Evidence-Based Reviews

Clozapine for schizophrenia: Life-threatening or life-saving treatment?

Current Psychiatry. 2009 December;8(12):56-63

References

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2. Schulte PFJ. Risk of clozapine-associated agranulocytosis and mandatory white blood cell monitoring. Ann Pharmacother. 2006;40:683-688.

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4. Lehman AF, Lieberman JA, Dixon LB, et al. Practice guideline for the treatment of patients with schizophrenia, second edition. Am J Psychiatry. 2004;161(2 suppl):1-56.

5. Citrome L, Jaffe A, Martello D, et al. Did CATIE influence antipsychotic use? Psychiatr Serv. 2008;59(5):476.-

6. Krakowski MI, Czobor P, Citrome L, et al. Atypical antipsychotic agents in the treatment of violent patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry. 2006;63(6):622-629.

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(1):82-91.Erratum in: Arch Gen Psychiatry. 2003;60(7):735.

8. McEvoy JP, Lieberman JA, Stroup TS, et al. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry. 2006;163(4):600-610.

9. Citrome L. Compelling or irrelevant? Using number needed to treat can help decide. Acta Psychiatr Scand. 2008;117(6):412-419.

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17. Annamraju S, Sheitman B, Saik S, et al. Early recognition of clozapine-induced myocarditis. J Clin Psychopharmacol. 2007;27(5):479-483.

18. Citrome L. Adjunctive lithium and anticonvulsants for the treatment of schizophrenia: what is the evidence? Expert Rev Neurother. 2009;9(1):55-71.

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Table

Common adverse effects of clozapine

Adverse effect	Frequency*
Hypersalivation	31% to 48%
Drowsiness/sedation/somnolence	39% to 46%
Weight increase	31%
Tachycardia	25%
Dizziness/vertigo	19% to 27%
Constipation	14% to 25%
Seizures	5% (can be higher with doses approaching 900 mg/d); slow titration needed
*Pooled data from clinical trials reporting percentage of patients taking clozapine who experienced adverse effects
Source: Prescribing information for Clozaril® brand clozapine tablets. Available at: http://www.pharma.us.novartis.com/product/pi/pdf/Clozaril.pdf. Accessed October 27, 2009

Myocarditis may be difficult to diagnose, and commonly used tests have limited sensitivity. A symptom questionnaire—such as described by Annamraju et al¹⁷—may help with earlier recognition of this potentially fatal complication, particularly during the first weeks of clozapine treatment.

Adjunctive treatments. Patients with a low baseline white blood cell count (WBC) and/or absolute neutrophil count (ANC) may benefit from adjunctive lithium treatment to increase their WBC, as demonstrated in case reports.¹⁸

When no other alternatives were clinically feasible, chronic treatment with granulocyte colony-stimulating factor (filgrastim) has been used successfully for some patients whose clozapine course was interrupted because of a low WBC and/or ANC.¹⁹

Related resources

Clozapine product information (as revised July 2009): www.pharma.us.novartis.com/product/pi/pdf/Clozaril.pdf.
Citrome L. Compelling or irrelevant? Using number needed to treat can help decide. Acta Psychiatr Scand. 2008;117(6):412-419.

Clozapine registries (by manufacturer):

Drug brand names

Chlorpromazine • Thorazine
Clozapine • Clozaril, FazaClo
Filgrastim • Neupogen
Haloperidol • Haldol
Lithium • Lithobid, others
Olanzapine • Zyprexa
Perphenazine • Trilafon
Quetiapine • Seroquel
Risperidone • Risperdal
Thioridazine • Mellaril
Ziprasidone • Geodon

Disclosures

Dr. Citrome is a consultant for, has received honoraria from, or has conducted clinical research supported by Abbott Laboratories, AstraZeneca, Avanir Pharmaceuticals, Azur Pharma Inc., Barr Laboratories, Bristol-Myers Squibb, Eli Lilly and Company, Forest Research Institute, GlaxoSmithKline, Janssen Pharmaceuticals, Jazz Pharmaceuticals, Pfizer Inc., Schering-Plough Corporation, and Vanda Pharmaceuticals. No writing assistance or external financial support was utilized in the preparation of this review article.