A case of clozapine-induced diabetic ketoacidosis

A 29-year-old male of Yemeni descent detained in a medium secure unit was commenced on clozapine; after 4 weeks of treatment he was taking a total of 275 mg in divided doses. He developed nausea and vomiting which progressed over 36 hours to a point where he needed to be urgently transferred to the local accident and emergency unit. At assessment he was experiencing breathing problems, vomiting and he was incontinent of urine; he had a Glasgow Coma Scale score of five. He was immediately transferred to the intensive care unit. The differential diagnoses included drug overdose, alcohol intoxication and clozapine-induced hyperglycaemia. His blood chemistry showed evidence of diabetic ketoacidosis; his blood glucose level was grossly elevated. The clozapine was stopped and the patient was given appropriate treatment with glycaemic agents.

In summary, the patient had become seriously unwell over a period of 36 hours. Apart from having a slightly raised body mass index, he was fit and well and had no family history of diabetes. His pre-treatment blood glucose had been normal.

Diabetic ketoacidosis is over ten times more common in patients treated with atypical antipsychotics than in the general population, ¹ although the evidence is largely restricted to case reports and series. ² Clozapine has a higher risk of ketoacidosis than other oral antipsychotics ³ and it tends to develop after a shorter duration of treatment, with a high proportion of patients developing it within 3-6 months. Low doses, being a young male and having a negative family history seem to be significant risk factors. ⁴ There is also significant mortality. ⁵ The unusual aspect of this case (although not unknown) was the occurrence of diabetic ketoacidosis during the titration phase of treatment.