Introduction

Tobacco smoking remains a leading cause of preventable illness and premature mortality in England [1]. Relative to the general population, people with mental health conditions are more likely to smoke, smoke more heavily, and show greater signs of dependence [2–5]. They are also at increased risk of tobacco-related morbidities, including cardiovascular disease [6, 7], which causes them to have substantially lower life expectancy [8, 9]. Quitting smoking can reduce these risks [10]. A range of smoking cessation aids have been found to increase successful smoking cessation in randomised controlled trials (RCTs) [11–14] and in real-world settings [15–24]. Understanding whether and, if so, how far their effectiveness differs between people with and without mental health conditions can help health professionals and patients to make informed choices around the use of aids for smoking cessation.

In England, a comprehensive range of smoking cessation medications and behavioural support are available [25]. Pharmacological aids include nicotine replacement therapy (NRT), which is available free of charge on prescription or can be bought over-the-counter (OTC), and varenicline (Champix) and bupropion (Zyban) which are only available on prescription. The supply of Champix, the most effective of these [14, 23, 24], was disrupted in 2021 due to nitrosamine impurities found by its supplier, Pfizer [26]. The supply of Zyban was disrupted in late 2022 due to similar concerns about nitrosamine impurities found by its supplier, GSK [27]. Both medications remain unavailable as of March 2024. Generic versions of varenicline are available in other countries and cytisine, a drug with similar properties to varenicline, is licensed [28] and has begun to be supplied in England since January 2024.

Vaping products (often referred to as e-cigarettes) and nicotine pouches are available from specialist ‘vape shops’, supermarkets, smaller convenience stores, and online [29]. Heated tobacco products have been available in the UK since 2016 but their efficacy for smoking cessation is uncertain [30]. Smokers also have access to free dedicated stop smoking services, which offer behavioural support, pharmacotherapy, and in some cases, vaping products [31]. Telephone support is available via a free Smokefree National Helpline, and websites offer information on quitting, other forms of support available, and how to access them. Other behavioural treatments, including hypnotherapy and Allen Carr’s Easyway method (a single-session pharmacotherapy-free behavioural programme) [32, 33], are provided by private companies.

Around one in two attempts to stop smoking in England involves the use of at least one of these cessation aids [34]. Vaping products are most commonly used (~30% of quit attempts), followed by NRT available OTC (~10%) and medications obtained on prescription (NRT, varenicline, or bupropion; ~5%) [34].

It is possible that the effectiveness of these smoking cessation aids may differ between people with and without mental health conditions [35]. People with mental health conditions may experience stronger reinforcing effects of nicotine, more severe withdrawal symptoms when they try to quit, and greater cessation fatigue (being tired of trying to stop smoking) [36]. As such, it is possible that they may benefit more from cessation aids that mimic the effect of nicotine (e.g., varenicline) or provide an alternative source of nicotine (e.g., NRT, vaping products, nicotine pouches) and less from other cessation aids (e.g., forms of behavioural support). On the other hand, people with mental health conditions may be less likely to adhere to treatments [37], causing effectiveness to be lower.

To our knowledge, just two large experimental studies have investigated whether the effectiveness of smoking cessation treatments is moderated by a person’s mental health status. These have focused on varenicline, bupropion, and NRT. One large RCT (‘EAGLES’) compared varenicline and bupropion with nicotine patch and placebo and showed similar efficacy of these medications for smokers with and without psychiatric disorders [38]. However, a recent secondary analysis of another RCT that compared the effectiveness of bupropion and varenicline reported a slightly different pattern of results [39]. While varenicline was associated with similar quitting outcomes for smokers with depressive symptoms than those without, bupropion appeared to be less effective as a smoking cessation aid for those with depressive symptoms [39]. Further research is required on these and other cessation aids. Observational data can shed light on any differences in treatment effectiveness in real-world settings [40].

Using data from the Smoking Toolkit Study, a large, nationally-representative survey of adults in England, this study aimed to comprehensively examine whether the real-world effectiveness of popular smoking cessation aids differs between users with and without mental health conditions. Data on smoking status in relation to history of mental health conditions have been published elsewhere [2], so this paper focused specifically on the use and effectiveness of different cessation aids among those attempting to quit smoking. Specifically, we aimed to address the following research questions:

1. To what extent does a history of one or more diagnosed mental health conditions moderate associations between use (vs. non-use) of various cessation aids in a quit attempt and chances of success?
2. Are any moderating effects similar for those with a single mental health condition and those with multiple mental health conditions?

Materials and methods

Results

Of 95,952 participants surveyed in eligible waves, 17,394 (18.1%) reported smoking in the past year, of whom 5,741 (33.0%) attempted to stop smoking in the past year. We excluded 148 participants with missing data on mental health conditions (there were no missing data on use of cessation aids), leaving a final sample for analysis of 5,593 participants.

Just under half (45.1% weighted) of participants reported having ever been diagnosed with a mental health condition; 16.8% reported a single mental health condition and 28.3% multiple conditions. Table 1 summarises the characteristics of participants with and without a history of mental health conditions. S1 Table presents corresponding data for those reporting single and multiple mental health conditions. Relative to those without, participants reporting a history of mental health conditions were more likely to be younger, identify as women or non-binary, and come from less advantaged social grades. They also reported a higher level of cigarette addiction, on average, but there were no notable differences in the characteristics of their most recent quit attempt.

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Table 1. Weighted sample characteristics.

https://doi.org/10.1371/journal.pmen.0000007.t001

Table 2 summarises use of cessation aids by participants’ history of mental health conditions. Participants with a history of mental health conditions were significantly more likely to report using one or more cessation aids (58.9%) than those without (52.9%) and to report using multiple aids (12.0% vs. 7.3%). Among those with and without a history of mental health conditions, vaping products were the most commonly used aid (38.8% and 30.7%, respectively), followed by NRT available over-the-counter (16.7% and 17.8%). All other aids were used by <5% of participants. Relative to those without, participants with a history of mental health conditions were more likely to report using vaping products, prescription NRT, and websites. Use of other aids did not differ significantly between groups. There was no significant difference in the prevalence of use of any cessation aid between those with single versus multiple mental health conditions (S2 Table).

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Table 2. Use of cessation aids in the most recent quit attempt by history of mental health conditions.

https://doi.org/10.1371/journal.pmen.0000007.t002

Table 2 also shows unadjusted quit success rates for those using each cessation aid. Although absolute differences appeared large for some aids (e.g., written self-help materials and nicotine pouches), wide confidence intervals meant there was no statistically significant difference in quit rates between users of aids with and without a history of mental health conditions, before adjustment for potential confounding variables and use of other aids.

Table 3 shows the results of the logistic regression analyses. The baseline model, which included use (vs. non-use) of each cessation aid, history of mental health conditions, and covariates, indicated participants who used vaping products (OR = 1.92, 95%CI 1.61–2.30), varenicline (OR = 1.88, 95%CI 1.19–2.98), or heated tobacco products (OR = 2.33, 95%CI 1.01–5.35) in their quit attempt had significantly higher odds of quitting successfully than those who did not. Those who used Allen Carr’s Easyway method (either via face-to-face session [19.8%], book [66.9%], or both [13.3%]) had significantly lower odds of quitting successfully than those who did not (OR = 0.41, 95%CI 0.18–0.94). Use of other aids was not significantly associated with odds of quit success, after adjustment.

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Table 3. Real-world effectiveness of cessation aids for successful smoking cessation and interactions with the user’s history of mental health conditions.

https://doi.org/10.1371/journal.pmen.0000007.t003

Tests of interactions showed no statistically significant moderating effect of history of mental health conditions on the effectiveness of any cessation aid (Table 3). Bayes factors indicated the data were largely insensitive to distinguish between evidence of moderation and no evidence of moderation, meaning we were unable to rule out potential differences in effectiveness by history of mental health conditions. The only exception was for vaping products, where the data favoured the null (Bayes factor = 0.20), indicating that the effectiveness of vaping products for smoking cessation did not differ significantly between those with and without a history of mental health conditions.

There was no notable difference in the pattern of results when history of mental health conditions was analysed as a 3-level variable (distinguishing between those with none, a single mental health condition, and multiple conditions; S4 Table).

Discussion

Nine in every 20 people who attempted to quit smoking had a history of one or more mental health conditions. Those with a history of mental health conditions were more likely to support their quit attempt with the use of cessation aids. Specifically, they were more likely than those without a history of mental health conditions to report using vaping products, prescription NRT, or websites, with no significant differences between groups in the use of other aids. After we adjusted for covariates and participants’ use of other cessation aids, those who used vaping products, varenicline, or heated tobacco products had significantly higher odds of quitting successfully than those who did not report using these aids. There was little evidence of benefits of using other cessation aids, or that the user’s history of mental health conditions moderated the effectiveness of any aid.

Our results echo the findings of the EAGLES trial [38], which found varenicline, bupropion, and nicotine patch were similarly effective for smokers with and without psychiatric disorders, under trial conditions. They also extend existing evidence by covering the whole range of cessation aids used by people who smoke in England and using observational data from people using these aids in the real world, where people do not necessarily receive continued monitoring and support from healthcare professionals.

The real-world effectiveness of varenicline and vaping products are established, having been reported in a number of previous studies [15–24]. In 2019, we used data from the Smoking Toolkit Study to examine the effectiveness of different cessation aids when used in real-world settings [23]. Our results suggested using varenicline or vaping products was associated with the highest odds of success in a quit attempt. When we controlled for use of other aids and other potential confounding variables (e.g., level of dependence), we found that people who used varenicline or vaping products in a quit attempt had 1.82- and 1.95-times higher odds, respectively, of remaining abstinent than those who did not. Our present results, which use data from the same survey but over a different time frame and with additional adjustment for history of mental health conditions, are consistent with these estimates.

However, to our knowledge, this is the first observational study to examine the effectiveness of heated tobacco products, because use of these products until recently has been rare in England [47]. We documented an association between use of heated tobacco products and increased odds of quit success [30]. Our data indicate use of these products in quit attempts remains relatively rare (consistent with low overall prevalence of use among adults in England [47]). As a result, the 95% CI around the estimate was wide and included the possibility of no meaningful difference (lower CI = 1.01), so conclusions may change with more data. It will be important to continue to monitor the effectiveness of heated tobacco products as the number of people using them to quit smoking grows.

The lack of evidence for differential effectiveness of any cessation aid by the user’s history of mental health conditions should provide reassurance to people with mental health conditions who want to stop smoking that their condition need not affect their choice of cessation aid. Of note, vaping products were both the most popular aid used by people with and without a history of mental health conditions and one of the most effective. Vaping products were also the only aid for which the data provided clear evidence that effectiveness was not lower for users with a history of mental health conditions (data for the other aids were insensitive).

Our results also suggest that healthcare professionals can base their recommendations for, and prescription of, smoking cessation treatments to people with mental health conditions on evidence of their effectiveness in the general population. Previous research has shown that people with mental health conditions have lower odds of being prescribed varenicline than NRT, despite having greater odds of quitting successfully with varenicline than NRT [54]. Consistent with this, our data show higher prevalence of use of prescription NRT among people with a history of mental health conditions than those without, and significantly higher odds of quit success among users of varenicline, but not NRT. Healthcare professionals may opt to prescribe NRT over varenicline for patients with mental health conditions due to concerns that varenicline may increase the risk of neuropsychiatric adverse events [55]. However, much evidence of this risk is based on information contained in case reports [55], and a large RCT of the relative neuropsychiatry safety of varenicline compared with nicotine patch and placebo among people with and without psychiatric disorders observed no significant increase in adverse events among those randomised to use varenicline [38]. If the risk of adverse events are similar, offering the more effective treatment (varenicline, once available again) is likely to be the better option.

This study had several limitations. First, questions on mental health conditions relied on self-reports, which may be less accurate than if linked health record data were used. Second, the items assessed ever (as opposed to current) diagnoses. As such, the results cannot tell us whether treatment effectiveness differs according to the user’s current mental health status. In addition, those with a history of multiple mental health conditions may also have been diagnosed with these conditions at different points in time, so a history of multiple mental health conditions may not reflect current comorbidity. Third, to boost statistical power for analyses, we grouped together participants reporting any of the mental health conditions we assessed. As the list of conditions was heterogeneous, covering a broad range of conditions from common mental health disorders (e.g., anxiety and depression) to severe mental illness (psychosis), we cannot rule out the possibility that certain conditions may moderate the effectiveness of cessation aids while others do not. Given the low prevalence of most of these conditions within the general population, much larger samples would be required to explore this. Fourth, despite combining all mental health conditions, Bayes factors indicated our data were insensitive to distinguish between evidence of absence of an interaction between aid use and mental health conditions (i.e., mental health conditions moderate treatment effectiveness) and absence of evidence for the majority of aids (all except vaping products). This means we are unable to conclusively rule out there being small to moderate differences in effectiveness by people’s history of mental health conditions. Fifth, although we adjusted for a range of potential confounders, there may be residual confounding by other variables not included in our models. Finally, it is possible that smoking cessation treatments offered to people with mental health conditions may differ from the general population, introducing potential selection bias from the treatment provider in addition to the user. Although clinical trials suggest varenicline and bupropion are effective for people with severe mental illness [38, 56], in the real world, people with these conditions are rarely offered these medications by clinicians [54]. Interactions with other medications is an important consideration in deciding on a treatment approach: bupropion is known to interact with other medications (including those indicated for treatment of mental health conditions), which may reduce the effectiveness of one or both treatments [57]. Nonetheless, our data provide useful insights into potential differences in the effectiveness of popular smoking cessation treatments in a real-world setting.

In conclusion, use of vaping products, varenicline, or heated tobacco products in a quit attempt was associated with significantly greater odds of successful cessation, after adjustment for use of other cessation aids and potential confounders. There was no evidence to suggest the effectiveness of any popular cessation aid differed according to the user’s history of mental health conditions.

Supporting information