A 42-year-old woman with a history of schizophrenia is brought to the clinic by her parents after attempting to drink rubbing alcohol in response to voices telling her to kill herself. The patient believes that a television newscaster is sending her secret messages and that the devil injects her with poison at night while she is sleeping. She first developed symptoms at age 23 and has had 7 previous psychiatric hospitalizations and 2 suicide attempts. Trials of haloperidol, risperidone, and olanzapine have yielded minimal improvement. Her medical conditions include hypertension and mild obesity. Physical examination is normal. Medication therapy with clozapine is initiated. Which of the following should be regularly monitored in this patient?
Indications |
|
Adverse effects |
|
The second-generation antipsychotic clozapine is the only antipsychotic that has consistently shown superior efficacy in treatment-resistant schizophrenia and schizophrenia associated with persistent suicidality. Clozapine has affinity for multiple dopamine and serotonin receptors, but the precise pharmacological mechanism responsible for its superior efficacy is unknown. Clozapine binds loosely and transiently to dopamine D2 receptors, causing significantly fewer extrapyramidal symptoms compared to first-generation antipsychotics.
Neutropenia (<1000 cells/mm3) and the potential for life-threatening agranulocytosis are the major adverse effects of clozapine. The risk of agranulocytosis is approximately 1%; therefore, treatment requires regular monitoring of the patient's absolute neutrophil count. Treatment should be stopped if neutropenia occurs. Seizures and myocarditis are other important adverse effects that require provider vigilance.
(Choice B) Clozapine plasma levels can be checked after an initial target dose is reached, but further dosage adjustments are usually based on clinical response. Clozapine levels are not regularly monitored.
(Choices C and H) Creatinine levels and thyroid function tests should be monitored in patients taking lithium due to this drug's potential to adversely affect thyroid and renal function.
(Choice D) Although a baseline ECG is required and physicians should be alert to the development of cardiovascular symptoms suggestive of myocarditis, routine ECGs are not required. Among the second-generation antipsychotics, ziprasidone is most often noted for causing a prolonged QT interval.
(Choices E and F) Liver function tests may be mildly elevated with the use of many psychotropic medications, including antipsychotics and anticonvulsants; thrombocytopenia can be caused by some anticonvulsants. However, routine monitoring of liver function tests and platelets is not required with clozapine.
(Choice G) Prolactin levels are not routinely monitored. Among the second-generation antipsychotics, risperidone has been associated with a greater risk of prolactin elevation.
Educational objective:
Patients treated with clozapine are required to have regular monitoring of the absolute neutrophil count due to the risk of life-threatening agranulocytosis.