There is strong evidence that tobacco smoking produces induction of the cytochrome P450 (CYP) 1A2 enzyme system in the liver, a major route for the metabolism of antipsychotic drugs such as haloperidol, chlorpromazine, olanzapine, and clozapine (George and Vessicchio 2001; Perry et al. 1993). Accordingly, smoking cessation may be expected to lead to increases in plasma concentrations of antipsychotic drugs metabolized by the 1A2 system, a finding demonstrated in both prospective and retrospective studies using both between-subject (Perry et al. 1993, 1998; Seppala et al. 1999) and within-subject (Meyer 2001) designs. Such an increase in circulating levels would be expected to increase the likelihood of extrapyramidal reactions and other antipsychotic drug side effects. A nomogram has been developed for clozapine in an attempt to aid clinicians in adjusting clozapine doses in smoking compared with nonsmoking schizophrenic subjects (Perry et al. 1998). Although no smoking cessation study in schizophrenics to date has prospectively measured antipsychotic plasma levels before and after smoking cessation, Meyer (2001) reported on serial clozapine levels measured in 11 patients with schizophrenia or schizoaf-fective disorder treated with stable doses in a state hospital before and after a hospital-wide ban on smoking. A mean increase of 57.4% was noted in these clozapine-treated patients who quit smoking; one patient in particular had an increase in his serum clozapine level to over 3,000 ng/mL that was associated with aspiration. In the few published controlled smoking cessation trials in this population (Addington 1998; George et al. 2000a, 2002b), no significant increases in medication side effects were noted in patients who quit smoking, including those treated with medications known to be metabolized by CYP 1A2, but further study is clearly warranted.
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