Mental and behavioural disorders due to alcohol use: acute intoxication, harmful use, dependence, withdrawal syndrome, delirium, psychotic disorders, amnestic syndrome. Treatment

01Definition and overview

Alcohol use disorders cover a range of drinking and its harms.

The six ICD-10 features of dependence are:

• a strong desire or sense of compulsion to drink;
• difficulty controlling when drinking starts or stops, or how much;
• a withdrawal state, or drinking to relieve or avoid withdrawal;
• tolerance, needing more for the same effect;
• neglect of other pleasures and interests, with more time spent getting, drinking or recovering;
• drinking despite clear evidence of harm.

ICD-11 condenses them into three: impaired control, drinking taking precedence over other parts of life, and physiological features (tolerance and withdrawal). Two of the three, usually over 12 months, or over 3 months of daily or near-daily drinking, make the diagnosis. DSM-5-TR uses one dimension, alcohol use disorder, graded mild, moderate or severe by how many of eleven criteria are met. In practice the drinking repertoire narrows, drinking becomes the centre of the day, and dependence returns quickly after a period of abstinence.

A UK unit is 10 ml or 8 g of pure ethanol; in much of Europe a standard drink is 10 g or more. The units in a drink are its volume in millilitres times its strength in per cent, divided by 1000.

The UK Chief Medical Officers advise men and women to drink no more than 14 units a week, spread over three or more days with several drink-free days, and no alcohol in pregnancy. The WHO's position is that no level of drinking is safe for health, because the risk of cancer rises from the first drink.

02Etiology and pathophysiology

Causes

• Genes: about half the risk of alcohol use disorders is heritable. Variants in alcohol and aldehyde dehydrogenase matter most: the inactive ALDH2 variant common in East Asia causes flushing and protects against heavy drinking. Many genes of small effect act on reward and stress.
• Environment: price, availability and drinking culture set a population's level of drinking, and the number of heavy drinkers follows it. Peers, family drinking, and childhood adversity add risk.
• Psychological: drinking to cope with anxiety, low mood or trauma, impulsivity, and the learning of cues and rewards.
• Comorbidity: depression, anxiety, PTSD, ADHD, personality disorders, bipolar disorder, psychosis and other drug use are common in both directions.

The brain on alcohol

Alcohol enhances inhibitory GABA-A receptors and blocks excitatory NMDA receptors, and it releases dopamine and endogenous opioids in the reward circuits, the basis for naltrexone and nalmefene. With regular heavy drinking the brain adapts: GABA-A receptors are reduced and NMDA receptors are increased, so tolerance develops. When drinking stops, the adapted brain is left over-excited, with a surge of glutamate and noradrenaline: tremor, sweating, tachycardia, anxiety, seizures and, at the extreme, delirium. Each withdrawal makes the next one worse, a process called kindling, so past seizures or delirium predict future ones.

Alcohol is broken down by alcohol dehydrogenase to acetaldehyde, which is toxic and causes much of the tissue damage, and then by aldehyde dehydrogenase to acetate, which disulfiram blocks. Heavy drinkers lack thiamine, from poor diet, poor absorption and poor storage in a damaged liver; glucose metabolism uses up what is left, which is why glucose without thiamine can trigger Wernicke's encephalopathy.

03Clinical features

Withdrawal

1. 6 to 12 hours

   Early withdrawal

   Tremor, sweating, nausea, anxiety, irritability, insomnia, tachycardia and hypertension, with craving. Without complications it peaks at 24 to 48 hours and settles within a few days.

2. 12 to 48 hours

   Hallucinations

   Transient visual, tactile or auditory hallucinations, in clear consciousness.

3. 6 to 48 hours

   Seizures

   Generalised tonic–clonic seizures, usually one or a short cluster, most often around 24 hours. They can occur before other signs.

4. 48 to 72 hours

   Delirium tremens

   Delirium with marked tremor, autonomic overactivity, fever, fear and vivid hallucinations, often of small animals or insects; it can begin up to about five days after the last drink and last up to a week.

Delirium tremens affects about 1 in 20 people in withdrawal, mostly those with long heavy drinking, previous delirium or seizures, or a concurrent illness such as infection, injury or liver disease. It is a medical emergency: patients die of arrhythmia, hyperthermia, dehydration, aspiration and the illness that led to admission. Before modern treatment up to about a fifth of patients died; with prompt treatment a few in 100 still do, most often when it was not expected and its first signs were missed, as after an operation.

Wernicke's encephalopathy and Korsakoff syndrome

Wernicke's encephalopathy is acute thiamine deficiency damaging the mammillary bodies, the thalamus and the periaqueductal grey. The classic triad is confusion, ataxia and eye signs (nystagmus, sixth nerve palsy, ophthalmoplegia), but only about 1 in 10 patients has all three. It is suspected in any heavy drinker with two of: poor diet, eye signs, cerebellar signs, and confusion or memory impairment. Untreated, it kills about 15 in 100 patients, and most survivors are left with Korsakoff syndrome.

Korsakoff syndrome is a lasting amnesia: new memories cannot be formed and older ones are patchily lost, while attention, immediate recall and most other abilities are relatively preserved. Gaps are often filled with confabulation. It may follow Wernicke's encephalopathy or develop gradually. About a fifth of patients recover fully and a quarter substantially, with abstinence, thiamine and rehabilitation; the rest change little.

Other psychiatric syndromes

Physical harms include fatty liver, alcoholic hepatitis and cirrhosis, pancreatitis, gastritis and bleeding varices, cardiomyopathy, atrial fibrillation and hypertension, cancers of the mouth, throat, oesophagus, liver, bowel and breast, neuropathy, cerebellar degeneration, myopathy, injuries, and fetal alcohol spectrum disorder.

04Diagnosis and management

Screening and assessment

The AUDIT, ten questions from the WHO, scores up to 40: below 8 is lower risk, 8 to 15 increasing risk, 16 to 19 higher risk, and 20 or more suggests dependence. Its first three questions, AUDIT-C, are a quick screen. The assessment then covers the drinking day by day, the time of the first drink, withdrawal symptoms, seizures and delirium in past withdrawals, other drugs, mental and physical health, family, work, driving and children at home. The Severity of Alcohol Dependence Questionnaire (SADQ) grades dependence: over 30 is severe.

Blood tests support the history and show harm: a raised gamma-glutamyl transferase and mean cell volume, an AST higher than ALT, low platelets, and in some places carbohydrate-deficient transferrin or phosphatidylethanol, a marker of recent drinking. Breath or blood alcohol shows current intoxication; a raised level without signs of drunkenness shows tolerance.

Brief advice, a few minutes of feedback on the risks with a clear recommendation, a choice of goals and support for the person's own ability to change, reduces drinking in hazardous and harmful drinkers. A motivational style meets the person at their stage of change.

Assisted withdrawal

Stopping abruptly is dangerous for a dependent drinker, who needs medically assisted withdrawal. It can usually be done at home with daily review. UK guidance advises considering admission for:

• drinking over 30 units a day, or a SADQ score over 30;
• seizures or delirium tremens in past withdrawals, or epilepsy;
• benzodiazepine dependence alongside;
• 15 to 30 units a day with significant physical or psychiatric illness, a learning disability or cognitive impairment;
• vulnerability: homelessness, older age, or being under 18.

1. 1

   Benzodiazepine

   A long-acting benzodiazepine, usually chlordiazepoxide (or diazepam), in a fixed reducing course over 5 to 7 days at home; in hospital, doses can be triggered by symptoms on a scale such as the CIWA-Ar. Oxazepam or lorazepam is used in severe liver disease.
2. 2

   Thiamine

   Oral thiamine for everyone in withdrawal, and parenteral thiamine for those in hospital who are malnourished, have liver disease or are acutely ill.
3. 3

   Monitoring

   Withdrawal is scored with the CIWA-Ar, ten items scoring up to 67, or in Scotland the Glasgow Modified Alcohol Withdrawal Scale. Fluids, potassium, magnesium, phosphate and glucose are checked and corrected.
4. 4

   Seizures

   A quick-acting benzodiazepine, such as lorazepam. Phenytoin does not treat alcohol withdrawal seizures.
5. 5

   Delirium tremens

   Oral lorazepam first; if symptoms persist or tablets are refused, parenteral lorazepam, haloperidol or olanzapine. Nursing in a calm, lit room, with treatment of infection and other causes.

Suspected Wernicke's encephalopathy needs high-dose intravenous thiamine, for example 200 to 500 mg three times a day for 3 to 5 days (in the UK as Pabrinex), then oral thiamine. Anaphylaxis is rare. Glucose is never withheld from a hypoglycaemic patient, but thiamine goes in first or with it.

Preventing relapse

Naltrexone is licensed to prevent relapse in alcohol dependence in the UK and much of Europe, though some generic tablets carry only the opioid licence. Baclofen is authorised in France to reduce drinking when other drugs have failed, and sodium oxybate in Austria, for withdrawal and to support abstinence, and in Italy for withdrawal; elsewhere they are specialist or unlicensed options.

The psychological treatments with evidence are cognitive behavioural therapy, behavioural couples therapy, social network approaches and motivational enhancement, set out in psychotherapy. Mutual help groups such as Alcoholics Anonymous, with its 12 steps, or SMART Recovery give long-term support, and in a review of trials Alcoholics Anonymous and 12-step facilitation produced abstinence at least as often as other treatments. Families can find help in Al-Anon. Comorbid depression, anxiety and trauma are treated alongside. At a population level, price is the most effective lever: minimum unit pricing has been in force in Scotland since 2018, Wales since 2020 and Ireland since 2022.

05Epidemiology

from alcohol worldwide, about 1 in 20 of all deaths

2.6 milliondeaths a yearfrom alcohol worldwide, about 1 in 20 of all deaths

with an alcohol use disorder, about 7 per cent of adults

400 millionpeoplewith an alcohol use disorder, about 7 per cent of adults

of pure alcohol per adult in the WHO European Region, the highest in the world

9.2litres a yearof pure alcohol per adult in the WHO European Region, the highest in the world

A little under half of the world's adults drink, and most adults in Europe do. About 209 million people, 3.7 per cent of adults, have alcohol dependence. Men drink more and develop dependence two to three times more often than women, though the gap is narrowing. Alcohol is a leading cause of death and disability in young and middle-aged adults, through injuries, violence, liver disease and cancer. In psychiatric and general hospitals, alcohol use disorders are common and often missed.

06Prognosis

Alcohol dependence is a chronic, relapsing condition. After treatment, about a third to a half of dependent drinkers are abstinent or drinking much less two years later; relapse is commonest in the first months. A good outlook goes with a stable relationship and job, less severe dependence, no other drug use, and engagement with treatment and mutual help. Heavy drinkers die on average many years earlier than the general population, of liver disease, cancer, cardiovascular disease, injuries and suicide. Stopping drinking reverses fatty liver and much of the brain damage and improves mood within weeks, and even cirrhosis has a better outlook with abstinence.