Clinical Issues and Strategies Associated With Smoking Cessation

Mar 20, 2015

Here: assessment approaches, treatment options, and potential risks inherent in treating tobacco dependence in individuals with major mental illnesses and substance use disorders.

Premiere Date: March 20, 2015
Expiration Date: March 20, 2016

This activity offers CE credits for:
1. Physicians (CME)
2. Other


To understand the obstacles standing in the way of smoking cessation in patients with mental illness and the strategies that can help patients abstain from smoking.


At the end of this CE activity, participants should be able to:

1. Understand the obstacles that stand in the way of smoking cessation in patients with mental illness

2. Describe the recommendations of the US public Health Service and the American Psychiatric Association to help patients quit smoking

3. Describe the evidence base for treating tobacco addiction in smokers with co-occurring mental illness or addictive disorders


This continuing medical education activity is intended for psychiatrists, psychologists, primary care physicians, physician assistants, nurse practitioners, and other health care professionals who seek to improve their care for patients with mental health disorders.


CME Credit (Physicians): This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of CME Outfitters, LLC, and Psychiatric Times. CME Outfitters, LLC, is accredited by the ACCME to provide continuing medical education for physicians.

CME Outfitters designates this enduring material for a maximum of 1.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Note to Nurse Practitioners and Physician Assistants: AANPCP and AAPA accept certificates of participation for educational activities certified for 1.5 AMA PRA Category 1 Credit™.


It is the policy of CME Outfitters, LLC, to ensure independence, balance, objectivity, and scientific rigor and integrity in all of their CME/CE activities. Faculty must disclose to the participants any relationships with commercial companies whose products or devices may be mentioned in faculty presentations, or with the commercial supporter of this CME/CE activity. CME Outfitters, LLC, has evaluated, identified, and attempted to resolve any potential conflicts of interest through a rigorous content validation procedure, use of evidence-based data/research, and a multidisciplinary peer-review process.

The following information is for participant information only. It is not assumed that these relationships will have a negative impact on the presentations.

Stephen E. Hall, MD, has no disclosures to report.

Judith J. Prochaska, PhD, MPH, reports that she has received an independent investigator award from Pfizer and is an ad hoc member of their advisory board and grant reviewer for their grant program. She has also served as an expert witness against the tobacco companies in several lawsuits for which she has received fees.

A. Eden Evins, MD, MPH (peer/content reviewer), has no disclosures to report.

Applicable Psychiatric Times staff and CME Outfitters staff have no disclosures to report.


Faculty of this CME/CE activity may include discussion of products or devices that are not currently labeled for use by the FDA. The faculty have been informed of their responsibility to disclose to the audience if they will be discussing off-label or investigational uses (any uses not approved by the FDA) of products or devices. CME Outfitters, LLC, and the faculty do not endorse the use of any product outside of the FDA-labeled indications. Medical professionals should not utilize the procedures, products, or diagnosis techniques discussed during this activity without evaluation of their patient for contraindications or dangers of use.

Questions about this activity? Call us at 877.CME.PROS (877.263.7767)

Tobacco smoking is the leading cause of preventable death in the US.1 Despite a steady decline in smoking in the general population since 1965, its prevalence among adults with mental health and substance use disorders remains high, with recent estimates from 50% to 85%, which currently represents about 16 million people.2,3 This group consumes about half of all cigarettes sold in the US and suffers a disproportionate share of medical burden, including cardiovascular and pulmonary diseases as well as cancer associated with smoking.4 Half of all smokers alive today will be killed prematurely by a disease linked directly to their tobacco use.5

This article addresses issues inherent in treating tobacco dependence in individuals with major mental illnesses and substance use disorders, including assessment approaches, treatment options, and potential risks.

Obstacles and solutions

Although some advances have been made in addressing the persistently high rate of smoking in the mentally ill, these are limited mainly to the research environment. A variety of factors that contribute to the lack of focus on this dangerous health risk have been suggested. These include:

• A perceived reluctance to address smoking in the clinical practice setting

• Historical use of cigarettes as contingency rewards in institutions

• The marketing of cigarettes to those with mental illness

• Inconsistent insurance coverage for tobacco use treatment

• Other psychiatric or substance abuse problems get priority

• The belief that smoking is a form of “self-medication” for some patients

• Clinicians’ fears that tobacco abstinence will cause decompensation of other conditions

• Lack of provider awareness, training, and education

Only half of US residency programs in psychiatry include training in the treatment of tobacco dependence.6 It is perceived that motivation to quit is low among smokers who have other substance abuse and mental health problems, but data suggest that this group is as interested in abstinence as is the general population.

Psychiatric inpatient hospitalization may be an especially fruitful time to mobilize interest in quitting and to initiate abstinence. In one recently published study of the efficacy of treatment for tobacco use on an inpatient service, measures of psychopathology did not predict abstinence, but measures of motivation and tobacco dependence did. Moreover, cessation treatment appeared to decrease the risk of rehospitalization, and the intervention was found to be highly cost-effective.7,8 Surveys of patients in substance abuse rehabilitation programs have found that the majority are motivated to quit, although a substantial number also express concern about their ability to quit tobacco and other substances simultaneously.9

To overcome some of these obstacles, clinical and research leaders and policy advocates have proposed a systematic integration of tobacco dependence treatments into mental health programs.5,9,10 A successful example using this model is a large study from the Veterans Administration, which demonstrated that patients with PTSD and tobacco dependence who were treated for both disorders simultaneously had 2-fold greater quit rates than those who received care through referral to a smoking cessation clinic.11 Moreover, smoking cessation had no adverse effects on PTSD recovery. Because smoking so commonly co-occurs with mental illness, integrated psychiatric/ tobacco dependence treatment may be more cost-effective than the traditional split. In the approaching era of population-based systems of care, economic and clinical imperatives may hasten the adoption of such a model.

The US Public Health Service

The US Public Health Service update of 2008 provides an excellent guide to the assessment and treatment of tobacco use and dependence.5 These guidelines are for smokers in general, but serve as the basis for recommended approaches for smokers with comorbid psychiatric or substance use disorders. The individualized approach includes:

• A review of tobacco habits

• Advice to quit in clear and personalized terms

• Understanding specific health concerns

• Assessment of the individual’s willingness to quit

• Assistance in forming a quit plan

• Creating follow-up actions

Clinicians can help patients move toward smoking cessation with motivational interviewing. This technique addresses specific content areas (relevance, risks, rewards, roadblocks, and repetition) and is associated with improved quit attempts.12,13

Treatment options include referral to smoking cessation programs or the national telephone “quit line” (1-800-QUIT-NOW), practical counseling (eg, problem-solving/skills training), and medication support. Medications include nicotine replacement therapy (approved by the FDA in the form of patch, gum, lozenge, nasal spray, and inhaler), antidepressants (bupro- pion SR and nortriptyline), and an α4ß2 nicotinic receptor partial agonist (varenicline).

Monotherapy with varenicline has been shown to be more effective than other monotherapies and comparable to the combination of multiple forms of nicotine replacement (eg, patch plus gum or lozenge).14 In addition, the combination of nicotine replacement and bupropion SR has shown greater efficacy than either used alone.5 Case reports and postmarketing data raised concerns about the risk of psychiatric adverse effects from both varenicline and bupropion SR, and in 2009, boxed warnings were added to labeling for both medications.15 Clinical trials data have not indicated a signal of concern, including in recent trials of varenicline use among smokers with current mental illness.

The American Psychiatric Association

In its practice guidelines for nicotine dependence and substance use disorders, the American Psychiatric Association recommends assessment of smoking status in all patients and assistance with quitting.16 The guidelines recommend use of motivational, behavioral, and pharmacological treatment; suggest using inpatient treatment as a good opportunity for initiating abstinence; and recommend nicotine replacement therapy for withdrawal symptoms. The guidelines note that with few exceptions, there is limited evidence for treatment interventions specific for smokers with particular psychiatric diagnoses.

Psychiatric comorbidity


Depression is twice as common in smokers as in nonsmokers, and 4 times as common in heavy smokers.17 Smokers with comorbid depression smoke more heavily than the average smoker, are more likely to relapse after an attempt to quit, and suffer greater physical morbidity and mortality than those in the general population.18 Prospective studies with adolescents and adults have implicated tobacco use as a predictor of future suicidal behavior.19,20 But some have expressed concern that past or currently depressed patients who quit smoking will lose a coping mechanism and decompensate.

Among patients with a history of depression, there are limited, discrepant data regarding the risk of smoking cessation. Findings from one prospective trial of sertraline for smoking cessation suggest that quitters had a higher rate of depressive relapse.21 However, a large percentage of continuing smokers were lost at follow-up, potentially underreporting depression recurrence in that group (sertraline itself was ineffective for abstinence).

In secondary analyses of 2 clinical tobacco treatment trials in smokers with a history of depression, smoking cessation did not increase rates of depressive symptoms or of major depressive relapses.22,23 Furthermore, in one of the only trials to test a cessation intervention among currently depressed smokers, quitting smoking, measured over 18 months, did not harm recovery from depression.24,25

Nicotine withdrawal can produce some depressive symptoms for a 2- to 4-week period irrespective of depression history. Long-term effects, however, are encouraging: a recent meta-analysis found that smoking cessation is associated with reduced depression, anxiety, and stress and improved positive mood and quality of life compared with continuing to smoke, true for smokers with and without a history of depression.26

Medications that are effective for tobacco cessation in smokers without mental illness have also shown similar effectiveness in patients with either current or prior depression. Bupropion SR does not have a differential effect on patients with a history of depression, as had once been hoped.

Varenicline more than doubled the odds of sustained tobacco abstinence compared with placebo for patients under stable treatment for current or past major depression, without exacerbating anxiety or depressive symptoms.27 In an analysis of data from the VA health care system that compared varenicline with nicotine replacement therapy, no differences in rates of neuropsychiatric hospitalization were observed; findings were similar in the subsets of patients with and without a neuropsychiatric history who received either varenicline or a nicotine patch.28


Rates of smoking in patients with schizophrenia are among the highest of any group. Combined with comorbid obesity and other metabolic disorders so common in this population, the results can be particularly deadly. Persons with serious mental illness die on average 25 years prematurely.29

Only in recent years has there been an effort to address tobacco dependence in those with schizophrenic spectrum illnesses. Quit rates have been low, particularly with nicotine replacement therapy as the sole medication adjunct to psychological approaches.9 However, the combination of nicotine replacement therapy and behavioral counseling has been found to be effective (20% quit rate) in smokers hospitalized with schizophrenia, which was comparable to other diagnostic patient groups.7

Concerns among clinicians that smoking cessation will exacerbate symptoms are not borne out by available data. In a trial that examined the use of bupropion for smoking cessation in schizophrenia, abstinence was not associated with worsened cognitive deficits or executive functioning.30 The combination of nicotine replacement therapy and bupropion was found more effective in 2 trials, with quit rates as high as 50% at the end of 12 weeks.31,32 However, relapse rates in both studies were high. Notably, there were no signals that abstinence or an attempt to quit worsened psychiatric symptoms.

More recently, varenicline was evaluated in a multicenter, randomized, controlled trial.33 Quit rates were 19% at 12 weeks and 11.9% at 24 weeks, with an odds ratio of about 5.0 relative to placebo. Varenicline was not associated with an exacerbation of schizophrenic symptoms or with changes in mood and anxiety ratings.

In a randomized placebo-controlled trial, extended use of varenicline (for 52 weeks) with CBT was found to prevent relapse among smokers with schizophrenia or bipolar disorder.34 From weeks 12 through 76, 30% of participants randomized to varenicline compared with 11% in the placebo group were continuously abstinent, with an odds ratio of 3.4. The CBT interventions focused on relapse prevention skills, such as understanding relapse, learning and applying skills, refusal skills, and problem solving.

A combination of social, psychological, and biological factors may lie behind the refractory nature of smoking among persons with schizophrenia. This population may be less aware of the associated health risks and feel that smoking is more important for their social functioning and acceptance. If noted during an evaluation, these factors could potentially be addressed in a personalized treatment plan.35 In general, heavy smokers have more difficulty in quitting, and persons with schizophrenia are generally heavy smokers.

Schizophrenia is characterized by deficits in executive planning as well as by resistance to change, so that even a motivated person may repeatedly lose focus on the goal of quitting cigarettes. Tobacco smoke (not nicotine) induces the metabolism of several antipsychotic medications (eg, olanzapine, haloperidol), which lowers blood levels and may reduce neurocognitive medication adverse effects. Nicotine also may have a facilitative role in cognitive processes that are impaired in schizophrenia.3 Thus, it may make sense to include nicotine replacement therapy in the smoking cessation plan for any patient with schizophrenia and to consider varenicline ahead of other medication options.

Substance abuse

Traditionally, tobacco has not been included with other abused substances by rehabilitation programs as a target for abstinence. Perhaps because of its previously wide social acceptance and long-standing legal status, it has been relegated to a second-tier concern. However, evidence indicates that for some substance use disorders, continued smoking is associated with lower levels of sobriety from illicit drugs and alcohol.36

A 2004 meta-analysis of 19 randomized controlled trials that evaluated tobacco cessation interventions with smokers in treatment or recovery for alcohol or illicit drug problems found significant posttreatment effects for quitting smoking, and nicotine replacement therapy was particularly helpful. Although tobacco cessation treatment effects were not maintained at long-term follow-up, notably there was a 25% improvement in long-term sobriety among those randomized to receive interventions for quitting smoking.37

A large-scale study of treatment for alcohol dependence with tobacco cessation treatment administered either concurrently or with a 6-month delay, suggests that the timing of the two treatments may be important.37,38 At 18 months, subjects in the concurrent group were more likely than those in the delayed group to participate in smoking interventions, although at 18 months, abstinence rates in the two groups were similar. Alcohol abstinence rates were worse in the concurrent group at month 6, although not at months 12 and 18. Further research is needed to identify of the optimal timing of tobacco cessation interventions within addiction treatment settings, which may differ depending on the approach taken (eg, action-oriented “quit now” versus matched to stage of change or motivation).

Other disorders

Other major mental illnesses have received relatively little attention with regard to the treatment of comorbid tobacco dependence. Although adults with bipolar disorder are 2 to 3 times more likely to smoke, and less likely to stop than those without psychiatric disorders, this area has received little attention. In patients with anxiety disorders, there is a high prevalence of co-occurring tobacco dependence, but few studies have addressed treatment beyond the study of integrated tobacco cessation for smokers in treatment for PTSD in the VA health care system.11


Treating tobacco dependence in smokers with mental health concerns is recommended as good clinical practice, is straightforward, and has demonstrated efficacy, without harm to mental health recovery. It is time to address the major health disparities related to tobacco use in this vulnerable population by providing evidence-based cessation treatment and referrals.



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Dr Hall is Clinical Professor of Psychiatry at the University of California, San Francisco; when this article was written, he was Director of Intensive Services at the Langley Porter Psychiatric Institute. He is currently Associate Director for Development in the department of psychiatry at The Jewish Home of San Francisco. Dr Prochaska is Associate Professor of Medicine with the Stanford Prevention Research Center in the department of medicine at Stanford University, Stanford, Calif.


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19. Breslau N, Schultz LR, Johnson EO, et al. Smoking and the risk of suicidal behavior: a prospective study of a community sample. Arch Gen Psychiatry. 2005;62:328-334.

20. Oquendo MA, Galfalvy H, Russo S, et al. Prospective study of clinical predictors of suicidal acts after a major depressive episode in patients with major depressive disorder or bipolar disorder. Am J Psychiatry. 2004;161:1433-1441.

21. Glassman AH, Covey LS, Stetner F, Rivelli S. Smoking cessation and the course of major depression: a follow-up study. Lancet. 2001;357:1929-1932.

22. Kahler CW, Brown RA, Ramsey SE, et al. Negative mood, depressive symptoms, and major depression after smoking cessation treatment in smokers with a history of major depressive disorder. J Abnorm Psychol. 2002;111:670-675.

23. Tsoh JY, Humfleet GL, Muñoz RF, et al. Development of major depression after treatment for smoking cessation [published correction appears in Am J Psychiatry. 2000;157:1359]. Am J Psychiatry. 2000;157: 368-374.

24. Prochaska JJ, Hall SM, Tsoh JY, et al. Treating tobacco dependence in clinically depressed smokers: effect of smoking cessation on mental health functioning. Am J Public Health. 2008;98:446-448.

25. Hall SM, Tsoh JY, Prochaska JJ, et al. Treatment for cigarette smoking among depressed mental health outpatients: a randomized clinical trial. Am J Public Health. 2006;96:1808-1814.

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27. Anthenelli RM, Morris C, Ramey TS, et al. Effects of varenicline on smoking cessation in adults with stably treated current or past major depression: a randomized trial [published correction appears in Ann Intern Med. 2013;159:576]. Ann Intern Med. 2013;159:390-400.

28. Meyer TE, Taylor LG, Xie S, et al. Neuropsychiatric events in varenicline and nicotine replacement patch users in the Military Health System. Addiction. 2013;108:203-210.

29. Colton CW, Manderscheid RW. Congruencies in increased mortality rates, years of potential life lost, and causes of death among public mental health clients in eight states. Prev Chronic Dis. 2006;3:A42.

30. Evins AE, Cather C, Deckersbach T, et al. A double-blind placebo-controlled trial of bupropion sustained-release for smoking cessation in schizophrenia. J Clin Psychopharmacol. 2005;25:218-225.

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33. Williams JM, Anthenelli RM, Morris CD, et al. A randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of varenicline for smoking cessation in patients with schizophrenia or schizoaffective disorder [published correction appears in J Clin Psychiatry. 2012;73:1035]. J Clin Psychiatry. 2012;73:654-660.

34. Evins AE, Cather C, Pratt SA, et al. Maintenance treatment with varenicline for smoking cessation in patients with schizophrenia and bipolar disorder. a randomized clinical trial. JAMA. 2014;311:145-154.

35. Kelly DL, Raley HG, Lo S, et al. Perception of smoking risks and motivation to quit among nontreatment-seeking smokers with and without schizophrenia. Schizophr Bull. 2012;38:543-551.

36. Prochaska JJ. Failure to treat tobacco use in mental health and addiction treatment settings: a form of harm reduction? Drug Alcohol Depend. 2010;110:177-182.

37. Prochaska JJ, Delucchi K, Hall SM. A meta-analysis of smoking cessation interventions with individuals in substance abuse treatment or recovery. J Consult Clin Psychol. 2004;72:1144-1156.

38. Hall SM. Nicotine interventions with comorbid populations. Am J Prev Med. 2007;33(6 suppl):S406-S413.