Anna Veluz-Wilkins

Long-term Nicotine Replacement Therapy: A Randomized Clinical Trial

IMPORTANCE The US Food and Drug Administration adopted labeling for nicotine patches to allow use beyond the standard 8 weeks. This decision was based in part on data showing increased efficacy for 24 weeks of treatment. Few studies have examined whether the use of nicotine patches beyond 24 weeks provides additional therapeutic benefit. OBJECTIVE To compare 8 (standard), 24 (extended), and 52 (maintenance) weeks of nicotine patch treatment for promoting tobacco abstinence. DESIGN, SETTING, AND PARTICIPANTS We recruited 525 treatment-seeking smokers for a randomized clinical trial conducted from June 22, 2009, through April 15, 2014, through 2 universities. INTERVENTIONS Smokers received 12 smoking cessation behavioral counseling sessions and were randomized to 8, 24, or 52 weeks of nicotine patch treatment. MAIN OUTCOMES AND MEASURES The primary outcome was 7-day point prevalence abstinence, confirmed with breath levels of carbon monoxide at 6 and 12 months (intention to treat). RESULTS At 24 weeks, 21.7% of participants in the standard treatment arm were abstinent, compared with 27.2% of participants in the extended and maintenance treatment arms (χ(2)(1) = 1.98; P = .17). In a multivariate model controlled for covariates, participants in the extended and maintenance treatment arms reported significantly greater abstinence rates at 24 weeks compared with participants in the standard treatment arm (odds ratio [OR], 1.70 [95% CI, 1.03-2.81]; P = .04), had a longer duration of abstinence until relapse (β = 21.30 [95% CI, 10.30-32.25]; P < .001), reported smoking fewer cigarettes per day if not abstinent (mean [SD], 5.8 [5.3] vs 6.4 [5.1] cigarettes per day; β = 0.43 [95% CI, 0.06-0.82]; P = .02), and reported more abstinent days (mean [SD], 80.5 [38.1] vs 68.2 [43.7] days; OR, 1.55 [95% CI, 1.06-2.26]; P = .02). At 52 weeks, participants in the maintenance treatment arm did not report significantly greater abstinence rates compared with participants in the standard and extended treatment arms (20.3% vs 23.8%; OR, 1.17 [95% CI, 0.69-1.98]; P = .57). Similarly, we found no difference in week 52 abstinence rates between participants in the extended and standard treatment arms (26.0% vs 21.7%; OR, 1.33 [95% CI, 0.72-2.45]; P = .36). Treatment duration was not associated with any adverse effects or adherence to the counseling regimen, but participants in the maintenance treatment arm reported lower adherence to the nicotine patch regimen compared with those in the standard and extended treatment arms (mean [SD], 3.94 [2.5], 4.61 [2.0], and 4.7 [2.4] patches/wk, respectively; F2,522 = 6.03; P = .003). CONCLUSIONS AND RELEVANCE The findings support the safety of long-term use of nicotine patch treatment, although they do not support efficacy beyond 24 weeks of treatment in a broad group of smokers. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01047527.

Rate of nicotine metabolism and smoking cessation outcomes in a community-based sample of treatment-seeking smokers.

BACKGROUND In samples from controlled randomized clinical trials, a smokers rate of nicotine metabolism, measured by the 3-hydroxycotinine to cotinine ratio (NMR), predicts response to transdermal nicotine. Replication of this relationship in community-based samples of treatment-seeking smokers may help guide the implementation of the NMR for personalized treatment for nicotine dependence. METHODS Data from a community-based sample of treatment seeking smokers (N=499) who received 8weeks of transdermal nicotine and 4 behavioral counseling sessions were used to evaluate associations between the NMR and smoking cessation. Secondary outcomes included withdrawal and craving, depression and anxiety, side effects, and treatment adherence. RESULTS The NMR was a significant predictor of abstinence (OR=.56, 95% CI: 0.33-0.95, p=.03), with faster metabolizers showing lower quit rates than slower metabolizers (24% vs. 33%). Faster nicotine metabolizers exhibited significantly higher levels of anxiety symptoms over time during treatment, vs. slower metabolizers (NMR x Time interaction: F[3,357]=3.29, p=.02). NMR was not associated with changes in withdrawal, craving, depression, side effects, and treatment adherence (ps>.05). CONCLUSIONS In a community-based sample of treatment-seeking smokers, faster nicotine metabolizers were significantly less likely to quit smoking and showed higher rates of anxiety symptoms during a smoking cessation treatment program, vs. slower nicotine metabolizers. These results provide further evidence that transdermal nicotine is less effective for faster nicotine metabolizers and suggest the need to address cessation-induced anxiety symptoms among these smokers to increase the chances for successful smoking cessation.

The Association between Changes in Alternative Reinforcers and Short-term Smoking Cessation

BACKGROUND While more than 50% of smokers make a serious quit attempt each year, less than 10% quit permanently. Evidence from studies of adolescent smoking and other substances of abuse suggest that alternative reinforcers, a construct of Behavioral Economic Theory, may contribute to the likelihood of smoking cessation in adults. This study examined the behavioral economics of smoking cessation within a smoking cessation clinical trial and evaluated how depressive symptoms and behavioral economic variables are associated with smoking cessation. METHODS A sample of 469 smokers, enrolled in an effectiveness trial that provided counseling and 8 weeks of 21 mg nicotine patches, was analyzed. Alternative reinforcers (substitute and complementary reinforcers) and depressive symptoms were examined in relation to 7-day point prevalence abstinence, verified with breath carbon monoxide, 8 weeks after the quit date. RESULTS Controlling for covariates associated with cessation (nicotine dependence, age of smoking initiation, patch adherence), participants who were abstinent at week 8 showed significantly higher substitute reinforcers at all time-points, compared to those who were smoking (ps<.05). Participants who were abstinent at week 8 showed lower complementary reinforcers and depressive symptoms at all time-points, compared to those who were smoking, but significant differences were confined to week 8 (ps<.01). There was no significant interaction between alternative reinforcers and depressive symptoms across the 8 weeks on week 8 abstinence. CONCLUSIONS These results support continued examination of Behavioral Economic Theory in understanding adult smoking cessation in order to inform future treatments and guidelines.

The use of varenicline to treat nicotine dependence among patients with cancer

Continuing to smoke after a cancer diagnosis can adversely influence the prognosis for patients with cancer. However, remarkably few studies have carefully examined the use of first‐line FDA‐approved medications for nicotine dependence in patients with cancer. This study evaluated the feasibility, safety, and effect on cessation of varenicline for smoking cessation in patients with cancer.

Is the Effect of Anhedonia on Smoking Cessation Greater for Women Versus Men

Introduction: Anhedonia has been recognized as a major risk factor for smoking persistence. Potential gender differences in the effect of anhedonia on smoking cessation have not been studied. Using data from a completed clinical trial of maintenance nicotine patch therapy, we hypothesized that gender would moderate the effect of anhedonia on short-term abstinence, such that anhedonic women would be less likely to achieve abstinence. Methods: Participants (N = 525; 50% female, 48.2% Black/African American, average age: 46 years) received 21mg/day nicotine patch and four brief behavior counseling sessions over 8 weeks. Participants were classified at baseline using the Snaith–Hamilton Pleasure Scale as anhedonic (scores > 2) or hedonic (scores ⩽ 2). Bioverified 7-day point prevalence abstinence was measured at week 8. Using logistic regression analysis, we tested the interaction of anhedonia by gender predicting abstinence, adjusting for age, race, nicotine dependence, and baseline depressive symptomatology. Results: Seventy participants (13%) were classified as anhedonic. Men were more likely to be anhedonic than women (16.6% vs. 10.2%, p = .03). Contrary to our hypothesis, the interaction of anhedonic status (hedonic vs. anhedonic) by gender was nonsignificant (p = .18). There was a main effect of hedonic capacity, such that anhedonia predicted abstinence, odds ratio = 3.24, 95% confidence interval = 1.39–7.51, p = .006. Conclusion: Both male and female anhedonic smokers were more likely to be abstinent, which contrasts with prior research indicating that anhedonia is a risk factor for difficulty quitting. This unexpected finding may be explained by a possible selective benefit of nicotine patch therapy, which has been observed in some studies to have antidepressant effects. Implications: This is the first study to examine whether the association between pretreatment anhedonia and smoking cessation differs by gender. For both women and men, anhedonia was associated with a greater likelihood of abstinence after 8 weeks of treatment with 21mg/day nicotine patch and behavior counseling. Our findings indicate that the association between anhedonia and smoking cessation is not as clear as has been assumed and may depend in part on the type of treatment delivered.

Cancer-Related Disease Factors and Smoking Cessation Treatment: Analysis of an Ongoing Clinical Trial

Smoking cessation treatment should be an important aspect of cancer care. In this study, we evaluated whether cancer‐related disease factors adversely influence smoking cessation treatment.

Longitudinal changes in smoking abstinence symptoms and alternative reinforcers predict long-term smoking cessation outcomes.

BACKGROUND Transdermal nicotine, with behavioral counseling, is among the most popular approaches used to quit smoking. Yet, 6-month cessation rates rarely exceed 20-25%. Identifying factors associated with cessation success may help researchers and clinicians develop enhanced interventions that can improve quit rates. This study examined longitudinal changes in withdrawal, craving, depression and anxiety symptoms, and alternative reinforcers, from a baseline assessment to a 6-month outcome, as predictors of 6-month smoking cessation outcomes following 8 weeks of nicotine patch treatment and counseling. METHODS A sample of 180 smokers, who completed an effectiveness trial that provided counseling and 8 weeks of 21mg nicotine patches, was analyzed. Generalized estimating equations evaluated changes in withdrawal and craving, depression and anxiety symptoms, and alternative reinforcers over time, between participants who were smoking at 6-months and participants who were abstinent (confirmed with carbon monoxide) at 6-months. Multiple logistic regression assessed changes in these variables as predictors of relapse. RESULTS Controlling for covariates associated with cessation (i.e., nicotine dependence, patch adherence, and rate of nicotine metabolism), participants who were abstinent at 6 months showed significantly lower craving and withdrawal and significantly higher substitute reinforcers from baseline to 6 months, vs. those who were smoking at 6 months (p<0.001). An increase in craving predicted relapse to smoking (p<0.05). CONCLUSIONS These results support continued efforts to strengthen interventions that reduce withdrawal and craving and the development of interventions to address alternative reinforcers in order to promote long-term smoking abstinence following nicotine patch treatment.

Accuracy of a brief screening scale for lifetime major depression in cigarette smokers

History of major depression is increasingly being measured in smoking cessation trials using brief screening scales, typically only 1-2 items, despite that their validity has not been fully established. The aim of this study was to evaluate the positive predictive value (PPV) of a 4-item screening scale of lifetime major depressive episode (MDE). Current (n = 475), former (n = 401), and never (n = 646) smokers were asked about a history of depressed mood and anhedonia lasting several days or longer. Endorsers of either depressed mood or anhedonia were then asked about whether the symptom(s) lasted most of the day nearly every day for two weeks or longer. Symptom endorsers, regardless of symptom duration, were administered the depression module of the Composite International Diagnostic Interview. Eight hundred and thirty-five (54.9%) participants had no history of either screening symptom, 296 (20.9%) had a history of depressed mood and/or anhedonia < 2 weeks, and 369 (24.2%) had a history of depressed mood and/or anhedonia ≥ 2 weeks. PPV of depressed mood and/or anhedonia ≥ 2 weeks was high (84.8%) for detecting lifetime MDE, as compared to only 23.9% for symptom(s) <2 weeks. PPV did not vary by either smoking status or gender. This 4-item screening scale has high predictive value in detecting lifetime MDE. Smoking cessation trials that do not require a history of depressed mood and/or anhedonia for two weeks or longer may overestimate rates of lifetime MDE and confound tests of the association between depression and treatment outcome.

Does menthol cigarette use moderate the effect of nicotine metabolism on short-term smoking cessation?

The nicotine metabolite ratio (NMR) has been shown to predict response to the transdermal nicotine patch, such that faster nicotine metabolism is associated with a lower abstinence rate. Menthol cigarette use, versus nonmenthol cigarette use, slows nicotine metabolism and therefore may attenuate the effect of NMR on smoking abstinence. In this study, we evaluated whether cigarette type (menthol vs. nonmenthol) modified the association between NMR and short-term abstinence. This was a secondary analysis examining treatment in the first 8 weeks of 21 mg/day nicotine patch therapy in a completed clinical trial (n = 474). Menthol cigarette use was based on self-report. NMR was defined dichotomously (0 = fast, 1 = slow) to distinguish between fast (≥0.47) versus slow NMR. Using logistic regression analysis, we tested whether cigarette type moderated the association between NMR and bioverified 7-day point prevalence abstinence at Week 8. Covariates include nicotine dependence, age, race, and gender. Three hundred two participants reported smoking menthol cigarettes, of which 234 (77%) were classified as slow NMR. Among the 172 nonmenthol smokers, 136 were classified as slow NMR (79%). Contrary to our expectations, the NMR ×Cigarette Type interaction effect on abstinence was not significant (odds ratio [OR] = 0.91, p = .86). Excluding the interaction variable, fast NMR was associated with decreased likelihood of abstinence (OR = 0.55, p = .03), but menthol cigarette use was not (OR = 1.15, p = .56). Further exploration of risk factors among menthol cigarette smokers, especially among racially diverse and light smokers, could clarify the association between menthol cigarette use and poorer smoking outcomes.

Treating Tobacco Use in Clinical Practice

Tobacco use is the leading cause of preventable death, yet cigarette-smoking rates in the USA have stagnated just below 20 %. With the signing of the Affordable Care Act came increased coverage for evidence-based tobacco cessation treatment, providing a wide range of effective cessation options that can now be offered to all tobacco-using patients, especially cigarette smokers. Health-care providers should be familiar with pharmacotherapy recommendations and counseling strategies for smoking patients at all stages of quitting. We discuss practical cessation approaches for patients ready to quit, unwilling to quit right away, and those who have recently quit. Certain groups, especially tobacco users with comorbid medical and/or psychiatric conditions, remain high tobacco burden populations that have not demonstrated declining rates of tobacco use as have been observed in the general population. Despite their higher tobacco burden status, treatments are effective for these populations and are especially important to include in their routine medical care. We end with a discussion of the emerging issues relevant for cessation treatment, including the increasing use of other tobacco and smoking products (such as e-cigarettes, hookah, and chewing tobacco) and their impact on smoking cessation efforts and the Affordable Care Act, keeping in mind that the exact parameters have not yet been set.