Hyperglycaemia and myoclonus with clozapine

Sir: Hyperglycaemia and myoclonus have been reported as uncommon adverse events with clozapine treatment. We report two cases in which they occurred together in close temporal association.

Case 1

A 42-year-old African-Caribbean man with a history of severe, treatment-resistant schizophrenia developed myoclonic jerks while taking clozapine 700 mg/day. Eight weeks later he developed diabetic ketoacidosis with a blood glucose of 44 mmol/l, for which he required intensive care treatment. Clozapine treatment was subsequently stopped. Following recovery he was reinstated on clozapine, has not developed further myoclonus and his glucose tolerance is not impaired.

Case 2

A 58-year-old White British man with a history of clozapine-induced hyper-glycaemia was restarted on clozapine 400 mg/day. After 2 weeks he developed severe myoclonus and deterioration of glycaemic control with random serum glucose as high as 21.5 mmol/l. Clozapine treatment was withdrawn. Within 7 days control of his blood sugar was re-established and myoclonus resolved.

Myoclonus has been reported in 0.2% of 24 000 clozapine treated patients on the UK Clozaril Patient Monitoring Service (CPMS) database. Results from case series suggest the incidence may be as high as 2.0% (Safferman et al, 1991) to 2.7% (Sajatovic & Meltzer, 1996).

Impaired glucose tolerance with clozapine treatment is also probably more common than the 0.4% quoted by the UK CPMS (Linda Annan, Advisor, CPMS, personal communication). In a case-note study of 82 patients, 36.6% were considered to have developed diabetes (Henderson et al, 2000). The true prevalence of these adverse events remains to be established.

The association between hyperglycaemia and movement disorders, including myoclonus, has been well documented (Moores & Dire, 1989). Hyperglycaemia is the commonest metabolic disorder to be associated with clonic activities of the extremities and other focal motor phenomena. Correction of the underlying metabolic disturbance prevents further focal seizures or movement abnormalities (Berkovic et al, 1982).

Since uncontrolled hyperglycaemia is potentially life threatening, the presence of myoclonus in clozapine treated patients may be of use in alerting clinicians to the presence of impaired glucose tolerance.