A puzzling case of seizures and visual hallucinations during clomipramine treatment with a high dose but causing a low serum concentration

We present a puzzling case of a 25-year-old depressive man suffering from s eizures and visual hallucinations during clomipramine treatment with a high dose but causing a low serum concentration. We examined alleles of cytochr ome P450 (CYP) isozymes. It was revealed that he was not an ultrarapid meta bolizer for CYP2D6, and that the genotypes were homozygous for CYP2D6J and heterozygous for CYP2C19(ml). Throughout the treatment period, his complian ce was good. Since he was a smoker, it seems likely that his low clomiprami ne level was due to smoking-induced CYP1A2 activity. These findings suggest that smoking-induced CYP1A2 activity overcomes the possibly inhibiting eff ects of homozygosity for CYP2D6J and heterozygosity for CYP2C19(ml), and th at high-dose clomipramine is not always a direct cause of seizures.