CLINICAL HANDBOOK OF SCHIZOPHRENIA

184 III. SOMATIC TREATMENTthose with weight gain, medication treatment can be attempted (e.g., sibutamine), withcareful monitoring of side effects. Additional adverse effects that may be associated withlong-term treatment include somnolence, sialorrhea, and urinary incontinence (all ofwhich may be dose dependent to some degree). Myocarditis may occur with patientsmaintained on clozapine therapy. In rare cases, agranulocytosis may occur even afteryears of uncomplicated treatment, and isolated cases of apparent movement disorders orTD have been reported.It is known that schizophrenia is associated with several chronic physical illnessesand a shorter life expectancy compared with that in the general population. A recent expertconsensus panel has recommended that mental health care providers perform appropriatephysical health monitoring that typically occurs in primary care settings for theirpatients with schizophrenia who do not receive such monitoring. Patients with severe,treatment-refractory illness are likely to belong to this group of disadvantaged individualswho often have difficulty accessing care in standard primary settings. Physical healthconsensus recommendations overlap somewhat with ADA–APA guidelines (body massindex, plasma glucose levels, lipid profiles). Additional parameters of physical healthmonitoring include monitoring for signs of myocarditis, sexual dysfunction, and EPS–TDin patients on clozapine (particularly individuals age 50 and older).Ongoing Symptom Evaluation and Functional Outcome AssessmentCognitive functioning and quality of life may improve in those who have good responseto clozapine therapy. Additionally, potential reduction in suicidality maintains safety andallows patients to engage in recovery interventions. There is also fairly consistent evidencethat clozapine therapy may reduce aggressive behavior and allow some individualswith previously extremely severe illness to transition to more independent, less restrictiveresidential settings. Maximization of clozapine dosage on the order of 600–900 mg/dayshould be attempted in patients who tolerate the drug but appear to be refractory (checkingserum levels may be somewhat useful, although there are no clear, standardized targetlevels). The median dose to reduce risk of suicidal behavior in clinical trials was approximately300 mg/day (range: 12.5–900 mg/day).Treatment adherence should remain an ongoing concern, although, perhaps becauseof the need for ongoing serum monitoring, a number of reports suggest that treatment adherenceis actually better for clozapine compared to other antipsychotic compounds. Forindividuals who are refractory with optimized clozapine dosing there have been reportsthat adjunctive treatment with other antipsychotics (high-potency conventional agentssuch as haloperidol, or atypical agents such as risperidone), or anticonvulsant compounds,such as lamotrigine, may be of benefit for some patients.KEY POINTS• Clozapine is the prototype drug from the antipsychotic class often referred to as atypicalantipsychotics.• Clozapine use is generally reserved for the most severe forms of schizophrenia and is thetreatment of choice for refractory patients.• In addition to its efficacy in severely ill/refractory patients with schizophrenia, clozapine hasbeen demonstrated to reduce the risk of recurrent suicidal behavior.• Clozapine therapy may reduce aggressive behavior and allow some individuals with previouslysevere illness to transition to more independent, less restrictive residential settings.