22 - Smoking and psychotropic drugs

Smoking and psychotropic drugs

892 The Maudsley® Prescribing Guidelines in Psychiatry CHAPTER 11 Smoking and psychotropic drugs Tobacco smoke contains polycyclic aromatic hydrocarbons that induce certain hepatic enzymes (CYP1A2 in particular).1 Other enzymes that may be induced by smoking are CYP2C19 and, possibly, CYP3A4 and some variants of UGT (glycosyltransferases).2 The extent of enzyme induction is determined by the number and type of cigarettes smoked and by the degree of smoke inhalation.3 For some drugs used in psychiatry, smoking significantly reduces drug plasma levels and higher doses are required than in non-­smokers. Smoking may also affect alcohol metabolism by inducing CYP2E1.3 When people stop smoking, enzyme activity halves roughly every 2 days.4 It is very important to appreciate that nicotine replacement and vaping have no effect on this process (they do not contain polycyclic aromatic hydrocarbons). Plasma levels of affected drugs will then rise, sometimes substantially. Dose reduction will usually be necessary. If smoking is restarted, enzyme activity increases, plasma levels fall and dose increases are then required. The process is complicated, and effects are difficult to predict. Of course, few people manage to give up smoking completely, so additional complexity is introduced by intermittent smoking and repeated attempts at stopping completely. Close monitoring of plasma levels (where useful), clinical progress and adverse effect severity are essential. Table  11.7 gives details of psychotropic drugs known to be affected by smoking status. Table 11.7  Effect of smoking on psychotropic drugs. Drug Effect of smoking Action to be taken on stopping smoking Action to be taken on restarting smoking Agomelatine5 Plasma levels reduced Monitor closely. Dose may need to be reduced. Consider reintroducing previous smoking dose. Benzodiazepines3,6 Plasma levels reduced by 0–50% (depends on drug and smoking status) Monitor closely. Consider reducing dose by up to 25% over 1 week. Monitor closely. Consider restarting ‘normal’ smoking dose. Carbamazepine3 Unclear, but smoking may reduce carbamazepine plasma levels to a small extent. Monitor for changes in severity of adverse effects. Monitor plasma levels. Chlorpromazine3,6,7 Plasma levels reduced. Varied estimates of exact effect. Monitor closely. Consider dose reduction. Monitor closely. Consider restarting previous smoking dose. Clozapine8–10 Reduces plasma levels by up to 50%. Effect may be maximal at as few as 2–5 cigarettes a day.11 Plasma level reduction and risk of relapse may be greater in those receiving valproate.12 Effect is reversed by co-­administered fluvoxamine.13 Take plasma level before stopping. On stopping, reduce dose gradually (over a week) until around 75% of original dose is reached (i.e. reduce by 25%). Repeat plasma level 1 week after stopping. Anticipate further dose reductions. Take plasma level before restarting. Increase dose to previous smoking dose over 1 week. Repeat plasma level. Deterioration is common if dose increases allow a fall in blood levels.14 Duloxetine15,16 Plasma levels may be reduced by up to 50%. Monitor closely. Dose may need to be reduced. Consider reintroducing previous smoking dose.

Pharmacokinetics CHAPTER 11 Table 11.7  (Continued ) Drug Effect of smoking Action to be taken on stopping smoking Action to be taken on restarting smoking Escitalopram17 In practice, smokers have lower blood levels despite being given higher doses. Reduction in levels may be up to 50% (possibly via induction of CYP2C19). Monitor closely. Consider 25% dose reduction. Monitor closely. Reinstate smoking dose. Fluphenazine18 Reduces plasma levels by up to 50% On stopping, reduce dose by 25%. Monitor carefully over following 4–8 weeks. Consider further dose reductions. On restarting, increase dose to previous smoking dose. Fluvoxamine19 Plasma levels decreased by around a third Monitor closely. Dose may need to be reduced. Dose may need to be increased to previous level. Haloperidol20,21 Reduces plasma levels by around 25–50% Reduce dose by around 25%. Monitor carefully. Consider further dose reductions. On restarting, increase dose to previous smoking dose. Loxapine22 (inhaled) Half-­life reduced from 15.7 to 13.6 hours Monitor Monitor Mirtazapine23 Unclear, but effect probably minimal Monitor Monitor Olanzapine10,24–26 Reduces plasma levels by up to 50%. Effect increases with number of cigarettes smoked.26 Take plasma level before stopping. On stopping, reduce dose by 25%. After 1 week, repeat plasma level. Consider further dose reductions. Take plasma level before restarting. Increase dose to previous smoking dose over 1 week. Repeat plasma level. Risperidone2,27 Active moiety concentrations probably lower in smokers. Minor effect (possibly via induction of CYP3A4). Smoking may not affect paliperidone concentrations.28 Monitor closely Monitor closely Trazodone29 Around 25% reduction Monitor for increased sedation. Consider dose reduction. Monitor closely. Consider increasing dose. Tricyclic antidepressants3,6,30 Plasma levels reduced by 25–50%. Some studies suggest more limited effect.2,31 Monitor closely. Consider reducing dose by 10–25% over 1 week. Consider further dose reductions. Monitor closely. Consider restarting previous smoking dose. Zuclopenthixol32,33 Unclear, but effect probably minimal Monitor Monitor Note (again: it bears repeating): only tobacco smoking induces hepatic enzymes in the manner described above. This includes cigarettes and cannabis/tobacco ‘joints’. Nicotine replacement, vaping devices and electronic cigarettes (which do not contain polycyclic aromatic compounds) have no effect on enzyme activity.34,35