Psychopharmacol 1996 Apr; 16(2): 177–87PubMedCrossRefGoogle Scholar
  26. 26.
    Novartis. Clozaril® (clozapine) tablets: prescribing information [online]. Available from URL: [Accessed 2002 Dec 11]
  27. 27.
    Edge SC, Markowitz JS, Devane CL. Clozapine drug-drug interactions: a review of the literature. Hum Psychopharmacol 1997 Jan; 12: 5–20CrossRefGoogle Scholar
  28. 28.
    Ciapparelli A, Dell’Osso L, Pini S, et al. Clozapine for treatment-refractory schizophrenia, schizoaffective disorder, and psychotic bipolar disorder: a 24-month naturalistic study. J Clin Psychiatry 2000 May; 61(5): 329–34PubMedCrossRefGoogle Scholar
  29. 29.
    Meltzer HY, Okayli G. Reduction of suicidality during clozapine treatment of neuroleptic-resistant schizophrenia: impact on risk-benefit assessment. Am J Psychiatry 1995 Feb; 152(2): 183–90PubMedGoogle Scholar
  30. 30.
    Modai I, Hirschmann S, Rava A, et al. Sudden death in patients receiving clozapine treatment: a preliminary investigation. J Clin Psychopharmacol 2000 Jun; 20(3): 325–7PubMedCrossRefGoogle Scholar
  31. 31.
    Reid WH, Mason M, Hogan T. Suicide prevention effects associated with clozapine therapy in schizophrenia and schizoaffective disorder. Psychiatr Serv 1998 Aug; 49(8): 1029–33PubMedGoogle Scholar
  32. 32.
    Sajatovic M, Bingham CR, Garver D, et al. An assessment of clinical practice of clozapine therapy for veterans. Psychiatr Serv 2000 May; 51(5): 669–71PubMedCrossRefGoogle Scholar
  33. 33.
    Sernyak MJ, Desai R, Stolar M, et al. Impact of clozapine on completed suicide. Am J Psychiatry 2001 Jun; 158(6): 931–7PubMedCrossRefGoogle Scholar
  34. 34.
    Walker AM, Lanza LL, Arellano F, et al. Mortality in current and former users of clozapine. Epidemiology 1997 Nov; 8(6): 671–7PubMedGoogle Scholar
  35. 35.
    Reinstein MJ, Chasonov MA, Colombo KD, et al. Reduction of suicidality in patients with schizophrenia receiving clozapine. Clin Drug Invest 2002; 22(5): 341–6CrossRefGoogle Scholar
  36. 36.
    Barnes TRE, McPhillips MA. Critical analysis and comparison of the side-effect and safety profiles of the new antipsychotics. Br J Psychiatry 1999 May; 174 Suppl. 38: 34–43Google Scholar
  37. 37.
    Honigfeld G, Arellano F, Sethi J, et al. Reducing clozapine-related morbidity and mortality: 5 years of experience with the Clozaril National Registry. J Clin Psychiatry 1998; 59 Suppl. 3: 3–7Google Scholar
  38. 38.
    Munro J, O’Sullivan D, Andrews C, et al. Active monitoring of 12760 clozapine recipients in the UK and Ireland: beyond pharmacovigilance. Br J Psychiatry 1999 Dec; 175: 576–80PubMedCrossRefGoogle Scholar
  39. 39.
    Herst L, Powell G. Is clozapine safe in the elderly? Aust N Z J Psychiatry 1997 Jun; 31(3): 411–7PubMedCrossRefGoogle Scholar
  40. 40.
    Barbui C, Campomori A, Bonati M. Clozapine and blood dyscrasias different from agranulocytosis [letter]. Can J Psychiatry 1997 Nov; 42(9): 981–2PubMedGoogle Scholar
  41. 41.
    Gianfrancesco FD, Grogg AL, Mahmoud RA, et al. Differential effects of risperidone, olanzapine, clozapine, and conventional antipsychotics on type 2 diabetes: findings from a large health plan database. J Clin Psychiatry 2002 Oct; 63(10): 920–30PubMedCrossRefGoogle Scholar
  42. 42.
    Kang UG, Kwon JS, Ahn YM, et al. Electrocardiographic abnormalities in patients treated with clozapine. J Clin Psychiatry 2000 Jun; 61(6): 441–6PubMedCrossRefGoogle Scholar
  43. 43.
    Hägg S, Spigset O, Bate A, et al. Myocarditis related to clozapine treatment. J Clin Psychopharmacol 2001 Aug; 21(4): 382–8PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

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