INTRODUCTION: We previously reported global regional differences in smoking cessation outcomes, with smokers of US origin having lower quit rates than smokers from some other countries. This post-hoc analysis examined global regional differences in individual-level and country-level epidemiological, economic and tobacco regulatory factors that may affect cessation outcomes. METHODS: EAGLES (Evaluating Adverse Events in a Global Smoking Cessation Study) was a randomised controlled trial that evaluated first-line cessation medications and placebo in 8144 smokers with and without psychiatric disorders from 16 countries across seven regions. Generalised linear and stepwise logistic regression models that considered pharmacotherapy treatment, psychiatric diagnoses, traditional individual-level predictors (eg, demographic and smoking characteristics) and country-specific smoking prevalence rates, gross domestic product (GDP) per capita, relative cigarette cost and WHO-derived MPOWER scores were used to predict 7-day point prevalence abstinence at the end of treatment. RESULTS: In addition to several traditional predictors, three of four country-level variables predicted short-term abstinence: GDP (0.54 (95% CI 0.47, 0.63)), cigarette relative income price (0.62 (95% CI 0.53, 0.72)) and MPOWER score (1.03 (95% CI 1.01, 1.06)). Quit rates varied across regions (22.0% in Australasia to 55.9% in Mexico). With northern North America (USA and Canada) as the referent, the likelihood of achieving short-term abstinence was significantly higher in Western Europe (OR 1.4 (95% CI 1.14, 1.61)), but significantly lower in Eastern Europe (0.39 (95% CI 0.22, 0.69)) and South America (0.17 (95% CI 0.08, 0.35)). CONCLUSIONS: Increased tobacco regulation was associated with enhanced quitting among participants in the EAGLES trial. Paradoxically, lower GDP, and more affordable cigarette pricing relative to a countrys GDP, were also associated with higher odds of quitting. Geographical region was also a significant independent predictor. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT01456936.

Significance There are sex effects in abstinence outcomes across all smoking cessation medications, but there is limited information regarding sex effects on cessation-related neuropsychiatric adverse events (NPSAEs) or interactions with psychiatric status.

Methods

Secondary analysis of data from EAGLES of 8144 adults who smoke cigarettes randomized to varenicline, bupropion, nicotine patch or placebo. Design characteristics included region (within/outside US), psychiatric cohort (absent/present), and treatment. Baseline variables included demographics, smoking history, prior use of study treatments, lifetime suicide-related history, and prior psychiatric co-morbidities and medication use. Design characteristics were forced into logistic regressions models, and then interactions among sex, design elements, and baseline characteristics were evaluated for NPSAEs and 6-month cessation outcomes.

Results

Findings demonstrated a significant interaction of sex and race (p < 0.02); Black women were more likely to report NPSAEs than Black men. For cessation outcomes, there were no significant interactions with psychiatric cohort and sex. Women vs men with higher baseline levels of smoking had lower odds of continuous abstinence. Women vs men who used varenicline previously had lower odds of continuous abstinence. For 6-month point prevalence, sex interacted with baseline cigarettes per day (p < 0.01) similar to the interaction for continuous abstinence. Sex interacted with medication (p < 0.03), such that women vs men had relatively greater success at achieving point prevalence abstinence on varenicline.

Conclusions

Overall, results demonstrated important sex and racial differences in the incidence of NPSAEs, but psychiatric status did not interact with sex on cessation outcomes. Findings did support prior work demonstrating relative increased efficacy of varenicline for women.

Introduction

Psychiatric and substance use disorders represent barriers to smoking cessation. We sought to identify correlates of psychiatric comorbidity (CM; 2 diagnoses) and multimorbidity (MM; 3+ diagnoses) among smokers attempting to quit and to evaluate whether these conditions predicted neuropsychiatric adverse events (NPSAEs), treatment adherence, or cessation efficacy (CE).

Aims and methods

Data were collected from November 2011 to January 2015 across sixteen countries and reflect the psychiatric cohort of the EAGLES trial. Participants were randomly assigned to receive varenicline, bupropion, nicotine replacement therapy, or placebo for 12 weeks and were followed for an additional 12 weeks posttreatment. NPSAE outcomes reflected 16 moderate-to-severe neuropsychiatric symptom categories, and CE outcomes included continuous abstinence at weeks 9-12 and 9-24.

Results

Of the 4103 participants included, 36.2% were diagnosed with multiple psychiatric conditions (20.9% CM, 15.3% MM). Psychiatric CM and MM were associated with several baseline factors, including male gender, nonwhite race or ethnicity, more previous quit attempts, and more severe mental health symptoms. The incidence of moderate-to-severe NPSAEs was significantly higher (p < .01) in participants with MM (11.9%) than those with CM (5.1%) or primary diagnosis only (4.6%). There were no significant (ps > .05) main effects or interactions with treatment condition for diagnostic grouping on treatment adherence or CE outcomes.

Conclusions

While having multiple psychiatric diagnoses increased risk of developing moderate-to-severe NPSAEs during a quit attempt, neither CM nor MM were associated with treatment adherence or odds of quitting. These findings reassure providers to advise smokers with multiple stable psychiatric conditions to consider using Food and Drug Administration (FDA)-approved medications when trying to quit.

Implications

Psychiatric MM may be associated with development of NPSAEs when smokers make a medication-assisted quit attempt, but it does not appear to be differentially associated with medication compliance or efficacy. Prescribing healthcare professionals are encouraged to not only promote use of FDA-approved pharmacotherapies by smokers with complex psychiatric presentations, but also to closely monitor such smokers for neuropsychiatric side effects that may be related to their mental health conditions.

Nct #

NCT01456936.