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NicVAX, a nicotine vaccine (3'AmNic-rEPA), has been clinically evaluated to determine whether higher antibody (Ab) concentrations are associated with higher smoking abstinence rates and whether dosages and frequency of administration are associated with increased Ab response. This randomized, double-blinded, placebo-controlled multicenter clinical trial (N = 301 smokers) tested the results of 200- and 400-µg doses administered four or five times over a period of 6 months, as compared with placebo. 3'AmNic-rEPA recipients with the highest serum antinicotine Ab response (top 30% by area under the curve (AUC)) were significantly more likely than the placebo recipients (24.6% vs. 12.0%, P = 0.024, odds ratio (OR) = 2.69, 95% confidence interval (CI), 1.14-6.37) to attain 8 weeks of continuous abstinence from weeks 19 through 26. The five-injection, 400-µg dose regimen elicited the greatest Ab response and resulted in significantly higher abstinence rates than placebo. This study demonstrates, as proof of concept, that 3'AmNic-rEPA elicits Abs to nicotine and is associated with higher continuous abstinence rates (CAR). Its further development as a treatment for nicotine dependence is therefore justified.

Aims: Nicotine addiction is a complex, chronic condition with physiological and psychological/behavioural aspects that make smoking cessation extremely difficult. This paper reviews current recommendations for smoking cessation and the efficacy of pharmacotherapy and behavioural modification techniques, used either alone or in combination, for smoking cessation., Results: Abstinence rates for pharmacotherapies range from approximately 16% to approximately 30% at 1-year follow-up, with efficacy odds ratios (ORs) compared with placebo of approximately 1.7 for nicotine replacement therapy (NRT), approximately 1.9 for bupropion sustained release and approximately 3.0 for varenicline. Behaviour modification therapies have achieved quit rates of between 8% and 43% for up to 1 year, with ORs in comparison to no treatment of between approximately 1.2 and approximately 2.2. No direct comparisons have been made between pharmacotherapy alone and psychological behaviour strategies alone. However, combining physiological approaches with counselling significantly increases the odds of quitting compared with either technique alone., Conclusions: Applying multimodal techniques for the treatment of nicotine addiction is the recommended approach and has demonstrated the potential to improve rates of permanent abstinence in smokers attempting cessation. While the numbers of patients receiving help and advice regarding smoking cessation is increasing, the multimodal approach appears to be currently underutilised by clinicians and therefore smoking cessation strategies are not being optimised.

Multiple, controlled clinical trials support the efficacy of nortriptyline as a smoking cessation agent. Although therapeutic plasma nortriptyline concentrations (PNCs) are known for the treatment of depression, little is known about PNCs in smoking cessation treatment. PNCs from three randomized, placebo-controlled smoking cessation trials (N=244) were analyzed both separately and pooled. PNCs normalized for dose and weight were associated with cigarettes per day and race, but not with sex or age. Greater smoking was associated with decreased normalized PNCs. In addition, both Asian and black populations had significantly higher normalized PNCs than the white populations. Weak and inconsistent associations between PNCs and self-reported side effects were observed. PNCs were linearly related to end of treatment and long-term biochemically verified smoking abstinence. Maximum therapeutic effects were observed over a range of plasma concentrations somewhat lower than those found effective for the treatment of depression.

Objective: Case studies suggest cigarette abstinence may precipitate a major depressive episode. This study examined the incidence and predictors of major depression in the 12 months after treatment for smoking cessation., Method: Participants (N=304, 172 women) were recruited from two trials of smoking cessation. Both trials provided psychological group intervention, but one group received treatment with nicotine gum and the other was given nortriptyline or placebo. The incidence of major depressive episodes was identified by the Inventory to Diagnose Depression, which was administered at follow-up assessments., Results: The 12-month incidence of major depression after treatment for smoking cessation was 14.1% (N=43). Multiple logistic regression analyses indicated that history of depression, baseline Beck Depression Inventory score, college education, and age at smoking initiation were significant predictors of major depression after treatment. Abstinence at the end of treatment did not significantly predict major depression., Conclusions: Patients who achieved abstinence from smoking showed a risk of developing depressive episodes similar to those who failed to achieve abstinence. As expected, patients who had a history of depression were more likely to experience depressive episodes after treatment for smoking cessation. The 12-month incidence of major depression in this study group was higher than that observed in the general population, but reasons for the elevation were not clear.

Background: A history of major depressive disorder (MDD) predicts failure to quit smoking. We determined the effect of nortriptyline hydrochloride and cognitive-behavioral therapy on smoking treatment outcome in smokers with a history of MDD. The study also addressed the effects of diagnosis and treatment condition on dysphoria after quitting smoking and the effects of dysphoria on abstinence., Methods: This was a 2 (nortriptyline vs placebo) x 2 (cognitive-behavioral therapy vs control) x 2 (history of MDD vs no history) randomized trial. The participants were 199 cigarette smokers. The outcome measures were biologically verified abstinence from cigarettes at weeks 12, 24, 38, and 64. Mood, withdrawal, and depression were measured at 3, 5, and 8 days after the smoking quit date., Results: Nortriptyline produced higher abstinence rates than placebo, independent of depression history. Cognitive-behavioral therapy was more effective for participants with a history of depression. Nortriptyline alleviated a negative affect occurring after smoking cessation. Increases in the level of negative affect from baseline to 3 days after the smoking quit date predicted abstinence at later assessments for MDD history-negative smokers. There was also a sex-by-depression history interaction; MDD history-positive women were less likely to be abstinent than MDD history-negative women, but depression history did not predict abstinence for men., Conclusions: Nortriptyline is a promising adjunct for smoking cessation. Smokers with a history of depression are aided by more intensive psychosocial treatments. Mood and diagnosis interact to predict relapse. Increases in negative affect after quitting smoking are attenuated by nortriptyline.

Background: Glucocorticoids have been linked to self-administration of a wide range of drugs in animals and are increased endogenously by chronic nicotine intake. Corticosteroids have also been shown to regulate nicotine receptor sensitivity and to be involved in behavioral sensitization to nicotine., Methods: Cortisol levels and cortisol suppression in response to dexamethasone were measured in a sample of smokers participating in a smoking cessation treatment trial., Results: Cortisol levels dropped significantly during the early quitting process (2 weeks post-quit) and returned to a level below baseline 1 month post-quit. The magnitude of the initial drop in cortisol was strongly related to post-quit distress and marginally predictive of abstinence. Neither baseline nor post-quit changes in percent cortisol suppression after dexamethasone were related to abstinence success or withdrawal distress., Conclusions: Withdrawal from cigarette smoking is marked by a reduction in cortisol levels that appears to be related to the degree of distress experienced during the early quitting period. Further work is needed to determine whether withdrawal-related cortisol changes or distress are predictive of abstinence success.

Earlier research indicated that a 10-session mood management (MM) intervention was more effective than a 5-session standard intervention for smokers with a history of major depressive disorder (MDD). In a 2 x 2 factorial design, the present study compared MM intervention to a contact-equivalent health education intervention (HE) and 2 mg to 0 mg of nicotine gum for smokers with a history of MDD. Participants were 201 smokers, 22% with a history of MDD. Contrary to the earlier findings, the MM and HE interventions produced similar abstinence rates: 2 mg gum was no more effective than placebo. History-positive participants had a greater increase in mood disturbance after the quit attempt. Independent of depression diagnosis, increases in negative mood immediately after quitting predicted smoking. No treatment differences were found in trends over time for measures of mood, withdrawal symptoms, pleasant activities and events, self-efficacy, and optimism and pessimism. History-positive smokers may be best treated by interventions providing additional support and contact, independent of therapeutic content.

This article describes the test of the hypothesis that a cognitive-behavioral mood management intervention would be effective for smokers with a history of major depressive disorder (MDD). The method was randomized trial; the assessments occurred at Weeks 0, 8, 12, 26, and 52. Ss were 149 smokers; 31% had a history of MDD. All received 2 mg of nicotine gum. Mood management was provided in 10 group sessions over 8 weeks. Standard treatment was provided in 5 group sessions over 8 weeks. Outcome was continuous abstinence. History-positive Ss were more likely to be abstinent when treated with mood management. Treatment condition differences were not significant for history-negative Ss. For history-positive Ss, less anger at baseline predicted abstinence. For history-negative Ss, more years smoked and higher baseline carbon monoxide (CO) predicted abstinence. Cognitive-behavioral therapy did not affect mood after quitting. Abstinence predictors differed as a function of baseline diagnosis.

Depression, whether conceptualized as a trait, symptom, or as a diagnosable disorder, is overrepresented among smokers. Depressed smokers appear to experience more withdrawal symptoms on quitting, are less likely to be successful at quitting, and are more likely to relapse. This article documents these relationships and explores several potential links between smoking and depression. The potential efficacy of antidepressant therapy, cognitive-behavioral therapy, and nicotine replacement therapy for smokers with depressive disorders or traits is discussed. Clinical implications and the role of patient treatment matching are also discussed.