[Delirium due to increase in clozapine level during an inflammatory reaction]

Between January 1999 and May 2000, the Netherlands Pharmacovigilance Foundation LAREB received five reports of patients with clozapine intoxication attributed to inflammation. The reports all concerned men with schizophrenia, aged 63, 54, 41, 45 en 42 years. The occurrence of increased clozapine levels during inflammation, and normalisation after recovery, strongly suggest a causal relationship. No other possible explanations were found. A three to five-fold increase occurred in most instances, but one patient experienced a ten-fold increase compared with the basal levels of clozapine. Three of the patients developed a delirium as an intoxication symptom, probably due to anticholinergic effects on the central nervous system. In case of an inflammatory reaction in patients on clozapine treatment, the physician should be aware of the possibility of clozapine intoxication and delirium. Measuring clozapine levels during infection and dosing based on these levels can minimise the adverse effects of clozapine intoxication.