Treating Nicotine Dependence in
Patients with Addictive Disorders
Eric Heiligenstein, M.D.
Director of Psychiatry
University Health Services
University of Wisconsin-Madison
• Evidence of effective strategies for
addressing the disproportionate rate of
tobacco use among smokers with cooccurring addictive disorders is lacking
• The 2008 update of the US Clinical
Practice Guidelines for treating
tobacco dependence was informed by
more than 8700 tobacco control
studies
• Fewer than 2 dozen randomized
controlled trials have focused on
smokers with addictive disorders
• Smokers with mental illness or
substance use disorders are among
the most likely to be excluded from
clinical trials because they are viewed
as too complicated
• That said, we cannot continue to
overlook the epidemic of tobacco
dependence that has plagued persons
with substance use disorders
• The following recommendations are
based on the best available evidence
and national expert consensus panels
Treatment Principles for
Nicotine Dependence in MHA
• All smokers trying to quit should be encouraged
to use both counseling and medication1
– Counseling and medication in combination are more
effective than either alone
• Dose level and duration of drug treatment
individualized
• Many will need
– Higher doses of medication
– Longer duration of treatment
– Combination treatments
1. PHS Clinical Practice Guideline, 2008
Clinical Solutions: Treating Nicotine
Dependence in
MHA
• Traditional cessation treatments may be
inadequate
– Flexibility in setting quit date
– Reduced smoking to reach abstinence
– Practice quit attempts
– Combination and tailored treatments
(behavioral & medical)
Peters & Hughes, 2009; McFall et al, 2010
Determining Readiness to Proceed
• Motivation
– “Interested” is sufficient
– Don’t rule out initiating some type of intervention if not
motivated to quit now
• Stability
– Need to be psychiatrically stable-do not need to be in
full remission
– No major medication changes
– No major life changes
– No active intoxication/withdrawal; consumer/client in
recovery process
Nicotine-Drug Interactions
• Smoking induces CYP1A2 isoenzyme
– Approximately doubles clearance of
• Antipsychotics: fluphenazine, haloperidol,
olanzapine, clozapine, chlorpromazine
• Antidepressants: amitriptyline, nortriptyline,
imipramine, clomipramine, doxepin, fluvoxamine
• Cessation may produce rapid, significant
increase in blood levels
• Need to monitor for increased side effects
First-line Pharmacotherapies
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Nicotine patch
Nicotine gum
Nicotine lozenge
Nicotine inhaler
Nicotine nasal spray
Buproprion SR
Varenicline
Reasons for Using NRT
• It helps the person feel more comfortable
(treats nicotine withdrawal syndrome).
• It is very safe: the person is getting “clean”
nicotine instead of “dirty” nicotine with
4000 plus chemicals.
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NRT Combinations
• Provide an increase in long-term quit rates
(42%)
• Limited safety concerns
• Which combinations?
– Patch + patch
– Patch + oral product
– Oral product + oral product
Pre-Quit Use of NRT (Patch)
• Starting patch 2 weeks before quitting
increases the odds of quitting about 4
fold
• Weakens link between smoking and
pleasure
• Need to switch to low-nicotine
cigarettes
NRT Summary
• NRT increases the odds of quitting about
2 fold
• Long-term and high-dose NRT (patch)
may not produce added benefit beyond
regular dose (14-25 mg) and duration (614 weeks)
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Bupropion SR
• Atypical antidepressant that acts as a
norepinephrine and dopamine
reuptake inhibitor
• Is a nicotinic antagonist that prevents
cravings and withdrawal symptoms
Bupropion SR
• Dose response efficacy in treating smokers
• Attenuates weight gain
• Can be prescribed to diverse populations of
smokers with expected comparable results
Hays JT & Ebbert JO. Mayo Clin Proc 78:1020, 2003
Bupropion SR Summary
• Bupropion SR increases the odds of quitting about
2 fold
• Insufficient evidence that adding Bupropion SR to
NRT provides an additional long-term benefit
• Extended therapy with Bupropion SR to prevent
relapse after initial cessation has not find evidence
of a significant long-term benefit
• Trials comparing Bupropion SR to Varenicline
showed a lower odds of quitting with Bupropion SR
• Concerns that Bupropion SR may increase suicide
risk are currently unproven
Varenicline
• Varenicline is a partial agonist activating the
α4β2 nAChR subtypes to prevent cravings
and withdrawal symptoms
• It also acts as a partial antagonist by
occupying receptor sites and blocking
nicotine binding leading to a reduction in the
satisfaction gained by smoking
Varenicline Summary
• Varenicline at standard dose increased the chances of
successful long-term smoking cessation between two- and
threefold
• Lower dose regimens also conferred benefits for cessation,
while reducing the incidence of adverse events
• More patients quit successfully with Varenicline than with
Bupropion
• Limited evidence suggests that Varenicline may have a role to
play in relapse prevention
• Possible links with serious adverse events, including
depressed mood, agitation and suicidal thoughts, have been
reported but are so far not substantiated
Behavioral Toxicity and
Pharmacotherapy for Nicotine
Dependence
• Bupropion SR and Varenicline have slight risk for
suicide or attempts (1.12 OR; 1.17 OR), and
suicidal ideation (1.20 OR; 1.43.OR)
• Untreated nicotine withdrawal can cause adverse
behavioral changes, including suicidal ideation
• All patients should be informed of this potential
when treatment is discussed
• Half of all smokers who don’t stop by middle age
will die from a tobacco-related disease
Gunnell, et al, 2009
Smoking and Substance Use Disorders
• The research on the association between
smoking and substance use outcomes is
limited by a lack of longer follow-ups
• Most studies have not exceed 18 months
and none examined prospectively the
impact of smoking on long-term outcomes
Treating Nicotine Dependence in SUD
• Smoking cessation attempts or concurrent
smoking cessation and substance use
treatment does not interfere with recovery
from substance use disorders
• Stopping smoking during the first year
after substance use treatment predicted
better long-term substance use outcomes
through 9 years after intake
Burling et al, 1996; Cooney et al, 2009; Tsoh et al, 2010
Treating Nicotine Dependence in
SUD
• Standard combinations of behavioral and
pharmacological treatment (e.g., weekly
counseling plus NRT) have produced
disappointing results in alcoholic smokers
• Bupropion SR not effective in one trial
• Combination NRT, Naltrexone, Topiramate,
and Varenicline hold promise
Kalman et al, 2006; Hays et al, 2009; Cooney et al , 2009; Ebbert et al 2009; Johnson et al, 2005; O’Malley et
al, 2006
Unique Tobacco Treatment
Needs
• Determine need for involvement from primary care/other
health care providers
• Determine need for more intensive behavioral therapy
• Address psychotropic medication issues
• Tailor treatment plan based on
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Current symptoms/recovery
Functional status
Current psychotropic medications
Previous quit history
– Stage of readiness
– Level of impairment/functional status