Substance Misuse

Key Facts

Alcohol withdrawal syndrome (AWS) results from neuroadaptive changes due to chronic alcohol exposure. Abrupt cessation leads to CNS hyperexcitability, autonomic dysfunction, and potentially fatal complications. It is a medical emergency requiring prompt recognition and treatment.

Epidemiology

• 5-10% of patients presenting to Emergency Departments have alcohol-related problems
• ~50% of alcohol-dependent individuals experience clinically significant withdrawal symptoms
• Withdrawal seizures occur in approximately 10% of those with significant withdrawal
• Delirium tremens develops in approximately 5% of those withdrawing; mortality 5-15% untreated
• Risk increases with: previous withdrawal episodes (kindling phenomenon), concurrent illness, older age

Aetiology

• Chronic alcohol use → enhanced GABA-A receptor function (inhibitory) and suppressed NMDA glutamate receptor function (excitatory)
• Compensatory upregulation of excitatory pathways and downregulation of inhibitory pathways during chronic use
• Cessation → sudden loss of GABA enhancement + unopposed excitatory glutamatergic activity
• Kindling: successive withdrawal episodes become progressively more severe due to cumulative neuroadaptation

Pathophysiology

• Autonomic hyperactivity: sympathetic overdrive → tachycardia, hypertension, diaphoresis, pyrexia
• CNS excitability: lowered seizure threshold, tremor, agitation, hallucinations
• Glutamate excitotoxicity: NMDA receptor upregulation leads to calcium influx and neuronal injury
• Electrolyte disturbances: hypomagnesaemia, hypokalaemia, hypophosphataemia exacerbate risk
• Thiamine depletion: impaired thiamine absorption and utilisation increases risk of Wernicke encephalopathy

Mild Withdrawal (6-12 hours)

• Tremor: fine bilateral hand tremor, often the earliest sign
• Anxiety and agitation: restlessness, irritability
• Insomnia: sleep disturbance, vivid dreams
• Nausea and vomiting
• Diaphoresis: sweating, particularly nocturnal
• Mild tachycardia and hypertension

Moderate Withdrawal (12-48 hours)

• Worsening tremor: coarse, visible at rest
• Alcoholic hallucinosis: typically visual (insects, animals), but also auditory and tactile; patient retains intact sensorium (distinguishing from delirium tremens)
• Withdrawal seizures: 12-48 hours post-cessation; generalised tonic-clonic; usually brief and self-limiting; may be recurrent (cluster seizures in ~60%)
• Autonomic instability: marked tachycardia (>100 bpm), hypertension, pyrexia

Severe Withdrawal - Delirium Tremens (48-72 hours, peak day 5)

• Delirium: acute confusion with fluctuating consciousness
• Visual hallucinations: vivid, often terrifying (Lilliputian hallucinations are classical)
• Severe autonomic instability: tachycardia, hypertension, hyperthermia, profuse diaphoresis
• Psychomotor agitation: extreme restlessness, picking at bedclothes
• Coarse tremor
• Risk of cardiovascular collapse: arrhythmias, myocardial ischaemia

Red Flags

• Temperature >38.5°C: suggests delirium tremens or concurrent sepsis
• CIWA-Ar score >20: severe withdrawal requiring aggressive treatment
• Seizures: risk of status epilepticus; do not use phenytoin (ineffective for alcohol withdrawal seizures)
• Chest pain or new arrhythmia: risk of alcohol-related cardiomyopathy, Takotsubo
• Head injury: consider subdural haematoma in confused alcoholic patient
• Hypoglycaemia: must check glucose; give thiamine before glucose

Bedside

• CIWA-Ar score: monitor every 1-2 hours in acute withdrawal; 10 items scored 0-7 each (max 67)
  • <10: mild withdrawal
  • 10-18: moderate withdrawal

  • 18-20: severe withdrawal

• Observations: HR, BP, temperature, RR, SpO2 - at least hourly in acute withdrawal
• Capillary blood glucose: essential before giving IV glucose
• GCS/AVPU: monitor conscious level
• ECG: arrhythmia, prolonged QTc, electrolyte effects

Bloods

• FBC: macrocytosis (raised MCV), thrombocytopenia
• U&Es: hyponatraemia, hypokalaemia, hypomagnesaemia
• LFTs: raised GGT, AST > ALT, deranged synthetic function (albumin, INR)
• Magnesium: commonly low; contributes to seizure risk
• Phosphate: refeeding risk assessment
• Calcium: may be low
• CRP: exclude concurrent infection
• Blood cultures: if pyrexial - sepsis can mimic and co-exist with withdrawal
• Clotting screen: coagulopathy suggests significant liver disease
• Blood alcohol level: useful to guide timing of withdrawal onset

Imaging

• CT head: if seizures are atypical (focal), first presentation, or head injury suspected
• Chest X-ray: if pyrexial - aspiration pneumonia common in heavy drinkers

Special Tests

• Lumbar puncture: if meningism present and CT normal
• EEG: if status epilepticus or non-convulsive seizures suspected
• MRI brain: if Wernicke encephalopathy suspected (mammillary body and periaqueductal changes)

Non-pharmacological

• Calm, well-lit environment: reduce sensory stimulation; maintain orientation
• 1:1 nursing: for severe withdrawal or delirium tremens
• Fluid and electrolyte replacement: IV fluids if unable to take oral; correct hypokalaemia and hypomagnesaemia
• Nutritional support: regular meals; refeeding risk assessment using NICE CG32 criteria
• Thromboprophylaxis: immobile patients at risk of VTE

Pharmacological

• Benzodiazepines (first-line - NICE CG115):
  • Chlordiazepoxide: standard UK choice for managed withdrawal
    • Mild dependence: 10-20 mg QDS, reducing over 5-7 days
    • Moderate dependence: 20-30 mg QDS, reducing over 7-10 days
    • Severe dependence: 40-50 mg QDS, reducing over 7-10 days
  • Lorazepam 1-2 mg IV/IM: preferred in severe liver disease (no active metabolites, glucuronidation)
  • Diazepam: alternative; longer-acting; symptom-triggered regimens in some units
• Thiamine (critical - must precede glucose):
  • IV Pabrinex: 2 pairs (IV ampoules) TDS for 3-5 days, then oral thiamine 100 mg TDS
  • Indications for IV Pabrinex: malnourished, unwell, vomiting, suspected Wernicke, previous withdrawal complications
• Electrolyte replacement:
  • IV magnesium sulphate 20 mmol over 4 hours if hypomagnesaemic
  • IV potassium chloride per local protocol
• Seizure management:
  • Lorazepam 4 mg IV for acute withdrawal seizure
  • Do NOT use phenytoin - ineffective for alcohol withdrawal seizures
  • Recurrent seizures: repeat lorazepam; consider ITU if status epilepticus
• Delirium tremens:
  • High-dose benzodiazepines: lorazepam 2-4 mg IV repeated every 10-15 minutes as required
  • Consider ITU admission if refractory or significant organ dysfunction
  • Haloperidol 2.5-5 mg IM: adjunctive for severe agitation/hallucinations only after adequate benzodiazepine loading (risk of lowering seizure threshold)

Surgical

• Not applicable to acute alcohol withdrawal management

Referral Criteria

• Inpatient detoxification: SADQ >30, previous DTs or withdrawal seizures, significant co-morbidity, homelessness
• ITU/HDU: delirium tremens refractory to treatment, haemodynamic instability, respiratory compromise
• Community alcohol team: for ongoing support after acute withdrawal
• Psychiatry: co-morbid mental illness, suicidal ideation

Mortality

• Untreated delirium tremens: mortality 5-15%
• Treated delirium tremens: mortality <1-2% with appropriate benzodiazepine therapy and supportive care
• Withdrawal seizures: self-limiting in most cases; <3% progress to status epilepticus
• Overall in-hospital mortality for alcohol withdrawal: ~1-5% depending on severity and co-morbidities

Complications

• Aspiration pneumonia: reduced consciousness + vomiting
• Rhabdomyolysis: prolonged seizures, immobility, agitation
• Wernicke encephalopathy: if thiamine not given promptly; ~80% progress to Korsakoff if untreated
• Cardiac arrhythmias: electrolyte disturbances + sympathetic overdrive
• Subdural haematoma: unwitnessed falls during withdrawal
• Kindling: each withdrawal episode increases severity of subsequent episodes; cumulative brain injury
• Prolonged cognitive impairment: may take weeks to months to resolve fully after severe withdrawal

CIWA-Ar Scoring Summary

Chlordiazepoxide Reducing Regimen (Moderate Dependence Example)

Timeline of Alcohol Withdrawal

Key Facts

Wernicke encephalopathy (WE) is a medical emergency resulting from acute thiamine deficiency. It is grossly under-diagnosed: post-mortem studies show that ~80% of cases are missed clinically. Prompt parenteral thiamine can prevent progression to the irreversible Korsakoff syndrome.

Epidemiology

• Post-mortem prevalence: 1-3% of the general population; up to 12.5% of chronic alcohol misusers
• Clinical diagnosis rate: only ~20% of cases identified ante-mortem
• Alcohol misuse is the most common cause in developed countries, but non-alcoholic causes account for up to 20% of cases
• No sex or ethnic predilection when adjusted for alcohol consumption

Aetiology

• Alcohol-related: chronic misuse → poor dietary intake + impaired GI absorption + reduced hepatic storage + increased metabolic demand
• Non-alcoholic causes: hyperemesis gravidarum, prolonged vomiting, anorexia nervosa, bariatric surgery, cancer (especially post-chemotherapy), prolonged IV glucose without thiamine, dialysis, AIDS, refeeding syndrome
• Thiamine stores are limited (body stores ~30 mg); depletion occurs within 2-3 weeks of zero intake

Pathophysiology

• Thiamine is a cofactor for pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, and transketolase - key enzymes in aerobic metabolism

Deficiency

impaired oxidative metabolism

cytotoxic oedema and energy failure in metabolically active brain regions

• Vulnerable areas: mammillary bodies, medial thalami, periaqueductal grey, superior cerebellar vermis, cranial nerve nuclei (III, VI)

Glucose administration without thiamine

increased metabolic demand

accelerated depletion of remaining thiamine

clinical deterioration

Classic Triad (present in only ~16%)

1. Ophthalmoplegia/oculomotor abnormalities (~29%)
   • Lateral rectus (CN VI) palsy - most common
   • Conjugate gaze palsy
   • Nystagmus (horizontal > vertical)
   • Complete ophthalmoplegia in severe cases
2. Ataxia (~23%)
   • Broad-based gait ataxia (cerebellar vermis involvement)
   • Truncal ataxia > limb ataxia
   • May be unable to stand or walk
3. Confusion/altered mental state (~82%)
   • Global confusional state
   • Apathy, disorientation, inattention
   • Memory disturbance (early feature)
   • May progress to stupor and coma

Other Features

• Hypothermia: due to posterior hypothalamic involvement
• Hypotension: autonomic dysfunction
• Peripheral neuropathy: concurrent thiamine-deficiency polyneuropathy
• Vestibular dysfunction: vertigo, nausea

Caine Criteria (more sensitive - requires 2 of 4)

1. Dietary deficiency
2. Oculomotor abnormalities
3. Cerebellar dysfunction
4. Altered mental state or mild memory impairment

Red Flags

• Any confused patient with history of alcohol misuse - assume Wernicke until proven otherwise
• Administration of IV glucose without thiamine - may precipitate or worsen Wernicke encephalopathy
• Post-bariatric surgery patients with vomiting and confusion
• Hyperemesis gravidarum with neurological symptoms
• Rapid deterioration of cognition suggesting progression to Korsakoff syndrome

Bedside

• Clinical diagnosis: Caine criteria (2 of 4: dietary deficiency, oculomotor abnormalities, cerebellar signs, altered mental state)
• Capillary blood glucose: exclude hypoglycaemia
• Neurological examination: cranial nerves (especially III, VI), cerebellar signs, gait assessment
• Nutritional assessment: BMI, signs of malnutrition

Bloods

• Red cell transketolase activity: most specific test for thiamine status; rarely available acutely - do not delay treatment
• Serum thiamine level: can be measured but poor sensitivity; results take days
• FBC: macrocytosis, anaemia
• LFTs: assess liver function; coagulopathy
• U&Es: electrolyte abnormalities
• Magnesium: often low; magnesium is a cofactor for thiamine-dependent enzymes - must be corrected
• Serum lactate: may be raised due to impaired aerobic metabolism
• Blood alcohol level: assess recent intake

Imaging

• MRI brain (investigation of choice):
  • Mammillary body signal changes (most specific, ~58% sensitivity)
  • Periaqueductal grey matter hyperintensity
  • Medial thalamic changes
  • Tectal plate involvement
  • FLAIR and DWI sequences most sensitive
• CT head: usually normal in Wernicke; useful to exclude other pathology (subdural, stroke)

Special Tests

• Neuropsychological testing: if progression to Korsakoff syndrome suspected
• Nerve conduction studies: if concurrent peripheral neuropathy
• EEG: non-specific diffuse slowing; helps exclude non-convulsive status epilepticus

Non-pharmacological

• Immediate hospital admission: medical emergency
• Nutritional rehabilitation: dietitian involvement, oral supplementation once tolerating oral intake
• Refeeding risk assessment: Wernicke patients are high-risk for refeeding syndrome (NICE CG32)
• Alcohol cessation support: once acute phase managed

Pharmacological

• IV Pabrinex (first-line - immediate treatment, do not wait for investigations):
  • Suspected Wernicke: 2 pairs of IV ampoules (each pair = 250 mg thiamine) TDS for 3-5 days minimum
  • EFNS guideline recommendation: thiamine 500 mg IV TDS for 3-5 days, then 250 mg IV OD for 3-5 days, then oral thiamine 100 mg TDS indefinitely
  • Administer before any glucose-containing fluids
  • Anaphylaxis risk with IV Pabrinex is rare (~1:5 million) - resuscitation facilities should be available but risk should not delay treatment
• Magnesium replacement: IV magnesium sulphate 20 mmol over 4 hours - magnesium is essential cofactor for thiamine utilisation
• Oral thiamine: following IV course, continue 100 mg TDS long-term if ongoing risk
• Alcohol withdrawal management: concurrent chlordiazepoxide reducing regimen if withdrawing
• Correct other deficiencies: folate, B12, potassium, phosphate as indicated

Surgical

• Not applicable

Referral Criteria

• All suspected cases: acute medical admission for IV Pabrinex
• Neurology: atypical presentation, failure to respond to treatment, consideration of alternative diagnosis
• Neuropsychology: if Korsakoff syndrome develops - assess capacity and rehabilitation potential
• Alcohol services: after acute episode for relapse prevention
• Social services: if Korsakoff develops - may require long-term supported accommodation

Outcomes

• Untreated: mortality approximately 17-20%
• With treatment: oculomotor abnormalities improve within hours to days of thiamine; ataxia improves in ~40%; confusion improves in ~50%
• Progression to Korsakoff syndrome: approximately 80% of untreated and ~56% of treated cases
• Complete recovery: only ~20% with full treatment
• Residual deficits: gait ataxia persists in >50%; nystagmus may be permanent

Complications

• Korsakoff syndrome: irreversible anterograde amnesia with confabulation; requires long-term care
• Permanent cerebellar damage: chronic ataxia
• Peripheral neuropathy: may persist despite thiamine replacement
• Recurrence: high risk if ongoing alcohol misuse and poor nutrition
• Death: from cardiovascular collapse or concurrent complications if diagnosis delayed

Caine Criteria for Wernicke Encephalopathy

Pabrinex Content (per pair of ampoules)

Thiamine Replacement Summary

Key Facts

Korsakoff syndrome (KS) is a chronic amnestic disorder most commonly seen as a sequel to Wernicke encephalopathy (together termed Wernicke-Korsakoff syndrome). The condition is characterised by a disproportionate memory impairment relative to other cognitive functions. It represents one of the most devastating consequences of chronic alcohol misuse.

Epidemiology

• Prevalence: approximately 1-2% of the general population at post-mortem; higher in chronic alcohol misusers
• Male:female ratio approximately 1.7:1 (reflecting alcohol misuse patterns)
• Mean age at presentation: 50-60 years
• Under-diagnosed in life: many cases only confirmed at post-mortem
• Non-alcoholic Korsakoff is rare but recognised (post-surgical, anorexia, hyperemesis)

Aetiology

• Progression from acute Wernicke encephalopathy (untreated or inadequately treated)
• Thiamine deficiency → irreversible damage to diencephalic structures
• Risk factors: chronic alcohol misuse, malnutrition, repeated episodes of Wernicke, genetic vulnerability (transketolase variant), concurrent liver disease

Pathophysiology

• Bilateral mammillary body neuronal loss and gliosis (most consistent finding)

anterior nucleus and dorsomedial nucleus - disrupts the Papez circuit (hippocampus

mammillary bodies

anterior thalamus

cingulate cortex)

• Disruption of Papez circuit → inability to consolidate new episodic memories
• Relative sparing of cortical structures → preservation of intellectual function, attention, and procedural memory
• Frontal lobe dysfunction often co-exists: contributes to apathy, poor insight, and confabulation

Core Features

• Anterograde amnesia: profound inability to learn new information; most prominent deficit
• Retrograde amnesia: loss of previously formed memories, typically showing temporal gradient (remote memories better preserved than recent)
• Confabulation: spontaneous (unprovoked) or provoked - fabrication of experiences to fill memory gaps; more common early in the disease course
• Lack of insight (anosognosia): patient often unaware of memory deficits
• Preserved consciousness: alert and orientated (in contrast to the confusion of acute Wernicke)

Associated Features

• Apathy: lack of motivation and spontaneity (frontal lobe involvement)
• Emotional blunting: flattened affect
• Preserved procedural memory: can learn motor tasks and routines
• Preserved intellectual function: IQ often relatively spared
• Residual signs from Wernicke: nystagmus (60%), gait ataxia (60%), peripheral neuropathy

Red Flags

• Rapid cognitive decline - may suggest ongoing thiamine deficiency or alternative diagnosis
• New onset confusion in known Korsakoff - consider intercurrent illness, medication, further Wernicke episode
• Self-neglect and inability to maintain activities of daily living
• Capacity concerns: most patients lack capacity for complex decisions about care and finances

Bedside

• Cognitive screening: AMT (Abbreviated Mental Test), MoCA (Montreal Cognitive Assessment)
• Neuropsychological assessment: detailed memory testing showing disproportionate amnestic deficit
  • Severely impaired anterograde verbal and visual memory
  • Relative preservation of immediate recall and working memory
  • Executive dysfunction on frontal tests (Wisconsin Card Sort, verbal fluency)
• Capacity assessment: under Mental Capacity Act 2005 - assess for specific decisions

Bloods

• Red cell transketolase: may be low (confirms prior thiamine deficiency) but often normalises with treatment
• Serum thiamine: often normal by time Korsakoff presents (as acute Wernicke has resolved)
• FBC, LFTs, U&Es: assess ongoing alcohol-related damage
• B12 and folate: exclude concurrent deficiencies
• TFTs: exclude hypothyroidism as contributing factor
• Syphilis serology: in differential of young-onset dementia

Imaging

• MRI brain: mammillary body atrophy (most specific), third ventricular dilatation, medial thalamic changes, cerebellar vermis atrophy
• CT head: may show generalised atrophy; less sensitive than MRI for specific Korsakoff lesions

Special Tests

• Formal neuropsychological battery: confirms disproportionate amnestic pattern
• PET/SPECT: may show diencephalic and frontal hypometabolism (research tool)

Non-pharmacological

• Cognitive rehabilitation: errorless learning techniques, external memory aids (diaries, calendars, labels, routines)
• Structured environment: consistent daily routine reduces confusion and supports residual function
• Occupational therapy: functional assessment and adaptive strategies for activities of daily living
• Alcohol abstinence: essential to prevent further damage; supported by addiction services
• Nutritional support: balanced diet with continued supplementation

Pharmacological

• Thiamine replacement (long-term): oral thiamine 100 mg TDS indefinitely - prevents further deficiency but does not reverse established damage
• Multivitamin supplementation: including B-complex vitamins and folate
• No specific pharmacological treatment has proven effective for the amnestic syndrome
• Memantine and acetylcholinesterase inhibitors: limited evidence; occasionally trialled but no robust efficacy data
• Treat concurrent conditions: depression (common - SSRIs), anxiety, insomnia

Surgical

• Not applicable

Referral Criteria

• Neuropsychology: formal cognitive assessment for diagnosis confirmation and rehabilitation planning
• Alcohol services: ongoing relapse prevention support
• Social services: care needs assessment, potential for supported accommodation or residential care
• Court of Protection: if patient lacks capacity for financial and welfare decisions
• Community mental health team: if concurrent psychiatric co-morbidity

Outcomes

• ~25% show significant improvement over 12-24 months with abstinence and nutritional support
• ~50% show some improvement but remain significantly impaired
• ~25% show no improvement and require long-term institutional care
• Full recovery is rare - probably fewer than 5-10%
• Younger patients and those with shorter duration of alcohol misuse have better prognosis

Complications

• Permanent disability: inability to live independently
• Long-term care costs: significant burden on health and social care
• Depression: common in those with some insight into deficits
• Continued alcohol misuse: further brain injury if abstinence not maintained
• Physical co-morbidities: ongoing alcohol-related organ damage
• Safeguarding concerns: vulnerability to exploitation, self-neglect

Wernicke-Korsakoff Syndrome: Key Distinctions

Papez Circuit

Key Facts

Alcoholic liver disease (ALD) is a major public health problem in the UK. It is the 3rd commonest cause of premature death in working-age adults. The rising trend in alcohol consumption has led to increasing rates of liver disease, in contrast to most other European countries.

Epidemiology

• >60% of liver disease deaths in the UK are alcohol-related
• Cirrhosis develops in approximately 10-20% of heavy drinkers after 10-20 years
• Risk increases significantly above 14 units/week; risk dose-dependent
• Women are more susceptible at lower levels of consumption (lower body water, reduced gastric ADH)
• Liver disease mortality has increased >400% since the 1970s in the UK
• Mean age at death from ALD: ~55 years

Aetiology

• Threshold: risk increases above 21 units/week (men) and 14 units/week (women) over prolonged periods
• Cofactors increasing risk: obesity (synergistic with alcohol), hepatitis B/C co-infection, genetic factors (PNPLA3 gene variant), iron overload, smoking
• Pattern of drinking: binge drinking may be more hepatotoxic than steady consumption

Pathophysiology

• Steatosis: alcohol metabolism generates excess NADH → shifts hepatic metabolism towards fat synthesis; reversible with abstinence

oxidative stress (CYP2E1, reactive oxygen species) + acetaldehyde toxicity

hepatocyte injury

neutrophilic inflammation; Mallory-Denk bodies on histology

• Fibrosis: activation of hepatic stellate cells → excess collagen deposition; initially pericentral/perivenular (zone 3)

progressive fibrosis

nodular regeneration

architectural distortion

portal hypertension

Alcoholic Fatty Liver (Steatosis)

• Often asymptomatic or vague right upper quadrant discomfort
• Hepatomegaly: smooth, non-tender liver
• Abnormal LFTs on routine blood tests
• Completely reversible with abstinence

Alcoholic Hepatitis

• Acute presentation: jaundice, fever, right upper quadrant pain, hepatomegaly
• Systemic inflammatory response: tachycardia, pyrexia, leucocytosis
• Hepatic decompensation: ascites, coagulopathy, encephalopathy
• Tender hepatomegaly with hepatic bruit in severe cases
• Features of chronic liver disease may coexist

Alcoholic Cirrhosis

• Chronic liver disease signs: spider naevi (>5 is significant), palmar erythema, gynaecomastia, testicular atrophy, Dupuytren contracture, parotid enlargement
• Portal hypertension: splenomegaly, ascites, caput medusae, oesophageal varices
• Hepatic decompensation: jaundice, ascites, variceal bleeding, hepatic encephalopathy, hepatorenal syndrome

Red Flags

• Maddrey DF ≥32: severe alcoholic hepatitis with high mortality
• Hepatic encephalopathy: confusion, asterixis, fetor hepaticus - indicates significant hepatocellular failure
• Variceal haemorrhage: haematemesis/melaena - 15-20% mortality per episode
• Spontaneous bacterial peritonitis: fever, abdominal pain, deterioration in patient with ascites
• Hepatorenal syndrome: rising creatinine in cirrhotic patient without other cause - very poor prognosis
• New hepatic mass: risk of hepatocellular carcinoma in cirrhosis

Bedside

• Clinical assessment: stigmata of chronic liver disease, nutritional status, signs of decompensation
• BMI and nutritional screening: MUST score
• Alcohol history: AUDIT, SADQ
• Abdominal examination: hepatomegaly, splenomegaly, ascites (shifting dullness, fluid thrill)

Bloods

• LFTs: AST:ALT ratio >2 (classic); GGT markedly elevated; bilirubin raised in hepatitis/cirrhosis
• FBC: macrocytosis (MCV), thrombocytopenia (hypersplenism/marrow suppression), leucocytosis (alcoholic hepatitis)
• Clotting: prolonged PT/INR (impaired synthetic function)
• Albumin: low in chronic liver disease (impaired synthesis)
• U&Es and creatinine: hepatorenal syndrome assessment
• CRP: elevated in alcoholic hepatitis
• Liver screen: hepatitis B/C serology, autoantibodies (ANA, SMA, AMA), immunoglobulins, ferritin, caeruloplasmin (if <40 years), alpha-1 antitrypsin

Scoring Systems

• Maddrey Discriminant Function: 4.6 × (patient PT − control PT) + serum bilirubin (μmol/L)/17.1; ≥32 = severe alcoholic hepatitis
• Glasgow Alcoholic Hepatitis Score (GAHS): age, WCC, urea, PT ratio, bilirubin; ≥9 = poor prognosis
• MELD score: Model for End-stage Liver Disease; used for transplant prioritisation
• Child-Pugh score: A (5-6), B (7-9), C (10-15); predicts survival in cirrhosis

Imaging

• Liver ultrasound: steatosis (echobright liver), cirrhotic morphology, portal hypertension (splenomegaly, ascites), hepatocellular carcinoma screening
• FibroScan: non-invasive fibrosis assessment; >8 kPa significant fibrosis, >12.5 kPa cirrhosis
• CT abdomen: staging, portal hypertension, HCC characterisation
• MRI with contrast: gold standard for characterising liver lesions

Special Tests

• Upper GI endoscopy: variceal screening - all patients with new diagnosis of cirrhosis
• Ascitic tap: diagnostic if new ascites - cell count, albumin (SAAG ≥11 g/L = portal hypertension), culture
• Liver biopsy: if diagnostic uncertainty; histology shows steatosis, Mallory-Denk bodies, neutrophilic infiltrate, pericellular fibrosis

Non-pharmacological

• Alcohol abstinence: single most important intervention; improves survival at all stages
• Nutritional support: high-protein, high-calorie diet (35-40 kcal/kg/day, 1.2-1.5 g protein/kg/day); nasogastric feeding if unable to eat
• Fluid and sodium restriction: for ascites management (sodium <2 g/day)
• Weight management: address co-morbid obesity
• Hepatocellular carcinoma surveillance: 6-monthly USS and AFP in cirrhosis (NICE CG49)

Pharmacological

• Alcoholic hepatitis (Maddrey DF ≥32):
  • Prednisolone 40 mg OD for 28 days then taper - STOPAH trial (2015): showed trend towards reduced 28-day mortality (OR 0.72) but no benefit at 90 days or 1 year
  • Assess response with Lille score at day 7: score >0.45 = non-responder → stop steroids
  • Pentoxifylline: no longer recommended (STOPAH showed no benefit)
  • Contraindications to steroids: active GI bleeding, uncontrolled sepsis, hepatorenal syndrome, hepatitis B
• Ascites management:
  • Spironolactone 100 mg OD (up to 400 mg) ± furosemide 40 mg OD (up to 160 mg) - aim weight loss 0.5-1 kg/day
  • Therapeutic paracentesis with albumin replacement (6-8 g/L drained) for tense/diuretic-resistant ascites
• Variceal prophylaxis:
  • Primary: propranolol (titrate to HR 55-60) or carvedilol 6.25-12.5 mg OD
  • Variceal band ligation: for large varices or intolerance to beta-blockers
• Hepatic encephalopathy: lactulose 15-30 ml TDS (aim 2-3 soft stools/day) ± rifaximin 550 mg BD (NICE TA612)
• Spontaneous bacterial peritonitis: IV cefotaxime 2 g BD (or co-amoxiclav); prophylaxis with ciprofloxacin 500 mg OD if prior SBP episode

Surgical

• Liver transplantation: definitive treatment for end-stage ALD; 5-year survival ~70-75%; traditionally requires 6 months abstinence (increasingly flexible for selected patients with severe alcoholic hepatitis)
• TIPSS: for refractory ascites or recurrent variceal haemorrhage

Referral Criteria

• Hepatology: all patients with suspected cirrhosis, severe alcoholic hepatitis, decompensated liver disease
• Transplant centre: end-stage liver disease, MELD ≥15, decompensated cirrhosis with poor quality of life
• Alcohol services: all patients with ALD for relapse prevention
• Dietitian: nutritional assessment and management
• Palliative care: if not transplant candidate with progressive decompensated disease

Mortality and Survival

• Steatosis: excellent prognosis with abstinence; complete reversibility
• Alcoholic hepatitis (Maddrey DF ≥32): 28-day mortality 30-50%; 1-year mortality ~40-50%
• Compensated cirrhosis: median survival ~12 years with abstinence; ~6 years if drinking continues
• Decompensated cirrhosis: median survival ~2 years without transplant
• Child-Pugh C cirrhosis: 1-year survival ~45%
• Post-transplant: 5-year survival ~70-75%

Complications

• Portal hypertension: varices, ascites, splenomegaly, hepatorenal syndrome, hepatopulmonary syndrome
• Hepatocellular carcinoma: annual incidence 1-3% in established cirrhosis
• Spontaneous bacterial peritonitis: occurs in ~10-30% of patients with ascites; in-hospital mortality ~20%
• Hepatorenal syndrome: type 1 (rapid, median survival 2 weeks without treatment) and type 2 (gradual)
• Hepatic encephalopathy: graded I-IV; precipitated by infection, GI bleed, constipation, medications
• Alcohol-related brain damage: concurrent Wernicke-Korsakoff, cerebellar degeneration

Child-Pugh Score

Child-Pugh Classification

Landmark Trials in Alcoholic Liver Disease

Key Facts

Opioid use disorder (OUD) is one of the most significant substance misuse problems in the UK. Heroin (diamorphine) is the most commonly injected drug, but prescription opioid misuse is an increasing concern. Opioid-related deaths have risen to record levels in recent years.

Epidemiology

• ~260,000 high-risk opioid users in England; ~310,000 across the UK
• Drug-related deaths in England and Wales: approximately 4,900/year (2021); opioids involved in ~50%
• Mean age of opioid-dependent population is rising (ageing cohort): now ~40-45 years
• Male:female ratio approximately 3:1
• Hepatitis C: prevalence approximately 50% among people who inject drugs (PWID)
• HIV: prevalence approximately 1-2% among PWID in England (higher in London)

Aetiology

opioids activate μ (mu) opioid receptors in the mesolimbic reward pathway (VTA

nucleus accumbens)

dopamine release

reinforcement

• Tolerance: receptor desensitisation and downregulation with chronic use
• Physical dependence: neuroadaptive changes; abrupt cessation → withdrawal
• Psychological factors: self-medication for trauma, chronic pain, mental illness; adverse childhood experiences (ACEs)
• Social factors: deprivation, homelessness, criminal justice involvement, peer influence

escalation from legitimate prescribing

dependence

illicit use

Pathophysiology

• Acute opioid effects: analgesia, euphoria, sedation, respiratory depression, miosis, constipation, nausea
• Chronic use → neuroadaptation: upregulation of cAMP pathway, noradrenergic hyperactivity (locus coeruleus)
• Withdrawal → sympathetic overdrive and rebound hyperalgesia: the basis of withdrawal symptoms
• Cross-tolerance exists between different opioids but is incomplete

Opioid Intoxication

• Miosis (pinpoint pupils) - classic sign
• Respiratory depression: reduced rate and depth
• Sedation/drowsiness: nodding
• Euphoria: sense of wellbeing
• Hypotension and bradycardia
• Constipation and reduced bowel sounds

Opioid Withdrawal (onset 8-24 hours after last heroin dose)

• Early features: yawning, lacrimation, rhinorrhoea, piloerection (gooseflesh - origin of "cold turkey")
• Progressive: dilated pupils, sweating, nausea, vomiting, diarrhoea, abdominal cramps
• Later features: muscle aches, insomnia, agitation, tachycardia, hypertension
• Peak: typically 36-72 hours after last heroin use; longer with methadone (72-96 hours)
• Duration: acute symptoms resolve over 5-10 days (heroin) or 2-3 weeks (methadone)

Complications of Injecting Drug Use

• Blood-borne viruses: hepatitis B, hepatitis C, HIV
• Bacterial infections: cellulitis, abscesses, endocarditis (especially right-sided - S. aureus), osteomyelitis, septic arthritis
• Vascular: DVT, PE, pseudoaneurysm, arterial occlusion
• Wound botulism: rare but life-threatening
• Groin injection complications: femoral vein thrombosis, ischaemia

Red Flags

• Respiratory rate <8/min or oxygen saturation <92%: opioid overdose - give naloxone immediately
• Unconscious with pinpoint pupils: overdose until proven otherwise
• Fever and new murmur in IVDU: infective endocarditis
• Injection site swelling with crepitus: necrotising fasciitis/wound botulism
• Sudden limb ischaemia: inadvertent intra-arterial injection

Bedside

• Clinical Opiate Withdrawal Scale (COWS): 11-item assessment; <5 no withdrawal, 5-12 mild, 13-24 moderate, 25-36 moderately severe, >36 severe
• Observations: RR, SpO2 (critical), HR, BP, temperature, GCS
• Pupil assessment: miosis in intoxication, mydriasis in withdrawal
• Urine drug screen: confirm opioid use and identify other substances
• Injection site examination: track marks, abscesses, signs of DVT

Bloods

• FBC: anaemia (chronic disease), leucocytosis (infection)
• LFTs: hepatitis C-related liver disease
• U&Es: renal function (rhabdomyolysis risk)
• CRP: infection screening
• Blood-borne virus screen: hepatitis B surface antigen, hepatitis C antibody (reflex PCR if positive), HIV test (with consent)
• Blood cultures: if febrile or suspected endocarditis
• CK: if prolonged immobility or seizures (rhabdomyolysis)

Imaging

• Chest X-ray: aspiration pneumonia, pulmonary oedema (non-cardiogenic with heroin)
• Echocardiography: if endocarditis suspected (transthoracic ± transoesophageal)
• Doppler ultrasound: if DVT suspected in injecting limb

Special Tests

• ECG: QTc prolongation (methadone is a known cause - check before and during treatment)
• FibroScan: non-invasive liver fibrosis assessment if hepatitis C positive
• Hepatitis C PCR: if antibody positive - confirms active viraemia
• Dry blood spot testing: available for BBV screening in community settings

Non-pharmacological

• Harm reduction: needle and syringe programmes, safe injecting advice, vein care
• Psychosocial interventions: keyworker support, structured counselling, contingency management (NICE TA114)
• Mutual aid: Narcotics Anonymous, SMART Recovery
• Social support: housing, employment, benefits advice, criminal justice liaison
• Hepatitis C treatment: direct-acting antivirals (DAAs) - cure rate >95%; treat and prevent re-infection
• Vaccination: hepatitis B vaccination for all PWID; tetanus, influenza

Pharmacological

• Opioid Substitution Therapy (NICE CG52):
  • Methadone (oral solution): start 10-30 mg OD (risk assessment-dependent); titrate over 2 weeks to 60-120 mg OD; supervised consumption initially
    • Long-acting μ agonist; T½ 24-36 hours
    • QTc prolongation risk: ECG before and during treatment
  • Buprenorphine (Subutex): start 4 mg SL on day 1 (must be in withdrawal - COWS ≥12); titrate to 8-24 mg OD
    • Partial μ agonist and κ antagonist; ceiling effect on respiratory depression
    • Suboxone (buprenorphine/naloxone): reduces diversion risk
    • Buvidal (prolonged-release buprenorphine injection): weekly or monthly SC injection; improves adherence
  • Supervised consumption: recommended for at least first 3 months of OST
• Symptomatic withdrawal management (if detoxification chosen):
  • Lofexidine 0.2 mg BD, titrate to max 2.4 mg/day: alpha-2 adrenergic agonist; reduces noradrenergic withdrawal symptoms
  • Loperamide for diarrhoea, metoclopramide for nausea, ibuprofen for aches
• Naltrexone 50 mg OD: opioid antagonist for relapse prevention after detoxification; patient must be opioid-free for ≥7-10 days

Surgical

• Abscess drainage: for injection site abscesses
• Cardiac surgery: valve replacement for endocarditis in selected cases

Referral Criteria

• Community drug team: all patients with opioid dependence for assessment and OST
• Inpatient detoxification: failed community treatment, complex co-morbidity, pregnancy
• Hepatology: hepatitis C with significant fibrosis; all hepatitis C-positive patients should access DAA treatment
• Psychiatry: severe co-morbid mental illness, suicidality
• Infectious diseases: HIV, complex BBV management, endocarditis

Mortality

• Drug-related deaths: opioid-related deaths approximately 2,300/year in England and Wales
• OST reduces all-cause mortality by ~50% compared to no treatment
• First 4 weeks of OST and first 4 weeks after leaving treatment are highest-risk periods for overdose death
• Overdose risk highest after periods of abstinence (loss of tolerance): prison release, after detoxification
• 10-year mortality for untreated heroin dependence: approximately 5-10%

Complications

• Overdose death: respiratory depression; risk increased with polydrug use (especially benzodiazepines and alcohol)
• Hepatitis C cirrhosis: if untreated; now curable with DAAs
• Infective endocarditis: typically right-sided (tricuspid); S. aureus most common; mortality ~20-30%
• DVT/PE: common with groin injection
• Social consequences: homelessness, imprisonment, family breakdown, poverty
• Neonatal abstinence syndrome: in babies born to opioid-dependent mothers

Clinical Opiate Withdrawal Scale (COWS) Summary

Comparison of OST Options

Key Policy and Guidance

Key Facts

Opioid substitution therapy is the gold standard treatment for opioid dependence. It replaces short-acting illicit opioids with longer-acting prescribed alternatives, stabilising the patient and enabling psychosocial recovery. It is one of the most evidence-based treatments in all of addiction medicine.

Epidemiology

• Approximately 140,000 people in England receive OST at any one time
• ~50% prescribed methadone, ~30% buprenorphine, remainder mixed or other
• Retention in OST at 12 months: approximately 60-70% for methadone, 50-60% for buprenorphine
• Adequate-dose OST associated with ~50% reduction in all-cause mortality

Aetiology/Rationale

• Pharmacological replacement: provides steady-state opioid receptor occupancy, preventing withdrawal and reducing craving
• Cross-tolerance: blocks euphoric effect of additional illicit opioids at adequate doses
• Harm reduction: eliminates injecting and associated risks (BBV, abscesses, endocarditis)
• Stabilisation: enables engagement with psychosocial support, housing, employment
• Gateway to recovery: OST as platform for eventual detoxification when patient is ready

Pathophysiology of Action

• Methadone: full μ opioid receptor agonist; oral bioavailability ~80%; half-life 24-36 hours; steady state reached at 3-5 days
• Buprenorphine: partial μ agonist and κ antagonist; sublingual bioavailability ~30%; half-life 24-48 hours; ceiling effect on respiratory depression (safer in overdose)
• Naloxone component (in Suboxone): poorly absorbed sublingually; blocks opioid effect if crushed and injected → deterrent to diversion
• Buvidal (CAM2038): depot buprenorphine; subcutaneous injection forming solid depot; slow release over 1 week or 1 month

Assessment Before Starting OST

• Comprehensive drug and alcohol history: substances used, route, frequency, quantity, duration
• Confirm opioid dependence: objective evidence (withdrawal signs, urine drug screen, tolerance)
• Risk assessment: overdose risk, injecting behaviour, BBV status, mental health, social circumstances, pregnancy
• Physical examination: injection sites, signs of liver disease, general health
• Mental health screening: depression, anxiety, psychosis, suicidality

Indications for OST

• Confirmed opioid dependence (typically heroin or prescription opioid)
• Failed attempts at abstinence-based approaches
• Patient willing to engage with treatment programme
• Risk assessment supports benefit of OST over alternative approaches

Monitoring During Treatment

• Supervised consumption: observe ingestion for at least 3 months; assess for stability before allowing take-home doses
• Urine drug screening: regular testing for illicit drug use and prescribed medication compliance
• Clinical review: regular appointments to assess progress, side effects, dose adequacy
• Key worker sessions: structured psychosocial support alongside prescribing

Red Flags

• Excessive sedation on current dose: risk of over-dosing, especially in first 2 weeks
• Continued injecting: dose may be inadequate or patient may need alternative approach
• Concurrent benzodiazepine or alcohol use: dramatically increases overdose risk with methadone
• QTc >500 ms on methadone: consider switch to buprenorphine
• Pregnancy: methadone or buprenorphine should be continued (not detoxed); specialist obstetric/addiction liaison required
• Missed doses: if 3+ days missed, dose must be reassessed (loss of tolerance)

Bedside

• COWS score: before starting buprenorphine (must be ≥12 for safe induction)
• Urine drug screen: baseline and ongoing; confirm opioid use, screen for other substances
• Pregnancy test: in women of childbearing age before initiation
• Observations: HR, BP, RR - especially during titration

Bloods

• LFTs: baseline hepatic function (methadone and buprenorphine are hepatically metabolised)
• Blood-borne virus screen: hepatitis B, hepatitis C, HIV
• FBC: baseline
• U&Es: baseline renal function

Imaging

• Not routinely required for OST
• Echocardiography: if clinical suspicion of endocarditis
• FibroScan: if hepatitis C positive

Special Tests

• ECG: recommended before starting methadone and at dose changes >100 mg/day; check QTc (concern >450 ms, high risk >500 ms)
• QTc monitoring: repeat ECG at dose stabilisation, annually, and if symptoms of arrhythmia
• Hair or oral fluid testing: may be used for longer-term compliance monitoring

Non-pharmacological

• Psychosocial interventions (NICE CG51): keyworker support, structured counselling, contingency management
• Harm reduction: needle exchange, safer injecting advice, naloxone provision
• Social stabilisation: housing, benefits, employment support, family interventions
• Recovery support: mutual aid (NA, SMART Recovery), peer mentoring, recovery communities

Pharmacological - Methadone Initiation

• Starting dose: 10-30 mg OD (depending on risk assessment, tolerance level, concurrent substance use)
• Titration: increase by 5-10 mg every 3-5 days (max increase 30 mg in first week)
• Optimal dose: 60-120 mg/day - individualised based on clinical response
• Supervised consumption: mandatory initially; daily attendance at community pharmacy
• Formulation: 1 mg/mL oral solution (preferred to reduce diversion risk)
• Drug interactions: CYP3A4 substrate - caution with inhibitors (fluconazole, erythromycin) and inducers (rifampicin, carbamazepine, phenytoin)

Pharmacological - Buprenorphine Initiation

• Prerequisite: patient must be in opioid withdrawal (COWS ≥12) - typically ≥12 hours after last heroin dose, ≥24-48 hours after last methadone dose
• Starting dose: 4 mg sublingual on day 1; can give further 4 mg after 2-4 hours if needed
• Day 2: 8 mg; titrate over first week to 8-24 mg/day
• Supervised consumption: as per methadone
• Buvidal: weekly SC injection (8-32 mg) or monthly (64-160 mg); after stabilisation on sublingual buprenorphine

Surgical

• Not applicable to OST

Referral Criteria

• Community drug and alcohol team: all patients with opioid dependence for assessment
• Specialist addiction psychiatrist: complex presentations, dual diagnosis, failed treatment
• Perinatal addiction service: pregnant women on OST
• Pain management: patients with chronic pain on OST
• Hepatology/BBV services: hepatitis C treatment, HIV co-management

Outcomes

• OST retention at 1 year: 60-70% (methadone), 50-60% (buprenorphine)
• Reduction in illicit opioid use: ~60-70% of patients significantly reduce or stop illicit heroin while on adequate-dose OST
• All-cause mortality reduction: approximately 50% while on OST
• Reduction in criminal activity: ~50% reduction in acquisitive crime
• Duration of treatment: often years; no maximum recommended duration; many patients benefit from long-term or indefinite OST

Complications

• Methadone-related: QTc prolongation and risk of torsades de pointes (especially doses >100 mg/day or with interacting drugs); constipation; weight gain; dental problems; hyperhidrosis
• Buprenorphine-related: precipitated withdrawal if initiated too early; headache; nausea; constipation; hepatotoxicity (rare at therapeutic doses)
• First 2 weeks of treatment: highest risk of overdose death (especially methadone titration phase)
• Drop-out from treatment: associated with return to illicit use and increased mortality
• Stigma: can affect engagement with healthcare and employment

Methadone vs Buprenorphine Comparison

Take-Home Dose Criteria

Key Facts

Opioid overdose is the leading cause of drug-related death in the UK. Prompt recognition and treatment with naloxone can be life-saving. The majority of opioid-related deaths are preventable. Take-home naloxone programmes are a key public health intervention.

Epidemiology

• ~2,300 opioid-related deaths per year in England and Wales (2021 data); rising trend
• Drug poisoning deaths overall: ~4,900/year - highest on record
• Peak age: 40-49 years (reflecting ageing cohort of opioid users)
• Male:female ratio: approximately 3:1
• Risk period: first 4 weeks after prison release - 7-8× increased risk of drug-related death
• Approximately 70% of opioid-related deaths involve multiple substances

Aetiology

• Heroin (diamorphine): most common opioid in UK overdose deaths
• Methadone: second most common; risk during initiation and if diverted
• Prescription opioids: codeine, tramadol, oxycodone, fentanyl - increasingly involved
• Illicit fentanyl and analogues: extremely potent (fentanyl ~100× morphine potency); increasingly detected in UK drug supply
• Polydrug use: benzodiazepines, alcohol, pregabalin/gabapentin, cocaine synergistically increase risk

Pathophysiology

• Opioids bind μ receptors in brainstem respiratory centre (pre-Bötzinger complex) → reduced respiratory drive

Progressive: reduced respiratory rate

hypoventilation

hypoxia

hypercapnia

respiratory arrest

cardiac arrest

• Hypoxic brain injury: irreversible if prolonged; even survivors may have permanent damage
• Non-cardiogenic pulmonary oedema: mechanism unclear; possibly related to acute negative intrathoracic pressure or direct alveolar membrane effects

Classical Presentation

• Respiratory depression: rate <12 breaths/min, may be apnoeic; shallow, irregular breathing
• Miosis: pinpoint pupils (bilateral) - may be absent with co-ingestants, hypoxia, or certain synthetic opioids
• Reduced consciousness: GCS reduced; may range from drowsiness to unresponsive (GCS 3)
• Cyanosis: peripheral and central in severe cases
• Bradycardia and hypotension
• Hypothermia: reduced metabolic activity
• Reduced or absent bowel sounds

Complications

• Aspiration pneumonia: vomiting while obtunded
• Non-cardiogenic pulmonary oedema: may develop hours after overdose or after naloxone administration
• Rhabdomyolysis: prolonged immobility on hard surface → crush injury
• Compartment syndrome: pressure on limbs during prolonged unconsciousness
• Hypoxic brain injury: anoxic encephalopathy if prolonged respiratory depression
• Needle-stick injury: risk to rescuers in the pre-hospital setting

Red Flags

• Apnoea or respiratory rate <8/min: immediate ventilatory support needed
• GCS ≤8: cannot protect airway
• No response to naloxone 2 mg total: consider non-opioid cause or massive overdose (fentanyl may require much larger doses)
• Recurrent sedation after naloxone wears off: especially with long-acting opioids (methadone)
• Pulmonary oedema: frothy pink sputum after naloxone; needs high-flow oxygen and possible CPAP/ventilation
• Body packing/stuffing: consider internal concealment - surgical emergency if packet rupture

Bedside

• Airway assessment: patent? Gag reflex? Vomit?
• Respiratory rate and SpO2: critical parameters
• GCS: serial monitoring
• Pupil size and reactivity: miosis supports opioid toxicity
• Capillary blood glucose: exclude hypoglycaemia
• Temperature: hypothermia common
• ECG: QTc prolongation (methadone), arrhythmias, ischaemia

Bloods

• ABG/VBG: assess oxygenation, ventilation (CO2), acid-base status, lactate
• U&Es: renal function, electrolytes (rhabdomyolysis risk)
• CK: rhabdomyolysis if immobile
• FBC: leucocytosis may suggest aspiration
• LFTs: paracetamol co-ingestion common
• Paracetamol and salicylate levels: always check in overdose
• Blood alcohol level: concurrent intoxication
• Urine drug screen: confirm opioid use, identify co-ingestants

Imaging

• Chest X-ray: aspiration pneumonia, non-cardiogenic pulmonary oedema
• CT head: if GCS does not improve with naloxone - exclude intracranial pathology
• Abdominal X-ray/CT: if body packing suspected

Special Tests

• Serum drug levels: specific quantification rarely influences acute management
• Carboxyhaemoglobin: if CO poisoning considered
• Toxicology consultation: National Poisons Information Service (TOXBASE) for complex overdoses

Non-pharmacological - Immediate Actions (ABCDE Approach)

• Airway: open airway (head tilt, chin lift, jaw thrust); suction if needed; recovery position if breathing
• Breathing: if respiratory rate <8/min or SpO2 <92% - bag-valve-mask ventilation with high-flow oxygen
• Rescue breaths: 5 initial rescue breaths if apnoeic (bystander or EMS)
• Call 999: early activation of emergency services
• Do not leave patient alone: monitor continuously

Pharmacological - Naloxone

• Naloxone (opioid antagonist):
  • IV route: 400 mcg (0.4 mg) bolus; repeat every 2-3 minutes up to 10 mg total
  • IM/SC route: 400 mcg (0.4 mg); repeat every 2-3 minutes; slightly slower onset (~5 minutes)
  • Intranasal (Nyxoid): 1.8 mg per nostril; no needle required; increasingly used pre-hospital
  • Goal: restore adequate spontaneous respiration (RR >12) - do NOT aim to fully reverse opioid effect (precipitates severe withdrawal)
  • Naloxone infusion: if repeated boluses needed - 10 mg in 50 mL 0.9% NaCl at rate guided by clinical response (typically 2/3 of initial response dose per hour)
  • Observation period: minimum 2 hours after last naloxone dose for short-acting opioids; minimum 4-6 hours (or longer) for methadone, slow-release preparations, or fentanyl patches
• Take-home naloxone:
  • Prenoxad: pre-filled syringe with 5 × 400 mcg doses for IM injection
  • Nyxoid: nasal spray, 1.8 mg per dose; available without prescription in some settings
  • Should be offered to all patients at risk of opioid overdose, their families, and carers (NICE NG225)

Additional Pharmacological Management

• Atropine 0.5-1 mg IV: for symptomatic bradycardia
• IV fluids: for hypotension and rhabdomyolysis
• Sodium bicarbonate: for rhabdomyolysis-related acidosis
• Antibiotics: if aspiration pneumonia suspected

Surgical

• Intubation and mechanical ventilation: if airway compromise or persistent respiratory failure despite naloxone
• Surgical removal of drug packets: body packing with suspected rupture - emergency laparotomy

Referral Criteria

• Resuscitation team/ICU: refractory respiratory depression, intubated, multiorgan failure
• Drug and alcohol services: all patients surviving opioid overdose - assess for OST
• Mental health assessment: if intentional overdose
• Take-home naloxone provision: before discharge from ED
• Prison in-reach/release planning: if overdose relates to prison discharge

Outcomes

• Prompt naloxone administration: near-complete reversal of respiratory depression in majority of cases
• Survival to hospital discharge: >95% if naloxone given promptly
• Hypoxic brain injury: if prolonged respiratory depression before treatment - variable outcome from mild cognitive impairment to persistent vegetative state
• Recurrent overdose: approximately 20-30% of individuals who survive overdose will experience another within 12 months

Complications

• Aspiration pneumonia: occurs in ~10-15% of patients with reduced consciousness
• Non-cardiogenic pulmonary oedema: may develop up to 24 hours after overdose
• Rhabdomyolysis: CK >5,000 IU/L; risk of acute kidney injury; requires aggressive IV fluid resuscitation
• Naloxone-precipitated withdrawal: agitation, nausea, vomiting, tachycardia, hypertension; rarely dangerous but distressing
• Death: opioid overdose is the leading cause of preventable death in drug misusers

Naloxone Dosing Summary

Risk Factors for Opioid Overdose Death

Take-Home Naloxone - Who Should Receive It

Key Facts

Benzodiazepine dependence is one of the most common forms of substance dependence. It may be iatrogenic (from prescribing) or related to recreational/illicit use. Withdrawal is medically serious and potentially fatal, requiring careful managed reduction rather than abrupt cessation.

Epidemiology

• Approximately ~11 million benzodiazepine prescriptions per year in England
• Estimated ~1 million long-term users in the UK
• Dependence can develop after as little as 4-6 weeks of regular use
• Z-drugs (zopiclone, zolpidem): similar problem; often overlooked
• Illicit benzodiazepine use: increasing problem; novel benzodiazepines (e.g. flualprazolam, etizolam) entering the illicit drug supply
• Benzodiazepines implicated in approximately 40% of opioid-related deaths as co-ingestants

Aetiology

• Pharmacological: benzodiazepines enhance GABA-A receptor function → anxiolysis, sedation, muscle relaxation, anticonvulsant effect
• Tolerance: develops to sedative and anxiolytic effects within 2-4 weeks; less tolerance develops to amnestic effects

chronic GABA-A receptor modulation

compensatory downregulation; abrupt cessation

CNS hyperexcitability

• Iatrogenic dependence: most common pathway; prescribed for insomnia/anxiety without time-limited use
• Recreational/illicit use: self-medication, enhancing effects of other drugs, managing stimulant/opioid withdrawal

Pathophysiology

• Chronic benzodiazepine exposure → GABA-A receptor downregulation and conformational changes
• Compensatory upregulation of excitatory (glutamatergic) pathways

Abrupt cessation

reduced GABAergic inhibition + unopposed glutamatergic excitation

withdrawal syndrome

• Similar mechanism to alcohol withdrawal - cross-tolerance exists between benzodiazepines and alcohol
• Short-acting benzodiazepines (e.g. lorazepam, alprazolam) associated with more rapid onset and more severe withdrawal

Dependence Features

• Tolerance: need for increasing doses to achieve the same effect
• Withdrawal symptoms on dose reduction or cessation
• Craving: strong desire to take benzodiazepines
• Difficulty controlling use: unable to reduce despite desire
• Continued use despite harm: cognitive impairment, falls, social consequences

Withdrawal Syndrome (onset depends on half-life: hours for short-acting, days for long-acting)

• Psychological: anxiety (often severe, rebound), insomnia, irritability, poor concentration, depersonalisation, perceptual disturbances
• Physical: tremor, sweating, palpitations, headache, muscle pain and stiffness, nausea
• Severe withdrawal: seizures (generalised tonic-clonic), psychosis, delirium - potentially fatal
• Protracted withdrawal syndrome: symptoms may persist for weeks to months (sometimes years) - anxiety, insomnia, sensory disturbances, cognitive difficulties

Red Flags

• Seizures: risk highest with abrupt cessation of short-acting, high-dose benzodiazepines
• Psychosis: paranoid ideation, visual hallucinations - particularly with rapid withdrawal
• Suicidal ideation: depression and anxiety during withdrawal increase suicide risk
• Concurrent alcohol or opioid withdrawal: life-threatening - manage simultaneously with specialist input
• Elderly patients: increased sensitivity to benzodiazepines and withdrawal effects; higher falls risk
• Illicit benzodiazepine use: unknown substances and doses - greater unpredictability

Bedside

• Comprehensive drug history: all benzodiazepines and Z-drugs, doses, duration, source (prescribed vs illicit)
• Equivalent diazepam dose calculation: essential for planning reduction
• Urine drug screen: confirm benzodiazepine use, identify other substances
• Mental state examination: assess anxiety, depression, suicidality
• Falls risk assessment: especially in elderly patients

Bloods

• LFTs: concurrent alcohol-related liver disease
• FBC and U&Es: baseline
• TFTs: exclude thyrotoxicosis mimicking withdrawal
• Blood-borne virus screen: if illicit injecting drug use

Imaging

• Not routinely required
• CT/MRI head: if seizures with atypical features
• EEG: if diagnostic uncertainty about seizures

Special Tests

• Neuropsychological testing: if persistent cognitive concerns after withdrawal
• Sleep study: if persistent insomnia after withdrawal to exclude primary sleep disorder

Non-pharmacological

• Patient education: explain withdrawal process, expected timeline, reassurance that symptoms are self-limiting
• Psychological support: CBT for anxiety and insomnia (NICE CG113); sleep hygiene advice
• Gradual reduction plan: agreed collaboratively with patient; written schedule
• Regular review: GP or specialist follow-up every 2-4 weeks during reduction
• Self-help resources: benzodiazepine support groups, Ashton Manual (widely used patient resource)

Pharmacological

• Conversion to diazepam: convert total daily benzodiazepine/Z-drug dose to diazepam equivalent
• Approximate equivalences (to 5 mg diazepam):
  • Chlordiazepoxide 15 mg
  • Lorazepam 0.5 mg
  • Nitrazepam 5 mg
  • Temazepam 10 mg
  • Alprazolam 0.5 mg
  • Zopiclone 7.5 mg
• Reduction schedule: reduce by ~10-12.5% of current dose every 2-4 weeks; slow the rate of reduction as dose decreases
• Final stages: reductions of 0.5-1 mg diazepam at a time; may use liquid diazepam (2 mg/5 mL) for fine adjustments
• Total duration: typically 3-12 months depending on starting dose and individual response
• If seizures occur: stabilise on adequate benzodiazepine dose and restart slower reduction
• Adjunctive medications: propranolol for somatic anxiety symptoms; antidepressants if co-morbid depression

Surgical

• Not applicable

Referral Criteria

• Community drug and alcohol services: high-dose or illicit benzodiazepine dependence, polysubstance use
• Inpatient detoxification: severe dependence, history of withdrawal seizures, concurrent alcohol dependence, unstable social circumstances
• Psychiatry: co-morbid severe mental illness, suicidality, complex dual diagnosis
• Elderly care/falls clinic: older adults with benzodiazepine-related falls and cognitive impairment

Outcomes

• Successful dose reduction: approximately 60-80% of motivated patients can taper off benzodiazepines with gradual reduction and support
• Protracted withdrawal symptoms: may persist for 6-12 months in some patients; rarely years
• Seizure risk: primarily with abrupt cessation; very low risk with gradual reduction
• Cognitive recovery: most cognitive impairment improves within 6-12 months of cessation; some deficits may persist

Complications

• Seizures: potentially fatal; risk proportional to dose and rapidity of cessation
• Falls and fractures: particularly in elderly (benzodiazepines increase hip fracture risk by ~50%)
• Cognitive impairment: long-term use associated with increased risk of dementia (odds ratio ~1.5-2.0 in some studies)
• Road traffic accidents: increased risk while on benzodiazepines (impaired psychomotor function)
• Drug-related death: significant contributor to polydrug fatalities (synergy with opioids and alcohol)
• Rebound insomnia and anxiety: may be worse than pre-treatment levels initially

Benzodiazepine Equivalence Table

Ashton Manual Reduction Principles

Key Facts

Cannabis is the most widely used controlled substance globally and in the UK. While often perceived as relatively harmless, increasing evidence demonstrates significant harms, particularly with high-potency products, early-onset use, and heavy/daily use. There is a strong association between cannabis use and psychotic disorders.

Epidemiology

• ~2.6 million adults in England and Wales used cannabis in the past year
• Prevalence highest: 16-24 age group (~18% past-year use)
• Dependence: ~9% of ever-users; ~17% of adolescent-onset users; ~25-50% of daily users
• Cannabis-related hospital admissions are increasing
• Treatment presentations: cannabis is the most common primary drug for under-18s entering treatment services

Aetiology

• Pharmacology: THC acts on CB1 cannabinoid receptors (primarily in brain - hippocampus, prefrontal cortex, basal ganglia, cerebellum) and CB2 receptors (periphery/immune)
• Endocannabinoid system: THC mimics endogenous cannabinoids (anandamide, 2-AG); modulates dopamine, GABA, and glutamate transmission
• Risk factors for dependence: early onset of use (<16 years), high-potency products, daily use, family history of addiction, co-morbid mental illness, social adversity
• CBD (cannabidiol): non-intoxicating cannabinoid; may have anxiolytic and antipsychotic properties; attenuates some effects of THC

Pathophysiology

• Acute THC effects: stimulates mesolimbic dopamine release → euphoria and reinforcement
• Chronic use: CB1 receptor downregulation and desensitisation → tolerance
• Adolescent vulnerability: endocannabinoid system is critical for neurodevelopment; exogenous THC disrupts normal pruning and myelination of prefrontal cortex
• Cannabis and psychosis: THC increases dopamine in mesolimbic pathway; gene-environment interaction (COMT Val158Met polymorphism moderates risk)

Acute Cannabis Intoxication

• Euphoria and relaxation: sense of wellbeing
• Altered perception: time distortion, enhanced sensory experience
• Impaired short-term memory and concentration
• Increased appetite ("munchies")
• Conjunctival injection (red eyes), dry mouth
• Tachycardia: dose-related increase in heart rate
• Anxiety or paranoia: particularly with high-THC products or in inexperienced users
• Psychomotor impairment: slowed reaction time, impaired coordination

Cannabis Use Disorder

• Impaired control over use
• Continued use despite social, occupational, or health consequences
• Tolerance and withdrawal
• Neglect of other activities

Cannabis Withdrawal Syndrome

• Onset 24-72 hours after cessation; peak 3-4 days; duration 1-2 weeks
• Irritability, anger, aggression
• Anxiety, nervousness
• Insomnia, disturbed sleep, vivid dreams
• Decreased appetite, weight loss
• Restlessness, depressed mood
• Physical: headache, sweating, abdominal pain, tremor (less common)

Red Flags

• First-episode psychosis: auditory hallucinations, paranoid delusions, thought disorder - urgent psychiatric assessment
• Cannabinoid hyperemesis syndrome: cyclical vomiting, compulsive hot bathing, abdominal pain - may mimic surgical abdomen
• Severe anxiety/panic attacks: can be distressing; usually self-limiting
• Adolescent use: disruption of brain development, educational failure, increased psychosis risk
• Driving under the influence: impaired psychomotor function; UK law: 2 μg/L blood THC legal limit

Bedside

• Urine drug screen: THC metabolites detectable for 3-4 days (occasional use) to >30 days (chronic heavy use)
• Mental state examination: assess for psychotic symptoms, mood disorder, anxiety
• Screening tools: CUDIT-R (Cannabis Use Disorder Identification Test - Revised), SDS (Severity of Dependence Scale)
• Risk assessment: suicide risk, safeguarding (particularly in young people)

Bloods

• Routine bloods: generally unremarkable in isolated cannabis use
• LFTs: if co-existing alcohol or other substance use
• Blood-borne virus screen: if concurrent injecting drug use
• Inflammatory markers: if cannabinoid hyperemesis (to exclude other causes of vomiting)

Imaging

• Not routinely indicated for cannabis use disorder
• MRI brain: if first-episode psychosis (exclude organic cause)
• CT abdomen: if cannabinoid hyperemesis mimics acute surgical abdomen

Special Tests

• Neuropsychological testing: if persistent cognitive concerns; may show deficits in memory, attention, processing speed
• Blood THC levels: not routinely measured clinically; used in medicolegal settings (driving offences)

Non-pharmacological

• Brief intervention: structured advice on risks of cannabis use; particularly effective for young people
• Motivational enhancement therapy (MET): 2-4 sessions; enhances motivation to change
• Cognitive behavioural therapy (CBT): address maladaptive thoughts and behaviours around cannabis use; NICE CG51 recommended
• Contingency management: incentive-based approach; NICE TA114 supports use in drug misuse
• Family therapy: particularly for adolescents - multidimensional family therapy (MDFT)
• Education and harm reduction: information about potency, legal consequences, mental health risks

Pharmacological

• No licensed pharmacotherapy for cannabis use disorder
• Symptomatic treatment during withdrawal:
  • Insomnia: short-term use of non-benzodiazepine hypnotics (e.g. zopiclone 3.75-7.5 mg, maximum 2 weeks); sleep hygiene
  • Anxiety: SSRIs if persistent anxiety disorder identified
  • Irritability/agitation: reassurance; in severe cases, short course of diazepam
• N-acetylcysteine (NAC): some evidence for reducing cannabis use in adolescents (Gray et al., 2012); not yet licensed for this indication
• Treatment of co-morbid psychosis: antipsychotics as per standard guidelines; cannabis cessation essential for recovery

Surgical

• Not applicable

Referral Criteria

• Community drug services: if dependence established, failed self-help, associated harms
• CAMHS/young people's substance misuse service: adolescents with cannabis use disorder
• Early Intervention in Psychosis (EIP): if first-episode psychosis associated with cannabis use
• Psychiatry: co-morbid severe mental illness, suicidality
• Gastroenterology: cannabinoid hyperemesis with severe vomiting, dehydration, electrolyte disturbance

Outcomes

• Spontaneous remission: many cannabis users reduce or cease use in their late 20s/30s
• Treatment outcomes: CBT + MET → abstinence rates of 20-30% at 12 months; significant reduction in use in further 30%
• Psychosis: cannabis-associated psychosis may remit with cessation; ~50% progress to chronic psychotic disorder (schizophrenia)
• Cognitive recovery: most deficits improve after 4 weeks of abstinence; adolescent-onset heavy use may have more persistent effects

Complications

• Psychotic disorders: strong dose-response relationship; ~33% of psychosis cases in London attributable to high-potency cannabis (Di Forti et al.)
• Amotivational syndrome: apathy, reduced goal-directed behaviour in chronic heavy users
• Respiratory effects: chronic bronchitis symptoms; smoking cannabis with tobacco increases lung cancer risk
• Cardiovascular: acute tachycardia; rare reports of acute coronary syndrome and stroke
• Cannabinoid hyperemesis syndrome: cyclical vomiting; resolves only with permanent cessation
• Impaired driving: increased accident risk; second most common intoxicant after alcohol in road traffic collisions
• Educational and occupational impairment: particularly with adolescent-onset use

Cannabis Potency and Risk

Key Studies in Cannabis and Psychosis

Legal Classification (UK)

Key Facts

Cocaine and other stimulants are among the most commonly misused substances in the UK. Cocaine-related harm has risen dramatically over the past decade, driven by increased purity and availability. Stimulant misuse carries significant cardiovascular, neurological, and psychiatric risks.

Epidemiology

• Cocaine: ~875,000 users in past year (England and Wales); highest rates in 20-29 age group
• Cocaine purity: average has increased from ~20% to >60% over the past decade
• Cocaine deaths: approximately 840/year (England and Wales); increasing trend
• Amphetamines: ~130,000 past-year users; declining trend but methamphetamine emerging
• MDMA (ecstasy): ~500,000 past-year users; typically intermittent recreational use

Aetiology

• Cocaine: derived from coca plant (Erythroxylum coca); two forms:
  • Powder cocaine (cocaine hydrochloride): snorted or injected
  • Crack cocaine (freebase): smoked; rapid onset, intense but brief high → highly reinforcing
• Amphetamines: synthetic stimulants; oral, intranasal, injected
• Methamphetamine (crystal meth): more potent, neurotoxic; emerging in UK, particularly in chemsex context
• Reinforcement: powerful dopaminergic reward → rapid development of psychological dependence

Pathophysiology

• Cocaine: blocks dopamine transporter (DAT), noradrenaline transporter (NET), serotonin transporter (SERT) → increased synaptic monoamines
  • Also blocks sodium channels (local anaesthetic effect) → cardiac arrhythmias
  • Vasospasm: coronary and cerebral arteries → ACS, stroke
• Amphetamines: reverse-transport mechanism → release of presynaptic dopamine, noradrenaline, serotonin stores
• Methamphetamine: additional neurotoxic effects on dopaminergic neurons
• Chronic use: dopamine receptor downregulation → anhedonia, depression, cognitive impairment

Acute Cocaine/Stimulant Intoxication

• Cardiovascular: tachycardia, hypertension, chest pain, palpitations, arrhythmias
• Neurological: mydriasis, tremor, hyperreflexia, seizures, headache, stroke
• Psychiatric: euphoria, grandiosity, agitation, paranoia, hallucinations (tactile - "cocaine bugs"/formication)
• General: hyperthermia, diaphoresis, anorexia

Complications of Acute Use

• Cocaine-associated acute coronary syndrome: chest pain within hours of use; coronary vasospasm ± thrombosis; may cause MI in young patients with normal coronary arteries
• Aortic dissection: acute tearing chest pain, hypertension
• Stroke: both ischaemic and haemorrhagic; especially with crack cocaine
• Seizures: usually generalised tonic-clonic; self-limiting
• Hyperthermia and rhabdomyolysis: particularly with MDMA and methamphetamine
• Serotonin syndrome: with MDMA; agitation, myoclonus, hyperthermia, autonomic instability

Stimulant Withdrawal ("crash")

• Onset within hours to days of cessation
• Dysphoria, depression, fatigue, hypersomnia
• Increased appetite
• Psychomotor retardation
• Intense craving
• Not medically dangerous but significant suicide risk

Red Flags

• Chest pain: assume cardiac aetiology; ECG and troponin
• Severe hypertension (>180/120 mmHg): risk of hypertensive emergency, dissection, stroke
• Hyperthermia >40°C: life-threatening; aggressive cooling required
• Seizures: may progress to status epilepticus
• Paranoid psychosis with aggression: may require emergency sedation
• Body packing: cocaine-filled packets in GI tract; rupture → massive overdose

Bedside

• ECG: ST changes (ACS), arrhythmias, QTc prolongation, Brugada pattern
• Observations: HR, BP (hypertensive emergency?), temperature, SpO2, GCS
• Capillary glucose: cocaine can cause hyper- or hypoglycaemia
• Urine drug screen: cocaine metabolite (benzoylecgonine) detectable for 2-4 days; amphetamines detectable for 1-3 days

Bloods

• Troponin: serial - cocaine-associated ACS
• FBC: leucocytosis (stress response)
• U&Es: renal function (rhabdomyolysis risk)
• CK: rhabdomyolysis (may be massively elevated)
• LFTs: cocaine-induced hepatotoxicity (rare)
• Coagulation screen: DIC in severe toxicity
• ABG/VBG: metabolic acidosis (lactic acidosis, rhabdomyolysis)
• Blood alcohol level: concurrent use common

Imaging

• Chest X-ray: pulmonary oedema, pneumomediastinum (crack cocaine), aspiration
• CT head: if seizures, focal neurology, or stroke suspected
• CT angiography: if aortic dissection suspected
• Abdominal X-ray/CT: if body packing suspected
• Echocardiography: if endocarditis or cardiomyopathy suspected

Special Tests

• Coronary angiography: for cocaine-associated ACS with ST-elevation
• Lumbar puncture: if subarachnoid haemorrhage suspected (thunderclap headache, CT-negative)
• MRI brain: for stroke characterisation

Non-pharmacological

• Calm environment: reduce sensory stimulation for agitated patients
• Active cooling: remove clothing, fans, cool IV fluids, ice packs for hyperthermia >39°C
• Supportive care: IV fluids, monitoring, observation

Pharmacological - Acute Intoxication/Emergency

• Agitation and seizures:
  • Diazepam 5-10 mg IV (repeat as needed) or lorazepam 1-2 mg IV: first-line for agitation, seizures, and cardiovascular complications
  • Benzodiazepines address most complications by reducing sympathetic drive
• Cocaine-associated chest pain/ACS:
  • GTN sublingual/IV: coronary vasodilation
  • Aspirin 300 mg: antiplatelet effect
  • Diazepam 5-10 mg IV: reduces sympathetic drive and BP
  • Avoid beta-blockers: risk of unopposed alpha-adrenergic stimulation → worsening hypertension and coronary vasospasm
  • Phentolamine 5-10 mg IV: alpha-blocker; if hypertension refractory to benzodiazepines
  • Primary PCI: if STEMI confirmed
• Severe hypertension: benzodiazepines first-line; add GTN or phentolamine if needed
• Hyperthermia: active cooling; dantrolene considered if refractory
• Serotonin syndrome (MDMA): cyproheptadine 12 mg PO initially, then 4 mg 2-hourly; benzodiazepines, cooling

Non-pharmacological - Longer-term Treatment

• CBT: most evidence-based psychosocial intervention for stimulant misuse (NICE CG51)
• Contingency management: incentive-based treatment; NICE TA114 recommends for stimulant misuse
• Motivational interviewing: enhance motivation to change
• Harm reduction: avoid injecting, avoid using alone, start with small amounts of unknown batches

Surgical

• Body packing: if packet rupture suspected - emergency laparotomy; whole bowel irrigation with PEG solution if intact packets

Referral Criteria

• Emergency department: acute toxicity, chest pain, seizures, psychosis
• Cardiology: cocaine-associated ACS, arrhythmias
• Drug and alcohol services: for ongoing psychosocial treatment
• Psychiatry: stimulant-related psychosis, severe depression during withdrawal, suicidality

Outcomes

• Acute cocaine toxicity: most patients recover with supportive care; mortality <5% with appropriate treatment
• Cocaine-associated MI: younger patients; often recoverable but cardiomyopathy may develop
• Stimulant psychosis: usually resolves within days to weeks of cessation; ~10-15% may develop chronic psychotic disorder
• Treatment outcomes: CBT + contingency management → ~30-40% achieve sustained abstinence at 6 months

Complications

• Sudden cardiac death: arrhythmias (VT/VF), even in young healthy individuals
• Dilated cardiomyopathy: chronic cocaine use → progressive heart failure
• Nasal septum perforation: chronic cocaine snorting
• Crack lung: pulmonary haemorrhage, eosinophilic pneumonia, thermal airway injury
• Cognitive impairment: executive dysfunction, impaired decision-making with chronic use
• Socioeconomic harm: financial ruin, relationship breakdown, criminal justice involvement

Stimulant Comparison

Cocaine-Associated Chest Pain: Key Management Points

Key Facts

Novel psychoactive substances represent a rapidly evolving challenge for healthcare. Hundreds of new compounds emerge each year, often with limited pharmacological data. Clinical presentations can be severe and unpredictable. Healthcare professionals must recognise common toxidromes and provide appropriate supportive care.

Epidemiology

• >800 NPS identified by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) since 2005
• Prevalence of past-year NPS use in UK: approximately 0.5-1% of 16-59 year olds
• Synthetic cannabinoids: most commonly used NPS; concentrated in homeless and prison populations (prevalence up to ~90% in some prison surveys)
• NPS-related deaths: increasing; ~200/year in England and Wales (often involving novel benzodiazepines)
• Mephedrone: was most popular NPS before classification as Class B in 2010

Aetiology - Major NPS Categories

1. Synthetic cannabinoid receptor agonists (SCRAs): Spice, Black Mamba, ADB-BUTINACA; full CB1 agonists (much more potent and dangerous than THC, which is a partial agonist)
2. Synthetic cathinones: mephedrone, MDPV, alpha-PVP ("flakka"); monoamine releasers/reuptake inhibitors
3. Novel benzodiazepines: flualprazolam, etizolam, flubromazolam; GABA-A modulators
4. Novel opioids: nitazenes (isotonitazene, metonitazene); extremely potent (some 100-1000× morphine potency)
5. Psychedelic phenethylamines and tryptamines: 2C-B, NBOMe, DMT analogues
6. Dissociatives: methoxetamine, novel PCP analogues; NMDA receptor antagonists

Pathophysiology

• SCRAs: full CB1 receptor agonism → much greater risk of seizures, psychosis, cardiovascular toxicity, and death compared to natural cannabis
• Synthetic cathinones: similar mechanism to amphetamines/MDMA → sympathomimetic and serotonergic toxicity
• Nitazenes: μ opioid receptor agonists with potency exceeding fentanyl → high overdose risk; may require very large naloxone doses
• Novel benzodiazepines: enhanced GABA-A agonism; variable potency and duration; frequently combined with opioids → respiratory depression

Synthetic Cannabinoids (SCRAs)

• Agitation, psychosis: more severe than natural cannabis; paranoia, aggression
• Seizures: generalised tonic-clonic
• Cardiovascular: tachycardia, hypertension, chest pain, myocardial ischaemia
• Bradycardia and hypotension: paradoxically in some compounds
• Acute kidney injury: associated with certain SCRAs
• Coma and respiratory depression: unlike natural cannabis
• Characteristic posturing: "Spice zombies" - cataleptic states in public

Synthetic Cathinones

• Sympathomimetic toxidrome: tachycardia, hypertension, hyperthermia, diaphoresis, mydriasis
• Agitation and paranoia: severe; may require physical restraint and sedation
• Serotonin toxicity: myoclonus, hyperthermia, autonomic instability
• Bruxism, jaw clenching: similar to MDMA
• Hyponatraemia: particularly with MDMA-like compounds (excess water intake + ADH release)

Novel Benzodiazepines

• Sedation and respiratory depression: often severe; potentiates opioid toxicity
• Unpredictable duration: some have very long half-lives
• May not respond to standard flumazenil doses

Nitazenes/Novel Opioids

• Classic opioid toxidrome: miosis, respiratory depression, reduced consciousness
• May require massive naloxone doses (10-20+ mg)
• Prolonged observation required

Red Flags

• Severe hyperthermia >40°C: medical emergency - aggressive cooling, dantrolene
• Seizures: status epilepticus risk with SCRAs
• GCS <8 with apnoea: may be novel opioid or benzodiazepine - trial of naloxone
• Severe agitation with rhabdomyolysis: CK, renal function, aggressive IV fluids
• Hyponatraemia <125 mmol/L: risk of cerebral oedema; restrict fluids, seek specialist advice
• Serotonin syndrome: clinical emergency - cyproheptadine, benzodiazepines, cooling

Bedside

• Observations: HR, BP, temperature, RR, SpO2, GCS - frequent monitoring
• ECG: arrhythmias, QTc prolongation, sodium channel blockade (wide QRS)
• Capillary glucose: exclude hypoglycaemia
• Urine drug screen: standard immunoassay - often negative for NPS; still useful to identify co-ingestants

Bloods

• ABG/VBG: acidosis, lactate, oxygenation
• U&Es: AKI (SCRAs), hyponatraemia (cathinones/MDMA-like compounds)
• CK: rhabdomyolysis (may be massively elevated)
• LFTs: hepatotoxicity (some cathinones)
• FBC: leucocytosis (stress response)
• Coagulation: DIC in severe cases
• Paracetamol and salicylate: routine in acute presentations

Imaging

• CT head: if seizures, focal neurology, prolonged reduced consciousness
• Chest X-ray: if aspiration, pulmonary oedema, or chest pain

Special Tests

• Specialist toxicology screen: liquid chromatography-mass spectrometry (LC-MS/MS) - identifies specific NPS; send via National Poisons Information Service
• TOXBASE/NPIS: contact for guidance on specific substances
• Wedinos: Welsh substance testing service providing information on circulating NPS in UK

Non-pharmacological

• Toxidrome-based approach: identify the predominant clinical picture and manage accordingly
• Calm, safe environment: reduce stimulation for agitated patients
• Active cooling: for hyperthermia >39°C
• IV fluid resuscitation: for dehydration, rhabdomyolysis, hypotension
• Continuous monitoring: in high-dependency setting for severe presentations

Pharmacological

• Sympathomimetic/serotonergic toxidrome (cathinones, stimulant NPS):
  • Diazepam 5-10 mg IV (repeat as needed): first-line for agitation, seizures, cardiovascular complications
  • Active cooling: external methods
  • Cyproheptadine 12 mg PO then 4 mg 2-hourly: for serotonin syndrome
  • Avoid antipsychotics in acute sympathomimetic toxicity (lower seizure threshold, impair thermoregulation)
• Cannabinoid toxidrome (SCRAs):
  • Benzodiazepines for agitation and seizures
  • Standard seizure management: lorazepam 4 mg IV
  • Supportive care; monitor renal function
• Sedative toxidrome (novel benzodiazepines):
  • Airway management: intubation if GCS <8 and airway compromise
  • Flumazenil generally avoided (risk of seizures in chronic benzodiazepine users and mixed ingestions)
  • Supportive monitoring
• Opioid toxidrome (nitazenes, novel opioids):
  • Naloxone: may require very high doses (>10 mg); repeated boluses or infusion
  • Prolonged observation (some nitazenes have long half-lives)

Surgical

• Not routinely applicable; intubation/ventilation for airway protection

Referral Criteria

• ICU/HDU: severe toxicity, refractory seizures, rhabdomyolysis with AKI, respiratory failure
• NPIS/toxicology: contact for specialist advice on unknown substances
• Drug and alcohol services: for ongoing support after acute presentation
• Mental health assessment: if psychosis persists beyond acute intoxication
• Social services: if homelessness, safeguarding concerns

Outcomes

• Most acute NPS presentations: resolve with supportive care within 24-48 hours
• SCRA-related psychosis: usually resolves within days of cessation; may unmask underlying psychotic disorder
• Nitazene overdose: high mortality if naloxone not administered promptly; survivors generally recover
• Rhabdomyolysis with AKI: may require temporary dialysis; most recover renal function

Complications

• Death: NPS-related deaths increasing; novel benzodiazepines + opioids most lethal combination
• Chronic psychotic disorder: may be triggered by repeated SCRA use
• Acute kidney injury: particularly with certain SCRA compounds
• Persistent cognitive impairment: after prolonged SCRA or cathinone use
• Social harms: homelessness, criminalisation, social exclusion

NPS Toxidrome Recognition

UK Regulatory Framework

Key Facts

Smoking remains the single largest preventable cause of morbidity and mortality in the UK. Despite declining prevalence, it continues to cause enormous health and economic burden, with stark socioeconomic inequalities. Effective cessation treatments exist and are highly cost-effective.

Epidemiology

• Smoking prevalence in England: ~12-13% (2022); down from ~46% in 1974
• Socioeconomic gradient: prevalence ~25% in most deprived quintile vs ~6% in least deprived
• ~76,000 deaths/year in England; ~500,000 hospital admissions attributable to smoking
• Smoking in pregnancy: ~9% at time of delivery; leading modifiable risk factor for adverse pregnancy outcomes
• Smokeless tobacco: betel/paan use in South Asian communities - oral cancer risk
• E-cigarette use: ~3.6 million adults in England use vapes; primarily current or ex-smokers

Aetiology

• Nicotine: primary addictive component; binds nicotinic acetylcholine receptors (nAChRs), particularly α4β2 subtype in the ventral tegmental area

nicotine

dopamine release in nucleus accumbens

reinforcement; tolerance develops rapidly

• Behavioural: conditioning to environmental cues (after meals, with alcohol, stress); habitual behaviour deeply ingrained
• Psychosocial: peer influence (particularly in adolescent initiation), stress coping, social identity
• Industry: tobacco product design optimises nicotine delivery and addiction

Pathophysiology - Smoking-Related Disease

• Cardiovascular: accelerated atherosclerosis, endothelial dysfunction, prothrombotic state

chronic inflammation, mucus hypersecretion, protease-antiprotease imbalance

COPD; direct carcinogenesis

lung cancer

• Carcinogenesis: >70 known carcinogens in tobacco smoke (nitrosamines, polycyclic aromatic hydrocarbons, benzene)
• Other organ damage: renal impairment, peptic ulcer disease, osteoporosis, age-related macular degeneration

Nicotine Dependence Assessment

• Fagerström Test for Nicotine Dependence (FTND): 6-item questionnaire
  • Most predictive item: time to first cigarette after waking (<5 minutes = high dependence)
  • Score: 0-3 low, 4-6 moderate, 7-10 high dependence
• Heaviness of Smoking Index (HSI): 2-item abbreviated version (cigarettes per day + time to first cigarette)
• Carbon monoxide (CO) reading: expired CO >10 ppm consistent with active smoking

Smoking-Related Diseases

• Cardiovascular: coronary artery disease, peripheral arterial disease, stroke, aortic aneurysm
• Respiratory: COPD (accounts for ~80% of COPD cases), lung cancer, asthma exacerbation
• Cancer: lung (~72% attributable to smoking), oral cavity, oesophageal, bladder, kidney, pancreatic, cervical
• Other: type 2 diabetes (50% increased risk), peptic ulcer disease, osteoporosis, cataracts, impaired wound healing, erectile dysfunction

Nicotine Withdrawal

• Onset: within 2-12 hours of last cigarette
• Peak: 24-72 hours
• Duration: physical symptoms improve over 2-4 weeks; cravings may persist for months
• Features: irritability, anxiety, restlessness, difficulty concentrating, increased appetite, depressed mood, insomnia

Red Flags

• Haemoptysis in a smoker: urgent 2-week-wait cancer referral
• Weight loss and new persistent cough: suspect lung malignancy
• New claudication symptoms: peripheral arterial disease
• Smoking in pregnancy: counsel on risks (low birth weight, preterm birth, stillbirth, SIDS); offer NRT

Bedside

• Expired carbon monoxide (CO): >10 ppm = active smoker; used to verify quit status; <4 ppm = non-smoker
• Fagerström Test/HSI: assess dependence severity
• Comprehensive smoking history: pack-years (packs/day × years smoked)
• Very Brief Advice: ASK, ADVISE, ACT at every healthcare contact

Bloods

• Cotinine level (urine or blood): metabolite of nicotine; gold standard for verifying smoking status; used in research and insurance
• FBC: polycythaemia in heavy smokers
• Lipid profile: dyslipidaemia
• HbA1c/glucose: diabetes risk assessment

Imaging

• Chest X-ray: if respiratory symptoms or suspected malignancy
• Low-dose CT thorax: NHS Lung Health Check programme - targeted lung cancer screening for 55-74 year olds with ≥20 pack-year history
• Spirometry: if COPD suspected

Special Tests

• ECG: baseline cardiovascular assessment if significant risk factors
• Abdominal aortic aneurysm screening: men aged 65 - smoking is the major modifiable risk factor

Non-pharmacological

• Very Brief Advice (VBA): recommended at every healthcare contact (NICE PH1, NICE NG209)
  • ASK: establish smoking status
  • ADVISE: "the best thing you can do for your health is to stop smoking"
  • ACT: refer to stop smoking service, prescribe pharmacotherapy, or offer self-help
• Behavioural support: stop smoking services provide structured support; doubles quit rates compared to pharmacotherapy alone
• Group or individual counselling: both effective; patient preference
• NHS Stop Smoking Services: free; combination of behavioural support + pharmacotherapy; 4-week quit rates ~50%; CO-verified abstinence at 12 months ~15-20%

Pharmacological

• Varenicline (Champix) 0.5 mg OD for 3 days, then 0.5 mg BD for 4 days, then 1 mg BD for 12 weeks (can extend to 24 weeks):
  • Partial agonist at α4β2 nAChR: reduces craving and withdrawal; blocks reward from smoking
  • Most effective single therapy: OR ~2.2-2.9 vs placebo for 6-month abstinence
  • EAGLES trial (2016): no increased neuropsychiatric risk compared to NRT or placebo
  • Side effects: nausea (most common), vivid dreams, headache
  • Note: supply issues from 2021; alternatives needed when unavailable
• Nicotine Replacement Therapy (NRT):
  • Increases quit rates by 50-60%; available OTC and on prescription
  • Combination therapy most effective: long-acting (patch) + short-acting (gum, lozenge, inhalator, nasal spray, mouth spray)
  • Patch: 21 mg/24h (heavy smokers), 14 mg/24h, 7 mg/24h - step-down over 8-12 weeks
  • Gum: 2 mg or 4 mg (for highly dependent smokers)
  • Inhalator, nasal spray, lozenge, mouth spray: for breakthrough cravings
  • Safe in cardiovascular disease; safe in pregnancy (preferable to smoking)
• Bupropion (Zyban) 150 mg OD for 6 days, then 150 mg BD for 7-9 weeks:
  • Noradrenaline and dopamine reuptake inhibitor
  • OR ~1.6 vs placebo
  • Contraindicated: seizure disorders, eating disorders, bipolar, concurrent MAOIs
• Cytisine (Desmoxan): partial nAChR agonist; emerging evidence of efficacy similar to varenicline; natural plant alkaloid; increasingly available
• E-cigarettes/vapes: not licensed medicines but endorsed by OHID (Office for Health Improvement and Disparities) as cessation aid; ~twice as effective as NRT (Hajek et al., NEJM 2019); swap-to-stop schemes in NHS

Surgical

• Not applicable to smoking cessation specifically

Referral Criteria

• NHS Stop Smoking Service: all smokers motivated to quit; GPs can refer directly
• Specialist services: pregnant smokers (specialist midwifery), mental health inpatients (higher smoking rates), secondary care inpatients (hospital smoking cessation teams)
• Respiratory/oncology: for smoking-related disease management alongside cessation support

Benefits of Cessation

• 20 minutes: heart rate and blood pressure begin to normalise
• 48 hours: CO eliminated; taste and smell improving
• 1 year: CVD risk halved compared to continuing smoker
• 10 years: lung cancer risk halved compared to continuing smoker
• 15 years: CVD risk equivalent to never-smoker
• Stopping at age 30: gain ~10 years life expectancy; stopping at age 60: gain ~3 years

Complications of Continued Smoking

• Life expectancy reduction: smokers die on average 10 years earlier than non-smokers
• COPD: progressive, irreversible airflow limitation; leading cause of respiratory disability
• Lung cancer: ~47,000 cases/year in UK; 5-year survival ~15-20% overall
• Cardiovascular disease: 2-4× risk of CAD; 2× risk of stroke
• Economic cost: estimated £2.4 billion/year to the NHS

Quit Attempt Statistics

• ~60% of smokers want to quit; ~30% make a quit attempt each year
• Unaided quit attempts: ~3-5% success at 12 months
• Pharmacotherapy alone: ~10-15% at 12 months
• Pharmacotherapy + behavioural support: ~15-25% at 12 months
• Average smoker makes ~7 quit attempts before successfully stopping long-term

Smoking Cessation Pharmacotherapy Comparison

Fagerström Test Items

Key Landmark Studies

Key Facts

Harm reduction is a cornerstone of UK drug policy and public health strategy. It recognises that some individuals cannot or do not wish to stop using substances, and focuses on minimising associated harms. The approach is endorsed by NICE, PHE/OHID, WHO, and UNAIDS.

Epidemiology and Context

• Approximately 300,000 high-risk drug users in England; not all are in treatment
• Needle and syringe programmes distribute approximately 30 million syringes per year in England
• Hepatitis C prevalence among people who inject drugs (PWID): approximately 50%; declining with increased treatment
• HIV prevalence among PWID in England: approximately 1% (low by international standards - attributed to early NSP implementation)
• Drug-related deaths: record levels (~4,900/year); harm reduction measures are crucial to reducing this toll

Principles

1. Pragmatism: drug use is a reality; focus on reducing harm rather than eliminating use
2. Human rights: drug users deserve access to healthcare and respect
3. Evidence-based: interventions proven to reduce morbidity, mortality, and BBV transmission
4. Hierarchy of goals: death prevention > disease prevention > reducing injecting risk > reducing drug use
5. Non-judgemental engagement: meeting people where they are

Policy Framework

• UK Drug Strategy 2021: "From Harm to Hope" - combines harm reduction with treatment and recovery
• NICE PH52 (2014): Needle and syringe programmes - evidence-based recommendations
• NICE NG225 (2022): Drug misuse prevention and harm reduction
• Dame Carol Black Review (2021): highlighted urgent need for increased investment in drug treatment and harm reduction

Target Populations for Harm Reduction

• People who inject drugs (PWID): highest risk for BBV transmission, overdose, injection-related infections
• People who smoke drugs: crack cocaine, heroin (chasing); lower BBV risk than injecting
• Opioid users not in treatment: at risk of overdose, particularly after tolerance loss
• Alcohol-dependent individuals: street drinkers, homeless populations
• Chemsex populations: MSM using GHB/GBL, crystal meth, mephedrone during sexual activity - risk of BBV, overdose, sexual health consequences
• People in criminal justice settings: prison, probation; high rates of substance use

Assessment for Harm Reduction Interventions

• Injecting risk assessment: sites used, sharing of equipment, knowledge of safer injecting
• BBV risk assessment: sharing history, sexual risk, vaccination status
• Overdose risk assessment: lone use, polydrug use, tolerance changes, recent prison release
• Housing and social circumstances: homelessness significantly increases all drug-related harms
• Mental health: co-morbidity assessment

Red Flags Indicating High-Risk Drug Use

• Groin injecting: risk of DVT, femoral artery damage, abscess
• Sharing injecting equipment: BBV transmission risk
• Using alone: no witness to administer naloxone in overdose
• Recent prison release or detoxification: loss of tolerance → overdose risk
• Polydrug use with opioids: benzodiazepines, alcohol, pregabalin synergistically increase overdose risk
• Pregnancy: neonatal abstinence syndrome, BBV vertical transmission

Bedside

• Injecting risk assessment: standardised assessment of injecting behaviour, equipment sharing, injection sites
• Overdose risk assessment: identify modifiable risk factors
• Hepatitis B vaccination status: check and offer if incomplete
• Expired CO reading: if smoking

Bloods / Point-of-Care Testing

• Dry blood spot (DBS) testing: hepatitis B, hepatitis C, HIV - can be done in community settings (pharmacies, outreach services)
• Hepatitis C antibody and PCR: confirm active infection; direct to treatment
• Hepatitis B surface antigen: identify chronic carriers; vaccinate susceptible individuals
• HIV test: opt-out testing recommended for all PWID
• FibroScan: non-invasive liver fibrosis assessment in hepatitis C-positive individuals

Imaging

• Not routinely part of harm reduction assessment
• Duplex ultrasound: if DVT suspected from groin injection

Special Tests

• Urine drug screen: support clinical assessment and treatment planning
• Sexual health screening: particularly for chemsex populations - STI screen, PrEP assessment for HIV
• Wound swab: if injection site infection; identify causative organism

Needle and Syringe Programmes (NICE PH52)

• Provision of sterile equipment: needles, syringes, filters, spoons, water, citric acid, swabs, tourniquets
• Foil provision: clean foil for smoking drugs - reduces injecting-related harm
• Sharps disposal: safe return and disposal of used equipment
• Advice on safer injecting: rotating injection sites, vein care, avoiding groin and neck injection
• Accessible locations: pharmacies, specialist services, mobile/outreach units, vending machines
• Distribute approximately 30 million syringes/year in England

Take-Home Naloxone

• Prenoxad: pre-filled syringe (5 × 400 mcg doses IM); provided to opioid users, families, and services
• Nyxoid: intranasal spray (1.8 mg per dose); no needle required
• Training: simple instruction on recognition of opioid overdose and naloxone administration
• Target groups: all people using illicit opioids, OST patients, prison leavers, family/carers, hostel staff
• Legal protection: no prosecution for administering naloxone in emergency

Blood-Borne Virus Prevention and Treatment

• Hepatitis B vaccination: accelerated schedule for PWID (0, 7, 21 days + 12-month booster); check seroconversion
• Hepatitis C treatment: direct-acting antivirals (e.g. sofosbuvir/velpatasvir - Epclusa - 12 weeks); >95% SVR; treat and prevent paradigm (NICE TA507)
• HIV PrEP: emtricitabine/tenofovir (Truvada) for HIV-negative PWID and chemsex populations at high risk
• HIV treatment: early ART initiation; undetectable = untransmissible (U=U)

Opioid Substitution Therapy

• Methadone or buprenorphine: reduces overdose risk, injecting, BBV transmission, crime (detailed in OST topic)

Supervised Consumption Rooms

• Legally sanctioned facilities where pre-obtained drugs can be consumed under medical supervision
• Not currently legal in England; pilot approved in Glasgow (2023)
• International evidence: reduces overdose death, BBV transmission, public injecting; does not increase drug use or crime

Managed Alcohol Programmes

• Controlled provision of alcohol (e.g. beer/wine at set intervals) to severely dependent homeless individuals
• Reduces consumption of non-beverage alcohol, emergency presentations, and alcohol-related harm

Referral Criteria

• Community drug and alcohol services: all people using substances harmfully
• Hepatology/BBV services: hepatitis C-positive individuals for DAA treatment
• Sexual health services: chemsex populations, BBV-positive individuals
• Housing and social services: homeless individuals using substances
• Mental health services: co-morbid mental illness (dual diagnosis)

Effectiveness of Harm Reduction

• NSPs: reduce hepatitis C incidence by approximately 50% among PWID; contributed to keeping UK HIV prevalence among PWID at ~1% (vs >30% in countries without NSPs)
• Take-home naloxone: associated with ~36% reduction in opioid overdose mortality at community level
• OST: reduces all-cause mortality by ~50%; reduces heroin use, injecting, and crime
• Hepatitis C treatment: >95% SVR with DAAs; WHO elimination target (80% reduction by 2030) potentially achievable in UK
• Hepatitis B vaccination: effective seroconversion in >80% of PWID completing accelerated schedule

Ongoing Challenges

• Drug-related deaths: continuing to rise despite harm reduction efforts; need for expanded access
• Treatment gaps: only ~50% of opioid users in treatment; significant unmet need
• Homelessness: strong association with drug-related harm; housing-first approaches complement harm reduction
• Stigma: barrier to accessing services; affects quality of healthcare received
• Novel substances: rapidly changing drug market challenges existing harm reduction infrastructure
• Funding: real-terms cuts to drug treatment budgets 2014-2020 (Dame Carol Black Review); investment recovering

Hierarchy of Harm Reduction Goals

Key UK Harm Reduction Policy Documents

Comparison of Harm Reduction Interventions

Key Facts

Motivational interviewing is one of the most widely studied and applied behavioural interventions in healthcare. It has a strong evidence base across multiple conditions including substance misuse, smoking cessation, medication adherence, weight management, and chronic disease self-management.

Epidemiology and Context

• MI is recommended in over 20 NICE guidelines across different clinical areas
• Brief motivational interventions (1-4 sessions) are the standard approach for hazardous/harmful alcohol use in primary care and Emergency Departments
• MI training is a core competency in postgraduate training for GPs, psychiatrists, and addiction specialists
• Stages of Change model (Prochaska & DiClemente, 1983): often used alongside MI - precontemplation, contemplation, preparation, action, maintenance, relapse

Theoretical Basis

• Self-determination theory: MI supports autonomy, competence, and relatedness - key psychological needs for sustained behaviour change
• Cognitive dissonance: MI creates discrepancy between current behaviour and personal values/goals, motivating change
• Self-perception theory: hearing oneself articulate reasons for change (change talk) strengthens commitment
• Reactance theory: directive, confrontational approaches increase resistance; MI avoids this by "rolling with resistance"

Pathophysiology/Mechanism of Action

• MI works through the language of change: the practitioner strategically evokes and reinforces change talk (patient statements favouring change)
• Research demonstrates that the proportion of change talk vs sustain talk in MI sessions predicts behavioural outcomes
• Empathic listening activates mirror neuron systems and builds therapeutic alliance
• MI reduces discord (resistance) in the therapeutic relationship by avoiding argumentation and supporting autonomy

Indications for Motivational Interviewing

• Substance misuse: alcohol, drugs, smoking - at any stage of change
• Chronic disease management: diabetes, hypertension, obesity, asthma adherence
• Lifestyle change: diet, exercise, sexual health
• Mental health: medication adherence, engagement with treatment
• Criminal justice: offending behaviour programmes
• Any situation where a patient is ambivalent about behaviour change

Assessment of Readiness to Change

• Precontemplation: not considering change; no perceived problem
• Contemplation: aware of problem; ambivalent; weighing pros and cons
• Preparation: intending to change; making plans
• Action: actively modifying behaviour
• Maintenance: sustained change; preventing relapse
• Relapse: return to previous behaviour - normalised as part of the change process

Core Processes of MI (Miller & Rollnick, 2013)

1. Engaging: establishing a working relationship; building rapport and trust
2. Focusing: developing and maintaining direction; agreeing on the target behaviour
3. Evoking: eliciting the patient's own motivations for change (change talk)
4. Planning: developing commitment to change and formulating a concrete plan

Red Flags / When MI May Not Be Appropriate

• Acute crisis: patient in immediate danger (overdose, psychosis, suicidality) - manage the emergency first
• Lack of capacity: patients who cannot engage in meaningful conversation (intoxication, delirium, severe cognitive impairment)
• When clear medical advice is needed: MI is not a substitute for giving unambiguous clinical information (e.g. "you need emergency surgery")
• Practitioner is not trained: poorly executed MI (especially "righting reflex" - telling the patient what to do) can be counterproductive

Assessment Tools Used Alongside MI

• Readiness to change rulers: 0-10 scale - "How ready are you to make this change?" followed by exploring responses
• Importance and confidence rulers: "On a scale of 0-10, how important is it for you to change? How confident are you that you could change?"
• Decisional balance: exploring pros and cons of change vs. status quo - structured exercise within MI framework
• AUDIT/AUDIT-C: screening for alcohol use disorders (used to identify patients who may benefit from MI)
• Stages of Change questionnaire: identifies current stage in the change cycle

Assessment of MI Fidelity

• MITI (Motivational Interviewing Treatment Integrity): gold standard for coding MI quality in research and training
  • Measures: empathy, MI spirit (partnership, autonomy, evocation, compassion)
  • Counts: reflections, questions (ratio of reflections to questions), MI-adherent behaviours (affirmations, seeking permission) vs MI-non-adherent behaviours (advising without permission, confronting)
• MISC (Motivational Interviewing Skill Code): more detailed coding system
• Training standards: MI competence typically requires 2-3 days initial training plus ongoing supervision and practice

Monitoring Outcomes

• Substance use measures: AUDIT, SADQ, urine drug screens, drinking diary
• Behavioural outcome measures: specific to target behaviour (e.g. HbA1c for diabetes, weight for obesity)
• Patient-reported outcomes: confidence in change, self-efficacy measures
• Session recordings: reviewed in supervision for MI fidelity

OARS - Core MI Skills

• Open questions: encourage patient to explore their experience
  • "What concerns you about your drinking?"
  • "How would you like things to be different?"
• Affirmations: recognise patient strengths, efforts, and values
  • "It took courage to come here today"
  • "You clearly care about your family's wellbeing"
• Reflective listening: the most fundamental MI skill; demonstrates understanding and encourages deeper exploration
  • Simple reflection: repeating or rephrasing what the patient said
  • Complex reflection: adding meaning, reflecting feeling, or continuing the paragraph (anticipating what the patient might say next)
  • Aim for reflection:question ratio of at least 2:1
• Summaries: collecting and linking what the patient has said; demonstrates careful listening and can strategically highlight change talk

Key MI Strategies

• Developing discrepancy: helping the patient see the gap between current behaviour and personal values/goals
  • "On one hand you enjoy drinking with friends, and on the other you're worried about your liver. What do you make of that?"
• Rolling with resistance (responding to sustain talk and discord):
  • Avoid arguing or confronting
  • Use reflections to acknowledge the patient's perspective
  • Emphasise personal autonomy: "It's entirely your decision"
• Supporting self-efficacy: build confidence in the patient's ability to change
  • "You've managed to cut down before - what worked for you then?"
• Eliciting change talk: ask evocative questions targeting desire, ability, reasons, need, commitment (DARN-C)
  • "What would be the best thing about making this change?"
  • "How might you go about it?"

Delivering MI in Practice

• Brief MI (5-15 minutes): adapted for time-limited settings (GP consultations, ED attendances); retains core spirit and OARS
• Extended MI (2-4 sessions, ~45 minutes each): motivational enhancement therapy (MET); used in specialist addiction services
• Group MI: adapted for group settings; effective in some contexts
• Telephone and digital MI: evidence for remote delivery; useful for accessibility

Training and Competence

• Initial training: typically 2-3 day workshop with role-play and feedback
• Ongoing supervision: essential for skill development and maintenance
• Coding and feedback: using MITI to assess and improve practice
• Integration with other approaches: MI is often combined with CBT, contingency management, or pharmacotherapy

Referral Criteria

• MI is a skill used across healthcare settings rather than a standalone referral pathway
• Brief MI: delivered by any trained healthcare professional (GP, nurse, pharmacist, ED doctor)
• Specialist MI/MET: addiction services, mental health teams, health psychology
• Training provision: Royal College of General Practitioners, various NHS trusts, Motivational Interviewing Network of Trainers (MINT)

Evidence of Effectiveness

• Alcohol use disorders: brief MI in primary care and ED reduces alcohol consumption; NNT ~8 for reduction to low-risk drinking (NICE CG115)
• UKATT trial (2005): motivational enhancement therapy (3 sessions) as effective as social behaviour and network therapy (8 sessions) - more cost-effective
• Project MATCH (1997): MET, CBT, and 12-step facilitation all effective; no significant matching effect
• Smoking cessation: MI increases quit attempts and abstinence rates (Lindson et al., Cochrane 2019)
• Drug misuse: modest but significant effects on reducing substance use (Smedslund et al., Cochrane 2011)
• Chronic disease: effective for medication adherence (OR ~1.5), diabetes self-management, weight loss

Limitations

• Effect sizes are modest: typically small to medium; MI is not a miracle cure
• Practitioner skill variation: effectiveness highly dependent on quality of MI delivery
• Less effective for: patients with no ambivalence (either strongly motivated or completely resistant), acute crises
• Evidence strongest for: brief interventions for alcohol, as adjunct to other treatments for drug misuse, and for engagement in treatment

Complications of Poor MI Practice

• "Righting reflex": telling the patient what to do → increases resistance
• Premature focus: pushing towards change before exploring ambivalence → discord
• Excessive use of closed questions: feels interrogative; reduces engagement
• Labelling: e.g. "you're an alcoholic" → increases resistance and shame
• Wrestling with resistance: arguing with the patient → entrenches status quo

MI Spirit and Principles Summary

Change Talk (DARN-CAT)

Key Landmark Studies

Key Facts

Dual diagnosis is the rule rather than the exception in both mental health and substance misuse services. The interaction between mental illness and substance use creates a cycle of mutual reinforcement that is challenging to treat. Integrated care models addressing both conditions simultaneously are recommended but inconsistently implemented.

Epidemiology

• General population: ~30% of people with any mental disorder have a co-morbid substance use disorder
• Severe mental illness (SMI): substance misuse prevalence:
  • Schizophrenia: ~40-50% lifetime substance use disorder
  • Bipolar disorder: ~40-60% lifetime substance use disorder
  • Personality disorder (especially EUPD/BPD): ~50-70%
• Substance misuse populations: psychiatric co-morbidity:
  • Depression: ~30-40%
  • Anxiety disorders: ~25-30%
  • PTSD: ~20-35%
  • Psychotic disorders: ~10-15%
  • ADHD: ~20-25% (often undiagnosed)
• Homeless population: rates of dual diagnosis up to ~70-80%
• Criminal justice: very high rates; dual diagnosis common among prison population

Aetiology

• Self-medication hypothesis: individuals use substances to alleviate psychiatric symptoms (e.g. alcohol for anxiety, cannabis for negative symptoms of schizophrenia)
• Shared vulnerability: common genetic, neurobiological, and environmental risk factors (e.g. dopamine system dysregulation, childhood adversity, social deprivation)
• Substance-induced mental illness: alcohol-related depression, cannabis-induced psychosis, stimulant-induced psychosis, drug-related anxiety disorders
• Mental illness predisposing to substance use: impulsivity, risk-taking, social marginalisation, cognitive deficits, peer group exposure
• Adverse childhood experiences (ACEs): childhood trauma is a common antecedent to both mental illness and substance misuse

Pathophysiology

• Dopamine dysregulation: central to both psychotic disorders and addiction; substance use further disrupts dopaminergic circuits
• HPA axis: chronic stress (from both mental illness and substance use) leads to dysregulated cortisol response
• Neuroinflammation: both chronic substance use and severe mental illness are associated with neuroinflammatory processes
• Structural brain changes: comorbid substance use accelerates grey matter loss in schizophrenia and bipolar disorder
• Pharmacokinetic interactions: substance use affects metabolism of psychotropic medications (e.g. smoking induces CYP1A2 → increased clozapine metabolism)

Common Dual Diagnosis Presentations

Psychosis and Substance Use

• Cannabis-associated first-episode psychosis: paranoid delusions, auditory hallucinations
• Stimulant-induced psychosis: persecutory delusions, tactile hallucinations (formication)
• Alcohol hallucinosis: auditory hallucinations with clear sensorium
• Chronic schizophrenia with co-morbid alcohol, cannabis, or polydrug use

Depression and Substance Use

• Alcohol-related depression: low mood, anhedonia, sleep disturbance worsened by alcohol
• Depression during opioid withdrawal or stimulant crash
• Persistent depression in chronic substance users
• Suicidal ideation commonly exacerbated by intoxication

Anxiety and Substance Use

Alcohol use as anxiolytic

dependence

anxiety worsened by withdrawal cycle

• Benzodiazepine dependence in anxiety disorders
• Cannabis-related panic attacks and generalised anxiety
• PTSD with substance use as avoidance strategy

Personality Disorder and Substance Use

• Emotionally unstable personality disorder (EUPD/BPD): impulsive substance use, self-harm under intoxication
• Antisocial personality disorder: overlaps with addiction behaviours, criminal justice involvement
• Substance use to manage emotional dysregulation

Red Flags

• Suicidal ideation with substance use: very high risk - intoxication disinhibits and increases lethality
• Psychosis with continued substance use: risk of violence, self-neglect, treatment non-adherence
• Rapid deterioration in mental state: may indicate escalation of substance use or new substance
• Non-concordance with medication: substance use commonly leads to medication non-adherence
• Safeguarding concerns: children of parents with dual diagnosis; vulnerable adults; domestic abuse
• Homelessness: severely impacts ability to engage with treatment; increases all risks

Bedside

• Comprehensive substance use history: all substances, routes, frequency, duration, consequences
• Mental state examination: full MSE including cognitive assessment
• Risk assessment: suicide, self-harm, violence, vulnerability, safeguarding
• Urine drug screen: confirm substances used; identify unknown substances
• Screening tools:
  • AUDIT / AUDIT-C (alcohol)
  • DAST-10 (Drug Abuse Screening Test)
  • PHQ-9 (depression), GAD-7 (anxiety)
  • PCL-5 (PTSD)
  • Conners / DIVA (ADHD - if suspected)
• Collateral history: essential for accurate assessment; family, carers, GP records

Bloods

• FBC, LFTs, U&Es: substance-related organ damage
• TFTs: exclude thyroid disease contributing to mood symptoms
• Blood-borne virus screen: hepatitis B, C, HIV
• Prolactin: if on antipsychotics (also elevated in some substance use)
• HbA1c and lipids: metabolic monitoring on antipsychotics
• Clozapine level: if on clozapine - smoking cessation significantly increases levels (CYP1A2 effect)

Imaging

• MRI brain: if first-episode psychosis, atypical presentation, or organic cause suspected
• CT head: acute presentations with altered consciousness, head injury

Special Tests

• Neuropsychological testing: if persistent cognitive impairment after period of abstinence
• ECG: QTc monitoring if on methadone or antipsychotics
• Structured clinical interview: e.g. SCID or MINI for formal diagnostic assessment
• Capacity assessment: under Mental Capacity Act 2005 - frequently required in dual diagnosis

Non-pharmacological

• Integrated treatment model: addressing substance use and mental health simultaneously within one team or through close collaboration
  • NICE CG120: recommends mental health services take the lead for people with severe mental illness and substance misuse
  • "No wrong door": neither service should refuse to treat based on the other condition
• Care coordination: CPA (Care Programme Approach) for those with SMI; key worker / care coordinator
• Psychosocial interventions:
  • CBT: adapted for dual diagnosis; addresses both substance use triggers and psychiatric symptoms
  • Motivational interviewing: addresses ambivalence about substance use change
  • Contingency management: incentive-based approaches for substance reduction
  • Family interventions: psychoeducation, carer support (particularly in psychosis)
• Trauma-informed care: recognising the high prevalence of trauma; avoiding re-traumatisation
• Housing and social support: housing-first approaches; benefits advice; social inclusion programmes
• Peer support: recovery workers with lived experience

Pharmacological

• Principles:

  • Treat both conditions - do not withhold psychiatric medication because of substance use
  • Choose medications with lower interaction potential and abuse liability
  • Monitor adherence closely; consider depot/long-acting formulations for psychosis
  • Be cautious with benzodiazepines (dependence risk, respiratory depression with opioids)

• Psychosis + substance use:

  • Antipsychotics: second-generation preferred; aripiprazole may have lower metabolic side-effect burden
  • Clozapine: evidence for reducing substance use in treatment-resistant schizophrenia; monitor carefully - smoking cessation/reduction significantly increases clozapine levels (CYP1A2 induction by smoking)
  • Depot antipsychotics: e.g. paliperidone palmitate, aripiprazole long-acting injection - improves adherence

• Depression + substance use:

  • Reassess mood after 2-4 weeks of abstinence - substance-induced depression often improves
  • If depression persists: SSRIs first-line (e.g. sertraline 50-200 mg OD; fluoxetine 20-60 mg OD)
  • Avoid TCAs: risk of toxicity in overdose; lower seizure threshold
  • Mirtazapine 15-45 mg ON: useful for insomnia and appetite stimulation; low seizure risk

• Anxiety + substance use:

  • SSRIs first-line for GAD, panic, social anxiety
  • Avoid benzodiazepines: high abuse potential, cross-tolerance with alcohol, respiratory depression risk with opioids
  • Pregabalin 150-600 mg/day: licensed for GAD but has abuse potential - prescribe cautiously in substance misusers
  • Propranolol 40 mg BD-TDS: for somatic anxiety symptoms without abuse potential

• ADHD + substance use:

  • Treat ADHD - untreated ADHD is a risk factor for substance misuse
  • Lisdexamfetamine (Elvanse): preferred stimulant - pro-drug with lower abuse potential
  • Atomoxetine 40-100 mg OD: non-stimulant alternative; no abuse potential
  • Stabilise substance use before or concurrently with ADHD treatment initiation

• Substance-specific treatment: OST for opioid dependence, managed withdrawal for alcohol, NRT/varenicline for smoking - should proceed alongside psychiatric treatment

Surgical

• Not applicable

Referral Criteria

• Community mental health team (CMHT): severe mental illness with substance misuse
• Early Intervention in Psychosis (EIP): first-episode psychosis with substance use
• Community drug and alcohol services: for substance-specific treatment alongside mental health care
• Crisis team / home treatment team: acute psychiatric crisis with substance involvement
• Inpatient psychiatric admission: acute psychosis, high suicide risk, severe self-neglect, failed community management
• Specialist dual diagnosis team: where available - provides integrated assessment and care

Outcomes

• Poorer outcomes than either condition alone: dual diagnosis associated with increased hospitalisation, homelessness, violence, victimisation, and mortality
• Suicide risk: substance misuse present in ~25-35% of completed suicides; risk is multiplicative when combined with depression or psychosis
• Treatment engagement: often lower than for single diagnosis; frequent loss to follow-up
• Integrated treatment: produces better outcomes than parallel or sequential treatment for engagement, substance use reduction, and psychiatric symptom improvement
• Recovery is possible: with sustained integrated support, many individuals achieve stability and improved quality of life

Complications

• Increased relapse of both conditions: substance use precipitates psychiatric relapse and vice versa
• Medication non-adherence: major contributor to psychiatric relapse; substance use disrupts routines and insight
• Physical health: dual diagnosis associated with worse physical health outcomes; cardiovascular disease, infections, liver disease
• Homelessness: both a cause and consequence of dual diagnosis; dramatically worsens prognosis
• Criminal justice involvement: higher rates of offending and incarceration
• Social exclusion: stigma from both mental illness and substance misuse; reduced employment, relationship breakdown
• Premature mortality: life expectancy reduced by 15-20 years compared to general population in people with SMI and substance misuse

Models of Care for Dual Diagnosis

Substance Use and Specific Psychiatric Conditions

Key Policy and Guidance