Problematic tobacco/nicotine use meeting >=2 DSM-5-TR criteria; treat with combined pharmacotherapy and counseling.
Also known as: tobacco dependence, nicotine addiction, smoking cessation, nicotine use disorder
Overview
A problematic pattern of tobacco use causing clinically significant impairment or distress, with >=2 of 11 DSM-5-TR criteria in 12 months. Includes combustible tobacco, e-cigarettes/vaping, and smokeless tobacco.
Epidemiology
About 10% of US adults currently smoke cigarettes (NHIS 2024); youth e-cigarette use rose sharply in late 2010s. Tobacco causes ~480,000 US deaths annually — leading preventable cause of death.
Try two board-style Tobacco Use Disorder questions
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Question 1PsychiatryMedium
A 51-year-old who smokes wants to quit and prefers a medication that also curbs craving. He has no seizure disorder or eating disorder. Which of the following is the most appropriate pharmacologic option?
AOral nortriptyline at bedtime
BOral fluoxetine once daily
CBupropion sustained-release
DTransdermal clonidine patch
EOral naltrexone once daily
Reveal answer & full explanation
Correct answer: C — Bupropion sustained-release
AOral nortriptyline at bedtime
BOral fluoxetine once daily
CBupropion sustained-release✓
DTransdermal clonidine patch
EOral naltrexone once daily
Why Bupropion sustained-release is correct
Bupropion SR is a first-line cessation aid that reduces nicotine craving and withdrawal.
It is contraindicated in seizure and eating disorders, both excluded in this patient.
Varenicline and nicotine replacement are the other guideline-endorsed first-line options.
Why the others are wrong
Oral naltrexone once daily — naltrexone is approved for alcohol and opioid use disorder and has not been shown to improve smoking abstinence, so it does not serve this patient's craving-driven request.
Transdermal clonidine patch — clonidine is a second-line agent reserved for patients who fail or cannot take first-line therapy, and it causes sedation, dry mouth, and rebound hypertension on withdrawal.
Oral nortriptyline at bedtime — nortriptyline is an off-label second-line option whose anticholinergic and cardiac conduction toxicity make it a poor choice when a first-line agent is available and safe here.
Oral fluoxetine once daily — because bupropion and nortriptyline are both antidepressants, an SSRI can seem like a reasonable substitute, but trials show fluoxetine does not improve smoking abstinence, so it offers no cessation benefit for this patient.
Question 2PsychiatryMedium
A 48-year-old man with a 30-pack-year smoking history asks for help quitting cigarettes at a routine visit. He smokes within 10 minutes of waking and has failed two prior attempts using nicotine patch alone. His history includes a generalized seizure disorder, well-controlled on levetiracetam. He is not depressed, drinks alcohol rarely, and is motivated to set a quit date in 2 weeks. Vital signs and exam are normal. He receives brief counseling and is referred to a quitline. Which of the following is the most appropriate initial pharmacotherapy?
ABupropion SR
BNortriptyline
CFluoxetine
DClonidine
EVarenicline
Reveal answer & full explanation
Correct answer: E — Varenicline
ABupropion SR
BNortriptyline
CFluoxetine
DClonidine
EVarenicline✓
Why Varenicline is correct
Varenicline is an alpha-4-beta-2 nicotinic partial agonist and the most effective single agent for tobacco cessation; it is started about 1 week before the quit date, which fits this patient's 2-week timeline.
It is the preferred first-line choice here because nicotine patch monotherapy has already failed twice and his seizure disorder excludes bupropion.
It is not contraindicated in a well-controlled seizure disorder; the label advises caution and weighing risk versus benefit in patients with a seizure history (stop it if a seizure occurs), whereas bupropion lowers the seizure threshold and should be avoided. The FDA neuropsychiatric boxed warning was removed in 2016 after the EAGLES trial showed no significant increase in serious neuropsychiatric events versus placebo. Pairing it with counseling and a quitline maximizes success.
Why the others are wrong
Bupropion SR is an effective first-line cessation agent, but it lowers the seizure threshold and should be avoided in a patient with a seizure disorder.
Nortriptyline has only second-line cessation evidence and is reserved for patients who cannot use or have failed first-line agents, so it is not an initial choice.
Clonidine has weak, second-line cessation data and causes sedation and hypotension, so it is not appropriate first-line therapy.
Fluoxetine — tempting because two other antidepressants, bupropion and nortriptyline, aid smoking cessation, but SSRIs have not been shown to improve quit rates and have no role as cessation pharmacotherapy.
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Loss of control, persistent desire to cut down, time spent obtaining, continued use despite harms — DSM-5-TR criteria parallel other SUDs
Signs / physical exam
Tobacco staining on fingers/teeth, halitosis, oral lesions, cough
Wheezing, decreased breath sounds in COPD
Elevated CO levels on exhaled testing
Differential diagnosis
Other SUDs — Frequent co-occurrence with alcohol, cannabis, stimulants
Anxiety/depression — Common comorbidity; tobacco often used for self-medication
ADHD — Higher rates of tobacco use; treat ADHD as part of cessation plan
Diagnostic workup
Diagnostic criteria
DSM-5-TR Tobacco Use Disorder: problematic pattern of tobacco use with >=2 of 11 criteria in 12 months. Severity by criterion count. Withdrawal symptoms support physiologic dependence.
Labs
Exhaled CO can confirm recent smoking (>=6-10 ppm)
Even brief (<3 min) clinician advice to quit increases cessation rates — never miss an opportunity.
Heart attack risk drops sharply within 1-2 years of quitting and the added risk of coronary heart disease is halved by 3-6 years; the added risk of lung cancer drops by about half 10-15 years after quitting but stays above never-smoker levels.
The varenicline boxed neuropsychiatric warning was removed from the FDA label in 2016 after the EAGLES trial showed no significant increase in serious neuropsychiatric events vs placebo; neuropsychiatric events and seizures remain under Warnings and Precautions, so monitor.
Patients with serious mental illness benefit from cessation without worsening psychiatric symptoms — do not defer.
Pregnancy: prefer behavioral interventions; NRT can be considered after risk discussion if behavioral approaches fail; avoid varenicline and bupropion.
References
USPSTF 2021 — Interventions for Tobacco Smoking Cessation in Adults: USPSTF Recommendation Statement. JAMA 2021
Surgeon General 2020 — Smoking Cessation: A Report of the Surgeon General (2020)
EAGLES Trial — Anthenelli RM et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch (EAGLES). Lancet 2016
DSM-5-TR — American Psychiatric Association. DSM-5-TR (2022)
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