Effects of Switching From Smoking to Vaping on Clozapine Concentration–Dose Ratios and Plasma Clozapine Concentrations: A Systematic Review of Case Reports

INTRODUCTION: Smoking tobacco cigarettes affects the metabolism of several antipsychotic medications by inducing CYP1A2 enzymes. Clozapine is particularly sensitive to this effect, as CYP1A2 induction increases the plasma clearance of the drug, resulting in lower clozapine plasma concentrations and a reduced clozapine concentration-dose (C/D) ratio than that in nonsmokers. Although the increase in clozapine concentrations and C/D ratios after smoking cessation is well-established, the effects of switching to e-cigarettes (electronic cigarettes or vapes) or initiating vaping without prior smoking is not well-understood. This review aimed to address these gaps. METHODS: The literature was searched for articles on patients taking clozapine who used or had used e-cigarettes, including those who switched from tobacco cigarettes. Eligible publications were reviewed and information on patient demographics, psychiatric history, smoking status, clozapine dose, plasma clozapine concentrations, and C/D ratios before and after vaping were extracted. When not reported in the articles, the C/D ratio was calculated using the available plasma clozapine concentrations and corresponding clozapine dose. RESULTS: Five articles were identified, all case reports describing 5 patients (4 male) who switched from tobacco cigarettes to e-cigarettes while taking clozapine. Switching resulted in increased C/D ratios and plasma clozapine concentrations, although the magnitude of this increase varied among individuals. The most commonly reported symptoms after switching from smoking to vaping are constipation, fatigue, and visual changes. CONCLUSIONS: Based on the small number of case reports, complete switching from tobacco smoking to e-cigarette vaping may have a similar effect on clozapine plasma concentrations and C/D ratios as smoking cessation without vaping. The authors found no research on the impact of vaping on clozapine concentrations and C/D ratios in people who had never smoked.