A 34-year-old man comes to the psychiatry outpatient clinic for follow-up accompanied by his parents. He has a 15-year history of schizophrenia characterized by auditory hallucinations, disorganized thoughts, and paranoid delusions. The patient was diagnosed at age 19 and has been hospitalized 6 times for acute psychotic episodes. He has had multiple trials of antipsychotic medication, including risperidone, olanzapine, and fluphenazine, with minimal improvement. He is currently taking aripiprazole. Despite adherence to his medication regimen, the patient has persistent psychotic symptoms. He has been unable to work, hears voices throughout the day, and is too paranoid to attend group therapy. He lives with his parents, who supervise his medication. The patient has no other medical problems. There is a family history of hypertension, diabetes, and coronary artery disease. After a discussion of the risks and benefits, the patient agrees to begin a trial of clozapine. What should he be told regarding treatment with this medication?

Question

A 34-year-old man comes to the psychiatry outpatient clinic for follow-up accompanied by his parents.  He has a 15-year history of schizophrenia characterized by auditory hallucinations, disorganized thoughts, and paranoid delusions.  The patient was diagnosed at age 19 and has been hospitalized 6 times for acute psychotic episodes.  He has had multiple trials of antipsychotic medication, including risperidone, olanzapine, and fluphenazine, with minimal improvement.  He is currently taking aripiprazole.  Despite adherence to his medication regimen, the patient has persistent psychotic symptoms.  He has been unable to work, hears voices throughout the day, and is too paranoid to attend group therapy.  He lives with his parents, who supervise his medication.  The patient has no other medical problems.  There is a family history of hypertension, diabetes, and coronary artery disease.  After a discussion of the risks and benefits, the patient agrees to begin a trial of clozapine.  What should he be told regarding treatment with this medication?

Quizplus · Accepted Answer

Explanation: Clozapine is a highly effective antipsychotic reserved for the treatment of refractory schizophrenia and schizoaffective disorder. Clozapine is not used as first-line treatment due to its association with neutropenia/agranulocytosis. It must be prescribed through a central patient registry that requires mandatory monitoring of the absolute neutrophil count. Blood tests must be performed weekly during the first 6 months of treatment, every other week for the second 6 months, and every 4 weeks thereafter. Physicians are guided by an algorithm that specifies the minimum absolute neutrophil count required to initiate and continue clozapine therapy. Patients should also be advised to immediately report symptoms consistent with infection (eg, fever, weakness, lethargy, sore throat). Other adverse events associated with clozapine include weight gain, metabolic syndrome, seizures, pulmonary embolus, myocarditis, excessive salivation, constipation, and ileus. (Choice A) It is uncommon for clozapine to cause hepatoxicity and thrombocytopenia, and periodic monitoring for these is unnecessary. Patients treated with the anticonvulsant mood stabilizer valproate should have baseline and periodic monitoring of liver function tests. (Choice B) Dietary restrictions (avoiding foods containing tyramine) are necessary while taking monoamine oxidase inhibitors, medications used in treatment-resistant depression. (Choice C) Although clozapine plasma levels may assist in dosage adjustment, they are not required. A clozapine plasma level can be checked after an initial target dose is reached and then adjusted based on clinical response and adverse effects. Serum drug levels are routinely monitored with medications such as lithium, valproate, and nortriptyline. (Choice E) Lithium (not clozapine) requires evaluation of thyroid and kidney function before initiation of therapy. Creatinine and thyroid function tests are monitored periodically (eg, every 3-6 months) in lithium-treated patients due to risks of hypothyroidism and renal toxicity. Educational objective: Clozapine treatment requires regular monitoring and registry reporting of absolute neutrophil counts due to the increased risk of developing neutropenia/agranulocytosis. References: Medical management of patients on clozapine: a guide for internists. (http://www.ncbi.nlm.nih.gov/pubmed/25809850) Guide to the management of clozapine-related tolerability and safety concerns. (http://www.ncbi.nlm.nih.gov/pubmed/27732102)

A 34-Year-Old Man Comes to the Psychiatry Outpatient Clinic for Follow-Up