Gemma M J Taylor

Change in mental health after smoking cessation: systematic review and meta-analysis

Objective To investigate change in mental health after smoking cessation compared with continuing to smoke. Design Systematic review and meta-analysis of observational studies. Data sources Web of Science, Cochrane Central Register of Controlled Trials, Medline, Embase, and PsycINFO for relevant studies from inception to April 2012. Reference lists of included studies were hand searched, and authors were contacted when insufficient data were reported. Eligibility criteria for selecting studies Longitudinal studies of adults that assessed mental health before smoking cessation and at least six weeks after cessation or baseline in healthy and clinical populations. Results 26 studies that assessed mental health with questionnaires designed to measure anxiety, depression, mixed anxiety and depression, psychological quality of life, positive affect, and stress were included. Follow-up mental health scores were measured between seven weeks and nine years after baseline. Anxiety, depression, mixed anxiety and depression, and stress significantly decreased between baseline and follow-up in quitters compared with continuing smokers: the standardised mean differences (95% confidence intervals) were anxiety −0.37 (95% confidence interval −0.70 to −0.03); depression −0.25 (−0.37 to −0.12); mixed anxiety and depression −0.31 (−0.47 to −0.14); stress −0.27 (−0.40 to −0.13). Both psychological quality of life and positive affect significantly increased between baseline and follow-up in quitters compared with continuing smokers 0.22 (0.09 to 0.36) and 0.40 (0.09 to 0.71), respectively). There was no evidence that the effect size differed between the general population and populations with physical or psychiatric disorders. Conclusions Smoking cessation is associated with reduced depression, anxiety, and stress and improved positive mood and quality of life compared with continuing to smoke. The effect size seems as large for those with psychiatric disorders as those without. The effect sizes are equal or larger than those of antidepressant treatment for mood and anxiety disorders.

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

Abstract 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.

How to compare instrumental variable and conventional regression analyses using negative controls and bias plots

Abstract There is increasing interest in the use of instrumental variable analysis to overcome unmeasured confounding in observational pharmacoepidemiological studies. This is partly because instrumental variable analyses are potentially less biased than conventional regression analyses. However, instrumental variable analyses are less precise, and regulators and clinicians find it difficult to interpret conflicting evidence from instrumental variable compared with conventional regression analyses. In this paper, we describe three techniques to assess which approach (instrumental variable versus conventional regression analyses) is least biased. These techniques are negative control outcomes, negative control populations and tests of covariate balance. We illustrate these methods using an analysis of the effects of smoking cessation therapies (varenicline) prescribed in primary care.

Does smoking reduction worsen mental health? A comparison of two observational approaches

Objectives The association between smoking reduction and mental health is of particular interest given that many smokers report that smoking offers mental health benefits. We aimed to assess the association between smoking reduction and change in mental health using two different analytical approaches to determine if there was any evidence of an association. There were no prior hypotheses. Design A secondary analysis of prospective individual level patient data from 5 merged placebo-controlled randomised trials of nicotine replacement therapy for smoking reduction. Participants All participants were adult smokers, selected because they wanted to reduce but not stop smoking, and had smoked for at least 3 years. Participants were excluded if they were pregnant, breastfeeding, under psychiatric care, deemed to be unfit by a general practitioner, or part of a cessation programme. 2066 participants were enrolled in the trials, 177 participants were biologically validated as prolonged reducers, and 509 as continuing smokers at both 6-week and 18-week follow-ups. Primary outcome Change in mental health from baseline to an 18-week follow-up was measured using the emotional well-being subscale on the Short Form Health Survey-36. Results After adjustment for confounding variables, the differences for reducers compared with continuing smokers were: regression modelling −0.6 (95% CI −4.4 to 3.2) and propensity score matching 1.1 (95% CI −2.0 to 4.1). Conclusions Smoking reduction, sustained for at least 12 weeks, was not associated with change in mental health, suggesting that reducing smoking was no better or worse for mental health than continuing smoking. Clinicians offering smoking reduction as a route to quit can be confident that, on average, smoking reduction is not associated with negative change in mental health.

The Effects of Prescribing Varenicline on Two-year Health Outcomes:: an Observational Cohort Study Using Electronic Medical Records

Abstract 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.

What are the effects of varenicline compared with nicotine replacement therapy on long-term smoking cessation and clinically important outcomes? Protocol for a prospective cohort study.

Introduction Smoking is a major avoidable cause of ill-health and premature death. Treatments that help patients successfully quit smoking have an important effect on health and life expectancy. Varenicline is a medication that can help smokers successfully quit smoking. However, there are concerns that it may cause adverse effects, such as increase in the occurrence of depression, self-harm and suicide and cardiovascular disease. In this study we aim to examine the effects of varenicline versus other smoking cessation pharmacotherapies on smoking cessation, health service use, all-cause and cause-specific mortality and physical and mental health conditions. Methods In this project we will investigate the effects of varenicline compared to nicotine replacement therapies on: (1) long-term smoking cessation and whether these effects differ by area level deprivation; and (2) the following clinically-important outcomes: rate of general practice and hospital attendance; all-cause mortality and death due to diseases of the respiratory system and cardiovascular disease; and a primary care diagnosis of respiratory illness, myocardial infarction or depression and anxiety. The study is based on a cohort of patients prescribed these smoking cessation medications from the Clinical Practice Research Datalink (CPRD). We will use three methods to overcome confounding: multivariable adjusted Cox regression, propensity score matched Cox regression, and instrumental variable regression. The total expected sample size for analysis will be at least 180 000. Follow-up will end with the earliest of either an ‘event’ or censoring due to the end of registration or death. Ethics and dissemination Ethics approval was not required for this study. This project has been approved by the CPRDs Independent Scientific Advisory Committee (ISAC). We will disseminate our findings via publications in international peer-reviewed journals and presentations at international conferences.

Cardiovascular and neuropsychiatric risks of varenicline: too good to be true?

www.thelancet.com/respiratory Vol 3 December 2015 e39 events. In table 1 of the Article, nicotine replacement therapy users have a higher rate of events for most of the defined outcomes and other comorbidities before the study entry date. Subsequently, higher-risk patients were more likely to be included in the reference group, resulting in an unintentional selection bias. This bias might explain the reduced risk of cardiovascular and neuropsychiatric events in varenicline users reported in the study by Kotz and colleagues. Propensity score matching can be used to reduce the eff ect of confounding by indication and selection bias; however, limited details about this procedure are provided in the study. Preferably, a table showing baseline characteristics of the propensity score-matched patients should be included. In conclusion, we emphasise that propensity score matching does not fully account for residual confounding and selection bias.

Does smoking cessation result in improved mental health? A comparison of regression modelling and propensity score matching

Objectives Smokers report that smoking is therapeutic; a recent meta-analysis suggests the contrary. However, the association in that review may be explained by group-membership bias and confounding. Propensity score matching (PSM) aims to produce causal estimates from observational data. We examined the association between cessation and change in mental health before and after PSM. Design A secondary analysis of prospective data from 5 placebo-controlled randomised trials for smoking reduction. Participants All participants were adult smokers and had smoked for at least 3 years. Participants were excluded if they were pregnant, breast feeding, under psychiatric care, deemed to be unfit by a general practitioner or part of a cessation programme. In total, 937 participants provided smoking data at both 6-month and 12-month follow-ups. Of these, 68 were confirmed as abstinent at both 6 and 12 months and 589 as continuous smokers at both follow-ups. Primary outcome Change in mental health (36-item Short Form Survey (SF-36), scored 0–100) from baseline (while all participants were smokers) to 12-month follow-up (after cessation) was compared between quitters and continuing smokers with and without adjustment, and after PSM. Results Before matching, quitters’ mental health scores improved compared with continuing smokers’, the mean difference and 95% CI was 5.5 (1.6 to 9.4). After adjustment, the difference was 4.5 (0.6 to 8.5), and after PSM, the difference was 3.4 (−2.2 to 8.9). Conclusions Improvements in mental health after smoking cessation may be partly but not completely explained by group membership bias and confounding.

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

Smoking prevalence is higher amongst individuals with schizophrenia and depression, compared to the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS). We conducted a GWAS of lifetime smoking behaviour (capturing smoking duration, heaviness and cessation) in a sample of 463,003 individuals from the UK Biobank, and validated the findings via MR analyses of positive control outcomes (e.g., lung cancer). Further MR analyses provided evidence that smoking is a causal risk factor for both schizophrenia and depression. We also found some evidence that genetic liability for both depression and schizophrenia cause increased lifetime smoking. These findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking. The genetic variants we identify for lifetime smoking have the potential to be used in further MR studies.

What about treatment of smoking to improve survival and reduce depression

In The Lancet Psychiatry, Amy Mulick and colleagues report long-term follow-up data from two randomised controlled trials of depression treatment for people with comorbid depression and cancer. The two trials—SMaRT Oncology-2 for people with good prognosis cancers and SMaRT Oncology-3 for patients with poor prognosis cancers—aimed to determine whether the Depression Care for People with Cancer (DCPC) treatment programme reduced depression symptoms. In their analysis of the follow-up data, the researchers aimed to identify whether DCPC also improved survival rates. Across the two trials, 642 patients were recruited and randomly assigned to receive DCPC or treatment as usual. Much of the association between depression and cancer can be explained by high smoking prevalence among people with depression. We know that people with depression are about twice as likely to smoke and are more heavily addicted than are the general population. These inequalities contribute to a reduction in life expectancy of almost 14 years for people with depression compared with those without depression, even though many smokers with depression are motivated to stop smoking. Given this, we were surprised that participants’ smoking status was not reported in the two trials and that the comorbid association between mental illness and smoking was not discussed. Smoking is the leading cause of cancer, and stopping smoking after diagnosis of cancer can improve prognostic outcomes. Moreover, stopping smoking is also associated with improvements in mental health, even in people with psychiatric conditions. There is therefore a strong case for offering parallel treatment of smoking and depression; by not offering smokers with depression help to quit, health-care providers might be worsening both their mental and physical health. We are currently investigating the implementation of smoking cessation treatment alongside routine psychological care for smokers with depression or anxiety. Due to the enormous beneficial impact that stopping smoking has on health outcomes, smoking cessation interventions are some of the most cost-effective treatments available to health services. There might be missed opportunities to deliver such treatments in the UK National Health Service, and potentially in similar health-care settings worldwide.