CLINICAL HANDBOOK OF SCHIZOPHRENIA

TABLE 18.1. Clinical tips for clozapine initiation and management18. Clozapine 181Clinical point/adverse effectMedical assessment prior toclozapine initiationPatient and family educationInitial dosing and titrationHematological effectsSedationSeizure riskCardiovascular risks (hypotension,myocarditis, etc.)Long-term weight gainContinued refractory symptomsManagement tips• History and physical.• Screen for blood dyscrasia, seizure disorder, cardiovasculardisorder, immunosuppressive disease.• Labs: complete blood count with differential, metabolic assay.• ECG• Discussion of hematological and cardiovascular risk.• Agreed upon (in advance) monitoring schedule, arrange inhomeblood draws if possible.• Healthy adults: 12.5mg once or twice daily, increased astolerated in increments of 25–50 mg/day to a target dose of300–450 mg/day. May require doses of 600–900 mg/day fortreatment of schizophrenia.• Median dose to reduce suicidal behavior on the order of300 mg/day.• Weekly WBC/ANC for first 6 months.• Every-other-week WBC/ANC for Months 6–12 if nocomplications.• Monthly WBC/ANC after 12 months and beyond, if nocomplications.• Most pronounced in first month; minimize with slow titrationand lowest effective dose.• Most pronounced with high overall dosage and fast titration.Minimize with slow titration. Use valproate if anticonvulsant isneeded.• Low starting dose, slow titration.• ECG follow-up, especially in those with past cardiac history.• Increase fluid intake, potential use of fludrocortisone forhypotension.• Follow ADA guidelines for monitoring parameters.• Education, diet control, and behavioral measures (involvefamily, case managers).• Potential benefit with sibutamine.• Add on high-potency conventional antipsychotic (haloperidol).• Add on risperidone.• Add on anticonvulsant (valproate or lamotrigine).ing pills. Patients who respond to clozapine should be continued on the lowest dose requiredto maintain remission.Management of Potential Early Side EffectsHematological EffectsAgranulocytosis (granulocyte count < 500/mm 3 ) and granulocytopenia (granulocytecount < 1,500/mm 3 ) are rare (less than 1%), but serious potential side effects of clozapinetherapy. Agranulocytosis and granulocytopenia, if they occur, usually develop in the first2–6 months of therapy. The risk is higher in older adults, women, and in patients of AshkenaziJewish descent with the human leukocyte antigen HLA-B38 phenotype. Mortalityis higher in African American populations who develop agranulocytosis. Coadministra-