Elevated Clozapine Plasma Level With Lamotrigine

Because of the promising results of this study, we prescribed lamotrigine to Mr. A, a 35-year-old outpatient. He had been taking clozapine, 400 mg/day, for 3 years and had responded partially to treatment. His plasma levels of clozapine (in six assays over 3 years) had been stable (between 300 and 500 μg/liter, measured 12 hours after a dose was taken). When lamotrigine treatment began, his clozapine plasma level was 350 μg/liter.

His lamotrigine dose was titrated up to 100 mg/day in steps of 25 mg every 2 weeks. When Mr. A had taken 100 mg/day for 2 weeks, he complained of dizziness and sedation. When we determined his plasma level of clozapine, it was found to have tripled, to 1020 μg/liter. Since Mr. A showed no clinical improvement, his lamotrigine dose was tapered over a period of 2 weeks. At the end of this period, his clozapine plasma level had returned to a therapeutic level of 450 μg/liter.