An application of the stress-diathesis model: A review about the association between smoking tobacco, smoking cessation, and mental health

Background: Worldwide, approximately 24% of all adults smoke, but smoking is up to twice as prevalent in people with mental ill-health. There is growing evidence that smoking may be a causal risk factor in the development of mental illness, and that smoking cessation leads to improved mental health. Methods: In this scholarly review we have: (1) used a modern adaptation of the Bradford-Hill criteria to bolster the argument that smoking could cause mental ill-health and that smoking cessation could reverse these effects, and (2) by considering psychological, biological, and environmental factors, we have structured the evidence to-date into a stress-diathesis model. Results: Our model suggests that smoking is a psychobiological stressor, but that the magnitude of this effect is mediated and modulated by the individual's diathesis to develop mental ill-health and other vulnerability and protective factors. We explore biological mechanisms that underpin the model, such as tobacco induced damage to neurological systems and oxidative stress pathways. Furthermore, we discuss evidence indicating that it is likely that these systems repair after smoking cessation, leading to better mental health. Conclusion: Based on a large body of literature including experimental, observational, and novel causal inference studies, there is consistent evidence showing that smoking can negatively affect the brain and mental health, and that smoking cessation could reverse the mental ill-health caused by smoking. Our model suggests that smoking prevention and treatment strategies have a role in preventing and treating mental illness as well as physical illness. (AU)

An application of the stress-diathesis model: A review about the association between smoking tobacco, smoking cessation, and mental health.

Background: Worldwide, approximately 24% of all adults smoke, but smoking is up to twice as prevalent in people with mental ill-health. There is growing evidence that smoking may be a causal risk factor in the development of mental illness, and that smoking cessation leads to improved mental health. Methods: In this scholarly review we have: (1) used a modern adaptation of the Bradford-Hill criteria to bolster the argument that smoking could cause mental ill-health and that smoking cessation could reverse these effects, and (2) by considering psychological, biological, and environmental factors, we have structured the evidence to-date into a stress-diathesis model. Results: Our model suggests that smoking is a psychobiological stressor, but that the magnitude of this effect is mediated and modulated by the individual's diathesis to develop mental ill-health and other vulnerability and protective factors. We explore biological mechanisms that underpin the model, such as tobacco induced damage to neurological systems and oxidative stress pathways. Furthermore, we discuss evidence indicating that it is likely that these systems repair after smoking cessation, leading to better mental health. Conclusion: Based on a large body of literature including experimental, observational, and novel causal inference studies, there is consistent evidence showing that smoking can negatively affect the brain and mental health, and that smoking cessation could reverse the mental ill-health caused by smoking. Our model suggests that smoking prevention and treatment strategies have a role in preventing and treating mental illness as well as physical illness.

Acceptability of integrating smoking cessation treatment into routine care for people with mental illness: A qualitative study.

INTRODUCTION: Improving Access to Psychological Therapies (IAPTs) Services could offer smoking cessation treatment to improve physical and psychological outcomes for service users, but it currently does not. This study aimed to understand participants' views and experiences of receiving a novel smoking cessation intervention as part of the ESCAPE trial (intEgrating Smoking Cessation treatment As part of usual Psychological care for dEpression and anxiety). We used the Capability, Opportunity and Motivation Model of Behaviour (COM-B) to understand the (i) acceptability of the integrated smoking cessation treatment, (ii) views of psychological well-being practitioners' (PWPs) ability to deliver the smoking cessation treatment and (iii) positive and negative impacts of smoking cessation treatment. METHODS: This was a qualitative study embedded within a feasibility randomized-controlled trial (ESCAPE) in primary care services in the United Kingdom (IAPT). Thirty-six participants (53% female) from both usual care and intervention arms of the ESCAPE trial, including both quitters and nonquitters, were interviewed using semi-structured interviews. Data were analysed using a framework approach to thematic analysis, using the COM-B as a theoretical frame. RESULTS: Psychological Capability: Integrated smoking cessation treatment was acceptable and encouraged participants to reflect on their mental health. Some participants found it difficult to understand nicotine withdrawal symptoms. MOTIVATION: Participants were open to change during the event of presenting to IAPT. Some described being motivated to take part in the intervention by curiosity, to see whether quitting smoking would help their mental health. Physical Opportunity: IAPT has a natural infrastructure for supporting integrated treatment, but there were some barriers such as session duration and interventions feeling segmented. Social Opportunity: Participants viewed PWPs as having good interpersonal skills to deliver a smoking cessation intervention. CONCLUSION: People with common mental illness generally accepted integrated smoking cessation and mental health treatment. Smoking cessation treatment fits well within IAPT's structure; however, there are barriers to implementation. PATIENT OR PUBLIC CONTRIBUTION: Before data collection, we consulted with people with lived experience of smoking and/or mental illness and lay public members regarding the aims, design and interview schedules. After analysis, two people with lived experience of smoking and mental illness individually gave feedback on the final themes and quotes.

Critical appraisal of interventional clinical trials assessing heated tobacco products: a systematic review.

OBJECTIVE: To critically assess the methodological characteristics and quality of interventional clinical trials investigating the effects of heated tobacco products (HTPs). DATA SOURCES: Web of Science (Core collection and MEDLINE), Scopus, MedRxiv, ClinicalTrials.gov and ICTRP trial databases and transnational HTP manufacturer online publication libraries were searched for clinical trials on HTPs published between January 2010 and April 2022. STUDY SELECTION: Interventional clinical trials of any design, in which at least one group of adult participants used a currently marketed HTP, were selected by two reviewers with good or very good agreement. DATA EXTRACTION: Data relating to trial characteristics and effects of intervention on primary outcomes were extracted using a predesigned form. Risk of bias was assessed using Cochrane's Risk of Bias tool v1. DATA SYNTHESIS: 40 trials were included, 29 of which were tobacco industry affiliated. Methodological characteristics, such as registration, design, setting, comparator interventions, participants, outcomes and analyses, varied between trials, though there were few significant differences between industry-affiliated and independent trials. Of the 40 trials, 33 were judged to be at high risk of bias and 6 at unclear risk of bias. Trial findings were not significantly associated with either affiliation or risk of bias. CONCLUSIONS: The conduct and reporting of HTP interventional clinical trials were poor in many respects and limited to investigating effects of short-term exposure. These trials fall short of what is needed to determine whether HTPs are beneficial to public health, meaning they may not be a sound basis for tobacco control policy decisions.

Effectiveness of weight management interventions for adults delivered in primary care: systematic review and meta-analysis of randomised controlled trials.

OBJECTIVE: To examine the effectiveness of behavioural weight management interventions for adults with obesity delivered in primary care. DESIGN: Systematic review and meta-analysis of randomised controlled trials. ELIGIBILITY CRITERIA FOR SELECTION OF STUDIES: Randomised controlled trials of behavioural weight management interventions for adults with a body mass index ≥25 delivered in primary care compared with no treatment, attention control, or minimal intervention and weight change at ≥12 months follow-up. DATA SOURCES: Trials from a previous systematic review were extracted and the search completed using the Cochrane Central Register of Controlled Trials, Medline, PubMed, and PsychINFO from 1 January 2018 to 19 August 2021. DATA EXTRACTION AND SYNTHESIS: Two reviewers independently identified eligible studies, extracted data, and assessed risk of bias using the Cochrane risk of bias tool. Meta-analyses were conducted with random effects models, and a pooled mean difference for both weight (kg) and waist circumference (cm) were calculated. MAIN OUTCOME MEASURES: Primary outcome was weight change from baseline to 12 months. Secondary outcome was weight change from baseline to ≥24 months. Change in waist circumference was assessed at 12 months. RESULTS: 34 trials were included: 14 were additional, from a previous review. 27 trials (n=8000) were included in the primary outcome of weight change at 12 month follow-up. The mean difference between the intervention and comparator groups at 12 months was -2.3 kg (95% confidence interval -3.0 to -1.6 kg, I2=88%, P<0.001), favouring the intervention group. At ≥24 months (13 trials, n=5011) the mean difference in weight change was -1.8 kg (-2.8 to -0.8 kg, I2=88%, P<0.001) favouring the intervention. The mean difference in waist circumference (18 trials, n=5288) was -2.5 cm (-3.2 to -1.8 cm, I2=69%, P<0.001) in favour of the intervention at 12 months. CONCLUSIONS: Behavioural weight management interventions for adults with obesity delivered in primary care are effective for weight loss and could be offered to members of the public. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021275529.

Addressing concerns about smoking cessation and mental health: theoretical review and practical guide for healthcare professionals.

Smoking rates in people with depression and anxiety are twice as high as in the general population, even though people with depression and anxiety are motivated to stop smoking. Most healthcare professionals are aware that stopping smoking is one of the greatest changes that people can make to improve their health. However, smoking cessation can be a difficult topic to raise. Evidence suggests that smoking may cause some mental health problems, and that the tobacco withdrawal cycle partly contributes to worse mental health. By stopping smoking, a person's mental health may improve, and the size of this improvement might be equal to taking anti-depressants. In this theoretical review and practical guide we outline ways in which healthcare professionals can raise the topic of smoking compassionately and respectfully to encourage smoking cessation. We draw on evidence-based methods like cognitive behavioural therapy, and outline approaches that healthcare professionals can use to integrate these methods into routine care.

The Potential Impact of Widespread Cessation Treatment for Smokers With Depression.

INTRODUCTION: Experts recommend integrating smoking-cessation treatments within U.S. mental health settings, but the population health benefits of doing so have not been estimated. This study simulates the impact of widespread cessation treatment for patients with depression under best-case treatment and maximum potential cessation scenarios. METHODS: Cessation interventions were simulated for U.S. adult smokers seeing a health professional for depression from 2020 to 2100. Interventions included (1) Any Treatment (behavioral counseling, pharmacological, combination) and (2) Pharmacological Treatment (including counseling), combined with increased mental health service utilization each. These were compared with a maximum potential cessation scenario where all patients with major depression quit smoking. Analyses were conducted in 2016-2020. RESULTS: Widespread uptake of Any Treatment among patients with depression would avert 32,000 deaths and result in 138,000 life-years gained by 2100; Any Treatment combined with 100% mental health service utilization would result in 53,000 and 231,000, respectively. Pharmacological Treatment would avert 125,000 deaths, with 540,000 life-years gained. Pharmacological Treatment combined with 100% mental health service utilization would result in 203,000 deaths averted and 887,000 life-years gained. Health gains under best-case treatment scenarios represent modest fractions of those projected under maximum potential cessation scenarios at current mental health service utilization levels (835,000 deaths averted, 3.73 million life-years gained) and at 100% utilization (1.11 million deaths averted, 5.07 million life years gained). CONCLUSIONS: Providing smoking-cessation treatment to patients with depression and increasing mental health service utilization would reduce the toll of tobacco on this population. These gains would be considerably larger if cessation treatments were more effective.

Views about integrating smoking cessation treatment within psychological services for patients with common mental illness: A multi-perspective qualitative study.

BACKGROUND: Tobacco smoking rates are significantly higher in people with common mental illness compared to those without. Smoking cessation treatment could be offered as part of usual outpatient psychological care, but currently is not. OBJECTIVE: To understand patient and health care professionals' views about integrating smoking cessation treatment into outpatient psychological services for common mental illness. DESIGN: Qualitative in-depth interviews, with thematic analysis. PARTICIPANTS: Eleven Improving Access to Psychological Therapies (IAPT) psychological wellbeing practitioners (PWPs), six IAPT patients, and six stop smoking advisors were recruited from English smoking cessation, and IAPT services. RESULTS: Patients reported psychological benefits from smoking, and also described smoking as a form of self-harm. Stop smoking advisors displayed therapeutic pessimism and stigmatizing attitudes towards helping people with mental illness to quit smoking. PWPs have positive attitudes towards smoking cessation treatment for people with common mental illness. PWPs and patients accept evidence that smoking tobacco may harm mental health, and quitting might benefit mental health. PWPs report expertise in helping people with common mental illness to make behavioural changes in the face of mood disturbances and low motivation. PWPs felt confident in offering smoking cessation treatments to patients, but suggested a caseload reduction may be required to deliver smoking cessation support in IAPT. CONCLUSIONS: IAPT appears to be a natural environment for smoking cessation treatment. PWPs may need additional training, and a caseload reduction. Integration of smoking cessation treatment into IAPT services should be tested in a pilot and feasibility study. PATIENT OR PUBLIC CONTRIBUTION: Service users and members of the public were involved in study design and interpretation of data.

Risk of neuropsychiatric and cardiovascular adverse events following treatment with varenicline and nicotine replacement therapy in the UK Clinical Practice Research Datalink: a case-cross-over study.

BACKGROUND AND AIMS: Varenicline and nicotine replacement therapy (NRT) are the most commonly used medications to quit smoking. Given their widespread use, monitoring adverse risks remains important. This study aimed to estimate the neuropsychiatric and cardiovascular risks associated with varenicline and NRT as used in routine UK care. DESIGN: Case-cross-over study. SETTING: UK-based electronic primary care records in the Clinical Practice Research Datalink from 2006 to 2015 linked to hospital and mortality data sets. PARTICIPANTS: Adult smokers (n =282,429) observed during periods when exposed and not exposed to either varenicline or NRT. MEASUREMENTS: Main outcomes included suicide, self-harm, myocardial infarction (MI), all-cause death and cause-specific death [MI, chronic obstructive pulmonary disease (COPD)]. In primary analyses, conditional logistic regression was used to compare the chance of varenicline or NRT exposure during the risk period (90 days prior to the event) with the chance of exposure during an earlier single reference period (91-180 days prior to the event) or multiple 90-day reference periods to increase statistical power. FINDINGS: In the primary analyses, findings were inconclusive for the associations between varenicline and the main outcomes using a single reference period, while NRT was associated with MI [odds ratio (OR) = 1.40, 95% confidence interval (CI) = 1.18-1.67]. Using multiple reference periods, varenicline was associated with an increased risk of self-harm (OR = 1.32, 95% CI = 1.12-1.56) and suicide (OR = 3.56, 95% CI = 1.32-9.60) but a reduction in all-cause death (OR = 0.75, 95% CI = 0.61-0.93). NRT was associated with MI (OR = 1.54, 95% CI = 1.36-1.74), self-harm (OR = 1.30, 95% CI = 1.18-1.44) and deaths from MI (OR = 1.53, 95% CI = 1.11-2.10), COPD (OR = 1.33, 95% CI = 1.14-1.56) and all causes (OR = 1.28, 95% CI = 1.18-1.40) when using multiple reference periods. CONCLUSIONS: There appear to be positive associations between (1) nicotine replacement therapy (NRT) and myocardial infarction, death and risk of self-harm and (2) varenicline and increased risk of self-harm and suicide, as well as a negative association between varenicline and all-cause death. The associations may not be causal. They may reflect health changes at the time of smoking cessation (nicotine replacement therapy is prescribed for people with cardiac problems) or be associated with quit attempts (exposure to both medicines was associated with self-harm).

Modeling smoking-attributable mortality among adults with major depression in the United States.

Tobacco-related health disparities disproportionately affect smokers with major depression (MD). Although tobacco simulation models have been applied to general populations, to date they have not considered populations with a comorbid mental health condition. We developed and calibrated a simulation model of smoking and MD comorbidity for the US adult population using the 2005-2018 National Surveys on Drug Use and Health. We use this model to evaluate trends in smoking prevalence, smoking-attributable mortality and life-years lost among adults with MD, and changes in smoking prevalence by mental health status from 2018 to 2060. The model integrates known interaction effects between smoking initiation and cessation, and MD onset and recurrence. We show that from 2018 to 2060, smoking prevalence will continue declining among those with current MD. In the absence of intervention, people with MD will be increasingly disproportionately affected by smoking compared to the general population; our model shows that the smoking prevalence ratio between those with current MD and those without a history of MD increases from 1.54 to 2.42 for men and from 1.81 to 2.73 for women during this time period. From 2018 to 2060, approximately 484,000 smoking-attributable deaths will occur among adults with current MD, leading to 11.3 million life-years lost. Ambitious tobacco control efforts could alter this trajectory. With aggressive public health efforts, up to 264,000 of those premature deaths could be avoided, translating into 7.5 million life years gained. This model can compare the relative health gains across different intervention strategies for smokers with MD.

Evidence for causal effects of lifetime smoking on risk for depression and schizophrenia: a Mendelian randomisation study.

BACKGROUND: Smoking prevalence is higher amongst individuals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS). METHODS: We conducted two-sample MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortium and (2) we conducted our own GWAS of lifetime smoking behaviour (which captures smoking duration, heaviness and cessation) in a sample of 462690 individuals from the UK Biobank. We validated this instrument using positive control outcomes (e.g. lung cancer). For schizophrenia and depression we used GWAS from the PGC consortium. RESULTS: There was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67-3.08, p < 0.001) and depression (OR 1.99, 95% CI 1.71-2.32, p < 0.001). Results were consistent across both lifetime smoking and smoking initiation. We found some evidence that genetic liability to depression increases smoking (ß = 0.091, 95% CI 0.027-0.155, p = 0.005) but evidence was mixed for schizophrenia (ß = 0.022, 95% CI 0.005-0.038, p = 0.009) with very weak evidence for an effect on smoking initiation. CONCLUSIONS: These findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking, providing further evidence for the detrimental consequences of smoking on mental health.

Prescribing Prevalence, Effectiveness, and Mental Health Safety of Smoking Cessation Medicines in Patients With Mental Disorders.

OBJECTIVE: We conducted a prospective cohort study of the Clinical Practice Research Database to estimate rates of varenicline and nicotine replacement therapy (NRT) prescribing and the relative effects on smoking cessation, and mental health. METHODS: We used multivariable logistic regression, propensity score matched regression, and instrumental variable analysis. Exposure was varenicline or NRT prescription. Mental disorders were bipolar, depression, neurotic disorder, schizophrenia, or prescriptions of antidepressants, antipsychotics, hypnotics/anxiolytics, mood stabilizers. Outcomes were smoking cessation, and incidence of neurotic disorder, depression, prescription of antidepressants, or hypnotics/anxiolytics. Follow-ups were 3, 6, and 9 months, and at 1, 2, and 4 years. RESULTS: In all patients, NRT and varenicline prescribing declined during the study period. Seventy-eight thousand four hundred fifty-seven smokers with mental disorders aged ≥18 years were prescribed NRT (N = 59 340) or varenicline (N = 19 117) from September 1, 2006 to December 31, 2015. Compared with smokers without mental disorders, smokers with mental disorders had 31% (95% CI: 29% to 33%) lower odds of being prescribed varenicline relative to NRT, but had 19% (95% CI: 15% to 24%) greater odds of quitting at 2 years when prescribed varenicline relative to NRT. Overall, varenicline was associated with decreased or similar odds of worse mental health outcomes than NRT in patients both with and without mental disorders, although there was some variation when analyses were stratified by mental disorder subgroup. CONCLUSIONS: Smoking cessation medication prescribing may be declining in primary care. Varenicline was more effective than NRT for smoking cessation in patients with mental disorders and there is not clear consistent evidence that varenicline is adversely associated with poorer mental health outcomes. IMPLICATIONS: Patients with mental disorders were less likely to be prescribed varenicline than NRT. We triangulated results from three analytical techniques. We found that varenicline was more effective than NRT for smoking cessation in patients with mental disorders. Varenicline was generally associated with similar or decreased odds of poorer mental health outcomes (ie, improvements in mental health) when compared with NRT. We report these findings cautiously as our data are observational and are at risk of confounding.

Long-term effectiveness and safety of varenicline and nicotine replacement therapy in people with neurodevelopmental disorders: A prospective cohort study.

This study aimed to determine the effectiveness and safety of varenicline versus NRT for smoking cessation in people with neurodevelopmental disorders, compared to those without, at up to four years after exposure. We analysed electronic medical records from the Clinical Practice Research Datalink using three different statistical approaches: multivariable logistic regression, propensity score matching (PSM), and instrumental variable analysis. Exposure was prescription of varenicline versus NRT and the primary outcome was smoking cessation at 2-years. We included 235,314 people aged 18 and above with eligible smoking cessation prescriptions in the effectiveness analysis. Smokers with neurodevelopmental disorders were 48% less likely (95% confidence interval: 42%, 54%) to be prescribed varenicline than NRT, compared to smokers without neurodevelopmental disorders. At 2-year follow-up, smokers with neurodevelopmental disorders prescribed varenicline were 38% more likely to quit smoking (95% confidence interval: 6%, 78%). Similar results were obtained using PSM and instrumental variable analyses. There was little evidence showing that varenicline increased the likelihood of mental health related adverse events in people with neurodevelopmental disorders. Varenicline is less likely to be prescribed to people with neurodevelopmental disorders despite results suggesting it is more effective than NRT and little evidence of increased likelihood of mental health related adverse events.

The effects of prescribing varenicline on two-year health outcomes: an observational cohort study using electronic medical records.

AIMS: To investigate whether smokers prescribed varenicline had lower risks of serious ill-health during the 4 years following treatment compared with those prescribed nicotine replacement therapy (NRT). DESIGN: Observational cohort study of electronic medical records. SETTING: A total of 370 UK general practices sampled from the Clinical Practice Research Datalink. PARTICIPANTS: A total of 126 718 patients aged 18 and over who were issued smoking cessation prescriptions between 1 September 2006 and 31 March 2014. MEASUREMENTS: Our primary outcome was all-cause mortality within 2 years of first prescription as indicated by linked Office of National Statistics data. Our secondary outcomes were cause-specific mortality, all-cause, cause-specific hospitalization, primary care diagnosis of myocardial infarction or chronic obstructive pulmonary disease (COPD), body mass index and attendance rate to primary care within 2 years of first prescription. Risk differences and 95% confidence intervals were estimated by multivariable adjusted regression and propensity score matched regression. We used instrumental variable analysis to overcome residual confounding. FINDINGS: People prescribed varenicline were healthier at baseline than those prescribed NRT in almost all characteristics, highlighting the potential for residual confounding. Our instrumental variable analysis results found that people prescribed varenicline had a similar risk of mortality at 2 years [risk difference per 100 patients treated = 0.67, 95% confidence interval (CI) = -0.11 to 1.46)] to those prescribed NRT, and there were similar rates of all-cause hospitalization, incident primary-care diagnoses of myocardial infarction and COPD. People prescribed varenicline subsequently attended primary care less frequently. CONCLUSIONS: Smokers prescribed varenicline in primary care in the United Kingdom do not appear to be less likely to die, be hospitalized or experience a myocardial infarction or chronic obstructive pulmonary disease during the following 2 years compared with smokers prescribed nicotine replacement therapy, but they gain more weight and attend primary care less frequently.

The effectiveness of varenicline versus nicotine replacement therapy on long-term smoking cessation in primary care: a prospective cohort study of electronic medical records.

Background: There is limited evidence about the effectiveness of varenicline and nicotine replacement therapy (NRT) for long-term smoking cessation in primary care, or whether the treatment effectiveness differs by socioeconomic position (SEP). Therefore, we estimated the long-term effectiveness of varenicline versus NRT (> 2 years) on smoking cessation, and investigated whether effectiveness differs by SEP. Methods: This is a prospective cohort study of electronic medical records from 654 general practices in England, within the Clinical Practice Research Datalink, using three different analytical methods: multivariable logistic regression, propensity score matching and instrumental variable analyses. Exposure was prescription of varenicline versus NRT, and the primary outcome was smoking cessation at 2 years' follow-up; outcome was also assessed at 3, 6, and 9 months, and at 1 and 4 years after exposure. SEP was defined using the Index of Multiple Deprivation. Results: At 2 years, 28.8% (N = 20 362/70 610) of participants prescribed varenicline and 24.3% (N = 36 268/149 526) of those prescribed NRT quit; adjusted odds ratio was 1.26 [95% confidence interval (CI): 1.23 to 1.29], P < 0.0001. The association persisted for up to 4 years and was consistent across all analyses. We found little evidence that the effectiveness of varenicline differed greatly by SEP. However, patients from areas of higher deprivation were less likely to be prescribed varenicline; adjusted odds ratio was 0.91 (95% CI: 0.90 to 0.92), P < 0.0001. Conclusions: Patients prescribed varenicline were more likely to be abstinent up to 4 years after first prescription than those prescribed NRT. In combination with other evidence, the results from this study may be used to update clinical guidelines on the use of varenicline for smoking cessation.