Unravelling the paradox of smoking cessation in multimorbidity: the roles of polypharmacy and treatment burden

Dear the Editor,

1.

We read with great interest the recent article by Kyrychenko et al., which explored the impact of physical multimorbidity on smoking cessation outcomes. ¹ We highly commend the authors for leveraging a massive real‐world cohort of over 120 000 treatment‐seeking smokers. Their finding that patients with multimorbidity exhibit lower quit rates, despite displaying higher motivation and greater utilisation of nicotine replacement therapy (NRT), is a profound clinical paradox that highlights the urgent need to tailor cessation strategies for this vulnerable population. Building upon their excellent work, we would like to highlight two critical clinical perspectives that warrant further discussion.

Firstly, while the authors commendably categorised physical multimorbidity by disease count, the study design overlooked a vital clinical corollary: polypharmacy and pharmacokinetic interactions. Tobacco smoke strongly induces the hepatic CYP1A2 enzyme. ² When patients abruptly quit, this enzyme activity rapidly normalises, which can cause blood levels of concurrent medications (like certain beta‐blockers or antidepressants) to spike. Patients might easily mistake these sudden toxicities for severe nicotine withdrawal or NRT intolerance, prompting a relapse simply to find physical relief. Since clinical guidelines recommend monitoring CYP1A2‐metabolised drugs upon cessation, future registries should track a ‘polypharmacy index’. ³ Integrating proactive medication reviews and dose‐tapering could significantly improve quit rates in this vulnerable group.

Secondly, the study evaluated the cessation programme as a standalone intervention, which may not optimally serve highly multimorbid patients due to ‘treatment burden’ and care fragmentation. ⁴ Managing multiple chronic illnesses is already exhausting, draining patients' time and energy through endless appointments and strict lifestyle rules. Stacking a completely separate cessation programme on top of this might easily overwhelm their capacity to cope, which perfectly explains why highly motivated patients still struggle. This aligns with minimally disruptive medicine, which warns against piling on healthcare demands. To translate these insights into practice, future trials should compare standalone interventions against integrated models. Weaving quitting support naturally into routine chronic disease care (such as diabetic clinics) offers a far more practical path forward.

In conclusion, the authors provided an invaluable epidemiological foundation demonstrating the unique vulnerabilities of multimorbid smokers. Recognising the invisible burdens of polypharmacy and fragmented care will be the next crucial step in optimising clinical pathways and truly turning these patients’ high motivation into lasting cessation success.

Data availability statement

Data sharing not applicable to this article as no datasets were generated or analysed during the current study.