The National Institute of Mental Health (NIMH) convened a meeting in September 2005 to review tobacco use and dependence and smoking cessation among those with mental disorders, especially individuals with anxiety disorders, depression, or schizophrenia. Smoking rates are exceptionally high among these individuals and contribute to the high rates of medical morbidity and mortality in these individuals. Numerous biological, psychological, and social factors may explain these high smoking rates, including the lack of smoking cessation treatment in mental health settings. Historically, "self-medication" and "individual rights" have been concerns used to rationalize allowing ongoing tobacco use and limited smoking cessation efforts in many mental health treatment settings. Although research has shown that tobacco use can reduce or ameliorate certain psychiatric symptoms, overreliance on the self-medication hypothesis to explain the high rates of tobacco use in psychiatric populations may result in inadequate attention to other potential explanations for this addictive behavior among those with mental disorders. A more complete understanding of nicotine and tobacco use in psychiatric patients also can lead to new psychiatric treatments and a better understanding of mental illness. Greater collaboration between mental health researchers and nicotine and tobacco researchers is needed to better understand and develop new treatments for cooccurring nicotine dependence and mental illness. Despite an accumulating literature for some specific psychiatric disorders and tobacco use and cessation, many unstudied research questions remain and are a focus and an emphasis of this review.

Summary Background There is substantial variability in therapeutic response and adverse effects with pharmacotherapies for tobacco dependence. Biomarkers to optimize treatment choice for individual smokers may improve treatment outcomes.Wetested whether a genetically-informed biomarker of nicotine clearance, the nicotine metabolite ratio (NMR; 3’hydroxycotinine/cotinine), predicts response to nicotine patch vs. varenicline for smoking cessation. Methods AnNMR-stratified multicenter, randomized, placebo-controlled clinical trial was conducted from November 2010-September 2013 at 4 sites. Treatment-seeking smokers (1246: 662 slow metabolizers; 584 normal metabolizers) were randomized to 11-weeks of nicotine patch (active patch + placebo pill), varenicline (active pill + placebo patch), or placebo (placebo pill + patch), plus behavioral counseling; an intent-to-treat analysis was conducted. Participants were followed for 12-months following the target quit date.The primary endpoint was biochemically verified 7-day point prevalence abstinence at the end of treatment (EOT) to estimate the pharmacologic effect of treatment by NMR. Secondary outcomes were side-effects, withdrawal symptoms, and 6- and 12-month abstinence rates. ClinicalTrials.govregistration: NCT01314001 Findings In the longitudinal model including all time points, the NMR-by-treatment interaction was significant (ratio of odds ratios (ORR)=1·96; CI=(1·11, 3·46); p=0·02). The results indicate that varenicline was more efficacious than nicotine patch for normal metabolizers, whilethe efficacy was equivalent for slow metabolizers. In cross-sectional analyses, the interaction was significant at EOT (ORR)=1·89; CI=(1·02, 3·45); p=0·04) andat 6-months (ORR=2·07; CI=(1·01, 4·22); p=0·05), but not at 12-months (p=0·14). An NMR-by-treatment interaction showed that slow (vs. normal) metabolizers reported greater overallside-effects severity with vareniclinevs. placebo (β−1·06; CI=(−2·08, −0·03); p=0·044). Interpretation Treating normal metabolizers with varenicline and slow metabolizers with nicotine patchmayoptimize quit rates while minimizing side-effects. Funding National Institutes of Health

This article reviews cigarette smoking in patients with psychiatric disorders (PD) and substance use disorders (SUD). Rates of smoking are approximately 23% in the U.S. population but approximately two-to four-fold higher in patients with PD and SUD. Many remaining smokers have had repeated smoking cessation failures, possibly due to the presence of co-morbid PD and SUDs. There is modest, evidence-based support for effective treatment interventions for nicotine addiction in PD and SUD. Further research is needed to increase our understanding of nicotine addiction in PD and SUD and develop more effective treatment interventions.Although smoking prevalence in the United States has decreased from 43.8% in 1965 to 23.3% in 2000, 1 there are many cigarette smokers who have been unable to quit. An important subset of refractory smokers are those with psychiatric disorders (PD) and substance use disorders (SUD), among whom smoking rates exceed those in the general population by two-to fourfold. 2 In a population-based study of smoking prevalence in the U.S., Lasser and colleagues found that smoking prevalence among persons with and without a psychiatric disorder were 41% and 22.5%, respectively. 2 The highest prevalence (67.9%) was found among persons with drug abuse. Consistent with these results, Degenhardt and Hall 3 reported similar findings in their study of smoking prevalence in Australia. The prevalence of smoking in various PD and SUD 4 is presented in Fig. 1. Other studies have found that individuals with PD and SUD are at higher risk for many tobacco-related diseases, including cardiovascular illness, respiratory disease, and cancer, than individuals in the general population. 5-8 Among "ever smokers," persons with PD or SUD are less likely to be former smokers than other smokers. Lasser et al. 2 found that the quit rate among ever smokers with no history of PD or SUD was 42.5%. Significantly lower quit rates were associated with several other PD and SUD, including alcohol use disorder (16.9%), bipolar disorder (25.9%), major depression (26.0%), and post-traumatic stress disorder (23.2%). Clearly, improved treatments for nicotine addiction are needed for these populations.Several explanations have been proposed for the high prevalence of smoking in individuals with PD and SUD. First, there may be intrinsic factors (eg, shared genes, abnormalities in brain

Cannabis use, and particularly heavy cannabis use, may be associated with an increased risk for developing depressive disorders. There is need for further longitudinal exploration of the association between cannabis use and developing depression, particularly taking into account cumulative exposure to cannabis and potentially significant confounding factors.

Cigarette smoking may selectively enhance VSWM and attentional deficits in smokers with schizophrenia, which may depend on nAChR stimulation. These findings may have implications for understanding the high rates of smoking in schizophrenia and for developing pharmacotherapies for cognitive deficits and nicotine dependence in schizophrenia.

Opioid tolerance, dependence, and addiction are all manifestations of brain changes resulting from chronic opioid abuse. The opioid abuser’s struggle for recovery is in great part a struggle to overcome the effects of these changes. Medications such as methadone, LAAM, buprenorphine, and naltrexone act on the same brain structures and processes as addictive opioids, but with protective or normalizing effects. Despite the effectiveness of medications, they must be used in conjunction with appropriate psychosocial treatments.

The results suggest that 1) smoking cessation rates with the nicotine transdermal patch are modest in schizophrenia, 2) specialized group therapy for schizophrenic patients is not significantly different from American Lung Association group therapy in its effect on smoking cessation, and 3) atypical agents may be superior to typical agents in combination with the nicotine transdermal patch for smoking cessation in schizophrenia.

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