Toxicity and Adverse Effects in Clozapine-Related Presentations to a Medical Toxicology Service in Western Sydney.

Background: Clozapine is an anti-psychotic agent, reserved for treatment-resistant schizophrenia, with demonstrated efficacy in an otherwise therapeutically challenging patient population. We aimed to review the full spectrum casemix of clozapine presentations to our tertiary toxicology service.

Methods: In this retrospective study, we reviewed consecutive clozapine related toxicity presentations to a tertiary medical toxicology inpatient and consultation service-including deliberate self-poisoning (DSP), adverse drug reaction (ADR), recreational use, and therapeutic misadventure over a 10-year period from 2011 to 2021. Data were extracted for demographics, ingested dose, exposure characteristics, and patient outcome.

Results: We identified 83 patients with clozapine-related presentations over the 10-year period. Twenty-two patients were excluded. Of the remaining 61 patients, 28 patients presented with DSP, 20 patients with accidental overdose, and 13 patients with an ADR; no patients presented with recreational use. It was noted that ADRs were largely idiosyncratic reactions and not always related to dose adjustments. In the context of therapeutic misadventure and DSP, we noted that a lower mean dose achieved a higher poison severity score (PSS) in clozapine-naive patients when compared to those patients on regular clozapine.

Conclusions: The presentation of clozapine-related toxicity differs depending on the modality of ingestion, whether DSP, accidental, or as a result of ADR. Patients naive to clozapine therapy tend to experience higher PSS with lower doses ingested either in a deliberate self-poisoning or accidental ingestion context. This is likely due to tolerance to the sedative properties of clozapine. No patients manifested clinical toxicity greater than 8 hours after ingestion, with an observation period of 6 hours accurately identifying toxicity in most patients.