Alcohol use disorder and withdrawal

At a glance

• Alcohol withdrawal is a GABA-deficit, glutamate-excess state. It can kill through seizures, delirium tremens, aspiration and arrhythmia.
• Predict who will get severe withdrawal (PAWSS 4 or more, previous seizures or delirium tremens), monitor with a validated scale, and treat with symptom-triggered benzodiazepines.
• Thiamine to every at-risk drinker, but correct hypoglycaemia with glucose first.
• Withdrawal from sedatives (alcohol, benzodiazepines, GHB, baclofen) looks alike: autonomic overactivity, seizures, delirium. Opioid withdrawal doesn't cause seizures or delirium in adults.
• After withdrawal, offer naltrexone or acamprosate with psychosocial treatment. Withdrawal alone doesn't treat alcohol use disorder.
• Screening, AUDIT and DSM-5-TR criteria are in Substance use disorders. Intoxication and organ damage are in Alcohol: acute and chronic effects.

Definitions

• Alcohol use disorder (DSM-5-TR): 2 or more of 11 criteria in 12 months; severe at 6 or more. Tolerance and withdrawal are 2 of the 11, so physiological dependence alone doesn't make a severe disorder.
• Alcohol withdrawal syndrome: symptoms after stopping or cutting down heavy, prolonged drinking, not explained by another condition.
• Complicated withdrawal: withdrawal seizures or delirium tremens.

Pathophysiology

• Alcohol enhances GABA-A inhibition and blocks NMDA glutamate receptors. With chronic use, GABA-A receptors down-regulate and change subunit make-up, and NMDA receptors up-regulate.
• Remove alcohol and the brain is left under-inhibited and over-excited, with surging noradrenaline. This explains the tremor, tachycardia, hypertension, sweating, seizures and delirium.
• Cross-tolerance: benzodiazepines and phenobarbital act at the same GABA-A receptor, which is why they treat withdrawal and why combined dependence makes it worse.
• Kindling: each withdrawal makes the next one more severe. A history of several detoxifications predicts seizures.
• Withdrawal can begin while the blood alcohol is still positive. A tolerant drinker with tremor at 0.15 g/100 mL is already withdrawing.

Recognition

Timeline

Hours after last drink	Feature
6 to 24	Tremor, sweating, anxiety, nausea, tachycardia, insomnia
6 to 48	Withdrawal seizures, generalised, usually one or a short cluster
12 to 48	Alcoholic hallucinosis (usually visual) with a clear sensorium
48 to 72	Delirium tremens: fluctuating delirium, hallucinations, autonomic instability, fever, lasting up to 5 days or more

• Delirium tremens carries a mortality of a few per cent even with treatment, mainly from arrhythmia, aspiration, hyperthermia and the illness that brought the patient in.
• Pitfall: calling a fever in delirium tremens "just withdrawal". Look for aspiration pneumonia, SBP, meningitis and head injury.

Predicting severity

• PAWSS (Prediction of Alcohol Withdrawal Severity Scale): 4 or more predicts complicated withdrawal in medical inpatients (Maldonado 2015). Its main items are previous withdrawal, seizures or delirium tremens, previous detoxification, combined use of other sedatives, a positive blood alcohol on arrival, and autonomic hyperactivity.
• Clinical red flags: previous seizures or delirium tremens, heavy daily drinking for years, concurrent benzodiazepine or GHB use, acute medical or surgical illness, older age, liver disease and low platelets or potassium.

Monitoring scales

• Alcohol Withdrawal Scale (AWS), used by most Australian hospitals, or CIWA-Ar. On CIWA-Ar, under 10 is mild and 10 or more usually triggers treatment.
• Both need a patient who can answer questions. They mislead in delirium, sepsis, pain, head injury or other causes of tachycardia.

The withdrawal toxidrome across drugs

Drug withdrawn	Onset	Key features	Life-threatening?
Alcohol	6 to 24 h	Tremor, sweating, tachycardia, seizures, delirium tremens	Yes
Benzodiazepines	1 to 2 days (short-acting) to over a week (diazepam)	As for alcohol, plus perceptual distortion; seizures	Yes
GHB	1 to 6 h	Rapid escalation to delirium, seizures, autonomic storm	Yes
Baclofen (intrathecal pump failure)	Hours	Itch, fever, rigidity, rhabdomyolysis, seizures	Yes
Opioids	6 to 24 h (heroin), 24 to 48 h (methadone)	Yawning, lacrimation, rhinorrhoea, mydriasis, piloerection, cramps, diarrhoea; clear sensorium	Rarely (dehydration, loss of tolerance)
Stimulants	Hours to days	Crash: hypersomnia, hyperphagia, dysphoria, suicidal thinking	Through suicide
Cannabis	1 to 2 days	Irritability, insomnia, anorexia, vivid dreams	No
SSRIs and SNRIs	1 to 3 days	Dizziness, electric-shock sensations, flu-like symptoms (paroxetine, venlafaxine)	No
Clonidine, beta-blockers	1 to 2 days	Rebound hypertension, tachycardia, angina	Yes, in coronary disease

• The GABA-ergic group shares one treatment: a long-acting benzodiazepine (or phenobarbital), with baclofen added for GHB and baclofen withdrawal. See Drug-induced delirium and agitation.
• Pitfall: a patient who becomes delirious within hours of admission with a negative blood alcohol. Think of GHB or benzodiazepine withdrawal, not alcohol.

Investigations

• Glucose, electrolytes with magnesium and phosphate, LFTs, FBC (macrocytosis, platelets), lipase, blood alcohol, and a venous gas if unwell.
• ECG for QTc and arrhythmia, especially before haloperidol.
• CT brain after a first seizure, a focal or prolonged seizure, head injury, or delirium not explained by withdrawal.
• Screen for infection, pancreatitis, GI bleeding and liver decompensation, which often precipitate or accompany withdrawal.

Management of withdrawal

Setting

• Ambulatory withdrawal suits mild predicted withdrawal with no history of seizures or delirium tremens, no serious medical or psychiatric illness, a support person and daily review.
• Admit with PAWSS 4 or more, previous complicated withdrawal, pregnancy, acute illness, or concurrent sedative dependence.
• In custody, the 2026 MJA consensus statement recommends universal withdrawal assessment at reception, validated tools, and placing the person where withdrawal is safest.

Benzodiazepines

• Diazepam is first line: long-acting, with active metabolites that give a smooth self-taper.
• Symptom-triggered dosing (for example diazepam 10 to 20 mg when the score reaches the threshold) uses less drug and shortens treatment compared with fixed schedules, but needs reliable scoring.
• Loading (repeated 20 mg doses every 1 to 2 hours until settled) is used for high-risk patients and those with previous seizures. Seek senior review when doses climb past local limits.
• Oxazepam (or lorazepam) in decompensated cirrhosis, older people and respiratory failure: no active metabolites, cleared by glucuronidation.
• Stop by day 5 to 7 in most patients. Withdrawal lasting longer points to another sedative, another diagnosis or iatrogenic dependence.
• Pitfall: over-sedation with diazepam in liver failure that looks like hepatic encephalopathy. See Cirrhosis.

Phenobarbital and other drugs

• Phenobarbital acts on GABA-A at a different site and has a long half-life. It is used for benzodiazepine-refractory withdrawal and, in some US centres, as a single front-loaded dose. In a 2026 US cohort of 24,643 inpatients, phenobarbital and diazepam gave similar length of stay and ventilation rates, with fewer self-discharges on phenobarbital (Bradley, JAMA Intern Med 2026). Australian practice keeps it for refractory cases under senior or ICU care.
• Refractory delirium tremens: phenobarbital, or propofol with intubation, in ICU.
• Antipsychotics (haloperidol, olanzapine) only for hallucinations or agitation not settled by adequate benzodiazepine; they lower the seizure threshold.
• Not effective or not used: phenytoin for withdrawal seizures, IV ethanol, and clonidine or beta-blockers as sole treatment (they mask signs without preventing seizures).
• Carbamazepine or gabapentin are options for mild outpatient withdrawal when benzodiazepines are unsafe (ASAM 2020).

Supportive care

• Thiamine: 300 mg IV or IM daily for 3 to 5 days in at-risk inpatients; 500 mg IV three times daily for 3 to 5 days if Wernicke encephalopathy is suspected. Give it before routine glucose-containing fluids, but glucose comes first in hypoglycaemia, with thiamine immediately after (TG 2025).
• Replace magnesium, potassium and phosphate. Refeed carefully. See Malnutrition and refeeding.
• Quiet, well-lit room, reorientation and fluids.

Relapse prevention

Start during the admission, with psychosocial treatment (motivational interviewing, CBT, mutual help groups) and referral to drug and alcohol services.

Drug	Evidence and use	Cautions
Naltrexone 50 mg daily	Reduces heavy drinking; the active drug in COMBINE (2006)	Blocks opioid analgesia and precipitates withdrawal in opioid users; avoid in decompensated liver disease
Acamprosate 666 mg three times daily (60 kg or more)	Helps maintain abstinence; no added benefit in COMBINE	Renally cleared: contraindicated if creatinine over 120 µmol/L (Australian PI); not in Child-Pugh C
Disulfiram 200 mg daily	Only with supervised dosing and an abstinence goal	Hepatotoxic; reaction with any alcohol
Baclofen 30 to 75 mg daily (off-label)	BacALD: longer time to relapse, more days abstinent, including in liver disease	Sedation, overdose, its own withdrawal syndrome
Topiramate, gabapentin (off-label)	Modest effect on heavy drinking	Cognitive slowing (topiramate), misuse (gabapentin)

• PBS: naltrexone and acamprosate are listed for alcohol dependence within a treatment program that includes counselling, aiming at abstinence.
• In alcohol-related liver disease, acamprosate (if renal function allows and not Child-Pugh C) or baclofen are the usual choices.

Special populations

• Pregnancy: admit at any gestation if at risk of moderate to severe withdrawal, for at least 5 days after onset. Consider a diazepam loading regimen, with parenteral thiamine and folate (at least 400 mcg daily to term), because untreated withdrawal threatens the fetus (NSW Health 2024). The NSW guidance says naltrexone should not be offered because its safety in pregnancy is not established; it does not address acamprosate or disulfiram, which also lack pregnancy safety data, so get specialist advice before any relapse-prevention drug. Alcohol in pregnancy causes fetal alcohol spectrum disorder.
• Older people: withdrawal starts later, lasts longer and is more often complicated by delirium and falls. Use oxazepam in small doses and look for cognitive impairment.
• Aboriginal and Torres Strait Islander people: work with Aboriginal Community Controlled Health Services and offer culturally safe residential and community withdrawal options. The custodial consensus has specific recommendations for First Nations people in custody.
• Driving: alcohol dependence is a driving licensing condition under Austroads standards; a conditional licence may be considered once remission is established.

Pitfalls

• Assuming withdrawal can't start while the blood alcohol is positive.
• Attributing early-onset delirium to alcohol when GHB or benzodiazepine withdrawal is the cause.
• Phenytoin for withdrawal seizures, and skipping the CT after a first or focal seizure.
• Relying on CIWA-Ar or AWS scores in a delirious, septic or non-verbal patient.
• Delaying glucose in hypoglycaemia to give thiamine first.
• Diazepam in decompensated cirrhosis.
• Prescribing naltrexone to a patient on opioids or who will need opioid analgesia.
• Discharging after withdrawal with no relapse-prevention plan.