Opioid dependence
Exam Tips
- ICD-11 style diagnosis: recurrent opioid use plus at least two dependence features (impaired control, priority of use, tolerance, withdrawal/relief use).
- Withdrawal timing is drug-dependent: heroin withdrawal often starts within about 12 hours and peaks over days; methadone withdrawal starts later and lasts longer.
- Do not rely solely on pinpoint pupils: miosis may be absent with some synthetic opioids (for example fentanyl analogues).
- Highest overdose risk periods include after detoxification, prison release, or any abstinence period because tolerance has fallen.
- In OSCEs, always include harm reduction (needle exchange, BBV screening/vaccination, take-home naloxone) and safeguarding assessment.
- See Figure: classic opioid toxidrome triad (reduced consciousness, respiratory depression, miosis) and compare with withdrawal autonomic hyperactivity for viva contrast.
Definition
Opioid dependence is a chronic relapsing-remitting disorder in which repeated opioid use leads to impaired control, compulsive use, tolerance, and withdrawal, with use continuing despite clear harm. In UK practice, diagnosis is clinical and typically requires a persistent pattern of opioid use with functional decline plus dependence features over time (often months, but can be diagnosed earlier with continuous near-daily use).
Pathophysiology
Repeated stimulation of central opioid receptors (mainly mu receptors in reward, pain, and brainstem pathways) causes neuroadaptation: reduced endogenous opioid tone, receptor/signalling changes, and upregulation of cAMP/noradrenergic activity (notably in the locus coeruleus). This drives tolerance (need for higher doses), withdrawal on cessation (autonomic and gastrointestinal hyperactivity), and reinforcement/craving via mesolimbic dopamine circuits. Dependence risk and severity are shaped by drug potency, route (injecting/smoking faster reinforcement), frequency, psychiatric comorbidity, trauma, and social deprivation.
Risk Factors
- High opioid availability and peer substance use
- Adverse childhood experiences (neglect, abuse, family disruption, homelessness)
- Past or current mental illness (for example depression, bipolar disorder, psychosis)
- History of substance misuse (including alcohol, benzodiazepines, cocaine, gabapentinoids)
- Social disadvantage, deprivation, unemployment, housing instability
- Genetic vulnerability/family predisposition
- Younger age
- Male sex
Clinical Features
Symptoms
- Strong craving or compulsion to use opioids
- Difficulty cutting down or controlling opioid use
- Prioritising opioid use over work, relationships, and self-care
- Tolerance (needing more opioid for same effect)
- Withdrawal symptoms on reduction/cessation: rhinorrhoea, lacrimation, yawning, sweating, abdominal cramps, nausea, vomiting, diarrhoea, myalgia/back pain, insomnia, anxiety, irritability
- History of overdose, relapse after abstinence, and polydrug use
Signs
- Injection-related findings: track marks, skin scarring, abscesses, necrosis
- Intoxication: sedation, reduced consciousness, slurred speech, impaired coordination/judgement
- Miosis (may be absent with some synthetic opioids), pruritus/scratching
- Respiratory depression/hypoventilation, bradycardia, hypotension in overdose states
- Withdrawal signs: mydriasis, piloerection, tremor, tachypnoea, hypertension, cool clammy skin, restlessness
- Complication clues: poor dentition, malnutrition, signs of cellulitis/endocarditis/DVT, low mood or psychotic features
Investigations
Management
Lifestyle Modifications
- Rapid referral/engagement with local drug and alcohol services; coordinated biopsychosocial care plan
- Harm reduction: needle and syringe programmes, safer injecting advice, smoking cessation, alcohol reduction
- Overdose prevention education (reduced tolerance after abstinence/prison/discharge), involve family/carers where appropriate
- Psychosocial interventions (motivational interviewing, relapse prevention, contingency management, peer support)
- Vaccination and prevention: hepatitis B immunisation, BBV testing/treatment, sexual health support
- Address social determinants: housing, benefits, safeguarding, and criminal justice liaison
Pharmacological Treatment
Opioid substitution treatment (full agonist)
- Methadone oral solution: typical initial 10-30 mg once daily under supervision; titrate cautiously by 5-10 mg every few days; common maintenance 60-120 mg once daily
First-line maintenance option in many UK services. Avoid rapid dose escalation due to delayed respiratory depression risk. Use caution/avoid in acute alcohol or sedative intoxication, severe respiratory compromise, and significant QT prolongation risk; review interacting QT-prolonging drugs.
Opioid substitution treatment (partial agonist)
- Buprenorphine sublingual: start when objective withdrawal is present (often 4 mg initial, then 2-4 mg increments on day 1); usual maintenance 8-16 mg daily (max commonly 32 mg/day)
Lower overdose risk than methadone when used alone, but still dangerous with benzodiazepines/alcohol. Starting too soon after full agonists can precipitate withdrawal. Caution in severe hepatic impairment.
Managed withdrawal (detox) adjunct
- Lofexidine: 200 micrograms four times daily, titrated according to symptoms; maximum 2.4 mg/day, usually for 7-10 days with taper
Used for withdrawal symptom control where appropriate, usually with specialist input. Monitor blood pressure/pulse; adverse effects include hypotension, bradycardia, sedation, and potential QT effects.
Overdose reversal and prevention
- Naloxone for suspected opioid overdose: 400 micrograms IV/IM initially, repeated every 2-3 minutes as needed (titrate to ventilation)
- Take-home naloxone (for example intranasal naloxone 1.8 mg/0.1 mL single-dose device) for patients and close contacts
Naloxone duration may be shorter than long-acting opioids, so recurrent toxicity can occur; observe and repeat doses/infusion if needed. Withdrawal may be precipitated after reversal.
Complications
- Fatal and non-fatal overdose (especially with injecting, polydrug use, or relapse after abstinence)
- Premature mortality from overdose, suicide, trauma/violence, and medical disease
- Skin/soft tissue infection, sepsis, necrotizing infection, bacteraemia
- Blood-borne viruses (HIV, hepatitis B, hepatitis C), plus risk of tuberculosis
- Infective endocarditis in people who inject drugs
- Vascular disease: superficial thrombophlebitis, DVT, pulmonary embolism, venous/arterial thrombosis
- Sexual and reproductive harms (STIs, unplanned pregnancy, fetal growth problems, neonatal opioid withdrawal)
- Mental health complications (depression, anxiety, self-harm/suicide risk, psychosis, cognitive impairment)
- Social harms (homelessness, exploitation, safeguarding concerns, criminal justice involvement, poverty)
Prognosis
Untreated opioid dependence has very high relapse rates and a markedly increased mortality risk compared with the general population. Outcomes improve substantially with sustained opioid substitution treatment plus psychosocial and social support, including lower overdose and all-cause mortality, though treatment often needs to be long term and relapse remains common, especially with mental health comorbidity and polydrug use.
Sources & References
💊BNF Drug References(2)
- Buprenorphine[management.pharmacological]
- Methadone hydrochloride[management.pharmacological]
✅NICE Guidelines(1)
- Opioid dependence[overview]
📖Textbook References(2)
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1042, 1043)[context]
- David Randall PhD MRCP (Editor), John Booth PhD MRCP (Editor), K - Kumar and Clark's Clinical Medicine (2025, American Elsevier Publishing Co.) - libgen.li.pdf(pp. 1041, 1042)[context]