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.
Consequently, we have no explanation for the great increase in the patient’s plasma level of clozapine during concomitant use of lamotrigine. When lamotrigine is added to clozapine, clinicians should be aware of this possibility.