CLINICAL HANDBOOK OF SCHIZOPHRENIA

180 III. SOMATIC TREATMENTof standard antipsychotic drug treatment and, (2) for reduction of the risk of recurrentsuicidal behavior in patients with schizophrenia or schizoaffective disorder who arejudged to be at risk of reexperiencing suicidal behavior. One generally accepted norm toestablish treatment resistance is failure in at least two trials of antipsychotic drugs for atleast 6 weeks each at doses equal to 10–20 mg of haloperidol per day, or its equivalent.Treatment-resistant patients often have at least moderate positive, negative, or disorganization(incoherence, loose association, inappropriate affect, and poverty of thought content)symptoms and impaired social functioning despite at least two adequate trials ofantipsychotic drugs chosen from two or more different classes of these agents. Off-labeluses of clozapine sometimes seen in clinical settings include use for patients with unmanageableextrapyramidal symptoms (EPS), tardive dyskinesia (TD), refractory bipolar disorder,refractory obsessive–compulsive disorder (OCD), and Parkinson’s disease.CLOZAPINE THERAPY INITIATION AND ISSUESRELATED TO EARLY STAGES OF TREATMENTMedical AssessmentsThe patient should have a thorough history and physical examination (Table 18.1).The history should include information regarding any history of blood dyscrasias, seizuredisorder, cardiovascular disease, hepatic and renal disease, as well as any immunosuppressivediseases such as HIV. Laboratory testing should include a complete baselineblood count with white blood cell (WBC) count and absolute neutrophil count (ANC),complete metabolic assay including serum electrolytes and renal function tests, and anelectrocardiogram (ECG) with QTc interval. Clozapine dosing and titration may requiremodification in individuals with any of the aforementioned preexisting conditions.Patient and Family EducationRisks, benefits, and treatment alternatives should be discussed with the patient and family,and documented in the treatment record (Table 18.1). The hematological and cardiovascularrisks must be discussed in detail. The specific monitoring protocol regardingblood draws should be discussed with patients and families, and agreed upon in advance.In some treatment settings, home visits for blood drawing may be arranged to facilitateadherence with monitoring.Dosing and TitrationThe starting dose of clozapine is 12.5 mg once or twice daily (Table 18.1). The smallstarting dose helps to assess for early hypotensive reactions. Patient should be observedfor sedation and changes in blood pressure and pulse. The dose can be increased by25–50 mg daily up to a target dose of 300–450 mg/day by the end of 2 weeks foryoung, medically healthy individuals. Subsequent dosage increments may be made onceor twice weekly in increments not to exceed 100 mg. Twice-daily dosage is recommendedin view of the half-life of clozapine. The dose generally need not exceed 450–600 mg/day in most adults < 60 years old in the initial phase of treatment. The maximumrecommended dose is 900 mg/day, if response is unsatisfactory at 600 mg/day.The dosage of clozapine in older adults is usually 100–300 mg/day. A quick-dissolvingformulation of clozapine is now available for individuals who have difficulty swallow-