THERAPY IN PRACTICE

CNS Drugs 2009; 23 (8): 661-668 1172-7047/09/0008-0661/$49.95/0

ª 2009 Adis Data Information BV. All rights reserved.

Tobacco Smoking in Individuals with Attention-Deficit Hyperactivity Disorder
Epidemiology and Pharmacological Approaches to Cessation
Kevin M. Gray and Himanshu P. Upadhyaya
Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA

Contents
Abstract. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Attention-Deficit Hyperactivity Disorder (ADHD) and Cigarette Smoking . . . . . . . . . . . . . . . . . . . . . . . 1.1 Epidemiology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3 Treatment Implications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3.1 ADHD Pharmacotherapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3.2 Nicotine Dependence Pharmacotherapy. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3.3 Psychosocial Treatment for Nicotine Dependence . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2. Practical Guide to Smoking Cessation in Patients with ADHD and Nicotine Dependence . . . . . . . . . 3. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 661 662 662 662 663 663 663 664 664 666

Abstract

The co-occurrence of attention-deficit hyperactivity disorder (ADHD) and nicotine dependence is common. Individuals with ADHD are more likely to initiate smoking and become dependent on nicotine than their non-ADHD counterparts, and recent evidence suggests that they may have more difficulty quitting smoking. Little is known about how to best approach treating these co-morbidities to optimize clinical outcome. Clinicians treating individuals with either ADHD or nicotine dependence should be aware of their common co-occurrence and the need to address both in treatment. This review of ADHD and nicotine dependence provides an overview of relevant epidemiology, bidirectional interactions and implications for pharmacological and adjunctive psychosocial treatment. Incorporating the current evidence base and their clinical experience, the authors propose a stepwise approach to treating patients with co-morbid ADHD and nicotine dependence. Given the potential for ADHD symptoms to interfere with smoking cessation success, the first priority is to stabilize ADHD. The first-line pharmacological approach should be a long-acting psychostimulant. Upon ADHD stabilization, motivational techniques should be used to encourage readiness for a smoking cessation attempt. In the context of behavioural cessation interventions sensitive to the patient’s needs and developmental stage, pharmacological intervention targeting smoking cessation may be initiated. The authors recommend varenicline as a first-line agent, given its superior effect size among available medication treatments. Symptoms of ADHD, as well as nicotine

[5] ª 2009 Adis Data Information BV. our research group found that both hyperactive/impulsive and inattentive symptoms were associated with cigarette smoking. 33% of 18.to 20-year-olds. The authors conclude that.[10] The quantity of present ADHD symptoms appears to be associated with the risk for early smoking initiation.[15] Still others have maintained that the link between ADHD and smoking is largely driven by common co-morbidities. involving significantly impairing core symptoms of inattention and hyperactivity/impulsivity. with onset in early childhood.[12] while others have suggested that hyperactive/impulsive symptoms are more predictive of cigarette smoking. should be monitored closely during the cessation attempt. Attention-Deficit Hyperactivity Disorder (ADHD) and Cigarette Smoking 1. and adjustments to therapy should be considered if warranted. some debate has continued over the nature and mechanism of the ADHD-smoking association. Aetiological and therapeutic interactions are discussed. Finally. with one in every five deaths in the US related to smoking.[8.[18] In addition to possessing an increased risk for cigarette smoking and nicotine dependence.9] is associated with smoking risk.4% of adults have ADHD. This article is intended to provide a framework for understanding the clinical implications of the common co-occurrence of attention-deficit hyperactivity disorder (ADHD) and nicotine dependence.[4] The average age of first cigarette use in the US is 16. a practical guide for approaching smoking cessation treatment for smokers with ADHD is provided.[16] In a sample (n = 334) of college students. social and health outcomes.7] However. ADHD has been closely linked to cigarette smoking in a number of epidemiological studies.[11] Some studies have suggested that inattentive symptoms drive this association. 1. While ADHD was previously recognized as a disorder primarily of childhood and adolescence. 39% of 21.[2.to 25-year-olds and 36% of 26.3] While overall rates of cigarette smoking in the US have declined. which itself is a robust predictor of nicotine dependence and substance abuse in general. In the US. increased smoking amount and increasing dependence on nicotine.[17] Another recent study revealed that some genetic polymorphisms may interact with ADHD symptoms to increase risk for smoking.[6. further research is needed to parse the complex associations between these disorders and prospectively study combined treatments. First. while current treatments may potentially be effective for co-morbid ADHD and nicotine dependence. while 19% of 16.662 Gray & Upadhyaya withdrawal and craving symptoms. All rights reserved.2 Interactions ADHD is a common behavioural disorder. a trait common among individuals with ADHD.to 29-year-olds have smoked in the last month.9 years. Individuals with ADHD become regular smokers at an earlier age and are about twice as likely to develop nicotine dependence when compared with their non-ADHD counterparts.14] or that the relative contributions of inattentive and hyperactive/impulsive symptoms to risk for nicotine dependence may differ depending on developmental period (adolescence vs young adulthood). with special attention to their co-occurrence. the epidemiology of both disorders is reviewed.1 Epidemiology 1.[13. Novelty seeking. 23 (8) .[1] ADHD is associated with a variety of adverse academic. smoking remains the leading cause of preventable death. emerging evidence suggests persistence of impairing symptoms into adulthood for many individuals with ADHD. individuals with ADHD may also have more CNS Drugs 2009. epidemiological evidence indicates that 3–10% of school-age children and 4.to 17-year-olds. such as conduct disorder.

cognitive enhancement. does not acutely increase smoking rate.2 Nicotine Dependence Pharmacotherapy As ADHD symptoms predict cigarette smoking and nicotine dependence.[28] Individuals with ADHD may additionally seek out nicotine for cognitive-enhancing effects. All rights reserved. including nicotine dependence. which in turn stimulates the release of several neurotransmitters.[28]) The core symptoms of ADHD have been posited to reflect an underlying deficit in behavioural inhibition.46] It has additionally shown efficacy in treating ADHD. which does not appear to increase or decrease subsequent risk of substance use disorders. reduction in anxiety/tension. Smoking leads to nicotine receptor activation. Atomoxetine. including irritability and difficulty concentrating.43] This concern may be tempered by evidence that bupropion.[21.e. may in part explain smoking as self-medication among individuals with ADHD. noradrenaline (norepinephrine). The mainstay of ADHD treatment is ª 2009 Adis Data Information BV. has not specifically been investigated in individuals with ADHD.[19] Neurobiological processes may underlie the link between cigarette smoking and ADHD. acetylcholine. serotonin.[19. may hold appeal in the treatment of patients with co-morbid nicotine dependence. glutamate.Tobacco Smoking in ADHD 663 difficulty quitting cigarettes. with resultant enhancement in behavioural inhibition. arousal.22] it has been suggested that smokers with ADHD may be ‘self-medicating’ with nicotine to reduce ADHD symptoms. 23 (8) . including dopamine. pleasure. a recent longitudinal study of adolescents with ADHD suggested that treatment with stimulants (vs no treatment) reduces the risk for later smoking.[38] Of potential concern.[41] It may also reduce subjective withdrawal symptoms and craving during acute nicotine abstinence.[23.3. cigarette smoking was monitored via self-report. it is important to explore the effects of ADHD treatment on smoking.3.[37] Those who were receiving pharmacotherapy for ADHD smoked significantly less than those who did not receive medication.[39-41] potentially owing to a synergistic effect of stimulants and nicotine on mesocorticolimbic dopamine levels.[30] The robust effect of nicotine on these systems. also acutely increases smoking rate in a laboratory setting. well established as a smoking cessation aid.3 Treatment Implications 1.[47] but has only been CNS Drugs 2009.[32-36] In one of the few clinical studies to monitor smoking rates and medication status among adolescent smokers with ADHD. However. laboratory studies among smokers without ADHD have shown that stimulant administration may acutely increase cigarette smoking.[31] 1.20] Given that nicotine administration has been shown to acutely reduce ADHD symptoms even among nonsmokers.24] When attempting to quit smoking. among other medications used in the treatment of ADHD.22] Bupropion is another effective smoking cessation treatment.[29] a process that may be modulated by cholinergic and catecholaminergic systems.[25] A recent controlled laboratory study demonstrated that nicotine abstinence among smokers with ADHD is associated with greater worsening of attention and response inhibition than among those without ADHD. which has been consistently shown to be effective for smoking cessation.[44] 1. Additionally. electronic diaries and salivary cotinine levels. evidence that ADHD symptoms improve with nicotine administration among nonsmokers suggests that there may be theoretical potential for a combined therapeutic effect for nicotine dependence and ADHD. though.[45. Bupropion is approved by the US FDA as a smoking cessation treatment. Nicotine replacement.1 ADHD Pharmacotherapy pharmacotherapy with psychostimulants.[42. all of which then mediate various effects of nicotine use (i. appetite suppression.[26] In an analysis of over 400 adult participants in smoking cessation treatment studies.[39] Atomoxetine and bupropion. childhood ADHD diagnosis was significantly associated with treatment failure. b-endorphin and GABA. for reviews see Mansvelder and McGehee[27] and Newhouse et al. in contrast to stimulants and bupropion. individuals with ADHD may have more severe withdrawal symptoms.[21.

Ideally. increasing readiness to quit. In light of that limitation. the goal of treatment of these co-morbid conditions is to provide the best evidence-based approach to each condition while incorporating understanding of the relationship between the two. particularly those treating ADHD. 23 (8) 1.3 Psychosocial Treatment for Nicotine Dependence A critical component in smoking cessation treatment is psychosocial intervention. initiating a smoking reduction attempt or initiating a quit attempt) are developed collaboratively.[55-57] Motivational enhancement therapy is designed to elicit and support readiness to quit smoking. Combined approaches. 2. In general. this initial step should include pharmacotherapy. either with or without pharmacotherapy.[55] Contingent rewards may include monetary payment. contingency management interventions provide contingent rewards for cigarette reduction and abstinence. assist and arrange). redeemable vouchers or opportunities to draw prizes from a bowl containing rewards of varying values. Varenicline has demonstrated efficacy superior to placebo. those that incorporate motivational enhancement.e. Of note. closely monitoring and addressing CNS Drugs 2009.[49-51] but no published studies have specifically investigated individuals with ADHD. with the goal of the patient developing self-efficacy with ª 2009 Adis Data Information BV.62] The principles underlying motivational enhancement therapy.59] Using this method. advise. although this did provide encouraging data on such use. cognitive-behavioural therapy and contingency management approaches may be most associated with success. we recommend stabilization of ADHD symptoms as the first priority of treatment. depending on individual patient considerations.[54] Among smoking cessation interventions targeting young people. cognitive-behavioural therapy and contingency management may indeed be more complementary than overlapping when applied to smoking cessation treatment.[61. and goals for behavioural change (i. beliefs and thoughts about smoking.[52] carrying out these techniques even after the course of therapy has concluded. may show added promise. involving multiple psychosocial modalities. Based on current evidence.[48] Further research is needed to determine whether bupropion can effectively treat both conditions simultaneously. nicotine replacement and bupropion in smoking cessation. a recent case report suggests that the smoking cessation effects of varenicline may be interrupted by administration of the psychostimulant amfetamine-dextroamfetamine. assess.664 Gray & Upadhyaya specifically investigated for smoking cessation in individuals with ADHD in one pilot study.[60] The patient works with the clinician to develop techniques for self-monitoring and improved coping and problem-solving skills. the third step is to initiate smoking cessation treatment. The second step is to encourage the patient’s motivation to quit smoking cigarettes. the clinician is faced with the task of compiling disparate areas of research into a practical approach to patient care. Ambivalence is addressed.[53] The cornerstone for provision of smoking cessation treatment should be the 5-A Method (ask. The fourth step is to work closely with the patient during the smoking cessation process. Clinicians. Once that is established. a single treatment would fully address both nicotine dependence and ADHD.3. the clinician and patient discuss the patient’s smoking patterns.[58. . Cognitive-behavioural therapy seeks to identify and combat maladaptive cognitive and behavioural patterns that support cigarette smoking. but evidence does not currently support any single intervention for both disorders. since smoking cessation over the background of untreated ADHD could lead to greater relapse to smoking. All rights reserved. should advise patients and families of the potential risks of tobacco use and monitor for use at every visit. Practical Guide to Smoking Cessation in Patients with ADHD and Nicotine Dependence Given the overall dearth of studies specifically investigating smoking cessation treatment in individuals with ADHD. Built upon the theoretical foundation of operant conditioning. and the level of motivation or desire to cease smoking.

Safety warnings for all FDAapproved medications may be accessed at http://www.cfm. bupropion (if not already on bupropion) or nicotine replacement Psychosocial interventions Cognitive-behavioural therapy Contingency management Practical strategies Have patient keep a self-report diary of daily smoking Monitor for worsening of ADHD symptoms Fig. since evidence indicates that active symptoms of ADHD convey increased risk for cigarette smoking[63] and difficulty quitting. Details of treatment choices for these interventions are discussed below. the CNS Drugs 2009. Note: all medications listed in this figure. varenicline. biological confirmation of abstinence may be achieved using a carbon monoxide breathalyzer and/or urine cotinine measurement. evidence-based alternatives include atomoxetine and bupropion. In regard to smoking cessation.[68] If available. it is important to incorporate psychosocial interventions into treatment.accessdata. adverse effects) may lead to the use of other medications in preference to varenicline. Building upon that. Other considerations (e. suggested that stimulants may acutely increase cigarette smoking. symptoms of ADHD and nicotine withdrawal. 23 (8) .[64] the first-line medication treatment for ADHD is a long-acting psychostimulant.51] Although bupropion and nicotine replacement may possess theoretical advantages in treating smokers with ADHD (as discussed in section 1.[50. Additionally. such as the ADHD Rating Scale IV. Clinical use of these medications should occur in the context of careful consideration of potential risks and benefits.66] While effect sizes for these agents are not as large as those for stimulants. If a patient has difficulty tolerating a stimulant because of adverse effects. no published placebocontrolled studies have demonstrated that bupropion is effective for ADHD symptoms in cigarette smokers or for smoking cessation among individuals with ADHD. since some research has ª 2009 Adis Data Information BV. based on the evidence. pharmacotherapy is a key component of treatment.[47. it is important to monitor smoking rates in ADHD patients initiating stimulant treatment. We recommend a combined approach. Regardless of the pharmacotherapy (if any) chosen for smoking cessation. they are significant when compared with placebo.Tobacco Smoking in ADHD 665 Treat ADHD First line Long-acting psychostimulant Second line Bupropion or atomoxetine Elicit motivation to quit smoking Motivational enhancement interventions Initiate smoking cessation treatment Pharmacotherapy Varenicline. An additional benefit of bupropion is that it is also an effective treatment for smoking cessation. Initially. have received ‘black-box’ safety warnings from the US FDA. the patient’s motivation to quit smoking cigarettes must be established.65.g. aside from nicotine replacement. bupropion and nicotine replacement are all firstline medication treatments. we recommend using the medication with the greatest probability for successful smoking cessation (varenicline). which incorporates motivational enhancement.[67] Cigarette smoking may be monitored using a self-report instrument. Of note. See figure 1 for an overview of our recommended approach. cognitive-behavioural therapy and/or contingency management. and since long-acting (compared with immediateacting) stimulants may possess reduced potential for misuse or diversion. in light of the paucity of clear evidence.3. Since psychostimulants convey the most robust effect size. fda. However. though. 1. Head-to-head studies comparing varenicline with bupropion indicate that varenicline may be more effective. medication treatment that successfully reduces symptoms may indirectly affect smoking cessation outcome. All rights reserved.gov/scripts/cder/drugsatfda/index. We recommend that ADHD symptoms be monitored during treatment with a rating scale. In regard to ADHD.2). such as the Timeline Follow-Back method. Step-wise approach to treating co-morbid attention-deficit hyperactivity disorder (ADHD) and nicotine dependence.

69] It is important to note that. Office of Applied Studies. Targeting tobacco use: the nation’s leading cause of preventable death 2007 [online]. the clinician should again provide a structured approach to cessation based on the current evidence. Audrain-McGovern J. The rewards should be developmentally and individually motivating and do not have to be of great monetary value. Hartsough CS. Gillberg C. Dr Upadhyaya is now employed by Eli Lilly & Co. Washington. their interactions and their treatments. who may struggle with organization and long-term planning. Additionally.samhsa. et al. AACAP and Pfizer Inc.gov/nccdphp/ publications/aag/pdf/osh.pdf [Accessed 2008 Nov 17] 5. Patterns of temperament and character in a clinical sample of Korean children with attention-deficit hyperactivity disorder. Acknowledgements No sources of funding were used to assist in the preparation of this review. ª 2009 Adis Data Information BV. 23 (8) . Sergeant J.. Dr Upadhyaya was a consultant and on the advisory board of Eli Lilly & Co and Shire Pharmaceuticals and received honoraria from the American Academy of Child & Adolescent Psychiatry (AACAP). if possible.cdc. the clinician must avoid becoming discouraged in light of patient relapse. Lambert NM. Centers for Disease Control and Prevention. 163: 716-23 4. 62: 160-6 10. J Am Acad Child Adolesc Psychiatry 1997. DC: American Psychiatric Association. Milberger S. The structure conveyed by a series of short-term contingent rewards may be especially helpful for patients with ADHD. Dr Gray has received research support from the National Institute on Drug Abuse (NIDA). plans for contingent rewards for smoking abstinence may be established. All rights reserved. Subst Use Misuse 2003.SMA08-4343) [online]. 2000 2. character. it is hoped that integrated treatment specific to patients with ADHD and nicotine dependence will be developed. While evidence-based treatments for both disorders have been developed. Faraone SV. Adler L. the clinician can make informed treatment decisions that can make potentially significant impacts on morbidity and mortality. American Psychiatric Association. et al. Available from URL: http://www. McClernon FJ. Faraone SV. Association between smoking and attention-deficit/hyperactivity disorder symptoms in a population-based sample of young adults. Recently published expert guidelines for the treatment of nicotine dependence may help guide pharmacological and psychosocial treatment. even among smokers without co-morbid ADHD. Biederman J. In the interim. DHHS Publication No. Tercyak KP. J Learn Disabil 1998. The worldwide prevalence of ADHD: is it an American condition? World Psychiatry 2003. Contingent reinforcement helps to maintain the motivation that was initially elicited using motivational enhancement interventions. Stahlberg O. et al. He was a former stockholder in New River Pharmaceuticals. Am J Psychiatry 2006. Larson T. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Psychiatry Clin Neurosci 2008. ADHD is associated with early initiation of cigarette smoking in children and adolescents. et al. When the patient is ready for another quit attempt. 2: 104-13 3. It is expected that many patients will have difficulty quitting and may relapse after quitting. The clinician should continue to treat ADHD and encourage the patient’s motivation to quit smoking. Available from URL: http://www. Substance Abuse and Mental Health Services Administration. Kessler RC. 163: 1239-44 9. Am J Psychiatry 2006. 4th rev. 31: 533-44 7. In the especially challenging circumstance of treating the patient with co-morbid ADHD and nicotine dependence.cfm#Ch4 [Accessed 2008 Nov 17] 6. Eli Lilly & Co and Pfizer Inc. 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