Clozapine metabolism may be affected by Gilbert's syndrome: case report and discussion

A 34-year-old man with treatment-resistant schizophrenia and Gilbert's syndrome was treated with clozapine and found to have unusually slow and fluctuating metabolism of clozapine, resulting in difficulty achieving a well-tolerated and stable plasma clozapine level. Gilbert's syndrome is a relatively common (3-10% prevalence) genetic condition which results in altered hepatic metabolism. This case report demonstrates in vivo the finding of previous in-vitro research suggesting that the UGT1A1 7/7 mutation most commonly associated with Gilbert's syndrome may result in decreased clozapine excretion. Given evidence of an increased prevalence of Gilbert's syndrome in patients with schizophrenia, further investigation into this possible correlation may improve understanding and prediction of clozapine dosage.