Clozapine Toxicity Associated with Smoking Cessation

Abstract

We report on a 28-year-old white woman with chronic psychotic-affective illness who abruptly stopped her decade-long habit of heavy daily cigarette smoking while maintained on clozapine at 450 mg/d. Within several days, she developed dry mouth, muscle spasms, dizziness, and blurred vision with dilated and sluggish pupils, with worsening sedation and confusion. Her combined serum concentration of clozapine + norclozapine was 2.5 microg/mL, compared with levels of about 600 ng/mL at daily doses of 350 mg at other times while smoking. Reducing the dose of clozapine led to rapid alleviation of these symptoms. Additional experience with and without smoking in this case further documented the effect of smoking to decrease circulating levels of clozapine. These observations add to the conclusion that cigarette smoke can increase clearance of many drugs, calling for special caution during treatment with potentially toxic substances and dose reduction in anticipation of smoking cessation.