Smoking cessation for improving mental health

Gemma MJ Taylor; Nicola Lindson; Amanda Farley; Andrea Leinberger-Jabari; Katherine Sawyer; Rebecca te Water Naudé; Annika Theodoulou; Naomi King; Chloe Burke; Paul Aveyard

doi:10.1002/14651858.CD013522.pub2

. 2021 Mar 9;2021(3):CD013522. doi: 10.1002/14651858.CD013522.pub2

Smoking cessation for improving mental health

Gemma MJ Taylor ^1,^✉, Nicola Lindson ², Amanda Farley ³, Andrea Leinberger-Jabari ⁴, Katherine Sawyer ¹, Rebecca te Water Naudé ⁵, Annika Theodoulou ², Naomi King ¹, Chloe Burke ¹, Paul Aveyard ²

Editor: Cochrane Tobacco Addiction Group

PMCID: PMC8121093 PMID: 33687070

Abstract

Background

There is a common perception that smoking generally helps people to manage stress, and may be a form of 'self‐medication' in people with mental health conditions. However, there are biologically plausible reasons why smoking may worsen mental health through neuroadaptations arising from chronic smoking, leading to frequent nicotine withdrawal symptoms (e.g. anxiety, depression, irritability), in which case smoking cessation may help to improve rather than worsen mental health.

Objectives

To examine the association between tobacco smoking cessation and change in mental health.

Search methods

We searched the Cochrane Tobacco Addiction Group's Specialised Register, Cochrane Central Register of Controlled Trials, MEDLINE, Embase, PsycINFO, and the trial registries clinicaltrials.gov and the International Clinical Trials Registry Platform, from 14 April 2012 to 07 January 2020. These were updated searches of a previously‐conducted non‐Cochrane review where searches were conducted from database inception to 13 April 2012.

Selection criteria

We included controlled before‐after studies, including randomised controlled trials (RCTs) analysed by smoking status at follow‐up, and longitudinal cohort studies. In order to be eligible for inclusion studies had to recruit adults who smoked tobacco, and assess whether they quit or continued smoking during the study. They also had to measure a mental health outcome at baseline and at least six weeks later.

Data collection and analysis

We followed standard Cochrane methods for screening and data extraction. Our primary outcomes were change in depression symptoms, anxiety symptoms or mixed anxiety and depression symptoms between baseline and follow‐up. Secondary outcomes included change in symptoms of stress, psychological quality of life, positive affect, and social impact or social quality of life, as well as new incidence of depression, anxiety, or mixed anxiety and depression disorders.

We assessed the risk of bias for the primary outcomes using a modified ROBINS‐I tool. For change in mental health outcomes, we calculated the pooled standardised mean difference (SMD) and 95% confidence interval (95% CI) for the difference in change in mental health from baseline to follow‐up between those who had quit smoking and those who had continued to smoke. For the incidence of psychological disorders, we calculated odds ratios (ORs) and 95% CIs. For all meta‐analyses we used a generic inverse variance random‐effects model and quantified statistical heterogeneity using I². We conducted subgroup analyses to investigate any differences in associations between sub‐populations, i.e. unselected people with mental illness, people with physical chronic diseases.

We assessed the certainty of evidence for our primary outcomes (depression, anxiety, and mixed depression and anxiety) and our secondary social impact outcome using the eight GRADE considerations relevant to non‐randomised studies (risk of bias, inconsistency, imprecision, indirectness, publication bias, magnitude of the effect, the influence of all plausible residual confounding, the presence of a dose‐response gradient).

Main results

We included 102 studies representing over 169,500 participants. Sixty‐two of these were identified in the updated search for this review and 40 were included in the original version of the review. Sixty‐three studies provided data on change in mental health, 10 were included in meta‐analyses of incidence of mental health disorders, and 31 were synthesised narratively.

For all primary outcomes, smoking cessation was associated with an improvement in mental health symptoms compared with continuing to smoke: anxiety symptoms (SMD −0.28, 95% CI −0.43 to −0.13; 15 studies, 3141 participants; I² = 69%; low‐certainty evidence); depression symptoms: (SMD −0.30, 95% CI −0.39 to −0.21; 34 studies, 7156 participants; I² = 69%' very low‐certainty evidence); mixed anxiety and depression symptoms (SMD −0.31, 95% CI −0.40 to −0.22; 8 studies, 2829 participants; I² = 0%; moderate certainty evidence). These findings were robust to preplanned sensitivity analyses, and subgroup analysis generally did not produce evidence of differences in the effect size among subpopulations or based on methodological characteristics. All studies were deemed to be at serious risk of bias due to possible time‐varying confounding, and three studies measuring depression symptoms were judged to be at critical risk of bias overall. There was also some evidence of funnel plot asymmetry. For these reasons, we rated our certainty in the estimates for anxiety as low, for depression as very low, and for mixed anxiety and depression as moderate.

For the secondary outcomes, smoking cessation was associated with an improvement in symptoms of stress (SMD −0.19, 95% CI −0.34 to −0.04; 4 studies, 1792 participants; I² = 50%), positive affect (SMD 0.22, 95% CI 0.11 to 0.33; 13 studies, 4880 participants; I² = 75%), and psychological quality of life (SMD 0.11, 95% CI 0.06 to 0.16; 19 studies, 18,034 participants; I² = 42%). There was also evidence that smoking cessation was not associated with a reduction in social quality of life, with the confidence interval incorporating the possibility of a small improvement (SMD 0.03, 95% CI 0.00 to 0.06; 9 studies, 14,673 participants; I² = 0%). The incidence of new mixed anxiety and depression was lower in people who stopped smoking compared with those who continued (OR 0.76, 95% CI 0.66 to 0.86; 3 studies, 8685 participants; I² = 57%), as was the incidence of anxiety disorder (OR 0.61, 95% CI 0.34 to 1.12; 2 studies, 2293 participants; I² = 46%). We deemed it inappropriate to present a pooled estimate for the incidence of new cases of clinical depression, as there was high statistical heterogeneity (I² = 87%).

Authors' conclusions

Taken together, these data provide evidence that mental health does not worsen as a result of quitting smoking, and very low‐ to moderate‐certainty evidence that smoking cessation is associated with small to moderate improvements in mental health. These improvements are seen in both unselected samples and in subpopulations, including people diagnosed with mental health conditions. Additional studies that use more advanced methods to overcome time‐varying confounding would strengthen the evidence in this area.

Keywords: Humans; Middle Aged; Affect; Anxiety; Anxiety/therapy; Confidence Intervals; Controlled Before-After Studies; Depression; Depression/therapy; Incidence; Mental Disorders; Mental Disorders/epidemiology; Mental Disorders/therapy; Mental Health; Quality of Life; Smoking; Smoking/adverse effects; Smoking/psychology; Smoking Cessation; Smoking Cessation/methods; Smoking Cessation/psychology; Social Interaction; Stress, Psychological; Stress, Psychological/therapy; Tobacco Use Cessation; Tobacco Use Cessation/methods; Tobacco Use Cessation/psychology

Plain language summary

Does stopping smoking improve mental health?

Smoking and mental health

Some health providers and people who smoke believe that smoking helps reduce stress and other mental health symptoms, like depression and anxiety. They worry that stopping smoking may make mental health symptoms worse. However, studies have shown that smoking may have a negative impact on people's mental health, and stopping smoking could reduce anxiety and depression.

Why we did this Cochrane Review

We wanted to find out how stopping smoking affects people's mental health. If stopping smoking improves mental health symptoms, rather than worsening them, then this may encourage more people to try to quit smoking and more health professionals to help their patients to quit. It may also discourage people from beginning to smoke tobacco in the first place.

What did we do?

We searched for studies that lasted for at least six weeks that included people who were smoking at the start of the studies. To be included, studies also had to measure whether people did or did not stop smoking and any changes in mental health during the study.

We were interested in how stopping smoking affected:

‐ symptoms of anxiety;

‐ symptoms of depression;

‐ symptoms of anxiety and depression together;

‐ symptoms of stress;

‐ overall well‐being;

‐ mental health problems;

‐ social well‐being, personal relationships, isolation and loneliness.

Search date: we included evidence published up to 7 January 2020.

What we found

We found 102 studies in more than 169,500 people: some studies did not clearly report how many people took part. The studies used a range of different assessment scales to measure people's mental health symptoms.

Most studies included people from the general population (53 studies); 23 studies included people with mental health conditions; other studies included people with physical or mental health conditions, or long‐lasting physical conditions, who had recently had surgery, or who were pregnant.

We combined and compared the results from 63 studies that measured changes in mental health symptoms, and from 10 studies that measured how many people developed a mental health disorder during the study.

What are the results of our review?

Compared with people who continued to smoke, people who stopped smoking showed greater reductions in:

‐ anxiety (evidence from 3141 people in 15 studies);

‐ depression (7156 people in 34 studies); and

‐ mixed anxiety and depression (2829 people in 8 studies).

Our confidence in our results was very low (for depression), low (for anxiety), and moderate (for mixed anxiety and depression). Our confidence was reduced because we found limitations in the ways the studies were designed and carried out.

Compared with people who continued to smoke, people who stopped smoking showed greater improvements in:

‐ symptoms of stress (evidence from 4 studies in 1792 people);

‐ positive feelings (13 studies in 4880 people); and

‐ mental well‐being (19 studies in 18,034 people).

There was also evidence that people who stopped smoking did not have a reduction in their social well‐being, and their social well‐being may have increased slightly (9 studies in 14,673 people).

In people who stopped smoking, new cases of mixed anxiety and depression were fewer than in those who continued to smoke (evidence from 3 studies in 8685 people). New cases of anxiety were also fewer (2 studies in 2293 people). We were unable to come to a decision about the numbers of new cases of depression, as the results from different studies were too variable.

Key messages

People who stop smoking are not likely to experience a worsening in their mood long‐term, whether they have a mental health condition or not. They may also experience improvements in their mental health, such as reductions in anxiety and depression symptoms.

Summary of findings

Summary of findings 1. Associations between quitting smoking and change in mental health symptoms.

Associations between quitting smoking and change in mental health symptoms
Patient or population: various, including general population, pregnant people, psychiatric populations (ADHD, alcohol use disorder, anxiety disorder, depression, psychosis, PTSD, various SMI) and populations with chronic health conditions (acute coronary syndrome, AIDS, AS, brain injury, cancer, CHD, COPD, HIV) Setting: Australia, Belgium, Canada, China, Japan, Netherlands, Portugal, South Korea, Spain, Turkey, UK, USA Intervention: Quitting tobacco smoking Comparison: Continuing to smoke tobacco
Outcomes	Probable outcome with intervention	№ of participants (studies)	Certainty of the evidence (GRADE)	Comments
Change in anxiety assessed with various anxiety symptom scales follow‐up: range 6 weeks to 2 years Higher score indicates higher‐intensity anxiety symptoms	The mean change in anxiety score was 0.28 SDs lower (95% CI: −0.43 to −0.13) in people who quit smoking compared to people who continued smoking	3141 (15 observational studies)	⊕⊕⊝⊝ LOW^a,b,c	According to Cohen 1988's interpretation of effect size 0.2 represents a small effect, 0.5 represents a moderate effect, and 0.8 represents a large effect. According to this rule of thumb, the effects found here are small to moderate. However, they are similar to the effects of antidepressant medications on anxiety disorder, which are deemed to be clinically meaningful (NCCMH 2011).
Change in depression assessed with various depression symptom scales follow‐up: range 6 weeks to 6 years Higher score indicates higher‐intensity depression symptoms	The mean change in depression score was 0.3 SDs lower (95% CI: −0.39 to −0.21) in people who quit smoking compared to people who continued smoking	7156 (34 observational studies)	⊕⊝⊝⊝ VERY LOW^d,e,f
Mixed anxiety and depression assessed with various mixed anxiety and depression symptom scales follow‐up: range 3 months to 6 years Higher scores indicates higher‐intensity mixed anxiety & depression symptoms	The mean change in mixed anxiety and depression score was 0.31 SDs lower (95% CI: −0.40 to −0.22) in people who quit smoking compared to people who continued smoking	2829 (8 observational studies)	⊕⊕⊕⊝ MODERATE^a
ADHD: attention deficit hyperactivity disorder; AIDS: acquired immune deficiency syndrome; AS: ankylosing spondylitis; CHD: coronary heart disease; CI: Confidence interval; COPD: chronic obstructive pulmonary disease; HIV: human immunodeficiency virus; PTSD: post‐traumatic stress disorder; SD: standard deviation; SMI: serious mental illness
GRADE Working Group grades of evidence High certainty: We are very confident that the true effect lies close to that of the estimate of the effect Moderate certainty: We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different Low certainty: Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect Very low certainty: We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of effect

Study	Outcome	Covariates adjusted for	Unadjusted SMD (95% CI)	Adjusted SMD (95% CI)
Becoña 2017	Depression	Treatment group allocation, age, sex, baseline marital status, baseline education level, baseline working status, baseline FTND score, baseline number of years smoking	−1.61 (−2.34 to −0.88)	−1.62 (−2.36 to −0.88)
Blalock 2008	Depression	Baseline carbon monoxide expiration, baseline nicotine withdrawal score, treatment group allocation	−0.54 (−1.42 to 0.34)	−0.58 (−1.01 to −0.15)
McDermott 2013	Anxiety	Baseline STAI score, age, baseline nicotine dependence level, baseline cigarette consumption, and treatment group allocation	−0.62 (−0.88 to −0.36)	−0.74 (−1.00 to −0.48)
Taylor 2015	Psychological quality of life	Baseline FTND score, treatment group allocation, age started smoking, baseline report of calming effects from smoking, baseline report of unpleasant symptoms from smoking, baseline length of time to last cessation attempt, baseline experience from last cigarette, baseline longest period without smoking, baseline SF‐36 mental health score	1.37 (0.41 to 2.33)	1.13 (0.13 to 2.13)

Outcome	N studies	Egger's test regression coefficient	Standard error	CI lower bound	CI upper bound	P‐value
Anxiety	15	−0.97	0.61	−2.28	0.34	0.13
Depression	34	−1.23	0.33	−1.91	−0.55	< 0.001
Mixed anxiety and depression	8	−0.28	0.58	−1.7	1.13	0.64
Stress	4	−3.08	1.69	−10.37	4.21	0.21
Positive affect	13	1.98	0.31	1.3	2.65	< 0.001
Psychological quality of life	19	0.72	0.4	−0.11	1.56	0.09
Social	9	0.47	0.41	−0.51	1.44	0.29

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Main continuous data analysis	15	3141	Std. Mean Difference (IV, Random, 95% CI)	‐0.28 [‐0.43, ‐0.13]
1.2 Sensitivity analysis: no biochemical validation	12		Std. Mean Difference (IV, Random, 95% CI)	‐0.26 [‐0.44, ‐0.09]
1.3 Sensitivity analysis: point prevalence or no abstinence definition	5		Std. Mean Difference (IV, Random, 95% CI)	‐0.40 [‐0.74, ‐0.06]
1.4 Sensitivity analysis: psychoactive/psychological treatment used	12		Std. Mean Difference (IV, Random, 95% CI)	‐0.35 [‐0.49, ‐0.21]
1.5 Subgroups: comparing clinical populations	15		Std. Mean Difference (IV, Random, 95% CI)	‐0.29 [‐0.45, ‐0.14]
1.5.1 Chronic physical condition	5		Std. Mean Difference (IV, Random, 95% CI)	‐0.34 [‐0.61, ‐0.07]
1.5.2 General (unselected) population	5		Std. Mean Difference (IV, Random, 95% CI)	‐0.25 [‐0.62, 0.11]
1.5.3 Post‐surgical patients	1		Std. Mean Difference (IV, Random, 95% CI)	‐0.27 [‐0.64, 0.10]
1.5.4 Pregnant	1		Std. Mean Difference (IV, Random, 95% CI)	‐0.06 [‐0.41, 0.29]
1.5.5 Psychiatric condition	3		Std. Mean Difference (IV, Random, 95% CI)	‐0.33 [‐0.66, ‐0.01]
1.6 Subgroups: motivation to quit	15		Std. Mean Difference (IV, Random, 95% CI)	‐0.28 [‐0.43, ‐0.13]
1.6.1 Participants were selected by being motivated to quit	10		Std. Mean Difference (IV, Random, 95% CI)	‐0.27 [‐0.45, ‐0.09]
1.6.2 Participants were not selected by being motivated to quit	5		Std. Mean Difference (IV, Random, 95% CI)	‐0.30 [‐0.57, ‐0.02]
1.7 Subgroups: comparing adjusted & unadjusted estimates	15		Std. Mean Difference (IV, Random, 95% CI)	‐0.28 [‐0.43, ‐0.13]
1.7.1 Adjusted estimates	6		Std. Mean Difference (IV, Random, 95% CI)	‐0.36 [‐0.62, ‐0.10]
1.7.2 Unadjusted estimates	9		Std. Mean Difference (IV, Random, 95% CI)	‐0.21 [‐0.38, ‐0.04]
1.8 Subgroups: comparing study designs	15		Std. Mean Difference (IV, Random, 95% CI)	‐0.28 [‐0.43, ‐0.13]
1.8.1 Longitudinal cohort study/Non‐randomised intervention study	5		Std. Mean Difference (IV, Random, 95% CI)	‐0.25 [‐0.54, 0.03]
1.8.2 Randomised experiment comparing people allocated to quit/continue to smoke	1		Std. Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.68, 0.30]
1.8.3 Secondary analysis of RCT	9		Std. Mean Difference (IV, Random, 95% CI)	‐0.29 [‐0.49, ‐0.09]
1.9 Subgroups: length of longest follow‐up	15		Std. Mean Difference (IV, Random, 95% CI)	‐0.28 [‐0.43, ‐0.13]
1.9.1 6 weeks to ≤6 months follow‐up	11		Std. Mean Difference (IV, Random, 95% CI)	‐0.24 [‐0.42, ‐0.06]
1.9.2 >6 months follow‐up	4		Std. Mean Difference (IV, Random, 95% CI)	‐0.39 [‐0.62, ‐0.15]
1.10 Subgroups: primary versus secondary outcome	15		Std. Mean Difference (IV, Random, 95% CI)	‐0.28 [‐0.43, ‐0.13]
1.10.1 Primary outcome	9		Std. Mean Difference (IV, Random, 95% CI)	‐0.28 [‐0.46, ‐0.10]
1.10.2 Secondary outcome	6		Std. Mean Difference (IV, Random, 95% CI)	‐0.26 [‐0.54, 0.03]
1.11 New incidence of anxiety	2		Odds Ratio (IV, Random, 95% CI)	0.61 [0.34, 1.12]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 Main continuous data analysis	34	7156	Std. Mean Difference (IV, Random, 95% CI)	‐0.30 [‐0.39, ‐0.21]
2.2 Sensitivity analysis: risk of bias	32		Std. Mean Difference (IV, Random, 95% CI)	‐0.27 [‐0.36, ‐0.19]
2.3 Sensitivity analysis: no biochemical validation	26		Std. Mean Difference (IV, Random, 95% CI)	‐0.41 [‐0.55, ‐0.27]
2.4 Sensitivity analysis: point prevalence or no abstinence definition	12		Std. Mean Difference (IV, Random, 95% CI)	‐0.30 [‐0.42, ‐0.19]
2.5 Sensitivity analysis: psychoactive/psychological treatment used	21		Std. Mean Difference (IV, Random, 95% CI)	‐0.30 [‐0.42, ‐0.19]
2.6 Sensitivity analysis: differing Ns analysed	29		Std. Mean Difference (IV, Random, 95% CI)	‐0.30 [‐0.40, ‐0.20]
2.7 Subgroups: comparing clinical populations	34		Std. Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.41, ‐0.22]
2.7.1 Chronic physical condition	7		Std. Mean Difference (IV, Random, 95% CI)	‐0.39 [‐0.53, ‐0.25]
2.7.2 General (unselected) population	11		Std. Mean Difference (IV, Random, 95% CI)	‐0.55 [‐0.79, ‐0.31]
2.7.3 Post‐surgical patients	2		Std. Mean Difference (IV, Random, 95% CI)	‐0.21 [‐0.73, 0.31]
2.7.4 Pregnant population	3		Std. Mean Difference (IV, Random, 95% CI)	‐0.16 [‐0.41, 0.09]
2.7.5 Psychiatric condition	11		Std. Mean Difference (IV, Random, 95% CI)	‐0.18 [‐0.32, ‐0.04]
2.8 Subgroups: motivation to quit	34		Std. Mean Difference (IV, Random, 95% CI)	‐0.30 [‐0.39, ‐0.21]
2.8.1 Participants were selected by being motivated to quit	25		Std. Mean Difference (IV, Random, 95% CI)	‐0.34 [‐0.45, ‐0.23]
2.8.2 Participants were not selected by being motivated to quit	9		Std. Mean Difference (IV, Random, 95% CI)	‐0.22 [‐0.39, ‐0.06]
2.9 Subgroups: comparing adjusted & unadjusted estimates	34		Std. Mean Difference (IV, Random, 95% CI)	‐0.30 [‐0.38, ‐0.21]
2.9.1 Adjusted estimates	10		Std. Mean Difference (IV, Random, 95% CI)	‐0.34 [‐0.49, ‐0.19]
2.9.2 Unadjusted estimates	24		Std. Mean Difference (IV, Random, 95% CI)	‐0.28 [‐0.39, ‐0.16]
2.10 Subgroups: comparing study designs	34		Std. Mean Difference (IV, Random, 95% CI)	‐0.30 [‐0.39, ‐0.21]
2.10.1 Longitudinal cohort study/Non‐randomised intervention study	11		Std. Mean Difference (IV, Random, 95% CI)	‐0.23 [‐0.36, ‐0.10]
2.10.2 Randomised experiment comparing people allocated to quit/continue to smoke	1		Std. Mean Difference (IV, Random, 95% CI)	‐0.38 [‐0.87, 0.11]
2.10.3 Secondary analysis of RCT	22		Std. Mean Difference (IV, Random, 95% CI)	‐0.36 [‐0.48, ‐0.24]
2.11 Subgroups: length of longest follow‐up	34		Std. Mean Difference (IV, Random, 95% CI)	‐0.30 [‐0.38, ‐0.21]
2.11.1 6 weeks to ≤6 months follow‐up	20		Std. Mean Difference (IV, Random, 95% CI)	‐0.27 [‐0.40, ‐0.14]
2.11.2 >6 months follow‐up	14		Std. Mean Difference (IV, Random, 95% CI)	‐0.36 [‐0.52, ‐0.20]
2.12 Subgroups: primary versus secondary outcome	34		Std. Mean Difference (IV, Random, 95% CI)	‐0.30 [‐0.39, ‐0.21]
2.12.1 Primary outcome	21		Std. Mean Difference (IV, Random, 95% CI)	‐0.28 [‐0.39, ‐0.17]
2.12.2 Secondary outcome	13		Std. Mean Difference (IV, Random, 95% CI)	‐0.38 [‐0.58, ‐0.18]
2.13 New incidence of depression	7		Odds Ratio (IV, Random, 95% CI)	Totals not selected

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Main continuous data analysis	8	2829	Std. Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.40, ‐0.22]
3.2 Sensitivity analysis: no biochemical validation	5		Std. Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.40, ‐0.21]
3.3 Sensitivity analysis: point prevalence or no abstinence definition	3		Std. Mean Difference (IV, Random, 95% CI)	‐0.27 [‐0.46, ‐0.08]
3.4 Sensitivity analysis: psychoactive/psychological treatment used	4		Std. Mean Difference (IV, Random, 95% CI)	‐0.36 [‐0.49, ‐0.24]
3.5 Sensitivity analysis: differing Ns analysed	5		Std. Mean Difference (IV, Random, 95% CI)	‐0.29 [‐0.46, ‐0.12]
3.6 Subgroups: comparing clinical populations	8		Std. Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.40, ‐0.22]
3.6.1 Chronic physical and/or psychiatric condition	1		Std. Mean Difference (IV, Random, 95% CI)	‐0.29 [‐0.56, ‐0.02]
3.6.2 Chronic physical condition	1		Std. Mean Difference (IV, Random, 95% CI)	‐0.50 [‐0.97, ‐0.03]
3.6.3 General (unselected) population	5		Std. Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.40, ‐0.21]
3.6.4 Psychiatric condition	1		Std. Mean Difference (IV, Random, 95% CI)	‐0.21 [‐1.07, 0.65]
3.7 Subgroups: motivation to quit	8		Std. Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.40, ‐0.22]
3.7.1 Participants were selected by being motivated to quit	6		Std. Mean Difference (IV, Random, 95% CI)	‐0.32 [‐0.41, ‐0.22]
3.7.2 Participants were not selected by being motivated to quit	2		Std. Mean Difference (IV, Random, 95% CI)	‐0.27 [‐0.50, ‐0.04]
3.8 Subgroups: comparing study designs	8		Std. Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.40, ‐0.22]
3.8.1 Longitudinal cohort study/Non‐randomised intervention study	3		Std. Mean Difference (IV, Random, 95% CI)	‐0.28 [‐0.45, ‐0.10]
3.8.2 Secondary analysis of RCT	5		Std. Mean Difference (IV, Random, 95% CI)	‐0.32 [‐0.42, ‐0.22]
3.9 Subgroups: length of longest follow‐up	8		Std. Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.40, ‐0.22]
3.9.1 6 weeks to ≤6 months follow‐up	3		Std. Mean Difference (IV, Random, 95% CI)	‐0.34 [‐0.52, ‐0.15]
3.9.2 >6 months follow‐up	5		Std. Mean Difference (IV, Random, 95% CI)	‐0.30 [‐0.40, ‐0.20]
3.10 Subgroups: primary versus secondary outcome	8		Std. Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.40, ‐0.22]
3.10.1 Primary outcome	5		Std. Mean Difference (IV, Random, 95% CI)	‐0.30 [‐0.46, ‐0.14]
3.10.2 Secondary outcome	3		Std. Mean Difference (IV, Random, 95% CI)	‐0.31 [‐0.42, ‐0.21]
3.11 New incidence of mixed anxiety and depression	3	8685	Odds Ratio (IV, Fixed, 95% CI)	0.76 [0.66, 0.86]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Main continuous data analysis	4	1792	Std. Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.34, ‐0.04]
4.2 Sensitivity analysis: no biochemical validation	2		Std. Mean Difference (IV, Random, 95% CI)	‐0.23 [‐0.38, ‐0.07]
4.3 Sensitivity analysis: point prevalence or no abstinence definition	2		Std. Mean Difference (IV, Random, 95% CI)	‐0.27 [‐0.41, ‐0.12]
4.4 Sensitivity analysis: differing Ns analysed	3		Std. Mean Difference (IV, Random, 95% CI)	‐0.18 [‐0.36, ‐0.00]
4.5 Subgroups: comparing clinical populations	4		Std. Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.34, ‐0.04]
4.5.1 Chronic physical condition	1		Std. Mean Difference (IV, Random, 95% CI)	‐0.22 [‐0.40, ‐0.04]
4.5.2 General (unselected) population	3		Std. Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.41, 0.03]
4.6 Subgroups: motivation to quit	4		Std. Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.34, ‐0.04]
4.6.1 Participants were selected by being motivated to quit	2		Std. Mean Difference (IV, Random, 95% CI)	‐0.23 [‐0.38, ‐0.07]
4.6.2 Participants were not selected by being motivated to quit	2		Std. Mean Difference (IV, Random, 95% CI)	‐0.18 [‐0.49, 0.13]
4.7 Subgroups: comparing study designs	4		Std. Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.34, ‐0.04]
4.7.1 Longitudinal cohort study/Non‐randomised intervention study	2		Std. Mean Difference (IV, Random, 95% CI)	‐0.18 [‐0.49, 0.13]
4.7.2 Secondary analysis of RCT	2		Std. Mean Difference (IV, Random, 95% CI)	‐0.23 [‐0.38, ‐0.07]
4.8 Subgroups: length of longest follow‐up	4		Std. Mean Difference (IV, Random, 95% CI)	‐0.19 [‐0.34, ‐0.04]
4.8.1 6 weeks to ≤6 months follow‐up	1		Std. Mean Difference (IV, Random, 95% CI)	‐0.25 [‐0.58, 0.08]
4.8.2 >6 months follow‐up	3		Std. Mean Difference (IV, Random, 95% CI)	‐0.18 [‐0.36, ‐0.00]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
5.1 Main continuous data analysis	13	4880	Std. Mean Difference (IV, Random, 95% CI)	0.22 [0.11, 0.33]
5.2 Sensitivity analysis: no biochemical validation	7		Std. Mean Difference (IV, Random, 95% CI)	0.33 [0.15, 0.51]
5.3 Sensitivity analysis: point prevalence or no abstinence definition	3		Std. Mean Difference (IV, Random, 95% CI)	0.46 [0.06, 0.87]
5.4 Sensitivity analysis: psychoactive/psychological treatment used	9		Std. Mean Difference (IV, Random, 95% CI)	0.13 [0.04, 0.22]
5.5 Sensitivity analysis: differing Ns analysed	11		Std. Mean Difference (IV, Random, 95% CI)	0.25 [0.12, 0.39]
5.6 Subgroups: comparing clinical populations	13		Std. Mean Difference (IV, Random, 95% CI)	0.22 [0.11, 0.33]
5.6.1 Chronic physical and/or psychiatric condition	1		Std. Mean Difference (IV, Random, 95% CI)	0.47 [0.04, 0.90]
5.6.2 Chronic physical condition	3		Std. Mean Difference (IV, Random, 95% CI)	0.59 [0.17, 1.00]
5.6.3 Post‐surgical patients	1		Std. Mean Difference (IV, Random, 95% CI)	0.19 [‐0.05, 0.43]
5.6.4 General (unselected) population	6		Std. Mean Difference (IV, Random, 95% CI)	0.08 [0.01, 0.14]
5.6.5 Psychiatric condition	2		Std. Mean Difference (IV, Random, 95% CI)	0.69 [0.33, 1.06]
5.7 Subgroups: motivation to quit	13		Std. Mean Difference (IV, Random, 95% CI)	0.22 [0.11, 0.33]
5.7.1 Participants were selected by being motivated to quit	9		Std. Mean Difference (IV, Random, 95% CI)	0.20 [0.09, 0.31]
5.7.2 Participants were not selected by being motivated to quit	4		Std. Mean Difference (IV, Random, 95% CI)	0.35 [0.02, 0.67]
5.8 Subgroups: comparing adjusted & unadjusted estimates	13		Std. Mean Difference (IV, Random, 95% CI)	0.22 [0.11, 0.33]
5.8.1 Adjusted estimates	5		Std. Mean Difference (IV, Random, 95% CI)	0.12 [0.01, 0.24]
5.8.2 Undjusted estimates	8		Std. Mean Difference (IV, Random, 95% CI)	0.30 [0.12, 0.48]
5.9 Subgroups: comparing study designs	13		Std. Mean Difference (IV, Random, 95% CI)	0.22 [0.11, 0.33]
5.9.1 Longitudinal cohort study/Non‐randomised intervention study	6		Std. Mean Difference (IV, Random, 95% CI)	0.22 [0.01, 0.42]
5.9.2 Seconary analysis of RCT	7		Std. Mean Difference (IV, Random, 95% CI)	0.24 [0.11, 0.37]
5.10 Subgroups: length of longest follow‐up	13		Std. Mean Difference (IV, Random, 95% CI)	0.22 [0.11, 0.33]
5.10.1 6 weeks to ≤6 months follow‐up	4		Std. Mean Difference (IV, Random, 95% CI)	0.60 [0.27, 0.93]
5.10.2 >6 months follow‐up	9		Std. Mean Difference (IV, Random, 95% CI)	0.13 [0.04, 0.22]
5.11 Subgroups: primary versus secondary outcome	13		Std. Mean Difference (IV, Random, 95% CI)	0.22 [0.11, 0.33]
5.11.1 Primary outcome	3		Std. Mean Difference (IV, Random, 95% CI)	0.42 [‐0.13, 0.97]
5.11.2 Secondary outcome	10		Std. Mean Difference (IV, Random, 95% CI)	0.21 [0.10, 0.32]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
6.1 Main continuous data analysis	19	18034	Std. Mean Difference (IV, Random, 95% CI)	0.11 [0.06, 0.16]
6.2 Sensitivity analysis: no biochemical validation	9		Std. Mean Difference (IV, Random, 95% CI)	0.11 [‐0.02, 0.24]
6.3 Sensitivity analysis: point prevalence or no abstinence definition	3		Std. Mean Difference (IV, Random, 95% CI)	0.30 [‐0.03, 0.63]
6.4 Sensitivity analysis: psychoactive/psychological treatment used	15		Std. Mean Difference (IV, Random, 95% CI)	0.12 [0.06, 0.18]
6.5 Sensitivity analysis: differing Ns analysed	18		Std. Mean Difference (IV, Random, 95% CI)	0.11 [0.06, 0.17]
6.6 Subgroups: comparing clinical populations	19		Std. Mean Difference (IV, Random, 95% CI)	0.11 [0.06, 0.16]
6.6.1 Chronic physical and/or psychiatric condition	1		Std. Mean Difference (IV, Random, 95% CI)	0.60 [0.17, 1.03]
6.6.2 Chronic physical condition	5		Std. Mean Difference (IV, Random, 95% CI)	0.13 [‐0.03, 0.29]
6.6.3 General (unselected) population	9		Std. Mean Difference (IV, Random, 95% CI)	0.08 [0.03, 0.14]
6.6.4 Post‐surgical patients	1		Std. Mean Difference (IV, Random, 95% CI)	0.07 [‐0.17, 0.31]
6.6.5 Psychiatric condition	3		Std. Mean Difference (IV, Random, 95% CI)	0.09 [‐0.12, 0.31]
6.7 Subgroups: motivation to quit	19		Std. Mean Difference (IV, Random, 95% CI)	0.11 [0.06, 0.16]
6.7.1 Participants were selected by being motivated to quit	10		Std. Mean Difference (IV, Random, 95% CI)	0.10 [0.05, 0.15]
6.7.2 Participants were not selected by being motivated to quit	9		Std. Mean Difference (IV, Random, 95% CI)	0.13 [0.03, 0.24]
6.8 Subgroups: comparing adjusted & unadjusted estimates	19		Std. Mean Difference (IV, Random, 95% CI)	0.11 [0.06, 0.16]
6.8.1 Adjusted estimates	8		Std. Mean Difference (IV, Random, 95% CI)	0.13 [0.06, 0.20]
6.8.2 Unadjusted estimates	11		Std. Mean Difference (IV, Random, 95% CI)	0.09 [‐0.01, 0.18]
6.9 Subgroups: comparing study designs	19		Std. Mean Difference (IV, Random, 95% CI)	0.11 [0.06, 0.16]
6.9.1 Longitudinal cohort study/Non‐randomised intervention study	12		Std. Mean Difference (IV, Random, 95% CI)	0.12 [0.04, 0.20]
6.9.2 Secondary analysis of RCT	7		Std. Mean Difference (IV, Random, 95% CI)	0.10 [0.03, 0.18]
6.10 Subgroups: length of longest follow‐up	19		Std. Mean Difference (IV, Random, 95% CI)	0.11 [0.06, 0.16]
6.10.1 6 weeks to ≤6 months follow‐up	6		Std. Mean Difference (IV, Random, 95% CI)	0.12 [0.05, 0.19]
6.10.2 >6 months follow‐up	13		Std. Mean Difference (IV, Random, 95% CI)	0.10 [0.03, 0.18]
6.11 Subgroups: primary versus secondary outcome	19		Std. Mean Difference (IV, Random, 95% CI)	0.11 [0.06, 0.16]
6.11.1 Primary outcome	5		Std. Mean Difference (IV, Random, 95% CI)	0.14 [0.04, 0.24]
6.11.2 Secondary outcome	14		Std. Mean Difference (IV, Random, 95% CI)	0.10 [0.02, 0.18]

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
7.1 Main continuous data analysis	9	14673	Std. Mean Difference (IV, Random, 95% CI)	0.03 [0.00, 0.06]
7.2 Sensitivity analysis: no biochemical validation	5		Std. Mean Difference (IV, Random, 95% CI)	0.04 [‐0.07, 0.15]
7.3 Sensitivity analysis: point prevalence or no abstinence definition	2		Std. Mean Difference (IV, Random, 95% CI)	0.13 [‐0.10, 0.36]
7.4 Sensitivity analysis: psychoactive/psychological treatment used	5		Std. Mean Difference (IV, Random, 95% CI)	0.06 [‐0.03, 0.16]
7.5 Sensitivity analysis: differing Ns analysed	7		Std. Mean Difference (IV, Random, 95% CI)	0.04 [0.00, 0.07]
7.6 Subgroups: comparing clinical populations	9		Std. Mean Difference (IV, Random, 95% CI)	0.03 [0.00, 0.06]
7.6.1 Chronic physical condition	3		Std. Mean Difference (IV, Random, 95% CI)	0.13 [‐0.09, 0.34]
7.6.2 General (unselected) population	4		Std. Mean Difference (IV, Random, 95% CI)	0.03 [‐0.04, 0.10]
7.6.3 Post‐surgical patients	1		Std. Mean Difference (IV, Random, 95% CI)	0.06 [‐0.18, 0.30]
7.6.4 Psychiatric condition	1		Std. Mean Difference (IV, Random, 95% CI)	0.05 [‐0.01, 0.11]
7.7 Subgroups: motivation to quit	9		Std. Mean Difference (IV, Random, 95% CI)	0.03 [0.00, 0.06]
7.7.1 Participants were selected by being motivated to quit	6		Std. Mean Difference (IV, Random, 95% CI)	0.06 [0.00, 0.11]
7.7.2 Participants were not selected by being motivated to quit	3		Std. Mean Difference (IV, Random, 95% CI)	0.02 [‐0.02, 0.06]
7.8 Subgroups: comparing adjusted & unadjusted estimates	9		Std. Mean Difference (IV, Random, 95% CI)	0.03 [0.00, 0.06]
7.8.1 Adjusted estimates	3		Std. Mean Difference (IV, Random, 95% CI)	0.04 [‐0.01, 0.10]
7.8.2 Unadjusted estimates	6		Std. Mean Difference (IV, Random, 95% CI)	0.04 [‐0.02, 0.10]
7.9 Subgroups: comparing study designs	9		Std. Mean Difference (IV, Random, 95% CI)	0.03 [0.00, 0.06]
7.9.1 Secondary analysis of RCT	4		Std. Mean Difference (IV, Random, 95% CI)	0.05 [‐0.00, 0.10]
7.9.2 Longitudinal cohort study/Non‐randomised intervention study	5		Std. Mean Difference (IV, Random, 95% CI)	0.03 [‐0.01, 0.06]
7.10 Subgroups: length of longest follow‐up	9		Std. Mean Difference (IV, Random, 95% CI)	0.03 [0.00, 0.06]
7.10.1 6 weeks to ≤6 months follow‐up	3		Std. Mean Difference (IV, Random, 95% CI)	0.04 [‐0.01, 0.10]
7.10.2 >6 months follow‐up	6		Std. Mean Difference (IV, Random, 95% CI)	0.04 [‐0.02, 0.10]

*Study characteristics*
Methods	Study design: RCT Country: Bosnia and Herzegovina, Croatia, Germany, Hungary, Romania, Russian Federation, Spain, United States Data collection period: March 2010 – June 2012 Registry ID: ClinicalTrials.gov: NCT01078298
Participants	Number of participants: N = 525 Sample characteristics (at baseline): Age (mean): 45.4 years (SD 10.9) varenicline group, 47.1 years (SD 10.8) placebo group; Sex (% male): 37.3% (196/525) Population category: psychiatric population; Specific population: persons with stably‐treated current or past major depressive disorder (MDD) Nicotine dependence: FTND 5.9 (SD 1.9) varenicline group, 5.9 (SD 2.0) placebo group; Baseline cigarettes per day: 22 cigarettes daily in the past month (varenicline group 21.9 (SD 7.5), placebo group 21.5 (SD 8.7)); Motivation to quit: selected by motivation to quit
Interventions	Behavioural support for smoking cessation: manual‐guided smoking cessation counselling developed by a study author in accordance with Agency for Healthcare Research and Quality guidelines – provided at each clinic and telephone visit from baseline through to week 52 Pharmacological support for smoking cessation: varenicline or placebo Psychotherapeutic or psychoactive support for mental health or mood: received mood management ‐ most participants (varenicline 70.7%, placebo 73.2%) were receiving antidepressant medications at study entry; selective serotonin reuptake inhibitors and serotonin–norepinephrine reuptake inhibitors the predominant choice (varenicline, 61.3%; placebo, 67.7%), other most common psychotropic treatment was alprazolam (varenicline, 8.6%; placebo, 13.4%)
Outcomes	Definition of cessation used: continuous abstinence rates week 9 – 12; self‐reported 7‐day point‐prevalence of abstinence at weeks 12, 24 and 52 Cessation definition used for outcome(s) in this analysis: continuous abstinence Measure of biovalidation: exhaled CO levels (≤ 10 ppm) Definition of people who continued smoking used: ‘non‐quitters’ (exact definition not reported), carbon monoxide levels > 10 ppm Time point(s) at which follow‐up was conducted: baseline, every week during treatment phase and weeks 13, 14, 16, 20, 24, 28, 43, 36, 40, 44, 48 and 52 Outcome category: Depression Outcome measure(s): Montgomery‐Asberg Depression Rating Scale (MADRS)
Funding source	Study was funded by Pfizer. Dr. Anthenelli’s writing of this manuscript was funded, in part, by a Department of Veterans Affairs Merit Review award (NEUA‐003‐08S) and by a National Institute on Alcohol Abuse and Alcoholism grant (AA019720). Dr. Morris was supported, in part, by grants from the University of California, San Francisco, Smoking Cessation Leadership Center and Colorado Department of Public Health and Environment. Drs. Ramey, Tsilkos, Russ, and Yunis and Ms. Dubrava are employees of Pfizer. Editorial support was provided by Abegale Templar, PhD, of Engage Scientific and funded by Pfizer
Author conflicts of interest	Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNumM13‐0777
Notes	Outcome data source: additional data requested, but this was not received by the deadline and we were unable to include it in this version of the review

*Study characteristics*
Methods	Study design: secondary analysis of RCT Country: USA Data collection period: not stated Registry ID: VA Cooperative study #519
Participants	Number of participants: N = 943 Sample characteristics (at baseline): Age (mean): 54.1 years (SD 8.7); Sex (% male): 94% (886/943) Population category: psychiatric population; Specific population: veterans with PTSD Nicotine dependence: not measured; Baseline cigarettes per day: 21.7 (SD 10.5); Motivation to quit: selected by motivation to quit
Interventions	Behavioural support for smoking cessation: integrated cognitive behavioural smoking cessation intervention into participant’s individual PTSD psychotherapy, or treatment as usual (TAU) where participants received separate standardised smoking cessation and individual PTSD treatment Pharmacological support for smoking cessation: no pharmacological support Psychotherapeutic or psychoactive support for mental health or mood: received mood management ‐ PTSD psychotherapy ‐ type and amount of PTSD treatment received (i.e. evidenced‐based) were not reported and monitored for as part of the paper
Outcomes	Definition of cessation used: prolonged abstinence (PA) ‐ defined as 1 year of self‐reported (via average cigarettes per day over past 3 months) and bioverified abstinence without relapse between the 6‐month to 18‐month follow‐up visits Cessation definition used for outcome(s) in this analysis: prolonged abstinence Measure of biovalidation: expired CO of < 8 ppm and urine cotinine level of < 100 ng/ml Definition of people who continued smoking used: not having prolonged abstinence (PA) Time point(s) at which follow‐up was conducted: pre‐treatment, post‐treatment (18‐months post‐enrolment) and every 3 months in between Outcome category: Positive Affect, Psychological Quality of Life (QoL), Social Outcome Outcome measure(s): Veterans Short‐Form (VR – 36; vitality, mental health, social functioning)
Funding source	Funding was provided by the Cooperative Studies Program of the Clinical Science Research and Development Service, U.S. Department of Veterans Affairs (DVA; CSP #519, NCT00118534) and the Tobacco‐Related Disease Research Program 19DT‐0003. Dr. Baker receives research support from the Department of Defense (Navy BUMED and CDMRP PTO 090738) and the DVA (HSR&D SDR09‐128) and is supported in part by the VA Center of Excellence for Stress and Mental Health. Dr. McFall receives research support from VA Merit #821 and DVA. Dr. Saxon receives research support from NIAAA (1 P20 AA017839‐01), NIDA (5 U10 DA013714‐08), and from VA HSR&D (1 IO1 HX000616‐01)
Author conflicts of interest	The authors report no financial relationships with commercial interests
Notes	Outcome data source: Published data

*Study characteristics*
Methods	Study design: longitudinal cohort Country: USA Data collection period: January 2003 – June 2004, June 2005 – December 2008 Registry ID: N/A (cohort)
Participants	Number of participants: N = 4003; Number included in meta‐analysis: N = 1484 Sample characteristics (at baseline): Age (mean): never smoked 62.8 years (SD 13.3), people who previously smoked 64.1 years (SD 10.7), people who recently quit 54.6 years (SD 9.8), people who continued to smoke 54.6 years (SD 9.8); Sex (% male): never smoked 55.4% (634 /1145), people who previously smoked 74.9% (1029/1374), people who recently quit 71.2% (486/683), people who continued smoking 66.7% (534/801) Population category: chronic physical condition; Specific population: people hospitalised with acute myocardial infarction (AMI) Nicotine dependence: not measured; Baseline cigarettes per day: not measured; Motivation to quit: not selected by motivation to quit
Interventions	Behavioural support for smoking cessation: no behavioural support Pharmacological support for smoking cessation: no pharmacological support Psychotherapeutic or psychoactive support for mental health or mood: did not receive mood management
Outcomes	Definition of cessation used: at 1‐year those who responded they had quit in the past year were designated as 'recent quitters' Cessation definition used for outcome(s) in this analysis: unclear point‐prevalence Measure of biovalidation: not bioverified Definition of people who continued to smoke used: reported not quit in the past year i.e. ‘persistent smokers’ Time point(s) at which follow‐up was conducted: 1, 6 and 12 months after AMI Outcome category: Psychological Quality of Life (QoL) Outcome measure(s): Medical Outcomes Study 12‐item Short Form (SF‐12; Mental Component Summary)
Funding source	Funding support was received for the Prospective Registry Evaluating Myocardial Infarction: Events and Recovery (PREMIER) Registry from CV Therapeutics, Inc and for the Translational Research Investigating Underlying disparities in acute Myocardial infarction Patient’s Health status (TRIUMPH) Registry from the National Heart Lung and Blood Institute. S. Cresci’s effort is supported in part by the National Institutes of Health
Author conflicts of interest	(Disclosures) J.A. Spertus owns the copyright for the Seattle Angina Questionnaire
Notes	Outcome data source: Published data

*Study characteristics*
Methods	Study design: randomised experiment Country: UK Data collection period: not stated Registry ID: not reported
Participants	Number of participants: N = 145; Number included in meta‐analysis: N = 64 Sample characteristics (at baseline): Age (mean): 34.5 years; Sex (% male): 47% (30/64) Population category: general population; Specific population: recruited through advertisement in South‐East London Nicotine dependence: FTND, people who quit 4.6 (SD 1.7), people who continued smoking 5.3 (SD 1.8); Baseline cigarettes per day: people who quit 17.8 (SD 5.9), people who continued smoking 18.5 (SD 6.3); Motivation to quit: not selected by motivation to quit
Interventions	Behavioural support for smoking cessation: no behavioural support but participants received financial incentive for maintaining smoking or abstinence status as allocated Pharmacological support for smoking cessation: no pharmacological support Psychotherapeutic or psychoactive support for mental health or mood: did not receive mood management
Outcomes	Definition of cessation used: continuous abstinence (maintained cotinine‐verified abstinence at all follow‐ups i.e. ‘successful quitters’) Cessation definition used for outcome(s) in this analysis: continuous abstinence Measure of biovalidation: breath CO levels < 11 ppm; salivary cotinine level of more than 20 ng/ml were considered non‐abstinent Definition of people who continued smoking used: participants from 'quit' group who reported more than 1 lapse since the last session, or with a salivary cotinine level > 20 ng/ml were classified as relapsers Time point(s) at which follow‐up was conducted: 7 days, 1 month and 3 months Outcome category: Anxiety, Depression Outcome measure(s): Hospital Anxiety and Depression Scale (HADS)
Funding source	National Institute of Drug Abuse (NIDA); grant code 3527427
Author conflicts of interest	None specified
Notes	Outcome data source: Published and unpublished data

*Study characteristics*
Methods	Study design: non‐randomised intervention study Country: Germany and Austria Data collection period: not stated Registry ID: not reported
Participants	Number of participants: N = 447; Number included in meta‐analysis: N = 224 Sample characteristics (at baseline): Age (mean): 45.5 years (range 21 ‐ 82); Sex (% male): 86.4% (386/447) Population category: chronic physical condition; Specific population: people living with HIV Nicotine dependence: not measured; Baseline cigarettes per day: up to 10 (24.0%), 11 – 20 (37.1%), 21 – 30 (22.2%), 31+ (13.1%); Motivation to quit: selected by motivation to quit
Interventions	Behavioural support for smoking cessation: 2 smoking cessation interventions delivered by trained physicians were offered to all people who smoked; a short intervention (5‐minute structured motivational intervention focused on increasing knowledge about benefits of smoking cessation) and a longer programme (full smoking cessation programme) with 5 sessions (approximately 30 minutes, focused on strengthening problem‐solving skills and developing social skills to improve patient social support) – people who smoked were invited to participate in full programme after short intervention, time‐frame between sessions was not pre‐determined to facilitate flexibility Pharmacological support for smoking cessation: pharmacological support (nicotine replacement products, bupropion, varenicline) was offered for participants to use if they wished; 4.0% participants received nicotine replacement products, 2.7% participants received varenicline and 1.8% bupropion in the recommended dosages Psychotherapeutic or psychoactive support for mental health or mood: some of the sample received mood‐management intervention (1.8% of participants; n = 4) received bupropion and 16% of total sample (14% of people who smoked) were receiving ‘antidepressant therapy’ not otherwise specified
Outcomes	Definition of cessation used: smoking status assessed with question ‘have you smoked within the last 7 days’ i.e. point‐prevalence abstinence Cessation definition used for outcome(s) in this analysis: point‐prevalence abstinence Measure of biovalidation: smoking status at baseline confirmed with CO level of > 6 ppm ; smoking status measured at study end using same protocol (i.e. CO measured at study end) but does not explicitly state it was used to confirm abstinence Definition of people who continued to smoke used: ‘participants who continued to smoke’ i.e. reported smoking in the previous 7‐days Time point(s) at which follow‐up was conducted: 8 months Outcome category: Psychological Quality of Life (QoL), Social Outcome Outcome measure(s): World Health Organisation Quality of Life – HIV‐Bref (WHOQOL HIV‐Bref)
Funding source	Study was funded by ViiV healthcare Germany and GSK Austria
Author conflicts of interest	The authors report no conflict of interest
Notes	Outcome data source: Published data

*Study characteristics*
Methods	Study design: longitudinal cohort (smoking cessation service data) Country: Spain Data collection period: 2005 ‐ 2008 Registry ID: N/A (cohort)
Participants	Number of participants: N = 569 Sample characteristics (at baseline): Age (mean): 43.3 years (SD 9.9); Sex (% male): 50.6% (288/569) Population category: general population; Specific population: general population Nicotine dependence: Fagerström score, 6 (SD 2.3); Baseline cigarettes per day: 23.1 (SD 9.9); Motivation to quit: selected by motivation to quit
Interventions	Behavioural support for smoking cessation: multicomponent treatment, including 9 sessions of psychological group therapy where the therapeutic relationship emphasised the active role of the participant Pharmacological support for smoking cessation: 1 of the 3 drugs recommended by clinical practice guidelines and based on participant preference: NRT in form of transdermal patches or chewing gum, bupropion or varenicline Psychotherapeutic or psychoactive support for mental health or mood: some participants in the cohort were using psychotropic drugs (13%) and 30.3% of total sample were prescribed bupropion i.e. received mood management
Outcomes	Definition of cessation used: continued abstinence – self‐reported no smoking since first day Cessation definition used for outcome(s) in this analysis: continuous abstinence Measure of biovalidation: self‐reported smoking status verified by expired carbon monoxide (CO ≤ 10 ppm) Definition of people who continued to smoke used: did not self‐report continued abstinence; participants for which no data available were assumed to still be smoking Time point(s) at which follow‐up was conducted: day of clinical assessment, day before quitting (Pre‐D), day after quitting (Post‐D), 1st week, 4th week (1‐month) and 12th week (3‐months) Outcome category: Anxiety Outcome measure(s): State Trait Anxiety Inventory (STAI)
Funding source	None specified
Author conflicts of interest	None specified
Notes	Outcome data source: Published data

*Study characteristics*
Methods	Study design: RCT Country: Spain Data collection period: January 2015 – July 2018 Registry ID: ClinicalTrials.gov: NCT03163056
Participants	Number of participants: N = 120 Sample characteristics (at baseline): Age (mean): CBT+BA 50.6 years (SD 10.2), CBT+BA+CM 52.7 years (SD 8.9); Sex (% male): CBT+BA 35% (21/60), CBT+BA+CM 23.3% (14/60) Population category: general population; Specific population: people who smoked and were seeking treatment recruited from the community via flyers, radio, television, web‐based, and newspaper advertisements Nicotine dependence: CBT+BA FTND 6.9 (SD 1.8), CBT+BA+CM 6.2 (SD 1.8); Baseline cigarettes per day: CBT+BA 23 (SD 8.2), CBT+BA+CM 20.7 (SD 6.7); Motivation to quit: selected by motivation to quit
Interventions	Behavioural support for smoking cessation: participants randomised to A) CBT plus behavioural activation (BA) – empirically‐supported psychological intervention for quitting smoking; main components were psychoeducation on cigarette use, nicotine fading (i.e. a 30% weekly reduction of nicotine consumption from the 1st to the 4th week and abstinence from 48 hours prior to the 5th session onwards), self‐monitoring and graphical representations of nicotine intake reductions, stimulus control, relaxation, role‐playing in alternative behaviours, development of a preventive relapse plan through training in coping skills, and enhancement of social support (BA element described below); or B) CBT plus BA plus contingency management (CM) which includes interventions previously described + CM protocol for reinforcing abstinence ‐ participants were given vouchers redeemable for a variety of uses contingent upon negative CO and cotinine samples, incentives followed an escalating schedule of reinforcement; if participants had CO or cotinine readings indicating smoking status (i.e. CO ≥ 5 ppm and cotinine levels ≥ 81 ng/ml), they did not receive the voucher and the next abstinent sample was reset to the initial value; after the reset occurred, if participants provided 3 consecutive abstinent samples, the voucher value that they received was the same as the one given before the reset ‐ total amount that participants could earn during the 8‐week treatment phase was EUR 175 (USD 200) Pharmacological support for smoking cessation: no pharmacological support Psychotherapeutic or psychoactive support for mental health or mood: received mood management ‐ participants in both conditions took part in BA module which was delivered from the 1st session, its main goal being to increase the number of pleasant activities participants engage in ‐ activation assignment was based on participants’ activity hierarchy of level of difficulty and interest; therapists worked with participants in a collaborative way to identify life values and objectives; through sessions 2 – 8, therapists and participants agreed on 2 – 3 activation goals aimed to enhance activation and decrease avoidance patterns of behaviour; other treatment components included ‐ discussion of the treatment rationale, psychoeducation on the relationship between smoking and depression (through functional analysis of behaviour and written materials developed by therapists), weekly activity and mood monitoring, and social support through social contracts that consisted of identifying which people in the participants’ lives they would like to get support from when engaging in new positive activities
Outcomes	Definition of cessation used: 2 measures of smoking were assessed, 1) point prevalence (i.e. the percentage of participants being abstinent for a minimum of 24 hours at the post‐treatment and 7 days prior to the visit at 1‐, 2‐, 3‐ and 6‐month follow‐ups) and 2) continuous abstinence, defined as number of days without smoking, not even a puff, since quit day in each of the time frames Cessation definition used for outcome(s) in this analysis: continuous abstinence Measure of biovalidation: expired CO; urine cotinine levels Definition of people who continued to smoke used: exact definition not reported; ‘smoker’; instances in which participants did not submit urine/CO samples were rendered as positive Time point(s) at which follow‐up was conducted: 1‐, 2‐, 3‐ and 6‐month follow‐up Outcome category: Depression Outcome measure(s): Beck Depression Inventory II (BDI‐II)
Funding source	This research was supported by the National Agency of Research of the Spanish Ministry of Science, Innovation and Universities and the European Regional Development Fund MINECO/FEDER(PSI2015‐64371‐P)and by two predoctoral grants from the National Agency of Research of the Spanish Ministry of Science, Innovation and Universities (BES‐2016‐076663/FPU15/04327)
Author conflicts of interest	No conflict declared
Notes	Outcome data source: Unpublished data

*Study characteristics*
Methods	Study design: ‘uncontrolled before‐and‐after study’ Country: Australia Data collection period: recruitment May 2007 – July 2008 and 6‐month follow‐up Registry ID: not reported
Participants	Number of participants: N = 227 Sample characteristics (at baseline): Age (mean): 45.2 years (SD 13.6); Sex (% male): 34.8% (79/227) Population category: psychiatric population; Specific population: people with depression Nicotine dependence: not measured; Baseline cigarettes per day: 23.0 (SD 11.3); Motivation to quit: selected by motivation to quit
Interventions	Behavioural support for smoking cessation: behavioural support and mood management provided via Quitline Pharmacological support for smoking cessation: 64.4% of total sample (n = 227) used cessation medication including NRT, varenicline or bupropion Psychotherapeutic or psychoactive support for mental health or mood: co‐management with doctor – tailored call‐back counselling was provided during which advisers focused on the emotional aspect of addiction and relationship between smoking and mood; strategies provided to monitor mood during quitting and to help quit smoking and regulate mood; 68.8% of total sample were taking prescription medication for well‐being, i.e. received mood management
Outcomes	Definition of cessation used: self‐reported point‐prevalence abstinence – quit for at least 24 hours between baseline and 2‐month follow‐up and at 6‐month follow‐up; sustained abstinence ‐ period prevalence (quit for 4 months) at 6‐month follow‐up Cessation definition used for outcome(s) in this analysis: prolonged abstinence Measure of biovalidation: not bioverified Definition of people who continued to smoke used: not making a quit attempt or failed quit attempt – had not tried/failed to quit for at least 24 hours between baseline and 2‐month follow‐up; had not quit for at least 4 months at 6‐month follow‐up Time point(s) at which follow‐up was conducted: baseline (after initial Quitline call), 2 months (end of treatment) and 6 months (after initial Quitline call) Outcome category: Depression Outcome measure(s): Patient Health Questionnaire 9 (PHQ‐9)
Funding source	Primarily funded by the Victorian Centre of Excellence in Depression and Related Disorders an (initiative between beyond‐blue and the State Government of Victoria, with contribution from Quit Victoria
Author conflicts of interest	Ainslie Hannan and Ian Ferretter are employed by Quit Victoria. Together with Catherine Segan, Kay Wilhelm and Sunil Bhar, they developed and implemented Quit Victoria’s tailored service for depression‐history smokers evaluated in this study. Ron Borland is employed by The Cancer Council Victoria, which houses Victoria’s Quitline. He has conducted research on the Quitline and has an ongoing interest in helping them improve the quality of their services
Notes	Outcome data source: Published data

Study	Reason for exclusion
Abrams 1987	Mental health was not measured before smoking cessation
Abrantes 2018	Did not analyse mental health outcomes, by smoking status
Acri 1992	Mental health outcome was measured during the withdrawal period.
Almeida 2011	Mental health outcome was measured during the withdrawal period.
Auer 2014	Ineligible outcomes
Bakhshaie 2015	Wrong study design
Balduyck 2011	Mental health was not measured before smoking cessation
Balfour 2017	Did not analyse mental health outcomes, by smoking status
Bekele 2017	Wrong study design
Billert 2006	Mental health outcome was measured during the withdrawal period.
Bock 2014	Did not analyse mental health outcomes, by smoking status
Bolliger 2002	Ineligible outcomes
Breslau 1998	Wrong exposure
Brody 2017	Wrong study design
Brook 2012	Did not analyse mental health outcomes, by smoking status
Brown 2014	Did not analyse mental health outcomes, by smoking status
Brunette 2018	Did not analyse mental health outcomes, by smoking status
Burris 2014	Did not analyse mental health outcomes, by smoking status
Campbell 2018	Wrong study design
Caponnetto 2013	Ineligible outcomes
Carter 2014	Mental health was not measured before smoking cessation
Chen 2012	Ineligible outcomes
Chengappa 2014	Ineligible outcomes
Dalack 1999	Mental health outcome was measured during the withdrawal period.
Dickson‐Spillmann 2012	Did not analyse mental health outcomes, by smoking status
Duffy 2012	Did not analyse mental health outcomes, by smoking status
El Hajj 2015	Ineligible outcomes
Etter 2006	Mental health outcome was measured during the withdrawal period.
Faseru 2013	Ineligible outcomes
Flensborg‐Madsen 2011	Wrong study design
Fond 2013	Did not analyse mental health outcomes, by smoking status
Frederick 1998	Mental health outcome was measured during the withdrawal period.
Garces 2004	Ineligible outcomes
George 2002	Did not analyse mental health outcomes, by smoking status
Gilbert 1998	Mental health outcome was measured during the withdrawal period.
Gilbert 1999	Mental health outcome was measured during the withdrawal period.
Gilbert 2002	Mental health outcome was measured during the withdrawal period.
Gilbert 2003	Mental health outcome was measured during the withdrawal period.
Guiterrez‐Bedmar 2009	No psychological outcome data presented at baseline.
Haibach 2016	Ineligible outcomes
Hall 1990	Mental health outcome was measured during the withdrawal period
Heffner 2012	Mental health was measured during the withdrawal period
Hendricks 2014	Did not analyse mental health outcomes, by smoking status
Hirdes 1994	Ineligible outcomes
Hsu 2015	Did not analyse mental health outcomes, by smoking status
Hughes 1992	Mental health was measured during the withdrawal period
Hurt 1997	Randomised controlled trial. Analysis by treatment group.
Hwang 2012	Ineligible outcomes
IRCT20100127003210N16 2019	Did not analyse mental health outcomes, by smoking status
Jang 2010	No mental health outcome
John 2004	Smoking status as the outcome. Binary outcome.
Kaetsu 2002	Ineligible outcomes
Kahler 2004	Mental health was measured during the withdrawal period.
Kahler 2009	Ineligible outcomes
Kerkvliet 2015	Did not analyse mental health outcomes, by smoking status
Khaled 2009	Does not present data of change in mental health.
Khaled 2012	Mental health was not measured before smoking cessation
Kim 2019	(Prevalence) do not know who had depression at baseline
Kinnunen 2006	Mental health was not measured before smoking cessation
Kocak 2015	Ineligible outcomes
Lam 2012	Mental health was measured during the withdrawal period.
Lappan 2018	Mental health was not measured before smoking cessation
Lerman 2004	Randomised controlled trial. Analyses data by treatment group.
Lewis 2011	(Prevalence) do not know who had depression at baseline
McClure 2009	Randomised controlled trial. Analyses data by treatment group.
Miguez 2019	Mental health was not measured before smoking cessation
Moreno‐Coutino 2007	Continuing smoking group included recent relapsers.
Morris 2011	Randomised controlled trial. Analyses data by treatment group.
Myneni 2018	No full text available
NCT01789125 2013	Did not analyse mental health outcomes, by smoking status
NCT02845687	Study not completed
Nieva 2017	Ineligible outcomes
O'Toole 2018	(Prevalence) do not know who had depression at baseline
Ong 2016	Mental health was not measured before smoking cessation
Park 2009	Ineligible outcomes
Piper 2012	Ineligible outcomes
Roson 2017	Did not analyse mental health outcomes, by smoking status
Schlyter 2016	Ineligible outcomes
Schwartz 1968b	No figures presented in paper
Seghatoleslam 2014	No full text available
Shaw 2001	Mental health outcome was measured during the withdrawal period
Shimadu 2016	Ineligible outcomes
Siahpush 2007	Ineligible outcomes
Solak 2018	Ineligible outcomes
Stepankova 2016	No full text available
Strong 2012	Did not analyse mental health outcomes, by smoking status
Thorsteinsson 2001	Mental health was measured during the withdrawal period
Vidrine 2007	Change in mental health measured during the withdrawal period
Vidrine 2015	Did not analyse mental health outcomes, by smoking status
Weaver 2015	Did not analyse mental health outcomes, by smoking status
Weinberger 2012	Ineligible outcomes
Welch 2015	Did not analyse mental health outcomes, by smoking status
Zvolensky 2014	Mental health was not measured before smoking cessation

Study name	Reduced nicotine cigarettes in smokers with mood and anxiety disorders
Methods	A 2‐site, 2‐arm, 34‐week, double‐blind, parallel‐group, randomised controlled trial of reduced nicotine cigarettes
Participants	Psychiatric population: adults who smoke and meet lifetime diagnostic criteria for mood or anxiety disorders
Interventions	(a) Usual Nicotine Content (11.6 mg); or (b) Reduced Nicotine Content: the nicotine content per cigarette is progressively reduced from approximately 11.6 mg to 0.2 mg in 5 steps over 18 weeks. Both arms offered brief smoking cessation counselling after week 10
Outcomes	Primary outcome measure is blood cotinine Key secondary outcomes are: exhaled carbon monoxide; urinary total NNAL‐ 4‐(methylnitrosamino)‐1‐(3‐pyridyl)‐1‐butanol and 1‐hydroxypyrene; oxidative stress biomarkers including 8‐isoprostanes; measures of psychiatric symptoms (e.g., depression, anxiety); smoking behaviour and dependence (e.g., cigarette consumption, quit attempts); and health effects (e.g., blood pressure, respiratory symptoms)
Starting date	Recruitment of participants started in September 2015
Contact information	Name: Sophia Allen; Email: sallen@phs.psu.edu
Notes	Registry ID: Clinicaltrials.gov NCT01928758 Funding source: National Institute on Drug Abuse of the National Institutes of Health under Award Number P50DA036107 (JM & JF PIs for parent grant; JF and AEE PIs for this study) and the Center for Tobacco Products of the U.S. Food and Drug Administration. NIH NIDA (P50DA036107), NCATS (UL1 TR000127), FDA Declaration of interests: JF has done paid consulting for pharmaceutical companies involved in producing smoking cessation medications, including GSK, Pfizer, Novartis, J&J, and Cypress Bioscience, and received a research grant from Pfizer Inc. (not related to reduced nicotine cigarettes). There are no competing interests to declare for other authors

Study name	A multicomponent intervention including texting to promote tobacco abstinence in emergency department smokers: a pilot study
Methods	A prospective, 2‐arm, parallel group, randomised controlled trial of a multicomponent intervention (brochure + text‐based smoking cessation intervention + NRT + quitline referral) compared to standard care (brochure only). Outcome assessments blinded, recruiting research staff not blinded to group assignment
Participants	General population: adults visiting a hospital emergency department
Interventions	Multicomponent intervention consisting of: a) brochure containing information on health benefits of cessation and local quitline number; b) 4‐week supply of NRT; c) referral to local quitline; d) enrolment by research team in supported texting programme for tobacco dependence. Texting programme used was ‘SmokefreeTXT’ (smokefree.gov/smokefreetxt) with message content based on principles of CBT and some tips/advice for remaining abstinent. Some texts also employed momentary assessment of mood, cravings, tobacco use and physician contact; texting programme lasted for 28 days Control arm/standard care: brochure only
Outcomes	Main objective: To assess feasibility of multicomponent ED‐initiated programme of tobacco dependence treatment using a publicly‐available text messaging programme and compare with control condition Primary outcome(s)/Primary end point(s): self‐reported 7‐day tobacco abstinence at 1‐ and 3‐months telephone follow‐up assessed using (“Have you smoked, even a puff, in the last 7 days?”). Time point(s) of evaluation of endpoint: 1‐month and 3‐month post‐enrolment; both 1 and 3 months considered primary in this study; biochemical verification not performed Secondary outcome(s)/Secondary end point(s): associations between responses/adherence to text‐delivered ecological momentary assessments (EMA) and tobacco abstinence. EMAs assessed mood and craving on 3‐point ordinal scale (mood: good, OK, bad; craving: low, medium, high). EMAs used were taken from SmokefreeTXT library of messages and participants received either 0 or 1 EMA message per day. Time point(s) of evaluation of endpoint: frequency of response to EMAs was measured throughout intervention, i.e. 28 days Secondary objectives: to obtain a measure of effect size for follow‐up trial and assess willingness of eligible participants to participate and undergo randomisation, to assess study procedures, follow‐up rates and adherence to intervention, i.e. proportion of participants engaging in quitline services to which they were referred
Starting date	Participants were enrolled in May 2014
Contact information	Name: Steven L. Bernstein; E‐mail: Steven.bernstein@yale.edu
Notes	Registry ID: NCT02081144 Funding source: Supported in part by grant R01CA141479 from the National Cancer Institute, National Institutes of Health Declaration of interests: Authors had no potential conflicts to disclose

PERMALINK

Smoking cessation for improving mental health

Gemma MJ Taylor

Nicola Lindson

Amanda Farley

Andrea Leinberger-Jabari

Katherine Sawyer

Rebecca te Water Naudé

Annika Theodoulou

Naomi King

Chloe Burke

Paul Aveyard

Abstract

Background

Objectives

Search methods

Selection criteria

Data collection and analysis

Main results

Authors' conclusions

Plain language summary

Summary of findings

Summary of findings 1. Associations between quitting smoking and change in mental health symptoms.

Background

Description of the condition

Description of the intervention

How the intervention might work

Why it is important to do this review

Objectives

Methods

Criteria for considering studies for this review

Types of studies

Types of participants

Types of interventions

Types of outcome measures

Primary outcomes

Secondary outcomes

Search methods for identification of studies

Electronic searches

Searching other resources

Data collection and analysis

Selection of studies

Data extraction and management

Assessment of risk of bias in included studies

Measures of treatment effect

Unit of analysis issues

Dealing with missing data

Assessment of heterogeneity

Assessment of reporting biases

Data synthesis

Subgroup analysis and investigation of heterogeneity

Sensitivity analysis

Summary of findings and assessment of the certainty of the evidence

Results

Description of studies

Results of the search

1.

Included studies

Participants

Intervention/exposure

Outcomes

Ongoing studies

Excluded studies

Risk of bias in included studies

2.

3.

Bias due to confounding

Bias in selection of participants into the study

Bias in the classification of follow‐up smoking status

Bias due to deviations from quitting smoking (i.e. relapsing) or through access to psychoactive treatments

Bias due to missing data

Bias in measurement of outcomes

Bias in selection of the reported result

Overall risk of bias assessment

Effects of interventions

Anxiety

1.1. Analysis.

4.

1.2. Analysis.

1.3. Analysis.

Study name	A cluster‐randomised trial to examine the impact of early intervention by practice nurse‐general practitioner (GP) teams on quality of life, health status and lung function of Chronic Obstructive Pulmonary Disease (COPD) patients
Methods	A pragmatic, parallel‐group, cluster‐randomised controlled trial of early intervention by a practice nurse‐GP partnership vs usual care for newly‐diagnosed COPD. Participating GPs, practice nurses and participants not blinded. Research staff collecting outcome measures and statistician blinded to group allocation
Participants	General population: patients at risk of COPD aged 40 ‐ 85 years with documented smoking history who have attended a GP practice at least twice, who are newly diagnosed with COPD through case‐finding visits
Interventions	Practice nurses will identify people who are at risk of COPD and undertake case finding. People newly diagnosed with COPD who attend the 'intervention practices' will be offered a management involving the GP and practice nurse working in partnership. The people who attend the 'control practices' will receive usual care from their GPs
Outcomes	Primary outcome [1]: The St George Respiratory Questionnaire (SGRQ) will be used for 2 purposes: 1) to collect participants' COPD‐related quality of data, and 2) participants' overall health status data (from the preamble question of (SGRQ): Timepoint [1] 1) at the first visit by project officer soon after the case‐finding visit by practice nurse; 2) 6 months from the first visit; 3) 12 months from the first visit. Secondary outcome [1]: Lung function ‐ forced expiratory volume in 1 second (FEV1) assessed by spirometry performed according to the standard methods. Timepoint [1] 1) at the first visit by project officer soon after the case‐finding visit by practice nurse; 2) 12 months from the first visit Secondary outcome [2]: Medication audit ‐ Participant report of medication use. These data will be collected by project officer at all 3 visits, except that at 6 months data will only be collected about respiratory medications. Timepoint [2]: 1) at the first visit by project officer soon after the case‐finding visit by practice nurse; 2) 6 months from the first visit; 3) 12 months from the first visit Secondary outcome [3]: Inhaler technique ‐ Assessment of inhaler technique assessed using published inhaler technique checklists. Timepoint [3]: 1) at first visit by project officer soon after the case‐finding visit by practice nurse; 2) 12 months from the first visit Secondary outcome [4]: Participant report of participation in a pulmonary rehabilitation programme Timepoint [4]: 1) at the first visit by project officer soon after the case‐finding visit by practice nurse; 2) 6 months from the first visit; 3) 12 months from the first visit Secondary outcome [5]: Patient knowledge ‐ Participant knowledge of COPD will be assessed using a previously‐published measure Timepoint [5]: 1) at the first visit by project officer soon after the case‐finding visit by practice nurse; 2) 12 months from the first visit Secondary outcome [6]: Health service use ‐ Participant report of hospital admissions, emergency department attendances, or unscheduled visits to a doctor in the previous 6 months Timepoint [6]: 1) at the first visit by project officer soon after the case‐finding visit by practice nurse; 2) 6 months from the first visit; 3) 12 months from the first visit Secondary outcome [7]: Smoking status ‐ Attendance at a smoking cessation programme and quit rates will be recorded (participant report). Validation of participant report of smoking status using Smokerlyser analysis Timepoint [7]: 1) at the first visit by project officer soon after the case‐finding visit by practice nurse; 2) 12 months from the first visit Secondary outcome [8]: Immunisation status ‐ Immunisation status (influenza and pneumococcal) by participant report Timepoint [8]: 1) at the first visit by project officer soon after the case‐finding visit by practice nurse; 2) 12 months from the first visit Secondary outcome [9]: Validation of COPD Diagnostic Questionnaire (CDQ) in Australian context Timepoint [9]: At the case‐finding visit by practice nurse. Secondary outcome [10]: COPD Assessment Test (CAT) ‐ a tool to quantify the impact of COPD on participants' health status Timepoint [10]: 1) at the first visit by project officer soon after the case‐finding visit by practice nurse; 2) 6 months from the first visit; 3) 12 months from the first visit
Starting date	Recruitment of participants started in 6th April 2011
Contact information	Name: Prof Nicholas Zwar (School of Public Health & Community Medicine, The University of New South Wales Sydney, NSW 2052 Country Australia, Phone +61 2 93852515); Email: n.zwar@unsw.edu.au
Notes	Registry ID: ACTRN12610000592044 Funding source: The study was funded by the National Health and Medical Research Council, Project Grant No. 630421 Declaration of interests: HR has participated on COPD advisory committees for Novartis, has spoken about COPD guidelines at symposia funded by AstraZeneca and BoehringerIngelheim, has received travel support from AstraZeneca, GlaxoSmithKlineand Novartis, and has received independent research funding fromGlaxoSmithKline for an investigator‐initiated COPD study. GBM is on an advisory board for Novartis and his institution has received funds fromAstraZeneca for consultancies. He has spoken at education symposia sponsored by AstraZeneca and GlaxoSmithKline. NZ has provided expert advice on smoking cessation education programs to Pfizer Pty Ltd andGlaxoSmithKline Australia Pty Ltd and has received support to attend smoking cessation conferences. Other authors have no competing interests

Study name	A controlled field trial to assess the effect of a community‐based tobacco cessation intervention package on tobacco use and expenditure on tobacco in women self‐help group members in rural Gadchiroli, Maharashtra, India: The Women’s Empowerment through Liberation From Tobacco (WE LiFT) project
Methods	A group‐randomised, parallel‐group, multiple‐arm field trial to assessed the effectiveness of a community‐based tobacco cessation intervention on tobacco use and expenditure on tobacco among women micro‐finance self‐help group (SHG) members. Blinding/Masking (N/A), randomisation performed at cluster level via computer‐generated randomisation
Participants	General population: women who are members of the MAVIM SHG in villages from selected clusters of Mahila Arthik Vikas Mahamandal (MAVIM) and their husbands, aged 18 ‐ 90 years old
Interventions	A) community‐based tobacco‐cessation intervention package from women SHG members (group health education, individual counselling of users, distribution of earthen saving pots to save money spent on tobacco, oral evaluation by dentists to assess oral lesions due to tobacco and distribution of iron and folic acid (ferrous sulphate 300 mg and folic acid 0.5 mg ‐ 1 tablet once a week by mouth for 7 months), B‐complex vitamin tablets (1 tablet twice daily by mouth for 7 days) and calcium tablets (calcium lactate 300 mg, 1 tablet twice daily by mouth for 7 days) as a health promotion measure and bisacodyl tablets (5 mg tablet, 1 tablet at bedtime for 7 days) for those reporting using tobacco to prevent constipation); B) community‐based tobacco cessation intervention package for women SHG members and their husbands (SHG members and their husbands receive tobacco cessation intervention package described above); C) no intervention (comparison cluster in which community‐based intervention package is not provided)
Outcomes	Primary outcome: decrease in % of SHG members using tobacco (7‐months); Secondary outcome(s): decrease in average daily expenditure on tobacco (7 months), amount of money saved in earthen money‐saving pots by families of tobacco users in the intervention areas (7 months), decrease in % of family members of the SHG members using tobacco (7 months), increase in % of SHG members and husbands with a sense of well‐being (7 months), decrease in % of SHG members and their husbands with oral discomfort (7 months)
Starting date	Date of first enrolment (India): 19 October 2012
Contact information	Name: Dr Abhay Bang; Site address: Gadchiroli, Search Shodhgram Gadchiroli, MAHARASHTRA; Tel: 07138255407; Email: search@sify.com
Notes	Registry ID: CTRI/2012/12/003262  Funding source: Indira foundation, Greenwich, CT, USA ; Mahila Arthik Vikas Mahamandal (Women Economic Development Corporation), Gadchiroli, Maharashtra, India Declaration of interests: None specified

Study name	Reducing stress, alcohol and tobacco use in pregnant women to improve the children’s later mental health (MINDFUL/PMI)
Methods	A 2‐arm, parallel‐group, randomised controlled trial of a 15‐week mindfulness‐oriented app‐based programme compared to an education app‐based programme. Assessor and data analyst are blinded. Control group is active control (i.e. effective treatment of control group)
Participants	Pregnant population: pregnant women aged 18 ‐ 50 years, between 8+0 to 14+0 weeks of pregnancy
Interventions	A) Intervention group: pregnancy mindfulness ‐ 15‐week mindfulness‐oriented app‐based programme B) Control group: pregnancy education ‐ 15‐week pregnancy education app‐based programme
Outcomes	Primary outcome(s): second‐to‐fourth finger length ratio (2D:4D) in the 11‐ to 12‐month‐old child. Secondary outcome(s):  A) Child (birth and 11‐ to 12‐month of age): Index “Orientation and Regulation“ of the Infant Behavior Questionnaire Revised (IBQ‐R); subscale scores of the German Parent Questionnaire of Child Development supplement to the Pediatric Screenings (EEE U6); subscale scores cognition, language, and motor function of the Bayley Scales of Infant and Toddler Development (BSID); sum and subscale scores of the Child Behavior Checklist (CBCL); infant anogenital distance; strength of the transient‐evoked oto‐acoustic emissions (TEOAEs); ethylglucuronide (EtG) in meconium;  B) Mother (longitudinal): sum and subscale scores of the Perceived Stress Scale (PSS10); sum scale score of the Pregnancy‐Related Anxiety Questionnaire (PRAQ‐R2); sum and subscale scores of the Mindful Attention and Awareness Scale (MAAS) and the Five Facet‐Mindfulness Questionnaire (FFMQ‐D); consumption quantified by the modified Alcohol Use Disorder Identification Test (AUDIT‐C); consumption quantified by the modified smoking questionnaire Robert Koch‐Institut; cotinine in maternal hair; ethylglucuronide (EtG) in maternal hair; cortisol in maternal hair
Starting date	Date of first enrolment: 12 November 2018
Contact information	Name: Johannes Kornhuber, Address: Schwabachanlage 6 91054 Erlangen Germany, Telephone: +49 9131 85 34166, Email: johannes.kornhuber@uk‐erlangen.de, Affiliation: Universitätsklinikum Erlangen, Psychiatrische und Psychotherapeutische Klinik
Notes	Registry ID: DRKS00014920 Funding source: With the public funded research project IMAC‐Mind: Improving Mental Health and Reducing Addiction in Childhood and Adolescence through Mindfulness: Mechanisms, Prevention and Treatment (2018–2022, 01GL1745C), the Federal Ministry of Education and Research contributes to improving the prevention and treatment of children and adolescents with substance use disorders and associated mental disorders. The project coordination is realised by the German Center of Addiction Research in Childhood and Adolescence at the University Medical Center Hamburg‐Eppendorf. For more information please visit our homepage www.IMAC‐Mind.de Declaration of interests: The authors quote some of their own publications on which this work and the idea of the study are based

Study name	Randomised placebo‐controlled trial assessing the efficacy and safety of BP1.4979 in smoking cessation
Methods	A multicentre, randomised, double‐blind, placebo‐controlled, phase IIb trial with parallel groups to assess safety and efficacy of BP1.4979 in people who smoke
Participants	General population: adults (18 ‐ 65 years) who smoke who have made at least 2 attempts to stop
Interventions	Product Code: BP1.4979; Pharmaceutical Form: Tablet; CAS Number; 1000036‐77‐0; Drug BP1.4979 at 3 mg, 10 mg, 15 mg or placebo during 3 months; Placebo form: tablet (oral use)
Outcomes	Primary outcome(s)/Main objective: To assess the efficacy (abstinence measured using diaries and confirmed by exhaled CO (abstinent = 10 ppm) and safety of BP1.4979 for smoking cessation, in people who smoke heavily and are willing to quit smoking Primary end point(s): 4‐week prolonged abstinence from smoking cigarettes at the end of a 12‐week double‐blind treatment phase (i.e. from V3 to V4); continuous abstinence measured by participant diary and verified by exhaled CO (abstinent < 10 ppm) will define response to the treatment. Secondary objective: No secondary objectives were established. Time point(s) of evaluation of this end point: During treatment phase and up to 3 months after treatment. Secondary outcome(s)/Secondary end point(s): 7‐day tobacco point prevalence abstinence (PPA) assessed at each visit by analysis of cigarettes consumption using self‐report diaries and measurement of exhaled CO; daily cigarettes consumption (mean consumption variation to baseline to determine % of participants having reduced cigarettes consumption between baseline and last week of treatment); assessment of craving and urge to smoke performed at each visit except screening (V0) by QSU‐Brief Questionnaire (Measure: variation from V1 to V2, V3, V4, V5 and V‐TQD), on (7‐days PPA) responders; continuous abstinence from V3 (W8) to V6 (W16) and from V3 (W8) to V8 (W24); nicotine withdrawal syndrome assessed by Minnesota Nicotine Withdrawal Scale (MNWS) (assessing urge to smoke, depressed mood, irritability, anxiety, poor concentration, restlessness, increased appetite and insomnia)(measure: variation from V1 to V2, V3, V4, V5 and V‐TQD ), on (7‐days PPA) responders; smoking satisfaction measured by the modified Cigarette Evaluation Questionnaire (mCEQ) (recording measures of smoking satisfaction, psychological reward, enjoyment of respiratory tract sensations, craving reduction and aversion) if the participant continues to smoke (measure: variation from V1 to V2, V3, V4, V5 and V‐TQD), in participants still smoking; body weight variation in treatment responders; BDI mean depressive score variation in responders; abstinence in a subgroup of participants having TQD up until treatment Day 8; safety will be assessed by evaluation of adverse events, various questionnaires and vital signs (measurement of heart rate, blood pressure, and body weight) at each study visit, by physical examinations (V0 and V4), ECG and laboratory tests (blood chemistry, haematology, urinanalysis tests, prolactin dosage) at screening (V0), after 4‐week treatment (V2) and at V4 (time points of evaluation of this end point: throughout the whole study duration)
Starting date	Date of first enrolment: 01 March 2013
Contact information	Name: Bioprojet Clinical Department, Address: 9 rue Rameau 75002 PARIS France, Telephone: +33(0)1 47 03 66 33, Affiliation: Bioprojet
Notes	Registry ID: EUCTR2012‐002731‐28‐CZ/NCT01785147 Funding source: Bioprojet  Declaration of interests: none specified

Study name	An effectiveness and safety study of varenicline for smoking cessation in hospitalised patients with psychiatric disorders
Methods	A 2‐arm, parallel group, randomised controlled trial of varenicline (12‐weeks) relative to nicotine patch (active comparator) for smoking cessation in hospitalised patients with psychiatric disorders. Blinding/Masking: None (Open‐Label)
Participants	Psychiatric population: aged 18 ‐ 65 years with at least 1 psychiatric disorder, hospitalised at 1 of 3 acute psychiatric facilities
Interventions	Trade Name: CHANTIX (varenicline) tablets, for oral use, Pharmaceutical form: film‐coated tablet, INN or proposed INN: VARENICLINE, CAS Number: 375815‐87‐5; Dose: 3 days of 0.5 mg, followed by 4 days of 1 mg, followed by 2 mg of varenicline until week 12. Trade Name: NICOTINELL TTS, Pharmaceutical Form: Cutaneous patch, INN or Proposed INN: NICOTINE, CAS Number: 54‐11‐5. Dose: 8 weeks of 21 mg patch, followed by 2 weeks of 14 mg patch and 2 weeks of 7 mg patch
Outcomes	Primary outcome(s). Main objective: This study will compare varenicline to nicotine patch initiated in‐hospital on smoking abstinence rates post‐discharge. In addition, safety will be assessed by comparing the incidence of severe neuropsychiatric adverse events in participants with varenicline or nicotine patch Primary end point(s): EFFICACY, 1. To compare smoking abstinence rates of varenicline relative to nicotine patch measured by CO‐confirmed continuous abstinence rate (CAR) between week 9 and week 12; 2. To compare smoking abstinence rates of varenicline relative to nicotine patch measured by CO‐confirmed continuous abstinence rate (CAR) between week 12 and week 16; SAFETY 1. The primary safety endpoint is the occurrence of at least 1 treatment‐emergent 'severe' neuropsychiatric event during or after hospitalisation. In case of a pre‐existing 'severe' neuropsychiatric event, only a worsening of this event will be reported. Time point(s) of evaluation of this end point: Efficacy: week 9 ‐ 12 and week 12 ‐ 16. Safety: number of severe neuropsychiatric events from the screening to the end of study Secondary objective: N/A. Secondary outcome(s)/Secondary end point(s): EFFICACY 1. To compare smoking abstinence rates of varenicline relative to nicotine patch measured by 7‐day CO‐confirmed abstinence at week 16. 2. To compare smoking withdrawal symptoms of varenicline relative to nicotine patch during and after hospitalisation; SAFETY It will be individual subscales scores on the following questionnaires: ‐ Hospital Anxiety and Depression Scale (HADS), ‐ Columbia Suicide Severity Rating Scale (C‐SSRS), ‐ Clinical Global Impression of Improvement (CGI‐I). Timepoint(s) of evaluation of this end point: 0, week 1, week 2, week 3, week 4, week 5, week 7, week 9, week 12, week 16
Starting date	Date of first enrolment: 04 July 2018
Contact information	Name: Psychiatry Department Vall d’Hebron, Address: Pg. de la Vall d’Hebron, 119‐129 08035 Barcelona Spain, Telephone: 3493489 42 95, Email: ebruguer@vhebron.net, Affiliation: Fundació Hospital Universitari Vall d’Hebron‐Institut de Recerca (VHIR)
Notes	Registry ID: EUCTR2017‐004715‐40‐ES Funding source: Pfizer Declaration of interests: none specified

Study name	Smartphone application for smoking cessation.
Methods	A 2‐arm, parallel‐group, pragmatic randomised controlled trial comparing an app which trains behavioural strategies for smoking cessation to a standard smartphone application to support people who smoke working to become quit‐free. Blinding/masking: single (outcomes assessor at follow‐up will be blind to group allocation).
Participants	General population: people who smoke aged 18 ‐ 65 years who own a smartphone and are motivated to quit smoking
Interventions	Intervention: smartphone app (Craving to Quit (www.cravingtoquit.com) which delivers mindfulness training and experience sampling for 22 days and consists of 22 modules of 10 ‐ 15 minutes each, designed to teach behavioural strategies for smoking cessation using psycho‐education‐based audio and videos, animations to reinforce key concepts and in vivo exercises. Active comparator: 3‐week smartphone application for smoking cessation in which people who smoke self‐monitor their smoking habits, mood and experience to quit smoking, comprising 6 prompts per day asking individuals about their experience, behaviour and smoking habits for 22 days
Outcomes	Primary outcome: 1‐week point‐prevalence abstinence at 6 months, verified by CO monitoring, analysed using intention‐to‐treat approach Secondary outcome(s): smoking, craving, mood and mindfulness as measured by experience sampling using the Tracker
Starting date	Study start date: October 2014; actual study completion date: June 2016
Contact information	Correspondence: kathleen.garrison@yale.edu 1 Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA 4 1 Church Street, Room 730, New Haven CT 06510, USA
Notes	Registry ID: Clinicaltrials.gov NCT02134509 Funding source: This research is funded by a grant from the American Heart Association (to KAG: 14CRP18200010). Additional research support is provided by a grant from the National Institutes of Health, National Institute on Drug Abuse (to KAG and JAB: K12DA00167) Declaration of interests: Judson A. Brewer and Prasanta Pal own stock in Claritas Mindsciences, the company that developed the apps used in this study. All other authors declare that they have no competing interests

Study name	Integrated smoking cessation treatment for emotional dysregulation
Methods	A 2‐arm, parallel‐group, randomised controlled trial comparing 2 group treatment approaches: (1): an educational‐supportive psychotherapy and standard smoking cessation treatment; and (2) an integrated smoking cessation and anxiety and depression management treatment programme (SDAT). Blinding/masking: single‐blind (outcome‐assessors will be blinded to group allocation)
Participants	Psychiatric population: aged 18 ‐ 65 years with elevated anxiety or depression who smoke an average of at least 6 cigarettes per day and report being motivated to quit smoking
Interventions	Comparing 2 group treatment approaches: A) cognitive behavioural treatment program which blends smoking cessation, anxiety and depression management/reduction treatment strategies (SDAT), with nicotine patch B) educational‐based psychotherapy and standard smoking cessation treatment programme (active comparator) with nicotine patch
Outcomes	Primary outcome: smoking status using the Timeline Follow‐Back Assessment (Time Frame: Change from baseline at 2, 4, 8, 10, 16, and 24 weeks post quit day)
Starting date	October 2014 (completed May 2017)
Contact information	Michael J Zvolensky, Ph.D. Anxiety and Health Research Laboratory and Substance Use Treatment Clinic, University of Houston Houston, Texas, United States, 77205
Notes	Registry ID: NCT02002858. Smoking Cessation for Depression and Anxiety Treatment. 2013 Funding source: University of Houston, National Institute on Drug Abuse (NIDA) Declaration of interests: none specified

Study name	Assessing the effectiveness of High Intensity Interval Training (HIIT) for smoking cessation in women: HIIT to quit study
Methods	A 2‐arm, parallel‐group, randomised controlled trial comparing the effects of 2 exercise interventions (HIIT and '10,000 steps' pedometer‐based intervention) combined with usual care smoking‐cessation support, on cessation rates in women who smoke and wish to quit. Blinding/masking: single (outcome assessor will be blinded to group allocations) Randomisation: allocation sequence generated by a computer programme and concealed within sealed opaque envelopes
Participants	General population: women aged 18 ‐ 55 years who smoke ≥ 5 cigarettes/day, and want to quit smoking
Interventions	Participants in both groups receive usual care smoking‐cessation support based on Smoking Cessation Guidelines for Australian General Practice (quit pack, signposting to other resources, directed to call Quitline). A) 10,000 steps: participants will receive a resource pack and pedometer, and will be asked to use the 10,000 steps log book to record steps and other physical activities. The aim will be to increase daily steps to 10,000 steps/day B) HIIT group: participants will complete 2 gym‐based supervised HIIT sessions/week and 1 home‐based HIIT session/week. At each training session participants will be asked to complete four 4‐min (4 × 4‐min) intervals at approximately 90% of maximum heart rate interspersed with 3‐min recovery periods
Outcomes	Primary outcome: % of participants who have ceased smoking using the Russell standard self‐reported abstinence (previous 2 weeks) and CO concentration < 10 ppm. Time points: 13 and 26 weeks after randomisation. Secondary outcome(s): number of cigarettes smoked on a daily basis (baseline, 13 and 26 weeks); withdrawal symptoms and cravings assessed using the Moods and Physical Symptoms Scale (MPSS; weeks 3, 6, 9 and 12); smoking dependency (FTND; baseline, weeks 6, 13 and 26); subjective stress (PSS; weeks 3, 6, 9 and 12); well‐being (SF36; baseline, 13 and 26 weeks); motivation assessed using the Behavioural Regulation in Exercise Questionnaire (BREQ‐2; baseline, 13 and 26 weeks); Cardiorespiratory fitness (VO2max) will be assessed using a graded exercise test to exhaustion; lung function will be assessed by forced vital capacity [FVC], forced expiratory volume in 1 sec [FEV1] and FEV1/FVC ratio, using a Vitalograph (2150, Ennis, Ireland); body composition will be assessed by researcher‐measured body mass index (height, weight), and waist circumference; physical activity and sedentary time will be measured using a wrist‐worn GENEActiv accelerometer, which will be worn for 1 week at each measurement time
Starting date	Date of first enrolment 10 December 2014, last enrolment 30 March 2016, date of last data collection 3 October 2016
Contact information	Dr Toby Pavey. Address: School of Human Movement Studies, Blair Drive, The University of Queensland, St. Lucia Campus, Brisbane, Australia, QLD 4072 Country Australia. Phone: +61 7 3346 9898. Email: t.pavey@uq.edu.au
Notes	Registry ID: ACTRN12614001255673 Funding source: This study is supported by a Heart Foundation of Australia Vanguard Grant (#100587). TP is supported by a National Health and Medical Research Council program grant (#569940) at The University of Queensland, School of Human Movement and Nutrition Sciences Declaration of interests: The authors declare that they have no competing interests

Study name	Smoking termination enhancement project (STEP)
Methods	A 2‐arm, parallel‐group, randomised controlled trial to compare the effectiveness of 2 smoking cessation programmes that integrate counselling and nicotine replacement with either a wellness programme or exercise. Blinding/masking: none (open‐label)
Participants	Psychiatric population: people who smoke (aged 18 ‐ 65 years) who report elevated anxiety sensitivity (AS) and report smoking an average of at least 10 cigarettes per day
Interventions	All participants receive standard treatment (ST) for smoking cessation based on the most recent clinical practice guideline from the US Department of Health and Human Services which broadly includes CBT for relapse prevention along with NRT. A) ST + EX: a 15‐week programme involving 3 x 45‐min exercise sessions each week B) ST + CTRL: a 15‐week programme involving 3 x 45‐min wellness sessions All participants asked to set a quit date for 6 weeks after the baseline visit
Outcomes	Primary outcome: % of participants who achieved point‐prevalence abstinence from smoking at 10‐ and 30‐weeks post‐quit‐day (EOT i.e. 10‐weeks post‐quit and 30‐week follow‐up). Main outcome analysis based on 7‐day point‐prevalence abstinence. Self‐reported abstinence verified by saliva cotinine (< 10 ng/mL) at 16 and 24‐week follow‐ups, or expired CO (< 8 ppm). Measures of putative mediators: Minnesota Withdrawal Scale (MWS); Anxiety Sedherence and patient adherence, adverse events and concurrent treatment
Starting date	Study start date: September 2009; Study completion date: August 2013
Contact information	Name: Dr Jasper Smits (PI) ‐ University of Texas at Austin, Email: jsmits@smu.edu
Notes	Registry ID: ClinicalTrials.gov, NCT01065506 Funding source: The study is funded by the National Institute of Drug Abuse (NIDA; R01DA027533) Declaration of interests: Drs Smits and Otto receive royalties from Oxford University Press for books on exercise for mood and anxiety disorders. All other authors declare that they have no competing interests

Study name	IntEgrating Smoking Cessation treatment As part of usual Psychological care for dEpression and anxiety (ESCAPE)
Methods	A 2‐arm, parallel‐group, multicentre randomised and controlled feasibility trial to compare the effectiveness of offering smoking cessation treatment alongside usual psychological care relative to usual psychological care plus referral to smoking cessation services. Blinding/masking: single (outcome assessments will be conducted by a researcher blinded to treatment allocation). Randomisation requested via RedCap
Participants	Psychiatric population: people who smoke (18+ years) with a current diagnosis of depression (PHQ‐9) or anxiety (GAD‐7) or both, who report smoking daily for at least 1 year and are interested in receiving help to quit smoking
Interventions	Participants are randomly allocated to 1 of 2 treatments (usual care vs usual care + integrated smoking cessation treatment). Both treatments are very similar and involve behavioural, psychological support and medicine to help participants to quit. The difference between the treatments is that one will be delivered alongside psychology therapy, and the other treatment will involve being referred to the local stop‐smoking service at the end of the IAPT therapy. Participants assigned to receive the smoking treatment alongside their psychology therapy will talk to their Psychological Well‐being Practitioner about their smoking for up to 15 minutes during each therapy appointment. They will be guided through behavioural techniques to support them through the quit attempt. The Psychological Well‐being Practitioner will also talk about the psychology of quitting, and how quitting might improve mental health. In addition, participants receive a smoking cessation medication of their choice to help with withdrawal symptoms. Participants assigned to receive smoking treatment after their psychology therapy is finished will receive a referral to their local stop‐smoking service, who will offer a very similar treatment as described above based at their service. Treatment will last a maximum of 12 weeks over 7 appointments
Outcomes	Primary outcome measure: Retention in the smoking cessation treatment, measured at treatment appointments 1 to 6 Secondary outcome measures: Smoking‐related: 1. Biochemically‐verified 7‐day point prevalence smoking cessation at 3 and 6 months after baseline 2. Number of cigarettes smoked per day, measured at enrolment, treatment appointments 1 to 6, and 3 and 6 months after baseline 3. Heaviness of Smoking Index, measured at enrolment, treatment appointments 1 to 6, and 3 and 6 months after baseline. Mental health‐related: Symptoms of depression, measured using PHQ‐9. Service‐related: Number of 'Did Not Attends', number of planned and completed IAPT sessions, measured at treatment appointments 1 to 6. Acceptability and feasibility: Participant and clinician acceptability and satisfaction of intervention as assessed by questionnaires and qualitative interviews; interviews also explore acceptability and feasibility of data collection procedures, and impact of smoking cessation treatment on usual care and psychological recovery Assessed at 3 months after baseline. Implementation‐related: intervention delivery checklist, qualitative analysis of intervention delivery, measured at treatment appointments 1 to 6
Starting date	January 2018 and estimated completion February 2021
Contact information	Name: Dr Gemma Taylor. Email: g.m.j.taylor@bath.ac.uk. Address: Addiction and Mental Health Group (AIM), Department of Psychology, University of Bath, 10 West, Bath BA2 7AY, UK
Notes	Registry ID: World Health Organization's International Clinical Trials Registry Platform ID: ISRCTN99531779/ Protocol reference: Pilot and Feasibility Studies 2019, 5:16 Funding source: The study is funded by Cancer Research UK. (Dr. Gemma Taylor is funded by a Cancer Research UK Postdoctoral Fellowship (C56067/A21330). Dr. Ali Shaw is funded through NIHR Research Capability Funding. The MRC Integrative Epidemiology Unit at the University of Bristol is supported by the Medical Research Council and the University of Bristol [MC_UU_12013/6]. Dr. David Kessler is funded by The Centre for Primary Care at the University of Bristol. Professor Paul Aveyard is an NIHR senior investigator and is funded by NIHR Oxford Biomedical Research Centre and CLAHRC. Dr. Gemma Taylor,and Professors Marcus Munafò and Paul Aveyard are members of the UK Centre for Tobacco and Alcohol Studies, a UKCRC Public Health Research: Centre of Excellence. Funding from the British Heart Foundation, Cancer Research UK,Economic and Social Research Council, Medical Research Council, and the National Institute for Health Research, under the auspices of the UK Clinical Research Collaboration. Dr. Kate Bartlem is funded by a National Health and Medical Research Council Early Career Fellowship (#1142272). Professor Chris Metcalfe is funded by the Higher Education Funding Council for England) Declaration of interests: Drs. Ali Shaw, David Kessler and Kate Bartlem have no conflicts of interest. Professor Chris Metcalfe has no conflicts of interest. Dr Gemma Taylor and Professor Marcus Munafò have received funding from Pfizer, who manufacture smoking cessation products Professor Paul Aveyard led a trial funded by the NIHR and Glaxo SmithKline donated nicotine patches to the NHS in support of the trial