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

¹⁶

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: https://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):

• Teva: www.clozapineregistry.com.
  
• Clozaril: www.clozarilcare.com.
  
• Caraco: www.caracoclozapine.com.
  
• FazaClo: www.fazacloregistry.com.
  
• Mylan: www.mylan-clozapine.com.
  

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.