Smoking in patients receiving psychotropic medications: a pharmacokinetic perspective

Many psychiatric patients smoke, and are believed to be heavier smokers than those without psychiatric disorders. Cigarette smoking is one of the environmental factors that contributes to interindividual variations in response to an administered drug. Polycyclic aromatic hydrocarbons (PAHs) present in cigarette smoke induce hepatic aryl hydrocarbon hydroxylases, thereby increasing metabolic clearance of drugs that are substrates for these enzymes. PAHs have been shown to induce 3 hepatic cytochrome P450 (CYP) isozymes, primarily CYP1A1, 1A2 and 2E1. Drug therapy can also be affected pharmacodynamically by nicotine. The most common effect of smoking on drug disposition in humans is an increase in biotransformation rate, consistent with induction of drug-metabolising enzymes. Induction of hepatic enzymes has been shown to increase the metabolism and to decrease the plasma concentrations of imipramine, clomipramine, fluvoxamine and trazodone. The effect of smoking on the plasma concentrations of amitriptyline and nortriptyline is variable. Amfebutamone (bupropion) does not appear to be affected by cigarette smoking. Smoking is associated with increased clearance of tiotixene, fluphenazine, haloperidol and olanzapine. Plasma concentrations of chlorpromazine and clozapine are reduced by cigarette smoking. Clinically, reduced drowsiness in smokers receiving chlorpromazine, and benzodiazepines, compared with nonsmokers has been reported. Increased clearance of the benzodiazepines alprazolam, lorazepam, oxazepam, diazepam and demethyl-diazepam is found in cigarette smokers, whereas chlordiazepoxide does not appear to be affected by smoking. Carbamazepine appears to be minimally affected by cigarette smoke, perhaps because hepatic enzymes are already stimulated by its own autoinductive properties. Cigarette smoking can affect the pharmacokinetic and pharmacodynamic properties of many psychotropic drugs. Clinicians should consider smoking as an important factor in the disposition of these drugs.