Agranulocytosis. Obtain white blood cell (WBC) count and differential at baseline, during treatment, and for 4 weeks after discontinuing clozapine, following the distribution program’s required schedule. Advise patients to immediately report flu-like complaints or signs that might suggest infection, such as lethargy, weakness, fever, sore throat, malaise, or mucous membrane ulceration.
Eosinophilia. In clinical trials, 1% of patients developed eosinophilia, which can be substantial in rare cases. If a differential count reveals a total eosinophil count >4,000/mm3 , stop clozapine therapy until the eosinophil count falls below 3,000/mm3 .
Myocarditis. Clozapine-treated patients are at much greater risk for developing myocarditis and of dying from it—especially during the first 6 weeks of therapy—than is the general population.3 Tachycardia can be a presenting sign.
Abnormal laboratory findings associated with clozapine-induced myocarditis may include increased WBC count, eosinophilia, increased erythrocyte sedimentation rate, and increased cardiac enzyme levels and plasma troponin. Because the mortality rate of clozapine-induced myocarditis approaches 40%, stop clozapine and refer the patient for medical evaluation as soon as possible when you suspect myocarditis.3
Endocrine and hepatic effects. Severe hyperglycemia, sometimes leading to ketoacidosis, can occur during clozapine treatment in patients without a history of hyperglycemia. Ketoacidosis symptoms include rapid breathing, nausea, vomiting, clouding of sensorium (even coma), weight loss, polyuria, polydipsia, and dehydration. Monitoring for blood glucose changes, as described in Table 1, is recommended with clozapine as with all other atypical antipsychotics.
Hepatitis during clozapine therapy has been reported in patients with baseline normal or preexisting abnormal liver function. After baseline liver function tests, we suggest follow-up LFTs:
- annually for patients with normal baseline values
- every 6 months for patients with minimally abnormal values
- every 3 months for patients with liver disease.
MONITORING SUBSTANCE ABUSE
Substance abuse is often associated with medical comorbidities that require laboratory workup and monitoring. These include overdose sequelae, sexual assault, cirrhosis, endocarditis, HIV infection, viral hepatitis, tuberculosis, and syphilis. Some testing is mandated by federal law for patients in methadone maintenance or opioid agonist therapy programs with methadone.
We recommend that new patients with substance abuse be screened for organic illness as described above, plus the workup in Table 4. Also gather a careful history for hepatitis, pancreatitis, diabetes, cirrhosis, unusual infections (cellulitis, endocarditis, atypical pneumonias, HIV), frequent hospitalizations, falls, injuries, and blackouts.
Obtain a blood alcohol level in alcohol-intoxicated patients and urine toxicology to screen for locally-available street drugs (typically marijuana, sedative/hypnotics, amphetamines, cocaine, opiates, and phencyclidine).
Confer with your laboratory staff about the capabilities and sensitivities of their drug testing methods. Marijuana may be detected for 3 days to 4 weeks, depending on level of use. Cocaine can be detected for up to 2 to 4 days in urine.
- Rosse RB, Deutsch LH, Deutsch SI. Medical assessment and laboratory testing in psychiatry. In: Sadock B, Kaplan HI (eds). Comprehensive textbook of psychiatry, 6th ed. Baltimore: Lippincott, Williams & Wilkins 1995:601-19.
- National Institute of Diabetes and Digestive and Kidney Diseases. Body mass index tables. www.niddk.nih.gov/health/nutrit/pubs/statobes.htm#table.
- National Cholesterol Education Program. Guidelines for managing patients at risk for coronary heart disease. www.nhlbi.nih.gov/about/ncep/
- Food and Drug Administration. Guidelines on hyperglycemia associated with atypical antipsychotics [example]. www.fda.gov/medwatch/SAFETY/2004/Clozaril-deardoc.pdf
Drug brand names
- Carbamazepine • Carbatrol, others
- Clozapine • Clozaril
- Lithium • Lithobid, others
- Mesoridazine • Serentil
- Pimozide • Orap
- Thioridazine • Mellaril
- Valproate • Depakote, Depakene
- Ziprasidone • Geodon
Disclosures
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.