Psychiatry/Behavioral · PANCE / PANRE

Tobacco Use Disorder

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

~12-14% of US adults currently smoke cigarettes; 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 naltrexone once daily
  • BTransdermal clonidine patch
  • COral nortriptyline at bedtime
  • DBupropion sustained-release
Reveal answer & full explanation
Correct answer: D — Bupropion sustained-release
  • AOral naltrexone once daily
  • BTransdermal clonidine patch
  • COral nortriptyline at bedtime
  • DBupropion sustained-release

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.
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
  • BVarenicline
  • CNortriptyline
  • DClonidine
Reveal answer & full explanation
Correct answer: B — Varenicline
  • ABupropion SR
  • BVarenicline
  • CNortriptyline
  • DClonidine

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 safe in patients with stable neurologic or psychiatric conditions; the FDA neuropsychiatric boxed warning was removed in 2016 after the EAGLES trial showed no increased risk 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.
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Risk factors

  • Adolescent initiation, peer/family use
  • Mental illness (schizophrenia, bipolar, MDD, SUD) — higher prevalence and consumption
  • Lower socioeconomic status, lower education
  • Stress, occupational exposure

Pathophysiology

Nicotine binds nicotinic acetylcholine receptors on VTA dopaminergic neurons, releasing dopamine in nucleus accumbens. Tolerance develops via receptor upregulation. Withdrawal driven by reduced dopaminergic tone.

Clinical presentation

Symptoms

  • Withdrawal: irritability, anxiety, depressed mood, difficulty concentrating, increased appetite, insomnia, restlessness — peaks 2-3 days, lasts 2-4 weeks (cravings can persist months)
  • 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)
  • Urine/serum cotinine — distinguishes recent use, confirms abstinence
  • Routine cardiovascular and pulmonary screening based on burden
  • Low-dose chest CT screening per USPSTF for ages 50-80 with >=20 pack-years and current smoking or quit within 15 years

Imaging

  • Low-dose chest CT for lung cancer screening as above

Diagnostic algorithm

TherapyNotes
VareniclineMost effective monotherapy; start 1 wk pre-quit; nausea, vivid dreams
NRT combo (patch + SA)Long-acting baseline + short-acting for cravings
Bupropion SRAvoid in seizure, eating disorder, active alcohol/benzo withdrawal
Behavioral counselingQuitlines, text programs, individual or group
Combination Rx + counselingBest outcomes
First-line tobacco cessation treatments.

Treatment

First-line

  • Brief intervention every visit — '5 As': Ask, Advise, Assess readiness, Assist, Arrange follow-up
  • Behavioral counseling — individual, group, telephone quitlines (1-800-QUIT-NOW), text-based programs
  • Pharmacotherapy (combine with counseling for best outcomes):
  • Varenicline — alpha-4-beta-2 nicotinic partial agonist; start 1 week before quit date; most effective single agent
  • Nicotine replacement therapy — combination of long-acting (patch) + short-acting (gum, lozenge, inhaler, nasal spray) outperforms monotherapy
  • Bupropion SR 150 mg — atypical antidepressant; avoid in seizure disorder, eating disorder, acute alcohol/benzodiazepine withdrawal

Second-line / adjunct

  • Combination pharmacotherapy: NRT patch + varenicline, or NRT patch + short-acting NRT, or NRT + bupropion
  • Nortriptyline, clonidine — less evidence
  • E-cigarettes as cessation aid — evidence growing but not FDA-approved for cessation; not first-line
  • Treat comorbid depression, anxiety, SUDs

Complications

  • Cancer: lung, oropharyngeal, esophageal, bladder, pancreatic, cervical, AML
  • Cardiovascular: CAD, stroke, peripheral arterial disease, AAA
  • Pulmonary: COPD, exacerbation of asthma
  • Pregnancy: low birth weight, preterm delivery, SIDS
  • Wound healing impairment, periodontal disease, osteoporosis

PANCE pearls

  • Even brief (<3 min) clinician advice to quit increases cessation rates — never miss an opportunity.
  • Cessation halves CV risk within 1 year; lung cancer risk falls toward baseline over 10-15 years.
  • Varenicline neuropsychiatric warning was removed from the FDA label in 2016 after EAGLES trial showed no increased risk vs placebo.
  • 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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