Substance Use Disorders & Withdrawal
A boards-focused walkthrough of DSM-5 substance use disorder criteria and the major intoxication and withdrawal syndromes, emphasizing withdrawal timelines, first-line pharmacotherapy, and high-yield next-best-step decisions for alcohol, opioids, sedatives, stimulants, and nicotine.
DSM-5 Framework & Epidemiology
Substance Use Disorder (SUD) is a single DSM-5 spectrum diagnosis: a problematic pattern of use causing clinically significant impairment or distress, with ≥2 of 11 criteria within a 12-month period. The criteria cluster into four groups: impaired control (using more/longer than intended, failed attempts to cut down, excess time obtaining/using/recovering, craving); social impairment (failed role obligations, interpersonal problems, giving up activities); risky use (physically hazardous use, use despite harm); and pharmacologic (tolerance, withdrawal). Severity: mild = 2–3, moderate = 4–5, severe ≥6 criteria.
Key boards point: tolerance and withdrawal do NOT count toward the diagnosis when a drug is taken as prescribed under appropriate medical supervision (opioids, sedatives, stimulants). DSM-5 collapsed the old abuse vs. dependence split, dropped 'recurrent legal problems,' and added 'craving.'
Epidemiology: alcohol and tobacco are the most prevalent substances; alcohol use disorder carries a lifetime prevalence near 29% (NESARC-III), men > women, with typical onset in adolescence/young adulthood.
- Life-threatening withdrawals = alcohol and sedatives/benzodiazepines (seizures, autonomic collapse). Opioid, stimulant, and nicotine withdrawal are miserable but not typically fatal.
- Alcohol withdrawal timeline: tremor/anxiety/autonomic hyperactivity 6–24h → withdrawal seizures 12–48h → alcoholic hallucinosis 12–48h (clear sensorium) → delirium tremens 48–96h (delirium + autonomic instability; up to ~5% mortality even when treated).
- First-line for alcohol/benzo withdrawal = benzodiazepines (chlordiazepoxide, diazepam); use lorazepam or oxazepam in liver disease (no active metabolites), often CIWA-Ar–guided.
- Give thiamine BEFORE glucose in any malnourished/alcohol-using patient to avoid precipitating Wernicke encephalopathy.
- Opioid overdose = miosis + respiratory depression + CNS depression → naloxone. Opioid withdrawal → methadone/buprenorphine; clonidine for autonomic symptoms.
- Stimulant (cocaine/amphetamine) intoxication: sympathetic storm (mydriasis, HTN, tachycardia, hyperthermia, chest pain/MI, seizures) → benzodiazepines; classically avoid pure beta-blockers (unopposed alpha).
Intoxication vs. Withdrawal by Substance
| Substance | Intoxication clues | Withdrawal (onset + signs) | Withdrawal Rx |
|---|---|---|---|
| Alcohol | Disinhibition, slurred speech, ataxia, nystagmus | 6–96h; tremor, seizures (12–48h), DTs (48–96h) | Benzodiazepines, thiamine |
| Opioids | Miosis, resp depression, ↓bowel sounds, sedation | 6–48h; mydriasis, lacrimation, rhinorrhea, diarrhea, myalgia, piloerection, yawning | Methadone/buprenorphine, clonidine |
| Benzodiazepines | Sedation, ataxia, resp depression (esp. with alcohol) | Onset varies with half-life; anxiety, tremor, seizures (life-threatening) | Long-acting benzo taper |
| Cocaine/amphetamine | Mydriasis, HTN, tachycardia, hyperthermia, psychosis, MI | "Crash": dysphoria, fatigue, hypersomnia, ↑appetite, vivid unpleasant dreams | Supportive |
| Nicotine | (Mild stimulation) | Irritability, anxiety, ↓concentration, ↑appetite, restlessness | NRT, varenicline, bupropion |
Vignette: A 54-year-old man admitted 3 days ago for acute pancreatitis becomes agitated and disoriented. He is diaphoretic and tremulous, picking at the air and describing spiders crawling on the walls. BP 178/104, HR 122, T 38.6°C. Labs are unremarkable except mild transaminitis.
Diagnosis: Delirium tremens — note the classic 48–96h onset after the last drink (hospital day 3) and the triad of delirium + autonomic hyperactivity + visual/tactile hallucinations.
Next best step: IV benzodiazepine (e.g., lorazepam) titrated to symptoms (symptom-triggered/CIWA-Ar), plus IV thiamine before dextrose, fluids, and electrolyte correction; admit to a monitored setting.
Distinguish: isolated alcoholic hallucinosis occurs earlier (12–48h) with a clear sensorium and stable vitals — no delirium or autonomic storm — and is not DTs. Withdrawal seizures are typically generalized and self-limited; phenytoin is ineffective — benzodiazepines prevent and treat them.
CAGE — screens for alcohol use disorder (≥2 'yes' = positive):
- C — Have you tried to Cut down?
- A — Do people Annoy you by criticizing your drinking?
- G — Do you feel Guilty about drinking?
- E — Do you need an Eye-opener (morning drink) to steady nerves/cure a hangover?
Opioid overdose triad: pinpoint pupils + respiratory depression + CNS depression (coma).
Wernicke encephalopathy triad: Confusion + Ataxia + ocular findings (Nystagmus / OPhthalmoplegia) — from thiamine/B1 deficiency. Add anterograde amnesia + confabulation and it has progressed to the irreversible Korsakoff syndrome.
Maintenance Pharmacotherapy (MAT)
| Disorder | Drug | Mechanism | Boards pearl |
|---|---|---|---|
| Alcohol | Naltrexone | μ-opioid antagonist | First-line; ↓ craving/heavy drinking; avoid in current opioid use & acute hepatitis/liver failure |
| Alcohol | Acamprosate | Glutamate/GABA (NMDA) modulation | Good with liver disease (renal clearance); start after abstinence; avoid in renal failure |
| Alcohol | Disulfiram | Aldehyde dehydrogenase inhibitor | Aversive (flushing/vomiting with alcohol); needs high motivation; not first-line |
| Opioid | Buprenorphine ± naloxone, Methadone | Partial / full μ-agonist | MAT ↓ mortality; buprenorphine can precipitate withdrawal if started too early |
| Opioid | Naltrexone | μ-antagonist | Only after full detox (~7–10 days opioid-free) |
| Nicotine | Varenicline, bupropion, NRT | Partial α4β2 nicotinic agonist | Varenicline most effective |
Vignette: A 24-year-old man is brought in unresponsive after being found in a restroom. RR 6/min and shallow; pupils 1 mm (pinpoint); GCS 6. Track marks are visible on both arms.
Diagnosis: Opioid overdose — the triad of miosis + respiratory depression + depressed consciousness is the giveaway.
Next best step: support the airway/ventilation (bag-valve-mask) and give naloxone (IV/IM/intranasal), titrating to adequate respirations — not full arousal — to avoid precipitating acute withdrawal. Naloxone is short-acting (~30–90 min), so redose and observe for re-sedation, especially with long-acting opioids (methadone, extended-release formulations).
Trap: don't reflexively attribute pinpoint pupils to a pontine hemorrhage — the reversible cause (naloxone) comes first. After stabilization, initiate MAT (buprenorphine/methadone) and provide take-home naloxone.
- Thiamine before glucose — glucose loading first can precipitate/worsen Wernicke encephalopathy in thiamine-depleted patients.
- Buprenorphine precipitated withdrawal: as a high-affinity partial agonist, it displaces full agonists — start only when the patient is already in mild–moderate withdrawal (COWS-guided).
- Naltrexone contraindications: current opioid use (precipitates withdrawal) and acute hepatitis/liver failure.
- Benzodiazepine withdrawal is potentially lethal (seizures) — taper, never stop abruptly; manage like alcohol withdrawal.
- Flumazenil is NOT routine for benzodiazepine overdose — it can precipitate seizures/withdrawal in chronic users; prioritize airway/supportive care.
- Cocaine chest pain: give benzodiazepines, aspirin, nitrates; avoid non-selective beta-blockers (classic 'unopposed alpha' teaching).
- Pregnancy + opioid dependence: use methadone or buprenorphine — not medically supervised withdrawal (relapse/fetal risk).
- Alcohol withdrawal seizures are generalized, early (12–48h), and self-limited — benzodiazepines, not phenytoin.
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