Hypercupraemia induced by antiepileptic drugs

Serum copper and zinc levels were measured in 84 treated male epileptics, aged between 6 and 18 years, by an atomic absorption spectroscopic method. These patients were selected randomly from a residential special school. Twenty drug-free healthy but educationally subnormal (ESN) male subjects of similar age group from the same school acted as controls. No abnormality in serum zinc level was observed. In nineteen (22.6%) epileptics, copper levels were above the upper level of normal range (20.5 mumol/l), whereas this was only marginally elevated (20.8 mumol/l) in one (5%) ESN subject. The mean copper level in all epileptics was higher than the controls (P less than 0.01), but there was no difference between the epileptics treated with sodium valproate alone and the ESN group. The patients who were receiving carbamazepine either as monotherapy or in combination with other drugs except phenytoin, had higher mean copper levels than the controls (P less than 0.01). A similar observation was made in relation with phenytoin polytherapy (but excluding carbamazepine). There also appeared to be an association between the high serum copper levels and diffuse/generalized electroencephalographic changes (P less than 0.001). Some antiepileptic drugs, particularly carbamazepine, can produce such electroencephalographic abnormalities. It is concluded that hypercupraemia observed in these treated epileptics were related to the induction of caeruloplasmin synthesis by phenytoin and carbamazepine.