Clozapine Toxicity in Patients Prescribed Therapeutic Doses of the Drug: a Case Series

Authors: Dr Christopher Rolé, Dr Gabriel J. Ellul

Aims and Hypothesis: To highlight the possibility of clozapine toxicity, even in patients being prescribed recommended therapeutic dosages, and the possibility of consequent adverse sequelae.

Background: Clozapine is an atypical antipsychotic which offers superior efficacy in the treatment of patients suffering from drug-resistant schizophrenia. Clozapine can reduce hospitalisation, duration of in-hospital stay and suicidality in patients with schizophrenia and schizoaffective disorder. It can however present with a number of adverse effects of variable severity which may in turn have potential fatal consequences, particularly in toxic serum levels. The monitoring of serum levels may assist clinicians in titrating the dose and preventing toxicity.

Methods: Cases of potential clozapine toxicity, referred to the psychiatric consult-liaison team during a six-month period, were compiled into a case series. The series includes patients receiving care within an acute medical hospital, with a nation-wide catchment area. All cases involved a clinical assessment, investigations including serum clozapine level and electroencephalography, and treatment review when warranted.

Results: Three cases were identified, with all cases involving clozapine toxicity, despite patients being prescribed the suggested therapeutic dose. In all cases, presentation involved confusional states and seizures. Clozapine toxicity was confirmed serologically in all cases, and through electroencephalography in two of the cases.  A myriad of potential aetiological factors were elicited, including patient-specific factors, such as variable metabolic clearance rates, and the presence of drug-drug interactions.

Conclusions: It is suggested that clinicians and psychiatrists should be more vigilant into the potential occurrence of clozapine toxicity, even when prescribing doses according to guidelines, and particularly in patients deemed at-risk. Prompt identification of toxic serum levels may be expedited through the provision of serum clozapine testing locally, thus avoiding the need to rely on foreign reference labs, with potential timely delay.

No financial interests declared