Overview
Alcohol Dependence
1. Clinical Overview
Summary
Alcohol dependence is a chronic, relapsing condition characterised by compulsive alcohol use despite harmful consequences, loss of control over drinking, tolerance (needing more to achieve the same effect), and physical withdrawal symptoms. It is a significant cause of morbidity and mortality worldwide, contributing to liver disease, cardiovascular disease, neurological damage, cancers, accidents, violence, and mental health problems. Early identification using screening tools (AUDIT, CAGE) and evidence-based treatment combining pharmacotherapy, psychosocial interventions, and mutual aid can substantially improve outcomes. The prevention and treatment of Wernicke's encephalopathy through thiamine supplementation is critical — it is a medical emergency with irreversible consequences if missed.
Key Facts
- Definition: Compulsive alcohol use with tolerance, withdrawal, and inability to control intake
- Prevalence (UK): ~1.6 million people with alcohol dependence; ~600,000 dependent drinkers not in treatment
- Mortality: 24,000 deaths/year in UK attributable to alcohol
- Key Dependence Features: Tolerance, withdrawal, compulsion, narrowing of drinking repertoire, reinstatement after abstinence
- Key Management: Medically-assisted withdrawal + thiamine + psychosocial support + relapse prevention medication
- Critical Emergency: Wernicke's encephalopathy — give IV Pabrinex BEFORE glucose
- Key Screening Tools: AUDIT (comprehensive), CAGE (quick), SADQ (severity)
Clinical Pearls
"Always Thiamine BEFORE Glucose": In any patient with alcohol problems and altered consciousness, give IV Pabrinex (thiamine) BEFORE giving IV glucose. Glucose without thiamine can precipitate or worsen Wernicke's encephalopathy.
CAGE Screening: Have you ever felt you should Cut down? Have people Annoyed you by criticising your drinking? Have you felt Guilty about drinking? Have you ever had a morning Eye-opener? 2+ positive = likely problem drinking.
Wernicke's Triad: Confusion, Ataxia, Ophthalmoplegia — but the full triad is present in only 10% of cases. Have a low threshold to treat suspected cases.
Why This Matters Clinically
Alcohol dependence is extremely common and often undetected. It affects virtually every organ system and is a leading cause of preventable death. Many patients present with physical consequences (liver disease, trauma, pancreatitis) without disclosing their drinking. Withdrawal can be life-threatening if not managed properly. Recovery is absolutely possible with appropriate support — many patients achieve long-term remission.
2. Epidemiology
Incidence & Prevalence
- Prevalence (UK): 1.6 million people meet criteria for alcohol dependence
- Hazardous drinking: 24% of adults in England drink at hazardous levels
- Prevalence (Global): 5.1% of global burden of disease; 3 million deaths/year
- Trend: Stable or slightly declining in younger age groups; increasing in older adults
Demographics
| Factor | Details |
|---|---|
| Age | Peak prevalence 25-34 years; increasing in over 65s |
| Sex | Male:Female = 3:1 (but gap narrowing) |
| Ethnicity | Lower rates in South Asian populations (cultural/religious); higher in certain occupations |
| Socioeconomic | Paradoxical: Higher socioeconomic groups drink more frequently, but lower socioeconomic groups have more alcohol-related harm |
Risk Factors
Non-Modifiable:
- Family history of alcohol dependence (heritability ~50%)
- Male sex
- Age of first drink (<15 years increases risk)
- Co-morbid psychiatric disorders (depression, anxiety, PTSD)
- Personality traits (impulsivity, novelty-seeking)
Modifiable:
| Risk Factor | Impact | Intervention |
|---|---|---|
| High stress occupation | Elevated risk | Occupational health support |
| Social norms (heavy drinking culture) | Normalises excess | Public health messaging |
| Availability and affordability | Direct relationship | Pricing policy, licensing |
| Mental health comorbidity | Bidirectional relationship | Treat both concurrently |
| Peer group drinking pattern | Strong influence | Social network interventions |
Burden of Disease
| Consequence | Scale |
|---|---|
| Deaths (UK/year) | ~24,000 directly attributable |
| Hospital admissions (UK/year) | ~1.2 million (alcohol-related) |
| Economic cost (UK/year) | ~£21 billion (healthcare, crime, lost productivity) |
| Alcohol-related liver disease | Leading cause of liver death in UK |
3. Pathophysiology
Mechanism
Step 1: Acute Alcohol Effects
- GABA-A receptor enhancement: Alcohol potentiates inhibitory GABA signalling → sedation, anxiolysis, ataxia
- NMDA receptor inhibition: Reduces excitatory glutamate signalling → cognitive impairment, amnesia
- Dopamine release: Reward pathway activation → reinforcement, pleasure, addiction
Step 2: Neuroadaptation (Chronic Use)
- GABA receptor downregulation: Fewer/less sensitive GABA receptors → tolerance
- NMDA receptor upregulation: More/sensitised glutamate receptors → tolerance
- Net result: Brain becomes hyperexcitable when alcohol removed
Step 3: Withdrawal State
- Removal of alcohol leaves unopposed glutamate hyperactivity
- Reduced GABA inhibition
- Sympathetic overactivity (tachycardia, hypertension, sweating, tremor)
- Severe cases: Seizures, delirium tremens, death
Step 4: Addiction Cycle
- Negative reinforcement: Drinking to avoid withdrawal
- Positive reinforcement: Dopamine-driven craving
- Compulsive use despite consequences
- Narrowing of behavioural repertoire around alcohol
Multi-Organ Damage
| Organ System | Pathology |
|---|---|
| Liver | Fatty liver → Alcoholic hepatitis → Cirrhosis → Hepatocellular carcinoma |
| Brain | Wernicke-Korsakoff syndrome (thiamine deficiency); Cerebellar degeneration; Cognitive impairment |
| Heart | Alcoholic cardiomyopathy; Arrhythmias (holiday heart); Hypertension |
| GI | Pancreatitis (acute and chronic); Gastritis; Oesophageal varices (cirrhosis) |
| Immune | Impaired immunity; Increased infection risk |
| Cancer | Mouth, throat, oesophagus, liver, breast, colorectal (dose-dependent risk) |
Wernicke-Korsakoff Syndrome
| Wernicke's Encephalopathy | Korsakoff's Syndrome |
|---|---|
| Acute, reversible (if treated) | Chronic, irreversible |
| Triad: Confusion, Ataxia, Ophthalmoplegia | Anterograde amnesia, Confabulation |
| Caused by acute thiamine (B1) deficiency | Occurs if Wernicke's untreated |
| Treatment: IV Pabrinex immediately | Prevention: Treat Wernicke's urgently |
4. Clinical Presentation
Symptoms
Dependence Features (ICD-11/DSM-5):
Withdrawal Symptoms (6-24 hours after last drink):
Delirium Tremens (48-72 hours, severe):
Signs
Red Flags
[!CAUTION] Red Flags — Urgent action required if:
- Wernicke's encephalopathy (confusion, ataxia, eye signs) → Pabrinex IV immediately (before glucose)
- Delirium tremens (severe confusion, hallucinations, autonomic instability) → Medical emergency, high-dose benzodiazepines
- Withdrawal seizures → Benzodiazepine, exclude other causes
- GI bleeding (haematemesis, melaena) → Suspect varices, urgent endoscopy
- Hypoglycaemia → Check glucose (impaired gluconeogenesis)
- Suicidal ideation → Common comorbidity; assess and manage risk
Compulsion to drink (strong urge, craving)
Common presentation.
Difficulty controlling drinking (quantity, timing, stopping)
Common presentation.
Tolerance (need more for same effect)
Common presentation.
Withdrawal symptoms when reducing/stopping
Common presentation.
Neglect of other activities/interests
Common presentation.
Continued use despite harmful consequences
Common presentation.
5. Clinical Examination
Structured Approach
General:
- Nutritional status (often poor)
- Signs of intoxication or withdrawal
- Stigmata of chronic liver disease
Specific Examination:
- Hands: Tremor, Dupuytren's contracture, palmar erythema, leuconychia
- Face: Parotid enlargement, telangiectasia, jaundice
- Chest: Spider naevi (in SVC distribution), gynaecomastia
- Abdomen: Hepatomegaly or small liver, splenomegaly (portal hypertension), ascites, caput medusae
- Neurological: Peripheral neuropathy, cerebellar signs (ataxia, dysarthria), Wernicke's signs
- Vital signs: Tachycardia, hypertension (withdrawal); low BP (if GI bleed, sepsis)
Screening Tools
| Tool | Components | Interpretation |
|---|---|---|
| AUDIT (Alcohol Use Disorders Identification Test) | 10 questions (consumption, dependence, harm) | 0-7 Low risk; 8-15 Hazardous; 16-19 Harmful; 20+ Dependence |
| AUDIT-C | First 3 questions (consumption) | Quick screen; 5+ in men, 4+ in women = positive |
| CAGE | Cut down? Annoyed? Guilty? Eye-opener? | 2+ positive = likely problem |
| SADQ (Severity of Alcohol Dependence Questionnaire) | 20 items | Assesses severity of dependence for treatment planning |
| CIWA-Ar (Clinical Institute Withdrawal Assessment) | Symptom severity scoring | Guides withdrawal medication dosing |
6. Investigations
First-Line (Bedside)
- Breathalyser/blood alcohol level — current intoxication
- Blood glucose — hypoglycaemia common
- Vital signs — tachycardia, hypertension (withdrawal)
Laboratory Tests
| Test | Expected Finding | Purpose |
|---|---|---|
| GGT (Gamma-glutamyl transferase) | Elevated (most sensitive) | Marker of recent heavy drinking |
| MCV (Mean Corpuscular Volume) | Elevated (macrocytosis) | Chronic alcohol use |
| AST:ALT ratio | >2:1 suggests alcoholic liver disease | Differentiates from other liver disease |
| LFTs (AST, ALT, Bilirubin, Albumin) | Abnormal in liver disease | Liver damage assessment |
| FBC | Macrocytosis, thrombocytopenia (hypersplenism/marrow toxicity) | Haematological effects |
| U&E | Hypokalaemia, hypomagnesaemia (common) | Electrolyte abnormalities |
| Coagulation (INR) | Prolonged if liver synthetic function impaired | Liver function |
| Vitamin B12, Folate, Ferritin | Deficiency common | Nutritional assessment |
| CDT (Carbohydrate-deficient transferrin) | Elevated with chronic heavy drinking | Objective biomarker |
| Ammonia | Elevated in hepatic encephalopathy | If confusion (cirrhosis context) |
Imaging
| Modality | Findings | Indication |
|---|---|---|
| Ultrasound Liver | Fatty change, cirrhosis, portal hypertension, ascites | Initial liver assessment |
| FibroScan | Liver stiffness (fibrosis staging) | Non-invasive fibrosis assessment |
| CT Abdomen | Liver, pancreas, spleen, varices | If complications suspected |
| MRI Brain | Wernicke's (mammillary body lesions), cerebral atrophy | Neurological complications |
Diagnostic Criteria
DSM-5 Alcohol Use Disorder (at least 2 in 12 months):
- Alcohol taken in larger amounts or longer than intended
- Persistent desire or unsuccessful efforts to cut down
- Great deal of time spent obtaining, using, or recovering from alcohol
- Craving
- Recurrent use resulting in failure to fulfil obligations
- Continued use despite social/interpersonal problems
- Important activities given up or reduced
- Recurrent use in physically hazardous situations
- Continued use despite physical or psychological problems
- Tolerance
- Withdrawal
Severity: Mild (2-3 criteria), Moderate (4-5), Severe (6+)
7. Management
Management Algorithm
Community vs Inpatient Withdrawal
| Factor | Community Suitable | Inpatient Required |
|---|---|---|
| Dependence severity | Mild-moderate | Severe (SADQ >30) |
| Previous complicated withdrawal | No | Yes (seizures, DTs) |
| Co-morbid medical illness | Stable/none | Significant |
| Co-morbid psychiatric illness | Stable | Active suicidality, severe |
| Social support | Good | Poor or homeless |
| Poly-substance use | No | Yes |
Medically-Assisted Withdrawal (Detoxification)
| Drug | Regime | Duration | Notes |
|---|---|---|---|
| Chlordiazepoxide (Librium) | Reducing regimen: e.g., 30mg QDS day 1, reduce by 20% daily | 7-10 days | First-line in UK; long half-life |
| Diazepam | Alternative reducing regimen | 7-10 days | Alternative; longer half-life |
| Lorazepam | Symptom-triggered or if liver disease | Variable | Shorter half-life; safer in liver failure |
| Carbamazepine | Alternative if BZD contraindicated | 7 days | Second-line |
Example Chlordiazepoxide Regime (Moderate Dependence):
- Day 1-2: 20-30mg QDS
- Day 3-4: 15-20mg QDS
- Day 5-6: 10-15mg TDS
- Day 7-8: 5-10mg BD
- Day 9-10: 5mg OD then stop
Thiamine/Vitamin Supplementation
| Scenario | Treatment |
|---|---|
| Wernicke's suspected | Pabrinex IV: 2 pairs TDS for 3-5 days, then 1 pair OD |
| High-risk (malnourished, vomiting) | Pabrinex IV: 1 pair OD for 3-5 days, then oral thiamine |
| Standard withdrawal | Oral thiamine 100-300mg daily for 1 month |
| Maintenance | Oral thiamine 100mg daily if continued drinking risk |
CRITICAL: Give Pabrinex BEFORE IV glucose in any malnourished/confused alcohol patient
Relapse Prevention Medications
| Drug | Mechanism | Dose | Notes |
|---|---|---|---|
| Acamprosate | Modulates glutamate/GABA | 666mg TDS (or 333mg TDS if <60kg) | Anti-craving; best evidence for abstinence maintenance |
| Naltrexone | Opioid antagonist | 50mg OD | Reduces rewarding effects; may reduce heavy drinking days |
| Disulfiram (Antabuse) | Aldehyde dehydrogenase inhibitor | 200-500mg OD | Deterrent effect (aversive if drinks); requires supervision |
| Nalmefene | Opioid modulator | 18mg PRN (before expected drinking) | Licensed for reducing, not abstinence |
Psychosocial Interventions
| Intervention | Description |
|---|---|
| Brief Intervention (IBA) | 5-10 min advice for hazardous drinkers; evidence-based |
| Motivational Interviewing | Enhance readiness to change |
| CBT | Address thoughts/behaviours around drinking |
| 12-Step Facilitation | Prepare for AA/mutual aid |
| Alcoholics Anonymous / SMART Recovery | Peer support; strong evidence for long-term outcomes |
| Family/couple therapy | Include support network |
Disposition
- Admit if: Severe withdrawal risk, seizure history, failed community detox, comorbidities, homelessness
- Community detox if: Mild-moderate, stable, supportive home, engaged with services
- Follow-up: Weekly during detox; ongoing addiction service involvement
8. Complications
Immediate (Hours-Days)
| Complication | Incidence | Presentation | Management |
|---|---|---|---|
| Withdrawal seizures | 3-5% of withdrawals | Tonic-clonic seizures 12-48h after stopping | Benzodiazepines; exclude other causes |
| Delirium tremens | 5% of hospitalized withdrawals | Confusion, hallucinations, autonomic storm | High-dose benzodiazepines, ICU if severe |
| Aspiration pneumonia | Variable | Fever, respiratory distress | Antibiotics, supportive care |
| Hypoglycaemia | Common | Confusion, sweating, tremor | IV dextrose (after Pabrinex) |
| Wernicke's encephalopathy | 2-3% | Classic triad (often incomplete) | Pabrinex IV immediately |
Early (Weeks-Months)
- Korsakoff syndrome (if Wernicke's not treated)
- Relapse to drinking (50-80% within first year)
- Depression and anxiety (may emerge during abstinence)
- Sleep disturbance
- Cognitive impairment
Late (Months-Years)
- Cirrhosis: 10-15% of heavy drinkers develop cirrhosis
- Hepatocellular carcinoma: Increased risk with cirrhosis
- Cardiomyopathy: Reversible if early abstinence
- Peripheral neuropathy: May be permanent
- Dementia: Alcohol-related brain damage
- Cancers: Mouth, oesophagus, liver, breast, colorectal
- Pancreatitis: Chronic with exocrine/endocrine failure
9. Prognosis & Outcomes
Natural History
Without intervention, alcohol dependence typically progresses with worsening physical health, social functioning, and increasing mortality. However, alcohol use disorder is highly treatable, and many people achieve long-term recovery with appropriate support.
Outcomes with Treatment
| Variable | Outcome |
|---|---|
| 1-year abstinence rates | 40-60% with comprehensive treatment |
| Long-term remission (5+ years) | ~50% of those who achieve initial abstinence |
| Mortality reduction | Abstinence reduces mortality to near-normal rates |
| Liver disease reversal | Fatty liver fully reversible; early fibrosis may reverse |
| Brain recovery | Significant cognitive improvement with abstinence (months-years) |
Prognostic Factors
Good Prognosis:
- Strong social support
- Stable housing and employment
- Motivation and engagement with treatment
- Participation in mutual aid (AA/SMART)
- Medication adherence (acamprosate, naltrexone)
- Absence of severe psychiatric comorbidity
- No previous complicated withdrawals
Poor Prognosis:
- Homeless or unstable housing
- Poly-substance use
- Severe psychiatric comorbidity (untreated)
- Previous failed treatment attempts
- No social support
- Continued alcohol-using social network
- Liver cirrhosis (reduced survival even with abstinence)
10. Evidence & Guidelines
Key Guidelines
- NICE CG115: Alcohol-use disorders: diagnosis, assessment and management of harmful drinking (high-risk drinking) and alcohol dependence (2011, updated) — Comprehensive UK guidance on screening, assessment, withdrawal management, and relapse prevention. NICE
- NICE NG135: Alcohol-use disorders: diagnosis and management of physical complications (2017) — Guidance on liver, brain, heart, and other physical complications. NICE
- SIGN 74: The Management of Harmful Drinking and Alcohol Dependence in Primary Care — Scottish guidance with primary care focus.
Landmark Trials
COMBINE Study (2006) — Large US trial comparing naltrexone, acamprosate, behavioural intervention, and combinations.
- 1,383 patients with alcohol dependence
- Key finding: Naltrexone with medical management effective; acamprosate did not separate from placebo in this study (different from European trials)
- Clinical Impact: Both medications have role; importance of psychosocial support
- PMID: 16672078
Project MATCH (1997) — Matched patients to different therapies (12-step, CBT, motivational enhancement).
- 1,726 patients
- Key finding: All three approaches similarly effective; matching did not improve outcomes
- Clinical Impact: Offer whichever therapy patient will engage with
Evidence Strength
| Intervention | Level | Key Evidence |
|---|---|---|
| Benzodiazepines for withdrawal | 1a | Cochrane reviews; reduces seizures and DTs |
| Thiamine for Wernicke's prevention | Expert consensus | Too dangerous to trial; clear biological rationale |
| Acamprosate for abstinence maintenance | 1a | European meta-analyses show benefit |
| Naltrexone for reducing drinking | 1a | Meta-analyses show reduced heavy drinking days |
| Brief interventions | 1a | Cochrane review; effective for hazardous drinkers |
| Alcohol-related liver disease screening | Expert consensus | FibroScan/elastography recommended |
11. Patient/Layperson Explanation
What is Alcohol Dependence?
Alcohol dependence means your body and mind have become so used to alcohol that you feel you need it to function normally. You might find it hard to stop drinking even though you want to, need to drink more to get the same effect (tolerance), and feel unwell when you stop (withdrawal). It's a medical condition, not a weakness, and it is treatable.
Why does it happen?
Alcohol affects chemicals in the brain that control mood, reward, and anxiety. With regular heavy use, the brain adjusts to expect alcohol, leading to:
- Needing alcohol to feel "normal"
- Strong cravings
- Physical symptoms when you stop
Risk factors include family history (genetics account for about half the risk), mental health problems like depression or anxiety, and starting to drink at a young age.
How is it treated?
- Detox (medically assisted withdrawal): A medication like chlordiazepoxide helps you stop drinking safely by preventing dangerous withdrawal symptoms.
- Vitamins: You'll be given thiamine (vitamin B1) to protect your brain — this is very important.
- Support: Talking therapies and support groups like Alcoholics Anonymous help you stay alcohol-free.
- Medication to prevent relapse: Drugs like acamprosate reduce cravings; naltrexone makes drinking less rewarding; disulfiram makes you feel ill if you drink (deterrent).
What to expect
- Withdrawal symptoms (tremor, anxiety, sweating) are worst in the first week but get better
- Many people feel much better physically and mentally within weeks of stopping
- Recovery is a journey — many people have setbacks, but each attempt builds towards success
- With the right support, lasting recovery is absolutely possible
When to seek help
- If you're drinking more than you want to and can't stop
- If you feel unwell when you don't drink (tremor, sweating, anxiety)
- If your drinking is affecting your work, relationships, or health
- Urgent: If you become confused, have a seizure, or see things that aren't there after stopping drinking — this is a medical emergency
12. References
Primary Guidelines
- National Institute for Health and Care Excellence. Alcohol-use disorders: diagnosis, assessment and management of harmful drinking and alcohol dependence. NICE guideline [CG115]. 2011 (updated 2020). NICE
- National Institute for Health and Care Excellence. Alcohol-use disorders: diagnosis and management of physical complications. NICE guideline [NG135]. 2017. NICE
Key Trials
- Anton RF, et al. Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE Study). JAMA. 2006;295(17):2003-2017. PMID: 16672078
- Project MATCH Research Group. Matching Alcoholism Treatments to Client Heterogeneity. J Stud Alcohol. 1997;58(1):7-29. PMID: 8979210
- Rösner S, et al. Acamprosate for alcohol dependence. Cochrane Database Syst Rev. 2010;(9):CD004332. PMID: 20824837
- Thomson AD, et al. The Royal College of Physicians report on alcohol: guidelines for managing Wernicke's encephalopathy in the accident and emergency department. Alcohol Alcohol. 2002;37(6):513-521. PMID: 12414541
Further Resources
- Drinkline (UK): 0300 123 1110
- Alcoholics Anonymous UK: www.alcoholics-anonymous.org.uk
- SMART Recovery: www.smartrecovery.org.uk
- Alcohol Change UK: www.alcoholchange.org.uk
Medical Disclaimer: MedVellum content is for educational purposes and clinical reference. Clinical decisions should account for individual patient circumstances. Always consult appropriate specialists. This content does not constitute medical advice for individual patients.