Misuse Of Substance
Misuse of substance is the harmful or hazardous use of psychoactive substances, including alcohol and illicit drugs, in a manner that deviates from approved medical or social patterns, leading to adverse physical, psychological, or social consequences.
Substance misuse (also known as substance use disorder or drug misuse) refers to the harmful or hazardous use of psychoactive substances, including both licit and illicit drugs, in a manner that causes physical, psychological, or social harm to the individual or others.
Let's break down the key terminology first, because exam questions frequently hinge on precise definitions [1][2]:
- Problem Use / Misuse: Use for pleasure but with disregard for the personal or social dangers [1]. The person is using recreationally but ignoring the consequences — they haven't necessarily become dependent yet.
- Craving: A strong and sometimes irresistible desire to use the substance — not necessarily pleasurable [1]. Think of it as an intrusive urge, often triggered by environmental cues (people, places, emotions associated with prior use). The word "irresistible" is key — the desire can overwhelm executive function.
- Dependence (Physical / Psychological): Physical adaptation → physical withdrawal symptoms. Psychological withdrawal symptoms also present [1]. The body and brain have recalibrated their "normal" around the substance being present. Remove it, and you get rebound — the opposite of what the drug does.
- Addiction: The extreme end of the dependent spectrum, characterised by social and personal decline, tolerance, and withdrawal symptoms [1]. This is the full-blown picture — compulsive use despite devastating consequences.
"Addiction is… an attachment to, or dependence upon, any substance, thing, person or idea so single-minded and intense that virtually all other realities are ignored or given second place — and consequences, even lethal ones, are disregarded." — John F. Mack (2002) [1]
Dependence ≠ Addiction
Medical students often conflate dependence and addiction. A patient on long-term prescribed opioids for cancer pain may be physically dependent (they'll get withdrawal if you stop abruptly), but they are not addicted — they don't exhibit compulsive drug-seeking, social decline, or loss of control. Addiction specifically implies a loss of control and continued use despite harm.
ICD-10 Criteria for Dependence Syndrome
≥3 out of 6 criteria present together for some time during the past year [1][2]:
- A strong desire or sense of compulsion to take the substance
- Difficulties in controlling substance-taking behaviour in terms of its onset, termination, or levels of use
- A physiological withdrawal state when substance use has ceased or been reduced
- Evidence of tolerance
- Progressive neglect of alternative pleasures or interests
- Persisting with substance use despite clear evidence of overtly harmful consequences
A useful mnemonic: "CANT Control Withdraw" — Compulsion, Alternative pleasures neglected, Noxious consequences despite use, Tolerance, Control difficulties, Withdrawal [2]
High Yield: ICD-10 Dependence
Know these 6 criteria cold. They come up in clinical vignettes where you need to determine whether a patient has "harmful use" vs "dependence." The key differentiator is that dependence requires ≥3 criteria including physical/psychological features, while harmful use simply means use causing demonstrable harm without meeting dependence criteria.
2. Epidemiology
- Worldwide, ~275 million people used drugs at least once in 2020 (UNODC World Drug Report 2023)
- Cannabis is the most widely used drug globally, followed by opioids, amphetamines, and cocaine
- Substance use disorders account for a significant burden of disability-adjusted life years (DALYs), particularly through opioid-related mortality, alcohol-related liver disease, and injection-related infections (HIV, HCV)
- Approximately 10% of people who experiment with drugs will develop dependence [2] — this is a critical statistic that underscores the role of individual vulnerability beyond mere exposure
Epidemiology in HK (2017) [2]:
- Burden: 6725 in all of HK, with 1535/year being newly reported drug abusers (downgoing trend)
- Demographics: average age of onset 18 years (overall 41 years), M:F ≈ 1:4.4
- Type (descending order): heroin > ice (methamphetamine) > ketamine > hypnotics > cocaine > cannabis
Updated HK trends (Central Registry of Drug Abuse, latest available data ~2023-2024):
- The downward trend in overall reported drug abuse has continued, though methamphetamine (ice) has remained a major concern
- Cannabis has been gaining popularity especially among younger users, reflecting global trends [2]
- Ketamine use, once Hong Kong's hallmark party drug, has declined significantly from its peak around 2009-2012
- Cocaine use has remained relatively stable at low levels
- There is an emerging concern about synthetic drugs and non-medical use of prescription drugs (benzodiazepines, opioids)
What substances are involved? [1]:
- Alcohol
- Opioids (e.g., heroin, morphine, codeine, methadone)
- Cocaine (e.g., cocaine, crack)
- Amphetamines
- Sedatives, hypnotics, anxiolytics
- Hallucinogens (e.g., LSD, ecstasy)
- Phencyclidine (e.g., PCP, ketamine)
- Inhalants
- Cannabis
- Nicotine
- Caffeine
HK-Specific Point
In HK, heroin has historically been the #1 drug of abuse (driven by the ageing cohort of long-term heroin users), but methamphetamine (ice) surpassed it among younger users. For exams, remember the HK-specific pattern differs markedly from Western countries where opioid prescription drug misuse and cannabis dominate.
3. Relevant Neuroanatomy and Function
Understanding why drugs are addictive requires understanding the brain's reward circuitry. This is one of the most important foundational concepts in addiction psychiatry.
- Ventral Tegmental Area (VTA): Contains dopaminergic (DA) cell bodies. This is the "source" of the reward signal. When something pleasurable happens (food, sex, social bonding), VTA neurons fire and release dopamine.
- Nucleus Accumbens (NAc): The "pleasure centre." Receives DA projections from VTA. Activation of the NAc underlies the subjective experience of reward and reinforcement [1]. All drugs of abuse, directly or indirectly, increase dopamine availability in the NAc.
- Prefrontal Cortex (PFC) / Orbitofrontal Cortex (OFC): Top-down executive control over impulses, judgment, and decision-making [2]. This is the "brake pedal" of the brain. In addiction, PFC function becomes progressively impaired → loss of self-control.
- Amygdala (extended amygdala): Emotional colouring of memory [2]. Associates drug-related cues with positive emotional responses (during use) and negative emotional states (during withdrawal). This drives conditioned craving.
- Hippocampus: Contextual information processing [2]. Encodes the where/when/who of drug experiences, so that contextual cues (a particular place, person, or even time of day) can trigger craving.
- Anterior Cingulate Cortex (ACC): Involved in craving/preoccupation phase — monitors conflict between desire to use and awareness of harm [1].
| Neurotransmitter | Role in Addiction |
|---|---|
| Dopamine (DA) | Primary "reward signal" — all drugs of abuse ultimately ↑ DA in NAc. Drives initial positive reinforcement ("this feels good, do it again") |
| GABA | Main inhibitory NT. Alcohol and benzodiazepines enhance GABAergic transmission → sedation, anxiolysis. Chronic use → GABA receptor downregulation |
| Glutamate | Main excitatory NT. Chronic substance use leads to upregulation of glutamatergic transmission. When drug is removed → excitotoxicity (withdrawal seizures). Also underlies shift from reward-based to habit-based circuitry [2] |
| Serotonin (5-HT) | Mood regulation. MDMA causes massive 5-HT release → euphoria. Chronic MDMA → 5-HT neurotoxicity |
| Noradrenaline (NA) | Opioid withdrawal → ↑↑ NA neuron firing → sympathetic activation (sweating, tachycardia, anxiety) |
| Endogenous opioids | Endorphins and enkephalins — the brain's "natural painkillers." Exogenous opioids hijack these receptors |
This is the cornerstone concept. Addiction is not simply "liking drugs" — it is a progressive neuroadaptive process [2]:
- Early use (Impulsive stage): Drug → ↑DA in NAc → positive reinforcement → "I like this"
- Repeated use: Tolerance develops (need more drug for same effect). Reward system recalibrates — natural rewards (food, social interaction) become less satisfying.
- Withdrawal/Negative affect stage: When drug wears off, the brain is in a state of dopamine deficit → dysphoria, anxiety, irritability. Negative reinforcement now drives use — "I use to feel normal, not to feel good" [2].
- Craving/Preoccupation stage: Drug use cues are paired with positive emotional response, and abstinence is paired with negative emotional response (classical conditioning involving hippocampus and amygdala) [2].
- Compulsive stage: Diminishing of top-down prefrontal/orbitofrontal control over desire for drug-seeking [2]. The PFC — which should be putting the brakes on — is weakened. Simultaneously, there is an increase in striatal activity, indicating a shift from dopamine/reward-based circuitry to a glutamate/habit-based circuitry [2]. The behaviour is now automatic, like a deeply ingrained habit, rather than a deliberate choice.
The Three-Stage Model of Addiction
Stages of addiction [1]:
- Binge/Intoxication → Drug reinforcement → Reward circuits (VTA, NAc)
- Withdrawal/Negative affect → Developed tolerance → Reward circuits (VTA, NAc) recalibrate
- Craving/Preoccupation → Reward circuits (ACC, PFC, amygdala) + Memory (hippocampus) + Conditional response (amygdala) → Prefrontal cortex, orbitofrontal cortex → Compulsivity
This is the core framework they want you to know. Each stage maps to specific brain regions and neurotransmitter systems.
4. Risk Factors and Etiology
Many youngsters experiment with drugs, but only ~10% will develop dependence [2]. So what determines who that 10% will be? The biopsychosocial model applies beautifully here.
4.1 Biological Factors
- Genetic factors are strongly implicated in drug use disorders, but less so in drug use itself [2]
- Translation: genes don't determine whether you try drugs (that's largely social/environmental), but they strongly influence whether trying → dependence
- Heritability of substance use disorders estimated at 40-60% (comparable to other chronic diseases like diabetes, hypertension)
- Genes may contribute to propensity to develop harmful use and dependence, but drug use in general is largely dependent on factors such as availability and social environment [2]
Specific genetic factors:
- Alcohol metabolism enzymes: ALDH2 (aldehyde dehydrogenase) inactivating mutation is much more common in East Asians (HK-relevant!). The ALDH2*2 variant causes accumulation of acetaldehyde → flushing, nausea, tachycardia after drinking → protective against alcohol dependence [2]
- Neurotransmitter-related genes: GABRG1, GABRA2 (GABA-A receptor subunits), COMT (catechol-O-methyltransferase — degrades dopamine), DRD2 (dopamine D₂ receptor) [2]
- Cloninger subtypes (for alcohol, but conceptually applicable):
- Cloninger Type 1: later onset, mildly genetic, both sexes
- Cloninger Type 2: earlier onset, strongly genetic, predominantly male, associated with criminality and antisocial personality disorder [2]
- Pharmacological properties of the drug: most drugs modulate the mesolimbic dopamine pathway to activate positive reinforcement, but some drugs achieve dopamine-independent reinforcement [2]
- Individual biological propensity: the trait of novelty-seeking is associated with lower levels of dopamine receptor availability in the midbrain, making it more likely to attribute salience to drug-related cues → ↑ risk of drug misuse [2]
- Why? If your baseline DA receptor density is low, normal pleasures feel underwhelming → you seek intense stimulation → drugs provide that supraphysiological DA hit
- Some biological abnormalities predate and predict later substance misuse: ↓ cognitive performance (esp executive function), abnormal P300 visual evoked potentials [2]
The faster the drug reaches its target site in the brain, the better it is liked and more psychologically reinforcing [1]. This is a critical pharmacological principle:
| Route | Onset | Reinforcement Potential |
|---|---|---|
| Ingestion (oral) | Slowest | Lowest |
| Inhalation / smoking | Very fast (lungs → brain in seconds) | High |
| Injection (subcutaneous, IM, IV) | IV fastest | Highest |
This explains why:
- Crack cocaine (smoked) is more addictive than powder cocaine (snorted)
- IV heroin is more addictive than oral methadone (same drug class, different kinetics)
- Crystal methamphetamine (smoked) is more addictive than tablet methamphetamine (oral)
4.2 Psychological Factors
The role of personality is controversial [1][2]:
- Sensation-seeking, impulsive personality traits, more extrovert → predispose to experimenting with both licit and illicit drugs [1]
- Obsessional, dependent or anxious → more likely to get dependent and difficult to stop [1]
Other personality associations [2]:
- Chronic anxiety, pervading sense of inferiority, self-indulgent tendencies
- Antisocial personality disorder — strong association with early-onset substance use disorders
- Positive reinforcement: initially, pleasurable effects act as positive reinforcers — "I take it because it feels good" [2]
- Negative reinforcement: later, drug-taking behaviour becomes driven by intent to avoid unpleasant withdrawal symptoms — "I take it because I feel terrible without it" [2]
- Behaviour modelling: children of substance users may model their parents' behaviour
- Classical conditioning: environmental cues (people, places, paraphernalia) become paired with drug effects → trigger craving even in absence of drug
This is an important part of assessment because it can lead to effective treatment [1]:
Top 10 reasons college students give for consuming alcohol (Adler & Rosenberg, 1994) [1]:
- Increases feelings of sociability
- Relieves anxiety or tension
- Makes me feel elated/euphoric
- Makes me less inhibited
- Enables me to go along with my friends
- Enables me to experience a different state of consciousness
- Makes me less inhibited sexually
- Enables me to stop worrying
- Alleviates depression
- Makes me less self-conscious
The key point: the reason is NOT always the same — it is dynamic [1]. Only about 20% are purely pleasure-seeking; the majority have complex, evolving motivations.
4.3 Social Factors
- Drug use is associated with some degree of personal vulnerability
- Childhood factors: disrupted families, poor school record, truancy, delinquency
- Social deprivation: unemployment, homelessness
- Psychiatric comorbidities: depression, anxiety, personality disorders — these can be both cause and effect of substance misuse (bidirectional relationship)
- Chronic substance use can precede psychiatric disorders
- Substance use can be a maladaptive response to distress from pre-existing psychiatric disorders (self-medication hypothesis)
- Childhood exposure to potentially traumatic events, especially emotional abuse [2]
- Other environmental factors: family disruption, poverty, social isolation [2]
- Immediate social circle: peer influence, social pressure to achieve status
- Availability of drugs:
- Legally without prescription: nicotine, alcohol
- With prescription: hypnotics, opioids, barbiturates, gabapentin
- Illicit sources
The Biopsychosocial Model of Addiction
Every exam answer on addiction aetiology should be structured along the biopsychosocial model:
- Bio: Genetics (heritability ~50%), neurobiological propensity (novelty-seeking, low DA receptor density), pharmacological properties of drug
- Psycho: Personality traits (impulsive vs anxious), cognitive factors (positive/negative reinforcement, conditioning), motivations for use
- Social: Childhood adversity, peer influence, drug availability, psychiatric comorbidities, socioeconomic deprivation
5. Classification of Substances of Abuse
Common drugs of abuse can be grossly classified into 3 main groups [2]:
| Stimulants | Hallucinogens | Depressants | |
|---|---|---|---|
| Examples (colloquial name) | Amphetamine, Methamphetamine (Speed, Ice, 冰), Cocaine (coke, 可樂, 汽水), MDMA (Ecstasy, 搖頭丸, 糖), Mephedrone (bath salt, 喵喵) | LSD (黑芝麻, FING霸), Phencyclidine (PCP), Ketamine (K仔, 香水, 茄, 雞) | Alcohol (酒), Opioids (heroin 白粉, morphine, codeine, methadone), Benzodiazepines (BDZs), Barbiturates, GHB |
| Core mechanism | ↑ monoamines (esp DA, NA) → CNS excitation | Alter perception (various receptor targets) | ↑ GABA / ↓ excitatory transmission → CNS depression |
| General effects | Euphoria, ↑energy, ↑HR/BP, ↑T°C, insomnia, anorexia | Hallucinations, perceptual distortion, dissociation | Sedation, anxiolysis, respiratory depression, ↓HR/BP |
Classification Nuances
Note the overlap: Ketamine is regarded as distinct from other hallucinogens by its mode of action (NMDA antagonist) [2], and MDMA also has mild hallucinogenic activity and is sometimes classified as a hallucinogen [2], though its primary mechanism is stimulant. Cannabis doesn't fit neatly into any single category — it has depressant, stimulant, and hallucinogenic properties depending on dose and strain.
5.1 Depressants (Detailed)
"Opioid" comes from "opium" (Greek opos = juice, referring to the juice of the poppy plant). These drugs mimic endogenous opioid peptides (endorphins, enkephalins, dynorphins).
Examples: Heroin (海洛英, 白粉, 粉), Morphine (吗啡), Codeine (咳水, B), Methadone (蜜瓜汁) [2]
Pharmacology:
- Acute effects: Mimic endogenous opioid peptide NTs → agonist at opioid receptors (μ, δ, κ) [2]
- Inhibitory effect on activation of neurons, especially NA neurons in brainstem → sedation, respiratory depression
- ↑ activity of DA neurons in VTA via inhibition of GABA → this is the indirect mechanism: opioids suppress GABAergic interneurons that normally inhibit DA neurons in VTA → disinhibition → ↑ DA release in NAc → euphoria, reward
- Chronic effects: Rapid development of tolerance by ↓ sensitivity of opioid receptors [2]. This is receptor downregulation — with chronic agonist exposure, the cell decreases receptor density and uncouples intracellular signalling.
- Withdrawal → ↑↑ firing of NA neurons → may exhibit ↑ sympathetic nervous system activation, e.g., sweating, ↑ HR, HTN, anxiety [2]
Medical use: Mainly as narcotic analgesics [2]
Misuse in HK: Heroin is the most commonly abused illicit drug [2]. Main source comes from medically prescribed analgesics and illicit supply.
Routes of administration (RoA): oral, nasal, subcutaneous, IV, smoke (heated on metal foil and inhaled, i.e., '追龍') [2]
Clinical Features:
| Physical effects | Psychological/Psychiatric effects | |
|---|---|---|
| Intoxication | ↓/normal HR/BP, ↓ RR, ↓/normal T°C (depressant → everything goes down) | Euphoria, anxiolysis |
| Neuro: sedation, coma, miosis (pinpoint pupils), seizures | Drowsiness, apathy, personality changes | |
| Others: ↑ appetite, nausea, pruritus, constipation, ↓ libido | ||
| Withdrawal | SN activation: piloerection ('cold turkey'), sweating, mydriasis, ↑ HR | Intense craving for the drug |
| Flu-like: fever, rhinorrhoea, nausea, stomach cramps, diarrhoea | Anxiety, restlessness, insomnia | |
| Others: 'pricking' pain, pain in muscles and joints, yawning |
The term "cold turkey" literally comes from the piloerection (goosebumps) seen during opioid withdrawal — the skin looks like a plucked turkey.
Withdrawal timing: usually begins 6 hours after last dose, peaks at 36-48 hours, then wanes [2].
It is rarely life-threatening, but often so distressing that it triggers drug-seeking behaviour [2]. — Compare this to alcohol/benzodiazepine withdrawal, which CAN be life-threatening (seizures, delirium tremens).
Why Miosis in Opioid Intoxication?
Opioids activate μ-receptors in the Edinger-Westphal nucleus (parasympathetic) → stimulation of the pupillary sphincter → constriction. This is one of the most reliable signs of opioid intoxication/overdose, persisting even in deep coma. Conversely, in withdrawal, the parasympathetic tone drops and sympathetic tone surges → mydriasis.
"Benzo-diaz-epine" — named after the chemical structure: a benzene ring fused to a diazepine ring (a 7-membered ring with two nitrogen atoms).
Pharmacology:
- Acute effects: Bind to BDZ receptor at GABA-A receptor → ↑ GABA activity [2]
- Result is general inhibitory effect on neurotransmission → sedation, anxiolysis, muscle relaxation, anticonvulsant
- Chronic effects: Tolerance by adaptive changes in GABA receptor → ↓ sensitivity to benzodiazepines [2]
- Withdrawal due to sudden decline in GABA activity → ↑↑↑ excitatory transmission → anxiety, insomnia, seizures [2]
Medical use: Usually as anxiolytics and hypnotics, occasionally used in alcohol withdrawal due to 'cross-tolerance' with other CNS depressants [2]
Misuse: Very common, especially commonly comorbid with alcohol misuse [2]. Mainly from medically prescribed sources (often arises from prolonged medical use) — should prescribe BDZ for short-term only [2].
Clinical features of intoxication [2]:
- Physical: Vitals typically normal (rarely cause significant toxicity without co-ingestant esp. alcohol). CNS depression with slurred speech, ataxia, nystagmus, stupor, coma. Respiratory depression usually only if very high dose.
- Psychological: Anxiolysis, feeling of well-being. Drowsiness, confusion, somnolence. Disinhibition, poor concentration.
Withdrawal [2]:
- Benzodiazepine withdrawal can be LIFE-THREATENING!
- Time: 24-48h (short-acting) vs up to 3 weeks (long-acting)
- Anxiety symptoms: anxiety, irritability, sweating, tremor, sleep disturbance
- Altered perception: depersonalization, derealization, hypersensitivity to stimuli, abnormal body sensation, abnormal sensation of movement
- Others (rare): depression, suicidal behaviour, psychosis, seizures, delirium tremens
- When treating anxiety disorders with BDZs, withdrawal symptoms closely mimic anxiety relapse [2] — this is a classic trap. If you stop BDZ in an anxiety patient and they get worse, is it relapse or withdrawal? Often it's withdrawal.
Dependence: ~1/3 of patients who take ≥6 months of therapeutic doses of BDZ may become dependent [2]
Treatment [2]:
- Acute poisoning: Supportive (ensure ABC), IV Flumazenil 0.2mg/30s — a competitive antagonist at the BDZ receptor site. Risk of precipitating withdrawal seizures in tolerant individuals.
- Dependence: Switch to long-acting BDZ (e.g., diazepam), gradual withdrawal over ≥8 weeks, usually lower 1/8 of dose every 2 weeks
See the dedicated alcohol section in GC 161 lecture for comprehensive coverage. Key points relevant to substance misuse:
- Alcohol enhances GABAergic transmission and blocks glutamatergic (NMDA) transmission → CNS depression
- Chronic use → upregulation of NMDA receptors and downregulation of GABA receptors [2] → when alcohol is suddenly stopped, the "brakes" (GABA) are weak and the "accelerator" (glutamate) is turbo-charged → excitotoxicity → withdrawal seizures, delirium tremens
- Genetic: ALDH2 inactivating mutation protective in East Asians [2]
- Screening: CAGE questionnaire (↑ sensitivity but modest specificity), AUDIT (↑ sensitivity + ↑ specificity, most useful — 10-item WHO tool) [2]
- Lab markers of chronic alcoholism: ↑ GGT (70%), ↑ MCV (60%), ↑ carbohydrate-deficient transferrin (more specific than GGT) [2]
5.2 Hallucinogens
"Ket-amine" — contains an amine group; PCP = "Phenylcyclidine/Piper-idine."
Pharmacology [2]:
- Antagonist at NMDA receptor → blocks glutamate → dissociative anaesthesia
- GABA inhibition → ↑ DA release
- Direct stimulation effect on DA release
- Tolerance occurs; little clear withdrawal symptoms in humans [2]
Medical use: Dissociative general anaesthetic agent [2]. Ketamine has a role in treatment-resistant depression (can induce a striking temporary remission of severe depression) [2] — this is esketamine (intranasal), FDA-approved.
Clinical features [2]:
- Low dose: analgesia, drunkenness, sedation, slight ↑ HR/BP
- Intoxication: mydriasis, nystagmus, ataxia, rigidity, convulsions, amnesia, absence-like effect (no response despite eyes open)
- Serious OD: sympathomimetic crisis (malignant HTN, ADHF, malignant hyperthermia), status epilepticus, rhabdomyolysis with renal failure
- Psychological: mood elevation → agitation, sensory and perceptual distortion, out-of-body experiences ("K-hole"), thought disorder, psychotic-like symptoms
Chronic use complication (HK-specific!): Ketamine-induced ulcerative cystitis/uropathy — haematuria, frequency, urge incontinence, ↓ bladder volume with detrusor overactivity [2]. This is a devastating and often irreversible complication seen frequently in young HK ketamine users.
- Primarily acts on 5-HT₂A receptors → profound perceptual alterations
- Synesthesia: cross-modal perception — colours are heard, sounds are perceived as visual, or movement is experienced as if heard [2]
- No significant physical dependence or withdrawal
- Risk of "bad trips" (acute anxiety, paranoia) and rarely hallucinogen persisting perception disorder (HPPD) — "flashbacks" occurring weeks to months after use
5.3 Stimulants
"Meth-amphetamine" = methyl group added to amphetamine → more lipophilic → crosses BBB faster → more potent CNS effects.
Examples: Tablet methamphetamine (麻古), Crystalloid methamphetamine (冰, 凍野, 滑雪) [2]
Pharmacology [2]:
- Acute effects: acts on monoamine system by:
- DA: most potent — direct stimulation of release AND block DA reuptake at mesocorticolimbic pathway
- Others: direct release of NA, adrenaline, 5-HT
- Chronic effects:
- Sensitization: augmentation of DA release (intermittent use)
- Tolerance: depletion of stored NTs (continuous use)
Medical use: Psychostimulant for ADHD and narcolepsy [2]
Misuse in HK: 2nd most common type of drug of abuse in HK [2]
Clinical features [2]:
- Physical: Sympathomimetic toxidrome if OD — ↑ HR, ↑ BP, ↑ T°C, mydriasis, seizures, MI, cardiomyopathy, sudden cardiovascular collapse, pulmonary oedema, bowel ischaemia
- Psychological: Euphoria, irritability, aggression, anxiety, disorganised thinking, persecutory delusions, auditory and visual hallucinations (usually subside ≤1 week but may persist > 1 month), homicidal and suicidal ideation
- Obstetric: miscarriage, premature labour, placental abruption [2]
Withdrawal [2]:
- Post-use 'crash' (usually resolves ≤2 weeks)
- Mild: low mood, anergia
- Severe: severe depression, anhedonia, irritability, poor concentration, hyperphagia, insomnia or hypersomnia, psychomotor agitation or retardation, suicidal ideation, intense craving
Dependence characteristics: Many recreational users do not progress to misuse and dependence. Often characterised by repeated periods of intense use with intermittent sobriety and relapse [2]. Can be detected in urine for ~2 days.
"Cocaine" — from coca (the plant) + -ine (alkaloid suffix).
Pharmacology [2]:
- Acute effects: Block DA reuptake → ↑ DA availability at synapses at mesolimbic pathway → acute reinforcing properties, sympathomimetic activation
- Chronic effects: Intermittent use → sensitization; Continuous use → tolerance by ↓ sensitivity of DA autoreceptors, change of post-synaptic receptors and secondary messenger systems [2]
Clinical features: Similar sympathomimetic toxidrome to methamphetamine. Additionally:
- β-blocker alone should NOT be used as it may lead to unopposed alpha-agonistic activity → coronary vasoconstriction [2]. Use benzodiazepines ± phentolamine instead.
"3,4-methylenedioxymethamphetamine" — the name tells you it's a modified methamphetamine with a methylenedioxy group.
Pharmacology [2]:
- Block reuptake + ↑ release of NA/DA → sympathomimetic, dopaminergic effects
- Structurally similar to 5-HT → ↑ release + ↓ reuptake of 5-HT → mild hallucinogenic effect
- Chronic effects: causes degeneration of 5-HT nerve terminals in cortex and forebrain (in animals; human data inconsistent)
Clinical features [2]:
- Physical: Sympathomimetic toxidrome + serotonin syndrome — ↑ HR, ↑ BP, ↑ T°C, hyperthermia, hyponatraemia (due to excessive water intake + SIADH), seizures
- Psychological: euphoria, sociability, intimacy, heightened perceptions, bruxism
- Life-threatening complications: MI, aortic dissection, arrhythmia, hepatotoxicity
Treatment specific points [2]:
- Hyponatraemia: fluid restriction (NOT normal saline bolus)
- Serotonin syndrome: cyproheptadine (5-HT₂A antagonist)
- Hyperthermia: benzodiazepine sedation; severe → NMB + GA
"Cannabis" — from the plant Cannabis sativa. Contains several pharmacologically active substances, the most potent being δ-9-tetrahydrocannabinol (THC) [2].
Forms [2]:
- Cannabis (weed, marijuana, 大麻, 草) — dried vegetative parts
- Cannabis resin (大麻精) — resin from flowering female plant
- Synthetic cannabinoids (skunk, K2, SPICE) — more potent with ↑↑ THC content
Pharmacology [2]:
- Acute: Agonist at cannabinoid receptor CB1 in CNS → ↓ GABA/glutamate, ↑ DA release
- Chronic: Tolerance occurs but withdrawal tends to be mild. Chronic use → downregulation of GABA receptors → ↓ inhibition on DA release → ↑ risk of schizophrenia [2]
Medical uses: ↓ chronic pain, ↓ muscle spasms, ↓ N/V in chemotherapy, ↓ anorexia in HIV, ↑ sleep, tics in Tourette syndrome [2]
HK context: Uncommon in HK but gaining popularity [2], especially among younger demographics reflecting global legalization trends. Cannabis remains illegal in HK.
6. Clinical Approach to Recognizing and Assessing Substance Misuse
Physical signs [2]:
- Needle tracks, thrombosed veins, wearing long-sleeved shirts in hot weather (to hide injection marks)
- Scars, subcutaneous/deep abscesses
- Hepatitis B/C (from needle sharing)
Behavioural signs [2]:
- ↓ self-care, absence from work/occupational decline
- Social isolation
- Minor criminal offences (especially for cash, e.g., theft, prostitution)
Seeking medical attention [2]:
- Drug-seeking behaviour (e.g., exaggerating pain for prescriptions)
- Route-related complications (cellulitis, pneumonia, hepatitis)
- Drug-related complications (intoxication, withdrawal)
Establishing time frame: 1st use, daily use, abstinence and relapse [2]
Types and quantity of drugs taken according to above time frame [2]
Describe a typical drug-using day and the day before consultation [2]
S/S of dependence: CANT Control Withdraw [2]
Impact: physical, psychological, social [2]
(Risky behaviour): dangerous injection (into groin, neck, infected sites), sharing needles [2]
Medical impact includes [1]:
- Route-related (infections from IV use, nasal septal perforation from snorting, lung damage from smoking)
- Form/substance-related (state of intoxication/withdrawal)
- Chronic use effects
- Self-care deterioration
7. Clinical Features by Substance — Symptoms and Signs with Pathophysiological Basis
| Substance | Key Physical Signs | Mechanism | Key Psychological Signs |
|---|---|---|---|
| Opioids | Miosis, ↓RR, ↓BP, constipation, sedation | μ-receptor agonism → parasympathetic pupil constriction, brainstem respiratory depression, ↓GI motility | Euphoria (↑DA via GABA disinhibition in VTA), drowsiness |
| BDZs | Slurred speech, ataxia, nystagmus, respiratory depression (high dose) | GABA-A enhancement → widespread CNS depression, cerebellar effects (ataxia), brainstem (respiratory centre) | Anxiolysis, disinhibition, confusion |
| Alcohol | Slurred speech, ataxia, nystagmus, ↓BP, ↓T°C | GABA enhancement + NMDA blockade → CNS depression, cerebellar/vestibular effects | Disinhibition, euphoria → sedation |
| Methamphetamine | ↑HR, ↑BP, ↑T°C, mydriasis, seizures | DA/NA/5-HT release → sympathomimetic activation, massive peripheral catecholamine surge | Euphoria, psychosis, aggression |
| Cocaine | ↑HR, ↑BP, chest pain, mydriasis | DA reuptake blockade + sympathomimetic | Euphoria, grandiosity, paranoia |
| MDMA | ↑HR, ↑BP, ↑T°C, bruxism, hyponatraemia | NA/DA release + massive 5-HT release → serotonin syndrome | Euphoria, empathy, intimacy |
| Ketamine | Nystagmus, rigidity, ↑HR/BP (mild), anaesthesia | NMDA antagonism → dissociative anaesthesia, DA release | Dissociation, perceptual distortion, "K-hole" |
| Cannabis | Conjunctival injection, ↑appetite, ↑HR, dry mouth | CB1 agonism → vasodilation (red eyes), hypothalamic effects (appetite), sympathetic effects | Euphoria, relaxation, perceptual distortion, paranoia (high dose) |
| Substance | Withdrawal Features | Pathophysiological Basis | Life-threatening? |
|---|---|---|---|
| Opioids | Mydriasis, piloerection, sweating, ↑HR, rhinorrhoea, diarrhoea, muscle/joint pain, yawning, craving | Chronic μ-receptor downregulation → sudden loss of opioid inhibition on NA neurons → ↑↑ sympathetic activation; rebound of all systems previously suppressed | Rarely (very distressing but not usually fatal) |
| BDZs | Anxiety, tremor, insomnia, seizures, psychosis, delirium | Chronic GABA-A downregulation → loss of inhibitory tone → ↑↑↑ excitatory (glutamate) transmission | YES (seizures, DTs) |
| Alcohol | Tremor, sweating, anxiety, seizures (6-48h), delirium tremens (48-72h), hallucinations | GABA-A downregulation + NMDA upregulation → severe excitotoxicity when alcohol removed | YES (mortality 5-15% if DTs untreated) |
| Methamphetamine | Depression, fatigue, hyperphagia, hypersomnia, intense craving | DA depletion (stores exhausted) → dopaminergic deficit → crash | Not directly (suicide risk from depression) |
| Cocaine | Depression, fatigue, increased appetite, vivid unpleasant dreams, psychomotor retardation | DA depletion post-binge | Not directly (suicide risk) |
| Cannabis | Irritability, insomnia, decreased appetite, anxiety (mild) | CB1 receptor downregulation → loss of endocannabinoid-mediated inhibition | No |
| Ketamine | Minimal | Minimal physical dependence develops | No |
Life-threatening Withdrawal: Alcohol and BDZs
The two substance withdrawals that can kill are alcohol and benzodiazepines — both are GABAergic depressants, and their withdrawal produces a hyperexcitable state that can lead to seizures, status epilepticus, and delirium tremens. Opioid withdrawal is miserable but rarely fatal. Stimulant withdrawal is characterised by "crash" (depression, hypersomnia) but is not directly life-threatening (though suicide risk is real).
This is essential for understanding how to approach patients with substance use disorders therapeutically. Treatment should consist of bio-/psycho-/social components [2].
The stages of change model facilitates motivational interviewing to enhance the patient's own motivation [2]:
Key principles:
- Match your intervention to the patient's current stage
- Pre-contemplation: raise awareness (not confrontation)
- Contemplation: motivational interviewing, explore ambivalence
- Action: provide practical support, pharmacotherapy, psychotherapy
- Maintenance: relapse prevention strategies
- Relapse: normalize, encourage re-engagement (not failure)
High Yield Summary
Definition: Substance misuse = use for pleasure with disregard of personal/social dangers; dependence = physical + psychological withdrawal; addiction = extreme end with social decline
ICD-10 Dependence: ≥3 of 6 — Compulsion, Control difficulty, Withdrawal, Tolerance, Neglect of alternatives, Persisting despite harm (CANT Control Withdraw)
Neurobiology: All drugs → ↑ DA in NAc via mesolimbic pathway. Three stages: Binge/Intoxication (VTA, NAc) → Withdrawal/Negative affect (tolerance, DA deficit) → Craving/Preoccupation (hippocampus, amygdala, PFC loss of control) → shift from DA/reward to glutamate/habit circuitry
Route matters: Faster onset = more reinforcing (IV > smoking > snorting > oral)
Only ~10% who experiment develop dependence — determined by biopsychosocial factors
HK epidemiology: Heroin #1 (ageing cohort), methamphetamine #2 (younger users), ketamine declining, cannabis rising
Life-threatening withdrawals: Alcohol and BDZs (GABAergic — seizures, DTs). Opioid withdrawal is NOT typically fatal.
Key drug-specific features:
- Opioids: miosis + respiratory depression + constipation (intox); mydriasis + piloerection + diarrhoea (withdrawal)
- BDZs: slurred speech, ataxia, nystagmus; withdrawal mimics anxiety relapse; 1/3 dependent after ≥6mo use
- Methamphetamine: sympathomimetic toxidrome + psychosis; post-use crash with severe depression
- Cocaine: DA reuptake blockade; NO β-blockers (unopposed alpha)
- MDMA: serotonin syndrome + hyponatraemia; Rx cyproheptadine
- Ketamine: dissociative; ketamine-induced cystitis (HK-relevant); role in treatment-resistant depression
- Cannabis: CB1 agonism; ↑ schizophrenia risk with chronic use
Active Recall - Substance Misuse (Definition, Epidemiology, Pathophysiology, Clinical Features)
Differential Diagnosis of Substance Misuse
When a patient presents with features suggesting substance misuse — whether that's intoxication, withdrawal, behavioural change, or the consequences of chronic use — the clinical task is not simply to confirm "they're using drugs." The real challenge is threefold:
- What substance(s)? — Often polysubstance use; identify all involved
- What level of use? — Problem use vs harmful use vs dependence vs addiction
- What else could explain the presentation? — Rule out medical mimics and comorbid psychiatric disorders
This section addresses all three layers systematically.
Before jumping into differentials, let's establish the diagnostic hierarchy. A patient presenting with substance-related symptoms could fall anywhere on this spectrum, and your job is to categorise accurately because management differs at each level [1][2]:
| Level | Definition | Key Features |
|---|---|---|
| Experimental / Recreational use | Occasional use, no harm | No dependence criteria, no significant consequences |
| Problem use / Misuse | Use for pleasure but with disregard for personal or social dangers [1] | Harm occurring but not meeting dependence criteria |
| Harmful use (ICD-10 F1x.1) | Pattern causing damage to health (physical or mental) | Documented health damage attributable to use |
| Dependence syndrome (ICD-10 F1x.2) | ≥3 of 6 criteria present for some time during past year [1] | Tolerance, withdrawal, compulsion, control difficulty, neglect, persistence despite harm |
| Addiction | Extreme end of dependent spectrum — social/personal decline, tolerance, withdrawal [1] | Compulsive use with severe functional impairment |
Diagnosis is based on diagnostic criteria — tolerance, withdrawal (physical/psychological), compulsion of act [1]. Drug screening/testing and tools such as CAGE as screening questionnaire for alcohol misuse supplement but do not replace clinical assessment [1].
Harmful Use vs Dependence
A common exam error is conflating these. Harmful use requires documented damage (e.g., alcoholic hepatitis, cannabis-induced psychosis) but the person may NOT have tolerance, withdrawal, or compulsive use. Dependence requires ≥3 of the 6 ICD-10 criteria — you can be dependent without having caused demonstrable organ damage yet (though you usually will eventually).
When a patient presents with an acute toxidrome or withdrawal syndrome, you must identify which substance is responsible. This is critical because management differs dramatically (e.g., naloxone for opioids, flumazenil for BDZs, supportive for stimulants).
The key clinical clues are the vital signs, pupil size, and mental state:
| Toxidrome | Vital Signs | Pupils | Mental State | Likely Substance |
|---|---|---|---|---|
| Opioid intoxication | ↓HR, ↓BP, ↓RR, ↓T°C | Miosis (pinpoint) | Sedation → coma | Heroin, morphine, codeine, methadone |
| Sedative-hypnotic intoxication | Normal or ↓BP/RR | Normal or miosis | Slurred speech, ataxia, drowsiness | BDZs, barbiturates, alcohol, GHB |
| Sympathomimetic intoxication | ↑HR, ↑BP, ↑T°C | Mydriasis | Agitation, euphoria, psychosis | Methamphetamine, cocaine, MDMA |
| Anticholinergic toxidrome | ↑HR, ↑T°C | Mydriasis | Delirium, hallucinations, "mad as a hatter" | Antihistamines, TCA overdose, atropine |
| Serotonin syndrome | ↑HR, ↑BP, ↑T°C | Mydriasis | Agitation, confusion, clonus, hyperreflexia | MDMA, SSRIs + MAOIs, tramadol |
| Dissociative | ↑HR, ↑BP (mild) | Mydriasis, nystagmus | Dissociation, "K-hole," eyes open but unresponsive | Ketamine, PCP |
| Cannabinoid intoxication | ↑HR, normal BP | Normal | Euphoria, relaxation, paranoia, ↑appetite | Cannabis, synthetic cannabinoids |
| Alcohol withdrawal | ↑HR, ↑BP, ↑T°C | Mydriasis | Tremor, anxiety, seizures, delirium tremens | Alcohol cessation |
| Opioid withdrawal | ↑HR, ↑BP | Mydriasis | Anxiety, restlessness, craving | Opioid cessation |
| BDZ withdrawal | ↑HR, ↑BP | Normal or mydriasis | Anxiety, seizures, perceptual disturbance | BDZ cessation |
Pupil Size is Your Best Friend
In the acute setting, pupil size immediately narrows your differential:
- Pinpoint (miosis) = opioid intoxication (or pontine lesion — but that's a different clinical context)
- Dilated (mydriasis) = stimulants, anticholinergics, opioid/alcohol withdrawal, hallucinogens
- Normal = BDZs, alcohol intoxication (unless severe)
Why? Opioids activate parasympathetic Edinger-Westphal nucleus → pupillary constriction. Stimulants cause massive NA/adrenaline release → sympathetic mydriasis. In withdrawal from depressants, the sympathetic rebound causes mydriasis.
C. Differential Diagnosis: Medical Conditions Mimicking Substance Misuse
This is clinically critical — many medical emergencies mimic intoxication or withdrawal, and missing them can be fatal.
| Medical Condition | How it Mimics Substance Misuse | Key Distinguishing Features |
|---|---|---|
| Hypoglycaemia | Confusion, slurred speech, ataxia, diaphoresis, agitation → looks like alcohol intoxication | Finger-prick glucose; responds to dextrose; diabetic history or insulin/OHA use |
| Hepatic encephalopathy | Confusion, asterixis, personality change → looks like alcohol/sedative intoxication | Jaundice, ascites, spider naevi; ↑NH₃; chronic liver disease history |
| Diabetic ketoacidosis | Fruity breath (acetone), confusion, Kussmaul breathing → may be mistaken for alcohol | Hyperglycaemia, metabolic acidosis, ketonuria; no ethanol on breath |
| Head injury / Intracranial pathology | ↓consciousness, confusion, focal neurology → looks like sedative intoxication | Focal neurological signs, unequal pupils, history of trauma; CT brain |
| Meningitis / Encephalitis | Fever, confusion, ↓consciousness → may mimic intoxication in young patient | Neck stiffness, photophobia, rash; LP for CSF analysis |
| Postictal state | Confusion, drowsiness, incontinence → may look like intoxication | Witnessed seizure, tongue bite, urinary incontinence; EEG |
| Wernicke's encephalopathy | Confusion, ophthalmoplegia, ataxia (classic triad) → patient may also be alcohol-dependent | Give IV thiamine empirically; ophthalmoplegia is the distinguishing sign |
| Hypothermia / Hypothyroidism | Bradycardia, ↓consciousness, confusion → mimics depressant intoxication | Temperature measurement; TFTs |
| Stroke | Acute onset focal neurology, dysarthria, ataxia → may mimic intoxication | Focal signs, onset timing, CT/MRI brain |
| Medical Condition | How it Mimics Withdrawal | Key Distinguishing Features |
|---|---|---|
| Thyrotoxicosis | Tachycardia, tremor, anxiety, diaphoresis, weight loss → looks like stimulant or alcohol withdrawal | Goitre, lid lag, exophthalmos; ↑FT4, ↓TSH |
| Phaeochromocytoma | Episodic hypertension, tachycardia, diaphoresis, anxiety → mimics stimulant withdrawal/intoxication | Episodic pattern; ↑urinary catecholamines/metanephrines |
| Sepsis | Fever, tachycardia, confusion, diaphoresis → mimics withdrawal syndrome | Source of infection, ↑WBC, ↑CRP, blood cultures |
| Acute MI | Chest pain, diaphoresis, anxiety, ↑HR → may mimic cocaine/stimulant withdrawal | ECG changes, troponin rise; note cocaine itself causes MI |
| Non-convulsive status epilepticus | Altered consciousness with subtle or no motor signs → may mimic intoxication or withdrawal confusion | EEG monitoring [2] |
| Delirium (from any cause) | Fluctuating consciousness, disorientation, perceptual disturbances → overlaps significantly with withdrawal delirium | Careful collateral history; delirium workup (infection, metabolic, medication review) [2] |
The Golden Rule
Never assume a confused or agitated patient is "just intoxicated" or "just withdrawing." Always perform a basic medical workup: glucose, temperature, oxygen saturation, pupils, focal neurology, and GCS. The most dangerous miss is hypoglycaemia in a patient smelling of alcohol (diabetic patients drink too), or subdural haematoma in a frequent faller who drinks.
D. Differential Diagnosis: Psychiatric Conditions Mimicking or Comorbid with Substance Misuse
This is where substance misuse intersects with the rest of psychiatry. The relationship is bidirectional — substance use can cause psychiatric symptoms, and psychiatric disorders can drive substance use [2][3].
These are psychiatric syndromes directly caused by the pharmacological effects of the substance. They should resolve with abstinence (though some persist):
| Presentation | Substances that cause it | Mechanism | Key differentiator from primary disorder |
|---|---|---|---|
| Psychosis | Methamphetamine, cocaine, cannabis, ketamine, LSD, alcohol (withdrawal) | Meth/cocaine: ↑↑DA in mesolimbic pathway → psychotic symptoms; Cannabis: chronic CB1 agonism → ↓GABA → ↑DA → ↑schizophrenia risk; Alcohol withdrawal: excitotoxicity | Substance-induced psychosis: long duration argues against; no evidence of illicit substance or alcohol use argues against [2]. Temporal relationship to substance use is key — onset during or shortly after use/withdrawal, resolves with abstinence |
| Depression | Alcohol (chronic), stimulant withdrawal ("crash"), cannabis | Alcohol: direct neurotoxicity + social consequences; Stimulant withdrawal: DA depletion | Onset temporally linked to use; resolves with sustained abstinence (though may take weeks-months) |
| Anxiety | Intoxication: alcohol, stimulants (amphetamines, cocaine, caffeine), cannabis, inhalants, hallucinogens (PCP) [2] | Sympathomimetic activation, direct CNS effects | |
| Withdrawal: alcohol, sedatives/hypnotics (BDZs, opiates), caffeine, cocaine, nicotine [2] | Rebound excitation after removal of CNS depressant | When treating anxiety with BDZs, withdrawal symptoms closely mimic anxiety relapse | |
| Mania-like state | Stimulants (amphetamines, cocaine), steroids, cannabis | ↑↑DA release mimics the hyperdopaminergic state of mania | Drug misuse: should diminish after admission; consider urine tox screen [2] |
| Cognitive impairment / Delirium | Alcohol (Wernicke-Korsakoff), benzodiazepines, ketamine, inhalants | Various: thiamine deficiency (alcohol), GABA disruption (BDZs), NMDA blockade (ketamine), direct neurotoxicity (inhalants) | Temporal relationship; substance-specific features |
Alcohol use can be a cause or effect of other psychiatric disorders [2]. Alcohol use can be a maladaptive response to ↓ distress from other psychiatric disorders [2]. This "self-medication hypothesis" applies to all substances:
| Primary Psychiatric Disorder | Pattern of Substance Use | Why |
|---|---|---|
| Depression | Alcohol, cannabis, opioids | To numb emotional pain, induce sleep, escape rumination |
| Social anxiety disorder | Alcohol | To reduce social inhibition and self-consciousness (note: this was the #1 reason in the college student survey — increases feelings of sociability [1]) |
| PTSD | Alcohol, cannabis, opioids, BDZs | To dampen hyperarousal, intrusive memories, insomnia |
| Bipolar disorder | Drug abuse/dependence: OR 5.2 (95% CI 2.5-11.0) vs general population; OR 3.7 (95% CI 1.7-8.1) vs MDD [4]. Alcohol abuse/dependence: OR 3.4 (95% CI 1.4-8.3) vs general population [4] | During mania: impulsivity, sensation-seeking, poor judgment; during depression: self-medication |
| Schizophrenia | Cannabis, nicotine, alcohol | Self-medication of negative symptoms; nicotine may improve cognitive function via nicotinic receptors |
| ADHD | Stimulants, cannabis, alcohol | Self-medication of inattention and restlessness; impulsivity leads to experimentation |
| Personality disorders (esp. BPD) | Any substance | Emotional dysregulation, impulsivity, self-harm |
Bipolar Disorder and Substance Use — A High-Yield Overlap
Comorbid substance use disorders are more common in bipolar disorder than in both the general population and major depressive disorder [4]. Misdiagnosis is very common — correct diagnosis and treatment often delayed by 5-7 years on average [4]. A manic patient may be misdiagnosed as having stimulant intoxication, and a substance-using patient with mood instability may have undiagnosed bipolar disorder underneath. Always consider bipolar disorder when substance misuse is accompanied by episodic mood disturbance.
When a patient presents with psychosis in the context of substance use, the differential includes [2]:
| Diagnosis | For / Against |
|---|---|
| Substance-induced psychotic disorder | For: temporal relationship to substance use (onset during intoxication/withdrawal); resolves with abstinence. Against: long duration of symptoms; no evidence of illicit substance or alcohol use [2] |
| Schizophrenia | For: symptoms > 1 month, first-rank symptoms, deterioration in functioning. Against: clear temporal link to substance use |
| Mood disorder with psychotic features | Against: mood mainly suspicious as opposed to lowered or elevated, and appeared secondary to delusional beliefs; no other prominent features of mania or depression; mood-incongruent delusions and hallucinations [2] |
| Schizoaffective disorder | For: concurrent mood and psychotic symptoms. Against: no prominent mood symptoms [2] |
| Psychotic disorder secondary to a medical condition | Against: no signs of medical illness or abnormalities on physical examination [2] |
| Delirium | Fluctuating consciousness, acute onset, identifiable medical cause |
The following flowchart represents the systematic approach to a patient presenting with features of substance misuse:
The assessment aims to achieve three things [1]:
- Differentiating the drug-using problem — making diagnosis [1]
- Formulation (What, Why, How) [1]:
- Understand the problems/difficulties
- Understand the needs
- Understand the person
- Facilitating the establishment of a treatment plan [1] — using the stage of changes model
The formulation is built through structured assessment [2]:
- Recognising substance misuse: physical signs (needle tracks, thrombosed veins, abscesses, hepatitis B/C), behavioural signs (↓self-care, occupational decline, criminal offences), medical attention-seeking (drug-seeking, route-related complications)
- Drug history: time frame, types and quantities, typical drug-using day, features of dependence (CANT Control Withdraw), impact (physical, psychological, social), risky behaviours (needle sharing, injection into dangerous sites)
- Laboratory diagnosis: confirm drug use whenever possible — urine (commonest), blood, saliva [2]
- Psychiatric formulation: assess problems, needs, the person, understand why they take drugs (only 20% for pleasure-seeking — reasons are dynamic, not fixed) [1][2]
Urine Drug Detection Windows [2]
| Drug | Detection Time |
|---|---|
| Amphetamines and analogues | 2 days |
| Buprenorphine and metabolites | 8 days |
| Methadone (maintenance dosing) | 7-9 days |
| Morphine | 2 days |
| Codeine, dihydrocodeine | 2 days |
| Cannabinoids (single use) | 3-4 days |
| Cannabis (daily use) | 20 days |
Cannabis: The Long Detection Window
Cannabis is lipophilic — THC is stored in fat tissue and released slowly. A single use clears in 3-4 days, but daily use can be detected for up to 20 days (and in heavy chronic users, even longer — up to 30+ days). This means a positive urine test doesn't necessarily mean recent use in a chronic user. Conversely, a negative test doesn't rule out infrequent use if the last use was > 4 days ago.
G. Special Considerations in Differential Diagnosis
In real clinical practice — and frequently in exams — patients use multiple substances simultaneously. This creates overlapping toxidromes that are harder to disentangle:
- Alcohol + benzodiazepines: synergistic CNS depression (cross-tolerance exists because both act on GABA-A) — risk of respiratory arrest even at moderate doses of each
- Cocaine + alcohol: produces cocaethylene (a unique metabolite formed only when both are co-ingested), which has its own cardiotoxicity and longer half-life
- Opioids + benzodiazepines: the combination most likely to cause fatal respiratory depression (the epidemic in Western countries)
- Stimulants + depressants ("speedballing" = cocaine + heroin): users try to balance the "up" and "down" — extremely dangerous, unpredictable vital sign fluctuations
- Adolescents: Differentiate substance-induced behavioural change from normal adolescent rebellion, emerging personality disorders (particularly BPD), ADHD, and early psychosis
- Elderly: Differentiate BDZ misuse/dependence from dementia (both cause confusion, memory impairment); differentiate alcohol-related cognitive decline from neurodegenerative dementia; polypharmacy effects
This comes up repeatedly in exams. The key differentiators:
| Feature | Substance-Induced Psychosis | Primary Psychotic Disorder |
|---|---|---|
| Temporal relationship | Onset during intoxication or within days-weeks of withdrawal | No clear temporal link to substance use |
| Duration | Usually resolves within days-weeks of abstinence | Persists beyond substance clearance |
| Type of hallucinations | Visual hallucinations more common (esp. stimulants, alcohol withdrawal) | Auditory hallucinations predominate (esp. 3rd person running commentary in schizophrenia) |
| Insight | Often retained initially | Typically impaired |
| First-rank symptoms | Uncommon (though can occur with cannabis/methamphetamine) | Present in schizophrenia (thought insertion, passivity, etc.) |
| Drug screen | Positive | May be negative (though primary psychosis patients may also use substances) |
| Course with abstinence | Improvement with abstinence | No improvement with abstinence alone |
However, the reality is messier: chronic cannabis use can precipitate a primary psychotic disorder (schizophrenia) in genetically vulnerable individuals, meaning the distinction can be impossible to make at first presentation. These patients need follow-up.
High Yield Summary
Levels of use: Experimental → Problem use/misuse → Harmful use → Dependence (≥3/6 ICD-10) → Addiction
Identify the substance: Use toxidrome pattern — vital signs + pupil size + mental state. Key: miosis = opioids; mydriasis + sympathomimetic = stimulants; nystagmus + dissociation = ketamine/PCP
Always rule out medical mimics: Hypoglycaemia, head injury, hepatic encephalopathy, DKA, sepsis, thyrotoxicosis, Wernicke's encephalopathy. NEVER assume "just intoxicated"
Psychiatric comorbidity is the rule, not the exception: Determine whether psychiatric symptoms are substance-INDUCED (resolve with abstinence) or a PRIMARY disorder with secondary substance misuse (self-medication). Temporal relationship is the key differentiator
Bipolar disorder: OR 5.2 for drug abuse/dependence vs general population; commonly misdiagnosed; 5-7 year delay to correct diagnosis
Assessment aims: Differentiate the problem (diagnosis), formulate (what/why/how), facilitate treatment plan (stage of change). Lab confirmation with urine drug screen is standard
Cannabis detection: Up to 20 days in daily users (lipophilic storage in fat)
Active Recall - Differential Diagnosis of Substance Misuse
References
[1] Lecture slides: GC 166. I cannot help myself, taking these pills just feels good Substance abuse and addiction.pdf [2] Senior notes: ryanho-psych.md (Chapter 5.2 Misuse of Substance; Chapter 6.1 Approach to Psychotic Symptoms; Chapter 4.1 Approach to Delirium) [3] Lecture slides: GC 161. Alcohol and the Brain From Psychiatric to Neuropsychiatric Perspectives.pdf [4] Lecture slides: GC 163. I am a superman Bipolar disorder.pdf
Diagnostic Criteria
Diagnosing substance misuse is fundamentally a clinical exercise — there is no single blood test or scan that "diagnoses" dependence. The diagnosis rests on a careful history mapped against validated criteria, supported by collateral information, examination findings, and targeted investigations. Let's work through this systematically.
The ICD-10 (still the primary coding system used in Hong Kong) classifies substance-related disorders under F10–F19, where the second digit denotes the substance and the third digit denotes the clinical syndrome:
| Code | Substance |
|---|---|
| F10 | Alcohol |
| F11 | Opioids |
| F12 | Cannabinoids |
| F13 | Sedatives/hypnotics |
| F14 | Cocaine |
| F15 | Other stimulants (incl. caffeine) |
| F16 | Hallucinogens |
| F17 | Tobacco |
| F18 | Volatile solvents |
| F19 | Multiple drug use / other substances |
The third digit specifies the syndrome:
| .0 | Acute intoxication |
|---|---|
| .1 | Harmful use |
| .2 | Dependence syndrome |
| .3 | Withdrawal state |
| .4 | Withdrawal state with delirium |
| .5 | Psychotic disorder |
| .6 | Amnestic syndrome |
| .7 | Residual and late-onset psychotic disorder |
So, for example, F10.2 = Alcohol dependence syndrome; F11.3 = Opioid withdrawal state [2].
This is the milder category — the patient's substance use is causing demonstrable harm (physical or mental), but they do NOT meet dependence criteria [2]:
- A pattern of use causing damage to health — physical (e.g., hepatitis from IV drug use) or mental (e.g., depressive episodes secondary to heavy cannabis use)
- The pattern of use has persisted for at least 1 month or occurred repeatedly within a 12-month period
- Does NOT meet criteria for dependence syndrome
- Acute intoxication or hangover alone is NOT sufficient for the diagnosis
Key point: Harmful use is NOT diagnosed if the patient meets dependence criteria under ICD-10 — it is an either/or, not both [2]. This differs from DSM-5 (see below).
≥3 of the following 6 criteria present together for some time during the previous year [1][2]:
a) A strong desire or sense of compulsion to take the substance
b) Difficulties in controlling substance-taking behaviour in terms of its onset, termination, or levels of use
c) A physiological withdrawal state when substance use has ceased or been reduced
d) Evidence of tolerance
e) Progressive neglect of alternative pleasures or interests
f) Persisting with substance use despite clear evidence of overtly harmful consequences
Let me unpack why each criterion matters from first principles:
| Criterion | What it means clinically | Pathophysiological basis |
|---|---|---|
| (a) Compulsion | The patient reports an overwhelming urge to use, often occupying their thoughts. Not the same as "wanting" — it feels involuntary | Reflects craving/preoccupation stage: hippocampal contextual cues + amygdalar emotional conditioning driving drug-seeking behaviour |
| (b) Loss of control | They intended to have "just one drink" but ended up binge-drinking; they tried to stop but couldn't | Diminished PFC/OFC top-down executive control over reward-driven behaviour |
| (c) Withdrawal | Physical or psychological symptoms upon cessation or dose reduction | Neuroadaptation: receptor up/downregulation means the brain now needs the drug to maintain homeostasis |
| (d) Tolerance | Need ↑ doses for the same effect, or the same dose produces ↓ effect | Receptor desensitisation (opioids: ↓ μ-receptor sensitivity), GABA-A downregulation (alcohol, BDZs), NT depletion (stimulants) |
| (e) Narrowing of repertoire | Life shrinks — hobbies, relationships, work all fall away; activities centre around obtaining and using the substance | Shift from dopamine/reward circuitry to glutamate/habit circuitry; natural rewards no longer activate NAc sufficiently |
| (f) Persistent use despite harm | Continues drinking despite knowing they have cirrhosis; continues injecting despite hepatitis C | Loss of PFC-mediated judgment; compulsive (habit-based) use overrides rational decision-making |
Mnemonic: CANT Control Withdraw [2]
- Compulsion
- Alternative pleasures neglected
- Noxious consequences despite continued use
- Tolerance
- Control difficulties
- Withdrawal
DSM-5 Alcohol Intoxication criteria (representative example) [3]:
A. Recent ingestion of alcohol
B. Clinically significant problematic behavioural or psychological changes (e.g., inappropriate sexual or aggressive behaviour, mood lability, impaired judgment) that developed during, or shortly after, alcohol ingestion
C. One or more of the following signs or symptoms developing during, or shortly after, alcohol use:
- Slurred speech
- Incoordination
- Unsteady gait
- Nystagmus
- Impairment in attention or memory
- Stupor or coma
D. The signs or symptoms are not attributable to another medical condition and are not better explained by another mental disorder, including intoxication with another substance
The key principle: intoxication is a transient state directly caused by the pharmacological effects of the substance. It is dose-related (generally), resolves when the substance is cleared, and must include both behavioural/psychological changes and physical signs. Criterion D is the critical rule-out step — you must exclude medical mimics.
Withdrawal is defined as a group of symptoms occurring after absolute or relative withdrawal of a substance after repeated, prolonged, high-dose use [2]:
- Onset and course are time-limited and related to the type and dose of substance used before abstinence
- The withdrawal syndrome must be characteristic of the particular substance
- Must not be better explained by a medical condition or another mental disorder
Note: "relative withdrawal" is important — a patient doesn't have to stop completely. Even a significant reduction in intake can precipitate withdrawal in a heavily dependent individual.
The DSM-5 takes a unified, dimensional approach — it collapses harmful use and dependence into a single entity called Substance Use Disorder (SUD), graded by severity. This is conceptually different from ICD-10.
DSM-5 Alcohol Use Disorder (as a representative model) [3]:
A problematic pattern of alcohol use leading to clinically significant impairment or distress, as manifested by at least two of the following, occurring within a 12-month period:
| # | Criterion | Domain |
|---|---|---|
| 1 | Alcohol is often taken in larger amounts or over a longer period than was intended | Impaired control |
| 2 | There is a persistent desire or unsuccessful efforts to cut down or control alcohol use | Impaired control |
| 3 | A great deal of time is spent in activities necessary to obtain alcohol, use alcohol, or recover from its effects | Impaired control |
| 4 | Craving, or a strong desire or urge to use alcohol | Impaired control |
| 5 | Recurrent alcohol use resulting in a failure to fulfil major role obligations at work, school, or home | Social impairment |
| 6 | Continued alcohol use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of alcohol | Social impairment |
| 7 | Important social, occupational, or recreational activities are given up or reduced because of alcohol use | Social impairment |
| 8 | Recurrent alcohol use in situations in which it is physically hazardous | Risky use |
| 9 | Alcohol use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by alcohol | Risky use |
| 10 | Tolerance, as defined by either: (a) A need for markedly increased amounts of alcohol to achieve intoxication or desired effect; (b) A markedly diminished effect with continued use of the same amount of alcohol | Pharmacological |
| 11 | Withdrawal, as manifested by either: (a) The characteristic withdrawal syndrome for alcohol; (b) Alcohol (or a closely related substance, such as benzodiazepine) is taken to relieve or avoid withdrawal symptoms | Pharmacological |
Severity grading (DSM-5):
- Mild: 2–3 criteria
- Moderate: 4–5 criteria
- Severe: ≥6 criteria
Specifiers: In early remission (none of criteria met for ≥3 months but < 12 months); in sustained remission (none met for ≥12 months); in a controlled environment (access restricted) [2]
| Feature | ICD-10 | DSM-5 |
|---|---|---|
| Categories | Harmful use AND Dependence (separate) | Single entity: Substance Use Disorder (dimensional) |
| Threshold | Harmful use: demonstrable harm; Dependence: ≥3/6 | SUD: ≥2/11 |
| Severity | Not graded (binary: present or absent for each category) | Mild/Moderate/Severe based on symptom count |
| Craving | Not explicitly a criterion | Explicitly included (criterion 4) |
| "Social" criteria | Less emphasised | Criteria 5, 6, 7 explicitly address role obligations, interpersonal problems, activity reduction |
| Used in HK | Yes (primary system) | Used in research; increasingly adopted clinically |
ICD-10 vs DSM-5 — Which to Use in Exams?
In HKUMed exams, you should know both but ICD-10 is the primary coding system in HK. However, the lecture slides explicitly present the DSM-5 Alcohol Use Disorder criteria, so be prepared to discuss either. The ICD-10 dependence criteria (6 criteria, ≥3 needed) and the DSM-5 SUD criteria (11 criteria, ≥2 needed) are both fair game. The ICD-10 dependence criteria are more commonly asked in short-answer questions.
C. Diagnostic Criteria for Specific Clinical Syndromes
Beyond the overarching use disorder/dependence diagnosis, you need criteria for intoxication and withdrawal of specific substances. Here are the key ones:
Timeline and features (critical for clinical management) [2]:
| Time after last drink | Feature | Mechanism |
|---|---|---|
| 6–12h | Tremor, anxiety, nausea, sweating, ↑HR, insomnia | Early sympathetic rebound from GABA-A downregulation |
| 12–24h | Alcoholic hallucinosis (typically visual, may be auditory) | Excitatory neurotransmission in sensory cortices |
| 12–48h | Withdrawal seizures (generalised tonic-clonic) | Glutamate/NMDA receptor upregulation → excitotoxicity |
| 48–96h | Delirium tremens (DT) | Peak of excitatory rebound; mortality < 5% if treated |
Delirium tremens features [2]:
- Delirium: altered, fluctuating consciousness, marked cognitive impairment
- Vivid hallucinations and illusions, e.g., Lilliputian visual hallucinations, formication (tactile hallucination of insects crawling under skin)
- Autonomic hyperactivity: heavy sweating, ↑HR, ↑↑BP, diaphoresis, fever
- Paranoid delusions
- Occurs in 1–4% of hospitalised patients for alcohol withdrawal
- Risk factors: history of DT, chronic alcoholism, concurrent physical illness, withdrawal from CNS depressants, age > 30, prior significant withdrawal symptoms despite ↑BAC [2]
Onset depends on half-life: short-acting (heroin) → 6–12h; long-acting (methadone) → 24–36h [2]
Features: mydriasis, piloerection, rhinorrhoea, lacrimation, yawning, muscle aches, diarrhoea, nausea, abdominal cramps, intense craving, anxiety, restlessness, insomnia. Peak 36–48h, wanes by 5–7 days. Rarely life-threatening.
Onset: 24–48h (short-acting, e.g., lorazepam) to up to 3 weeks (long-acting, e.g., diazepam) [2]
Features: anxiety, irritability, tremor, insomnia, depersonalisation, derealisation, hypersensitivity to stimuli, seizures, delirium. Can be life-threatening (seizures, DTs).
The following mermaid flowchart represents the complete diagnostic pathway when a patient presents with suspected substance misuse:
The Assessment Funnel
Think of diagnostic assessment as a funnel:
- Stabilise — Is this acute intoxication/withdrawal? Is it life-threatening? (ABC first)
- Identify — What substance? (Toxidrome + drug screen)
- Categorise — Harmful use, dependence, or problem use? (Criteria)
- Quantify — How severe? (SADQ, CIWA-Ar, AUDIT, DSM-5 grading)
- Contextualise — Why? Comorbidities? Social context? (Formulation)
- Plan — Where on the stage of change? What intervention matches? (Treatment plan)
Investigations in substance misuse serve several purposes: (1) confirm substance use, (2) detect complications of use, (3) establish baseline before treatment, (4) exclude medical mimics, and (5) monitor treatment response.
E.1 Laboratory Confirmation of Drug Use
Laboratory diagnosis: confirm drug use whenever possible [2]. Drug screening/testing is a core component of diagnosis [1].
The urine drug screen is the most commonly used and most important investigation [2]. It is an immunoassay-based screening test that detects drug metabolites.
| Drug | Detection Window | Notes |
|---|---|---|
| Amphetamines and analogues | 2 days | Short detection window; a negative test doesn't rule out recent use if > 2 days ago |
| Buprenorphine and metabolites | 8 days | Longer half-life of buprenorphine |
| Methadone (maintenance dosing) | 7–9 days | Long half-life; can distinguish from heroin metabolites |
| Morphine | 2 days | Heroin is metabolised to 6-MAM then morphine; 6-MAM is specific for heroin but short-lived |
| Codeine, dihydrocodeine | 2 days | Can cross-react with morphine assay → requires confirmatory testing |
| Cannabinoids (single use) | 3–4 days | THC-COOH (metabolite) is what's detected |
| Cannabis (daily use) | 20 days | Lipophilic → accumulates in fat → slow release → prolonged detection |
| Benzodiazepines | 3 days (short-acting) to 30 days (long-acting) | Depends on specific BDZ and chronicity of use |
| Cocaine (benzoylecgonine) | 2–4 days | Metabolite benzoylecgonine has longer detection than parent compound |
| LSD | 2–5 days | Very low doses used → difficult to detect |
Interpretation principles:
- UDS is a screening test — positive results should be confirmed by gas chromatography-mass spectrometry (GC-MS) or liquid chromatography-mass spectrometry (LC-MS) for legal or definitive purposes
- False positives occur: e.g., poppy seeds → morphine positive; pseudoephedrine → amphetamine positive; sertraline → BDZ positive
- False negatives occur: drug not in panel, used outside detection window, dilute specimen, synthetic drugs not covered by standard assays
- A positive UDS does not diagnose dependence — it only confirms exposure. Clinical criteria are still needed
- A negative UDS does not rule out substance use — consider timing and detection limits
| Test | Substance | Clinical Use |
|---|---|---|
| Blood alcohol concentration (BAC) | Alcohol | Reflects current intoxication; legal threshold in HK for driving = 50 mg/dL. No intoxication despite ↑↑BAC can denote development of tolerance [2] — this is diagnostically significant |
| Serum drug levels | Lithium, paracetamol, specific drugs | When quantitative levels are needed (e.g., overdose management) |
| Ethanol | Alcohol | Can also be measured in breath (breathalyser) — non-invasive, rapid |
- Saliva: increasingly used; non-invasive; reflects recent use (hours to 1–2 days)
- Hair: detects use over months (each cm of hair ≈ 1 month of growth); useful for retrospective assessment, forensic/legal cases, or monitoring in treatment programmes
- Sweat patches: worn for days to weeks; integrative measure of use over that period
E.2 Screening Questionnaires
Tools e.g., CAGE as screening questionnaire for alcohol misuse [1]:
| Letter | Question |
|---|---|
| C | Have you ever felt you should Cut down on your drinking? |
| A | Have people Annoyed you by criticising your drinking? |
| G | Have you ever felt Guilty about your drinking? |
| E | Have you ever had a drink first thing in the morning (Eye-opener) to steady your nerves or get rid of a hangover? |
- Scoring: ≥2 "yes" = positive screen
- ↑ Sensitivity but modest specificity only [2] — good for catching cases but has false positives
- Best used as a rapid screening tool, not a diagnostic instrument
- 10-item screening tool by WHO [2]
- ↑ Sensitivity + ↑ Specificity, probably most useful [2]
- Covers three domains: hazardous alcohol use (questions 1–3), dependence symptoms (questions 4–6), harmful alcohol use (questions 7–10)
- Score 0–40; threshold of ≥8 suggests hazardous or harmful drinking
- Validated across cultures and settings; translated into many languages including Chinese
| Scale | What it measures | Scoring | Clinical use |
|---|---|---|---|
| SADQ (Severity of Alcohol Dependence Questionnaire) | Estimates severity of dependence and thus predicts risk in detoxification [2] | 0–60 | *** > 30 is an indication for in-patient detoxification*** [2] |
| CIWA-Ar (Clinical Institute Withdrawal Assessment for Alcohol, revised) | Quantifies severity of withdrawal [2] | Out of 67 | *** < 10 very mild; 10–15 mild; 16–20 modest; > 20 severe*** [2]. Guides pharmacotherapy: symptom-triggered dosing when CIWA-Ar ≥8 |
| COWS (Clinical Opiate Withdrawal Scale) | Quantifies opioid withdrawal severity | 0–48 | Guides buprenorphine/methadone initiation timing |
These are not for diagnosing substance use disorder per se, but for detecting its consequences, establishing baseline before treatment, and excluding secondary causes [2]:
| Investigation | What it detects | Relevance to substance misuse |
|---|---|---|
| CBC | ↓Hb (anaemia), ↑MCV, ↑WBC | ↑MCV (60%): more commonly in F, strong indicator of excessive drinking (once rule out other causes — B12/folate deficiency, hypothyroidism), takes weeks to return to baseline after abstinence [2]. ↑WBC may indicate infection (e.g., from IV drug use) |
| LFT | ↑GGT, ↑AST/ALT, ↓albumin | ↑GGT (70%): useful screening tool but non-specific, dose-related [2]. AST:ALT ratio > 2 suggests alcoholic liver disease. ↓Albumin suggests chronic liver disease/malnutrition |
| Carbohydrate-deficient transferrin (CDT) | Chronic heavy alcohol use | More specific than GGT [2]; rises with sustained intake of > 60g alcohol/day for > 2 weeks. Useful for monitoring abstinence |
| RFT (Renal function) | Cr, urea, eGFR | Baseline for medication dosing; dehydration in withdrawal; ketamine-induced renal damage; rhabdomyolysis from stimulant/MDMA use |
| Electrolytes | Na, K, Mg, PO₄, Ca | Hyponatraemia (MDMA, beer potomania); hypoK/hypoMg/hypoPO₄ (alcohol withdrawal); hypoCa (alcohol-related malnutrition) |
| Glucose | Hypoglycaemia, DKA | Alcoholic hypoglycaemia (inhibits gluconeogenesis); DKA in alcoholic ketoacidosis; stimulant-related DKA |
| Coagulation (PT/INR) | Synthetic liver function | Alcohol-related liver disease |
| TFT | Thyroid function | Rule out thyrotoxicosis (mimics stimulant intoxication/withdrawal); hypothyroidism (mimics depressant intoxication); baseline before lithium |
| Vitamin B12, folate, thiamine | Nutritional deficiency | Chronic alcoholism → Wernicke-Korsakoff (thiamine deficiency), megaloblastic anaemia (B12/folate) |
| Hepatitis B/C, HIV serology | Blood-borne infections | Essential in all IV drug users; needle sharing is a major transmission route |
| Syphilis serology (RPR/VDRL) | STI screening | High-risk behaviour (e.g., sex work, disinhibited behaviour) |
| Urine toxicology | Confirm substance use | As above; confirm drug use whenever possible [2] |
| Urine pregnancy test | Pregnancy | Substance exposure during pregnancy → teratogenicity; affects management decisions |
| Investigation | Indication | Key Findings |
|---|---|---|
| CT brain | Seizures in alcohol withdrawal (to rule out alternative diagnosis) [2]; head injury in intoxicated patients; cognitive decline | Cerebral cortical atrophy with enlarged ventricles (chronic alcoholism); subdural haematoma; cerebellar vermis atrophy (alcoholic cerebellar degeneration) |
| MRI brain | Cognitive decline, suspected Wernicke-Korsakoff | Cerebral cortical atrophy with enlarged lateral ventricles; loss of grey matter in cortical and subcortical areas; white matter changes with demyelination on DTI [2] (alcohol-related dementia). Mammillary body atrophy (Korsakoff) |
| ECG | Baseline; chest pain in stimulant users; medication monitoring | Prolonged QTc (methadone, TCAs); ST changes (cocaine/stimulant-induced MI); arrhythmias |
| CXR | IV drug users; respiratory symptoms | Aspiration pneumonia (depressant OD); pulmonary oedema (stimulant OD/heroin); endocarditis emboli; TB (immunocompromised) |
| EEG | Seizures, altered consciousness | Differentiate epileptic from non-epileptic seizures; non-convulsive status epilepticus |
| Echocardiography | IV drug users with fever/new murmur | Infective endocarditis (typically right-sided — tricuspid valve — in IVDU) |
| Cystoscopy/Urodynamics | Chronic ketamine users with urinary symptoms | Ketamine-induced ulcerative cystitis — ↓bladder capacity, mucosal ulceration, detrusor overactivity |
| Liver ultrasound/FibroScan | Chronic alcohol users, hepatitis B/C | Fatty liver, cirrhosis, hepatocellular carcinoma screening |
The 'Must-Do' Investigations in Substance Misuse
For any patient with confirmed or suspected substance misuse, your baseline workup should include:
- Urine drug screen (confirm substance)
- CBC (MCV for alcohol, WBC for infection)
- LFT (GGT for alcohol, hepatitis complications)
- RFT + electrolytes (dehydration, electrolyte derangement)
- Glucose (hypoglycaemia, DKA)
- Hepatitis B/C + HIV (if IV drug use or high-risk behaviour)
- ECG (baseline, esp if using methadone or stimulants)
Additional based on clinical picture: CT brain (seizures, cognitive decline), B12/folate/thiamine (chronic alcohol), pregnancy test, CIWA-Ar/SADQ scoring.
↑GGT with ↑MCV: This combination is highly suggestive of chronic heavy alcohol use. GGT is induced by alcohol (and other hepatotoxins) — it's an enzyme on hepatocyte membranes that gets released when they're damaged or induced. MCV rises because alcohol directly suppresses folate metabolism and has a direct toxic effect on erythroid precursors in the bone marrow, causing macrocytosis. However, both are non-specific — GGT can be elevated by medications (phenytoin, carbamazepine), liver disease of any cause, or obesity. MCV can be elevated by B12/folate deficiency, hypothyroidism, or myelodysplasia. That's why CDT is more specific [2].
BAC with no intoxication: If a patient has a blood alcohol level of 300 mg/dL but is walking and talking relatively normally, this strongly suggests tolerance [2] — their brain has adapted to chronic alcohol exposure (GABA-A downregulation, NMDA upregulation). This is diagnostically significant for dependence.
AST:ALT ratio > 2: Characteristic of alcoholic liver disease (alcohol preferentially damages mitochondria → disproportionate AST release from mitochondrial isoenzyme). In viral hepatitis, ALT is usually higher than AST.
Hyponatraemia in a young person after a party: Think MDMA — ecstasy stimulates ADH release (SIADH) AND users often drink excessive water → dilutional hyponatraemia. Can cause seizures and cerebral oedema. Treatment is fluid restriction (NOT normal saline bolus).
High Yield Summary
ICD-10 Dependence: ≥3/6 criteria (CANT Control Withdraw) present for some time in past year. Harmful use is diagnosed ONLY if dependence criteria are NOT met.
DSM-5 SUD: ≥2/11 criteria within 12 months. Severity: Mild (2-3), Moderate (4-5), Severe (≥6). Includes craving as explicit criterion (ICD-10 does not).
Diagnosis is based on: (1) Diagnostic criteria — tolerance, withdrawal, compulsion; (2) Drug screening/testing; (3) Screening tools (CAGE, AUDIT)
Key screening tools: CAGE (sensitive, modest specificity), AUDIT (sensitive + specific, best overall). SADQ > 30 = inpatient detox. CIWA-Ar guides severity of alcohol withdrawal ( > 20 = severe).
Urine drug screen: Most common confirmatory test. Cannabis detectable for 20 days in daily users. Positive UDS ≠ dependence; negative UDS ≠ no use.
Blood markers of chronic alcoholism: ↑GGT (70%, sensitive but non-specific), ↑MCV (60%), ↑CDT (most specific). BAC with no intoxication = tolerance.
Alcohol withdrawal timeline: Tremor (6-12h) → Hallucinations (12-24h) → Seizures (12-48h) → Delirium tremens (48-96h). DT: delirium + vivid hallucinations + autonomic hyperactivity + paranoid delusions. Mortality < 5% if treated.
Must-do baseline investigations: UDS, CBC, LFT, RFT + electrolytes, glucose, Hep B/C + HIV (if IVDU), ECG.
Active Recall - Diagnostic Criteria, Algorithm and Investigations
References
[1] Lecture slides: GC 166. I cannot help myself, taking these pills just feels good Substance abuse and addiction.pdf [2] Senior notes: ryanho-psych.md (Chapter 5.2 Misuse of Substance; Chapter 5.1 Alcohol-related Disorders; Chapter 2.2 Physical Examination and Investigation) [3] Lecture slides: GC 161. Alcohol and the Brain From Psychiatric to Neuropsychiatric Perspectives.pdf
Management of Substance Misuse
Management of substance misuse is always biopsychosocial — this is non-negotiable. There is no single pill that "cures" addiction. The approach must address the biological neuroadaptation, the psychological drivers, and the social context simultaneously. Let me walk you through this systematically.
A. Principles of Management
Aim of treatment: Ideally, complete abstinence with good personal and social adjustment. If this cannot be achieved, then aim for harm reduction. [2]
This two-tier approach is pragmatic:
- Complete abstinence is the gold standard for dependent patients — particularly for alcohol, opioids, and benzodiazepines where continued use causes progressive organ damage
- Harm reduction acknowledges reality — some patients are not ready or able to stop completely. Reducing the amount, switching to safer routes (e.g., oral methadone instead of IV heroin), needle exchange programmes, and reducing risky behaviours (sharing needles, driving intoxicated) are all valid intermediate goals
The goal of treatment depends on severity [2]:
- Controlled drinking (or controlled use): for those detected early, non-dependent, with minimal health sequelae
- Total abstinence: for those who are dependent, with failed prior attempts at controlled use
Assessment of motivation can be done based on Prochaska and DiClemente's stages of change model [2].
Significance: facilitates motivational interviewing to enhance the patient's own motivation [2].
This is critical because addiction treatment only works when the patient is internally motivated. Imposing abstinence on a pre-contemplative patient is futile — they'll relapse immediately. Your job is to match the intervention to the stage:
| Stage | Patient's position | Appropriate intervention |
|---|---|---|
| Pre-contemplation | "I don't have a problem" | Raise awareness non-judgmentally; plant seeds of doubt |
| Contemplation | "Maybe I have a problem, but..." | Motivational interviewing — explore ambivalence, develop discrepancy |
| Preparation | "I want to change and I'm making plans" | Help plan concrete steps; discuss treatment options |
| Action | "I'm actively changing" | Pharmacotherapy, psychotherapy, structured programmes |
| Maintenance | "I've changed and I'm trying to sustain it" | Relapse prevention, ongoing support, mutual help groups |
| Relapse | "I've slipped back" | Normalise, re-engage, identify triggers, restart cycle |
Understanding why people take drugs is important to devise a management plan that can address this reason [2]:
- Pleasure-seeking: for the "high and buzz"
- Self-medication: for underlying anxiety/depression, social anxiety, anger, pain, boredom
- Social pressure: peer effect, life events, adversity
- Others: search for meaning or mystical experiences
C. Management of Acute Intoxication (by Substance)
The overarching principle of acute intoxication management is: Stabilise first, identify the substance, give specific antidote if available, and provide supportive care until the drug clears.
| Step | Action | Mechanism / Rationale |
|---|---|---|
| ABC | Secure airway (intubate if GCS ≤ 8), ventilatory support | Opioids depress brainstem respiratory centres → respiratory arrest is the primary cause of death |
| Naloxone | IV/IM/IN 0.4–2 mg, repeat every 2–3 min (max ~10 mg) | Naloxone = competitive μ-opioid receptor antagonist. It displaces the opioid from the receptor, rapidly reversing respiratory depression, sedation, and miosis |
| Monitor for re-sedation | Observe for ≥2h after last dose; consider naloxone infusion if long-acting opioid | Naloxone has a shorter half-life (~30–90 min) than most opioids (heroin: ~4–5h, methadone: ~24–36h) → patient can re-sedate after naloxone wears off |
Naloxone Cautions
Naloxone in a dependent patient will precipitate acute withdrawal — piloerection, vomiting, diarrhoea, mydriasis, tachycardia. This is extremely distressing but not dangerous. The goal is to restore adequate ventilation, NOT to fully awaken the patient. Titrate naloxone to respiratory rate > 12, not to full consciousness. Over-reversal also risks the patient discharging themselves against medical advice to use again, potentially causing re-overdose.
| Step | Action | Mechanism / Rationale |
|---|---|---|
| ABC | Ensure airway, support ventilation | BDZs cause CNS depression; respiratory depression significant esp with co-ingestants (alcohol, opioids) |
| IV Flumazenil | 0.2 mg/30s ± repeat dose [2] | Non-specific competitive antagonist of the BDZ receptor, can reverse BDZ-induced sedation [2] |
| Caution | Risk of withdrawal seizures in tolerant individuals [2]; contraindicated if co-ingestion with TCA (seizure risk) or chronic BDZ use | Flumazenil has a short half-life (~1h) → re-sedation possible |
In practice, flumazenil is used cautiously and infrequently — supportive care with airway management is often preferred over pharmacological reversal in dependent patients.
| Step | Action | Rationale |
|---|---|---|
| ABC | Recovery position, protect airway from aspiration | Vomiting + ↓consciousness = aspiration risk |
| Supportive | IV fluids, correct hypoglycaemia (check glucose!), rewarm if hypothermic | Alcohol inhibits gluconeogenesis → hypoglycaemia; vasodilation → hypothermia |
| Thiamine | IV Pabrinex before glucose | Glucose loading without thiamine can precipitate Wernicke's encephalopathy in thiamine-depleted patients |
| Monitor | Serial GCS, vitals | Rule out head injury (intoxicated patients fall), subdural haematoma |
| Step | Action | Rationale |
|---|---|---|
| ABC | Secure airway; BP control; fluid support; cardiac monitoring | Sympathomimetic toxidrome → hypertensive crisis, MI, arrhythmia |
| Sedation: IV benzodiazepine | First-line for agitation, seizures, hypertension, hyperthermia [2] | BDZs enhance GABA → counters the excitatory catecholamine surge |
| Mx of hyperthermia | BDZ sedation; NMB + GA if severe [2] | Active cooling; severe hyperthermia (> 40°C) → rhabdomyolysis, multi-organ failure |
| Antipsychotics | May be required to control psychotic symptoms [2] | Usually haloperidol or olanzapine for persistent psychosis after BDZ sedation |
| Avoid | β-blocker alone should NOT be used → may lead to unopposed alpha-agonistic activity → coronary vasoconstriction [2] | With β₂ vasodilation blocked, α₁-mediated vasoconstriction is unopposed → ↑ afterload, coronary spasm |
| Step | Action | Rationale |
|---|---|---|
| ABC | Supportive: ensure ABC | Sympathomimetic + serotonergic toxicity |
| Treat hyponatraemia | Fluid restriction [2] | MDMA → ↑ADH (SIADH) + excessive water intake → dilutional hypoNa → cerebral oedema. Do NOT give NS bolus |
| BDZ | For cardiac effects, psychomotor agitation, seizures, hyperthermia [2] | GABA enhancement to counter excitatory state |
| Cyproheptadine | For serotonin syndrome [2] | Cyproheptadine = 5-HT₂A receptor antagonist → directly blocks the excess serotonergic activity causing the syndrome |
| Step | Action | Rationale |
|---|---|---|
| ABC | Secure ABC, atropine for bradycardia/hypersalivation, IV fluid for ↓BP [2] | Ketamine causes hypersalivation (cholinergic effect); haemodynamic support |
| BDZ | For psychomotor agitation, muscle rigidity, hallucination [2] | First-line for managing agitation; safer than antipsychotics in this context |
D. Management of Withdrawal
This is one of the most commonly tested management scenarios. Alcohol withdrawal can kill — it requires structured, protocol-driven management.
Setting — Indications for in-patient detoxification [2]:
- Severe dependence (e.g., SADQ > 30)
- History of severe withdrawal symptoms (e.g., seizures, DT)
- Very high alcohol consumption ( > 30 units/day)
- Concomitant BDZ misuse (↑↑ withdrawal severity)
- Significant medical/psychiatric comorbidity
Step-by-step management [2]:
| Step | Action | Rationale |
|---|---|---|
| 1. Rule out alternatives | R/o alternative diagnosis: CNS infection, drug OD, metabolic derangement, liver failure [2] | Never assume "just withdrawal" |
| 2. Supportive | NPO, correct volume deficits, stabilise haemodynamics [2] | Dehydration and electrolyte derangement are common |
| 3. Correct metabolic derangements | HypoGly, hypoK, hypoMg, hypoPO₄, ketoacidosis [2] | Alcohol depletes magnesium (impairs K reabsorption → refractory hypoK); inhibits gluconeogenesis |
| 4. Thiamine + glucose | To prevent Wernicke's encephalopathy [2]. Give thiamine before or with glucose | Glucose metabolism consumes thiamine → can precipitate Wernicke's in depleted patient |
| 5. Multivitamins with folate | For nutritional supplements [2] | Chronic alcoholics are malnourished; folate deficiency → macrocytic anaemia |
| 6. Benzodiazepines | ↓ agitation and ↓ withdrawal [2] | Cross-tolerance with alcohol at GABA-A receptor; replaces alcohol's GABAergic effect safely |
BDZ prescribing details [2]:
- Indication: symptom-triggered (CIWA-Ar ≥ 8) — this requires intensive monitoring (e.g., Q1h). May be prophylactic if not possible (i.e., fixed-schedule dosing if monitoring resources insufficient) [2]
- Choice: prefer long-acting BDZs, e.g., diazepam (Valium), chlordiazepoxide (Librium) [2]
- Why long-acting? They provide a smoother decline in blood levels, reducing breakthrough withdrawal symptoms and the risk of seizures. The drug essentially "auto-tapers" via its long half-life.
- Oxazepam if severe liver disease present [2] — because oxazepam undergoes glucuronidation (Phase II) only, which is preserved even in advanced liver disease, unlike diazepam which requires oxidation (Phase I)
For refractory cases [2]:
- Barbiturates or propofol for refractory DT [2]
- BDZs, phenobarbital, propofol for status epilepticus [2]
Prophylaxis [2]:
- Oral chlordiazepoxide; oxazepam if severe liver disease
- Indication: ↑ risk of severe withdrawal (e.g., Hx of seizures/DT) after heavy alcohol consumption, but currently admitted for other reasons with minimal withdrawal symptoms
Symptom-Triggered vs Fixed-Schedule BDZ Dosing
Symptom-triggered (CIWA-Ar based): Dose BDZ only when CIWA-Ar ≥ 8. Advantages: less total BDZ used, shorter treatment duration, fewer complications. Requires Q1h nursing monitoring.
Fixed-schedule: Give BDZ at regular intervals regardless of symptoms, then taper. Used when intensive monitoring is not feasible (e.g., busy ward, non-ICU setting). Disadvantage: may over- or under-treat.
Symptom-triggered is the preferred approach where resources allow.
Opioid withdrawal is rarely life-threatening, but often so distressing that it triggers drug-seeking behaviour [2]. Management can be symptomatic or substitution-based:
Symptomatic treatment (for patients NOT going onto maintenance):
| Symptom | Drug | Mechanism |
|---|---|---|
| Autonomic symptoms (sweating, tachycardia, anxiety) | Clonidine / Lofexidine | α₂-adrenergic agonist → ↓ NA release from locus coeruleus → ↓ sympathetic overdrive. Lofexidine is preferred (less hypotension than clonidine) |
| Diarrhoea, abdominal cramps | Loperamide | μ-opioid receptor agonist in gut (doesn't cross BBB) → ↓ GI motility |
| Muscle/joint pain | NSAIDs / paracetamol | Analgesic; avoid prescribing opioid analgesics |
| Insomnia | Short-course BDZ or zopiclone | Sedation; use cautiously, short-term only |
| Nausea/vomiting | Metoclopramide / prochlorperazine | Anti-emetic |
Substitution therapy (see Section E below for long-term maintenance):
- Methadone or buprenorphine can be initiated during withdrawal to provide a smooth transition to maintenance treatment
- Buprenorphine must NOT be given until the patient is in moderate withdrawal (typically ≥ 12h after last heroin dose), otherwise it precipitates withdrawal (see below)
Treatment of withdrawal and dependence [2]:
- Switch to long-acting BDZ, e.g., diazepam [2]
- Why? Convert all BDZ use to a single long-acting equivalent. Diazepam has a long half-life (~100h including active metabolites) → provides smoother blood levels, easier to taper
- Gradual withdrawal over a period of ≥ 8 weeks, usually lower 1/8 of dose every 2 weeks [2]
- Why so slow? GABA-A receptor recovery takes time. Too-rapid tapering → rebound anxiety, insomnia, seizures
- Withdrawal symptoms are most troublesome when the dose is completely tapered off [2] — the final steps are the hardest
- Some patients may continue to experience withdrawal-like symptoms for months to years (prolonged withdrawal) [2]
BDZ Withdrawal — The Last Steps are the Hardest
When tapering BDZs, patients often do well until the final 25% of the dose. At this point, each dose reduction represents a proportionally larger percentage decrease. Consider slowing the taper further at lower doses (e.g., 1/10 reductions). Adjunct CBT for insomnia and anxiety is very helpful during this phase.
There is no specific pharmacotherapy for stimulant withdrawal — management is primarily supportive [2]:
| Aspect | Management | Rationale |
|---|---|---|
| Supportive | Rest, nutrition, hydration | Post-use "crash" involves exhaustion, dehydration, poor nutritional intake |
| BDZ | May be useful for acute severe withdrawal syndrome [2] | For marked agitation, insomnia |
| Monitor mood | Assess for severe depression and suicidality | Severe depression, anhedonia, suicidal ideation occur during withdrawal "crash" [2] — suicide risk is real |
| Antidepressants | Bupropion, mirtazapine: promising treatment but not yet established [2] | Bupropion acts on DA/NA reuptake → may partially address DA depletion; mirtazapine's α₂-antagonism and 5-HT effects may help sleep and appetite |
E. Pharmacotherapy for Long-Term Maintenance/Relapse Prevention
This is where the substance-specific medications come in. These are the drugs used after acute detoxification to maintain abstinence and prevent relapse.
Approach to management of alcohol misuse (NICE 2014) [2]:
- For mild dependence: offer a high-intensity psychotherapy
- For moderate/severe dependence: offer acamprosate/PO naltrexone in combination with a high-intensity psychological treatment
- For those with ↑ intake ( > 15 units/day) and/or ≥ 15–30 on SADQ: offer acute treatment vs withdrawal in community or inpatient settings
| Drug | Mechanism | Indication | Key Points | Contraindications |
|---|---|---|---|---|
| Acamprosate | Modulates glutamate/GABA balance: weak NMDA antagonist + GABA-A agonist → stabilises the hyperexcitable state of early abstinence | First-line for relapse prevention in moderate-severe dependence | Start after detoxification is complete. Continue for ≥6 months. Side effects: headache, fatigue, dizziness, depression [2] | Severe renal impairment (renally excreted); severe hepatic failure |
| Naltrexone (oral) | μ-opioid receptor antagonist → blocks the endogenous opioid-mediated reward from alcohol → drinking becomes less pleasurable | First-line for relapse prevention (alternative/adjunct to acamprosate) | Can be taken while still drinking (unlike disulfiram). Reduces "heavy drinking days." Must ensure no concurrent opioid use (precipitates withdrawal) | Hepatic failure (hepatotoxic at high doses); concurrent opioid use; acute hepatitis |
| Nalmefene | Opioid antagonist → similar to naltrexone but with additional partial agonist at κ-receptor | Superior to placebo in severe dependence only [2] | Taken "as needed" before anticipated drinking occasions | Similar to naltrexone |
| Disulfiram | Irreversibly inhibits aldehyde dehydrogenase (ALDH) → acetaldehyde accumulates → flushing, nausea, vomiting, headache, tachycardia after drinking | Aversion therapy — deterrent approach | Requires high motivation and supervised administration. Patient must be fully informed. Must NOT drink for ≥24h before starting. Effect lasts ~2 weeks after last dose | Severe heart disease, CVA, liver failure, psychosis, pregnancy, unreliable patient without supervised administration |
| Antidepressants | May be useful in those with comorbid depression [2] | Comorbid depression with alcohol dependence | SSRIs or mirtazapine; treat the depression → ↓ self-medication with alcohol | Should wait until abstinence is established to distinguish substance-induced from primary depression |
Understanding the pharmacology of disulfiram from first principles: Normal alcohol metabolism: ethanol → (alcohol dehydrogenase) → acetaldehyde → (aldehyde dehydrogenase / ALDH) → acetate → CO₂ + H₂O. Disulfiram blocks ALDH → acetaldehyde accumulates → toxic reaction. This is essentially the same reaction that occurs naturally in East Asians with the ALDH2 inactivating mutation — the "Asian flush" is a mild form of the disulfiram reaction.
Opioid substitution/maintenance therapy is one of the most evidence-based treatments in addiction medicine:
| Drug | Mechanism | Indication | Key Points | Contraindications |
|---|---|---|---|---|
| Methadone | Full μ-opioid receptor agonist, long half-life (~24–36h) | Maintenance therapy for opioid dependence | Dispensed daily (supervised) from methadone clinics. Provides steady-state opioid effect → prevents withdrawal, ↓ craving, blocks the "high" from additional heroin (cross-tolerance). In HK, available through SARDA (Society for the Aid and Rehabilitation of Drug Abusers) methadone clinics | QTc prolongation (ECG monitoring needed); respiratory depression risk; drug interactions (CYP3A4 substrates). Must not co-prescribe with BDZ without careful monitoring |
| Buprenorphine | Partial μ-opioid agonist + κ-opioid antagonist | Alternative to methadone for maintenance; also used for detoxification | "Ceiling effect" on respiratory depression → safer in overdose than methadone. Sublingual formulation. Must initiate when patient is in moderate withdrawal (COWS ≥ 12), otherwise precipitates withdrawal (partial agonist displaces full agonist at receptor) | Severe hepatic impairment; concurrent full opioid agonist use (precipitated withdrawal) |
| Buprenorphine/naloxone combination | Buprenorphine (partial agonist) + naloxone (antagonist — inactive sublingually but active if injected) | Opioid maintenance — preferred over plain buprenorphine | Naloxone component deters IV misuse: if tablet is crushed and injected, naloxone becomes bioavailable → precipitates withdrawal → aversive → discourages diversion | Same as buprenorphine |
| Naltrexone (oral or depot) | μ-opioid receptor antagonist → blocks opioid effects completely | Relapse prevention after detoxification in highly motivated patients | No agonist effect → no "replacement" → less accepted by patients. Must be fully detoxified first (7–10 days opioid-free). Depot IM injection (monthly) overcomes adherence issues | Must confirm opioid-free (naloxone challenge test); hepatic impairment |
Why Buprenorphine Can Precipitate Withdrawal
Buprenorphine is a partial agonist with very high receptor affinity. If given to a patient who still has a full agonist (heroin/methadone) occupying μ-receptors, buprenorphine displaces it — but because buprenorphine only partially activates the receptor, the net effect is a sudden DROP in opioid receptor activation → precipitated withdrawal. This is why you must wait until the patient is already in withdrawal (receptors partially vacated) before initiating buprenorphine.
Treatment of amphetamine dependence can be difficult as the drug effect can be intense [2]:
| Approach | Details |
|---|---|
| Psychosocial intervention | Mainstay (no established anti-craving Tx) [2]. CBT and contingency management are the best-supported modalities |
| Pharmacological for cocaine | Usually reserved for treatment-resistant patients; options include DA agonist, disulfiram [2] |
| Antidepressants | Bupropion, mirtazapine: promising but not yet established [2] |
| Contingency management | Particularly effective for stimulant use — patients receive tangible rewards (vouchers, prizes) for negative drug screens. Works by providing an alternative positive reinforcement to compete with drug reward |
Why is there no good pharmacotherapy for stimulants? Unlike opioids (where you can use a longer-acting opioid as substitution) or alcohol/BDZs (where you can use cross-tolerant GABAergic agents), stimulants act primarily via monoamine release/reuptake blockade. There is no safe "replacement" stimulant that provides a controlled, sustained dopamine effect without the reinforcing rush. Methylphenidate and dexamfetamine have been trialled but results are inconsistent.
- No established pharmacotherapy
- Treatment is entirely psychosocial: CBT, motivational interviewing, contingency management
- Withdrawal is mild and self-limiting; symptomatic treatment (sleep aids, anxiolytics short-term) if needed
F. Psychosocial Interventions
Treatment should consist of bio-/psycho-/social components [2]. Psychosocial interventions are the backbone of addiction treatment — pharmacotherapy alone is insufficient.
- Basis: transtheoretical model of behaviour change asserts that there are different levels of readiness to change among individuals [2]
- MI assesses readiness for change followed by attempts to build internal motivation to change based on patient's stage [2]
- Principles: express empathy, develop discrepancy, roll with resistance, support self-efficacy [2]
- Techniques [2]:
- Engage patient thoughtfully by reflective listening
- Focus on a specific issue to be changed
- Evoke the patient's own thoughts that motivate them towards change
- Planning, at least in the conceptual aspect, for changes
- Efficacy: effective at short- and long-term across all substances [2]
- Utility: allows patient to generate own arguments and motivation for change; facilitates change especially when patient is ambivalent [2]
- Involves [2]:
- Psychoeducation to let patients understand how their thought processes contribute to their behaviour
- Behavioural treatment to help patients develop new and adaptive ways of behaving and alter their social environment → in turn leads to change in thoughts and emotions
- Efficacy: modest positive effects on substance use [2]
- Particularly useful for identifying triggers, developing coping strategies, managing cravings, and addressing comorbid anxiety/depression
- Efficacious for non-dependent, at-risk alcohol use [2]
- Involves: simple education and advice about safe levels of alcohol consumption [2]
- Efficacy: usually modest reduction in alcohol consumption over next few years [2]
- Utility: best for those with at-risk drinking (alcohol use above limit but non-dependent) [2]
- E.g., Alcoholics Anonymous (AA) [2], Narcotics Anonymous (NA)
- 12-step programme model: peer support, sponsorship, shared experience
- Free, widely available, ongoing (lifetime)
- Evidence base: moderate-quality evidence of benefit, particularly when combined with professional treatment
- Cue exposure therapy: to ↓ effect of drinking cues and to prevent relapse [2] — systematic desensitisation to environmental triggers
- Contingency management: offer incentives to encourage abstinence or discourage substance use [2] — particularly effective for stimulants and cannabis
- Family therapy: address family dynamics, improve communication, reduce enabling behaviour
| Intervention | Purpose |
|---|---|
| Housing support | Stable accommodation is foundational — you cannot address addiction in a homeless patient without addressing homelessness |
| Employment support | Vocational rehabilitation; sheltered employment |
| Needle exchange programmes | Harm reduction for IVDU — reduces HIV, HCV transmission |
| Methadone clinics | HK has an extensive methadone maintenance programme via SARDA — free, easily accessible, critical for harm reduction in heroin users |
| Drug rehabilitation centres | Residential programmes (e.g., Christian-based centres in HK) for motivated patients |
| Legal/forensic liaison | Support with court-mandated treatment, probation requirements |
| Financial counselling | Many addicted patients have debt from drug expenditure or loss of income |
When abstinence is not achievable, harm reduction is the pragmatic alternative:
| Strategy | Application |
|---|---|
| Needle and syringe exchange | Reduces blood-borne virus transmission among IVDU |
| Supervised consumption facilities | Present in some countries; ↓ overdose deaths by providing medical supervision |
| Naloxone distribution (take-home) | Community naloxone kits for opioid users and their families → bystander can reverse overdose before ambulance arrives |
| Opioid substitution therapy | Methadone/buprenorphine maintenance reduces heroin use, crime, HIV risk, and overdose death — even if the patient is still using on top |
| Harm reduction education for MDMA | Take breaks from dancing when intoxicated, consume isotonic replacement fluid during vigorous exercise → ↓ hyperthermia [2] |
| Nicotine replacement therapy (NRT) | Patches, gum, lozenges for nicotine dependence — replaces the nicotine without the carcinogens of smoking |
| Substance | Acute Intoxication | Withdrawal | Maintenance / Relapse Prevention |
|---|---|---|---|
| Opioids | ABC, naloxone | Clonidine/lofexidine (symptomatic) OR methadone/buprenorphine (substitution) | Methadone or buprenorphine maintenance; naltrexone for motivated patients |
| Alcohol | ABC, thiamine, glucose, supportive | BDZs (symptom-triggered CIWA-Ar or fixed-schedule); thiamine, electrolytes | Acamprosate, naltrexone (first-line); disulfiram (supervised); psychotherapy |
| BDZs | ABC, flumazenil (caution in dependent) | Switch to long-acting BDZ, gradual taper ≥ 8 weeks | CBT for insomnia/anxiety; no specific relapse prevention medication |
| Methamphetamine | ABC, IV BDZ for agitation/seizures; antipsychotics for psychosis | Supportive; BDZ if severe; monitor depression/suicide | Psychosocial (mainstay): CBT, contingency management. No established pharmacotherapy |
| Cocaine | ABC, IV BDZ; NO β-blockers alone | Supportive | Psychosocial; DA agonist/disulfiram in treatment-resistant |
| MDMA | ABC, fluid restriction for hypoNa, BDZ, cyproheptadine for serotonin syndrome | Supportive (post-crash) | Psychosocial; harm reduction education |
| Ketamine | ABC, atropine, BDZ for agitation | Minimal (supportive) | Psychosocial; treat ketamine cystitis if present |
| Cannabis | Supportive (usually no acute danger) | Mild (symptomatic if needed) | Psychosocial: CBT, MI |
| LSD/Hallucinogens | Calm environment, BDZ; haloperidol 2nd line | Minimal | Psychosocial |
High Yield Summary
Treatment aims: Complete abstinence ideally; harm reduction if not possible. Match intervention to stage of change.
Treatment must be biopsychosocial: Pharmacotherapy alone is insufficient.
Acute intoxication: Stabilise (ABC) → Identify substance → Specific antidote if available (naloxone for opioids, flumazenil for BDZs — both with cautions) → Supportive care.
Alcohol withdrawal: CIWA-Ar guided BDZ dosing (symptom-triggered preferred); long-acting BDZ (diazepam/chlordiazepoxide); oxazepam if liver failure; thiamine BEFORE glucose; barbiturates/propofol for refractory DT.
Opioid withdrawal: Symptomatic (clonidine/lofexidine + supportive) OR substitution (methadone/buprenorphine). Buprenorphine must wait for moderate withdrawal (COWS ≥ 12) or it precipitates withdrawal.
BDZ withdrawal: Switch to long-acting (diazepam), taper ≥ 8 weeks (1/8 Q2w).
Stimulant intoxication: BDZ first-line for agitation/seizures/hyperthermia. NO β-blockers alone for cocaine. Antipsychotics for persistent psychosis. Hyperthermia: BDZ → NMB + GA if severe.
Relapse prevention: Alcohol — acamprosate + naltrexone (first-line); disulfiram (supervised aversion). Opioids — methadone/buprenorphine maintenance; naltrexone. Stimulants — psychosocial only (no established pharmacotherapy).
Key psychosocial therapies: Motivational interviewing (all substances, all stages), CBT (moderate evidence), contingency management (esp stimulants), mutual help groups (AA/NA), brief intervention (non-dependent at-risk drinkers).
Harm reduction: Needle exchange, take-home naloxone, opioid substitution, supervised consumption, MDMA harm reduction education.
Active Recall - Management of Substance Misuse
References
[1] Lecture slides: GC 166. I cannot help myself, taking these pills just feels good Substance abuse and addiction.pdf [2] Senior notes: ryanho-psych.md (Chapter 5.2 Misuse of Substance; Chapter 5.1 Alcohol-related Disorders; Chapter 3.1 Benzodiazepines; Chapter 3.3 Psychotherapy)
Complications of Substance Misuse
Complications of substance misuse are vast, touching virtually every organ system, every psychiatric diagnosis, and every domain of social functioning. The key organising principle is that complications arise from three distinct mechanisms:
- Direct pharmacological effects of the substance (acute and chronic toxicity)
- Route of administration (what you put the drug through — IV, smoking, snorting)
- Behavioural consequences of intoxication, dependence, and the addictive lifestyle
The impact of addiction spans [1]:
- Route — ingestion, inhalation/smoking, injection (subcutaneous, muscle, intravenous)
- Form/substances (state of intoxication/withdrawal)
- Chronic use
- Self-care
Let's work through this systematically.
A. Medical Complications
The route of administration determines which organ systems are damaged mechanically and which infectious risks the patient faces.
| Route | Complications | Pathophysiological Basis |
|---|---|---|
| Intravenous injection | Injection site: cellulitis, subcutaneous/deep abscesses, thrombophlebitis, thrombosed veins, needle tracks, scarring | Direct tissue damage + introduction of bacteria (non-sterile technique, skin flora introduced into subcutaneous tissue/veins) |
| Blood-borne infections: Hepatitis B, Hepatitis C, HIV | Needle sharing → direct blood-to-blood transmission. HCV is the most efficiently transmitted (even with tiny blood residue) | |
| Infective endocarditis (typically right-sided — tricuspid valve) | Bacteria from non-sterile injection enter venous circulation → seed on valve leaflets. Right-sided because venous blood passes through right heart first. Staph. aureus is the most common organism | |
| Septic emboli → pulmonary abscesses, septic pulmonary emboli | From right-sided vegetations → lungs | |
| DVT, PE | Venous damage + immobility during intoxication + repeated venous puncture → Virchow's triad | |
| Tetanus, botulism | Especially with skin-popping (subcutaneous injection) and injection into muscle; anaerobic organisms from contaminated drug preparations | |
| Smoking/Inhalation | COPD, chronic bronchitis, emphysema, lung cancer | Combustion products → chronic airway inflammation, mucociliary damage, carcinogen exposure |
| Crack lung (cocaine) — diffuse alveolar damage, haemoptysis | Inhaled cocaine causes direct thermal/chemical injury to alveolar epithelium + vasoconstriction → ischaemia | |
| Aspiration pneumonia | Depressed consciousness during intoxication → loss of protective airway reflexes → aspiration of gastric contents | |
| Intranasal (snorting) | Nasal septal perforation, chronic rhinitis, sinusitis | Cocaine/methamphetamine cause intense local vasoconstriction → mucosal ischaemia → tissue necrosis → perforation |
| Oral | GI complications (hepatotoxicity, GI bleeding — esp with alcohol) | Fewer route-specific complications; most harm is from the pharmacological effects of the substance itself |
Physical Signs That Should Alert You to IV Drug Use
Physical signs: needle tracks, thrombosed veins, wearing of long-sleeved shirts in hot weather, scars, subcutaneous/deep abscesses, hepatitis B/C [2]. On examination, check the antecubital fossae, dorsal hands, feet, and neck veins. Long-term IVDU may resort to femoral vein injection ("groin injecting") which carries the highest risk of DVT, femoral artery pseudoaneurysm, and necrotising fasciitis.
A.2 Substance-Specific Medical Complications
Alcohol is arguably the substance with the broadest spectrum of medical complications because of its direct toxicity to multiple organ systems, combined with secondary nutritional deficiency.
| System | Complication | Mechanism |
|---|---|---|
| Liver | Fatty liver → alcoholic hepatitis → cirrhosis → hepatocellular carcinoma | Ethanol metabolism generates acetaldehyde (toxic) + NADH excess → fatty acid synthesis, oxidative stress, stellate cell activation → fibrosis → cirrhosis. The progression is: steatosis (reversible) → steatohepatitis → fibrosis → cirrhosis (irreversible) |
| GI | Oesophageal varices, GI bleeding, pancreatitis (acute and chronic), Mallory-Weiss tears, oesophageal cancer | Cirrhosis → portal hypertension → varices; direct mucosal irritation → Mallory-Weiss; acetaldehyde is a direct carcinogen; alcohol is the most common cause of chronic pancreatitis |
| CVS | Alcoholic cardiomyopathy (dilated), atrial fibrillation ("holiday heart"), hypertension | Direct myocardial toxicity → myocyte death → fibrosis → dilated CMP; acute binge drinking → adrenergic surge → AF. Chronic hypertension mechanism is multifactorial (↑SNS, ↑cortisol, ↑RAAS) |
| Haem | Macrocytic anaemia (↑MCV), pancytopenia, folate deficiency, iron deficiency (GI blood loss) | Direct marrow toxicity + folate deficiency (poor diet + ↓absorption) → megaloblastic anaemia; hypersplenism from cirrhosis → pancytopenia |
| Metabolic | Hypoglycaemia, alcoholic ketoacidosis, hypomagnesaemia, hypokalaemia, hypophosphataemia | Ethanol inhibits gluconeogenesis → hypoglycaemia; accumulation of NADH shifts metabolism towards ketogenesis; Mg wasting (↑renal excretion + poor dietary intake) → secondary hypoK (Mg required for K reabsorption) |
| Endocrine | Hypogonadism, gynaecomastia, testicular atrophy, reduced fertility | Direct gonadotoxicity; liver impairment → ↓ oestrogen clearance → gynaecomastia; ↓testosterone production |
| Immune | Immunosuppression → ↑risk of TB, pneumonia, other infections | Alcohol suppresses innate and adaptive immunity; malnutrition compounds this |
| Musculoskeletal | Myopathy (acute and chronic), osteoporosis, avascular necrosis | Direct myotoxicity; ↓osteoblast activity + ↑osteoclast activity; impaired calcium/vitamin D metabolism |
This is extremely high-yield for exams, especially the Wernicke-Korsakoff spectrum.
a. Wernicke-Korsakoff Syndrome (WKS) [2]
This is really one disease spectrum caused by thiamine (vitamin B₁) deficiency:
Wernicke's encephalopathy (WE): acute, potentially reversible [2]
The classic triad:
- Encephalopathy: delirium with profound disorientation, apathy, inattention, amnesia [2]
- Oculomotor dysfunction [2]:
- Truncal ataxia (vermis type): ataxic, wide-based gait with short steps [2]
- Others: polyneuropathy (50%), hypothermia (1-4%), vestibular dysfunction, coma (rare) [2]
Why thiamine deficiency? Alcohol inhibits the active process for thiamine absorption in the GI tract [2]. Thiamine is a cofactor for pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase — enzymes critical for aerobic metabolism. Without thiamine, neurons (which are entirely dependent on aerobic glucose metabolism) undergo energy failure and death, particularly in the mammillary bodies, medial thalamus, periaqueductal grey, and cerebellar vermis.
Diagnosis: Caine criteria (≥ 2 out of 4) [2]:
- Dietary deficiency
- Oculomotor abnormalities
- Cerebellar dysfunction
- Altered mental state or amnesia
Management: parenteral thiamine immediately upon suspicion [2]. Oral thiamine as maintenance [2].
Course: prompt administration of thiamine leads to improvement in ocular signs within hours to days, with confusion subsiding in days to weeks [2].
Prognosis: mortality 17% in acute stage; majority have residual deficits (nystagmus, ataxic gait, memory deficits); 84% develop Korsakoff syndrome (irreversible) [2].
Korsakoff syndrome: The chronic, irreversible sequela of untreated or inadequately treated Wernicke's. Characterised by:
- Anterograde amnesia (cannot form new memories) — most prominent
- Retrograde amnesia (loss of old memories, temporally graded — recent > remote)
- Confabulation (unconscious fabrication of memories to fill gaps — NOT deliberate lying)
- Relatively preserved other cognitive functions and personality
b. Other Alcohol-Related Neurological Sequelae [2]
| Complication | Pathogenesis | Features |
|---|---|---|
| Alcoholic cerebellar degeneration | Nutritional deficiency + neurotoxicity → degeneration of Purkinje cells in cerebellar cortex → vermis atrophy [2] | Subacute/chronic onset of ataxic gait → truncal ataxia [2]. Stabilises with abstinence; progresses with continued drinking. CT/MRI: cerebellar cortical atrophy, especially affecting anterior vermis [2][3] |
| Alcohol-related dementia | Usually multifactorial: head injury, vascular changes, direct alcohol neuronal toxicity [2] | Cognitive impairment simulating frontal lobe dementia [2] (frontal lobes most susceptible). Prevalence: ~50-70% of alcohol abusers have some degree of cognitive deficits [2]. Diagnosed 8 weeks after abstinence [2]. Neuroimaging: cerebral cortical atrophy with enlarged lateral ventricles; loss of grey matter; white matter changes with demyelination on DTI [2] |
| Marchiafava-Bignami disease | Rare demyelinating disorder of corpus callosum due to hypovitaminosis B (esp B₁) [2] | Frontal syndrome (frontal dementia, personality changes), seizures, spasticity, rigidity, paralysis, coma, death [2]. Neuroimaging: hypodense/vacuolation of corpus callosum with white matter lesions [2] |
| Central pontine myelinolysis | Rapid correction of hypoNa in acute intoxication → osmotic demyelination of pons [2] | Spastic paralysis of 4 limbs, personality changes, inappropriate affect, delusions [2]. Prevention: never correct hypoNa quicker than ~10 mmol/24h [2] |
| Alcohol-tobacco amblyopia | Heavy drinking + smoking → thiamine or B₁₂ deficiency → optic atrophy [2] | ↓ visual acuity with central scotoma and loss of colour vision [2] |
| Peripheral neuropathy | Direct neurotoxicity + thiamine/B₁₂ deficiency → axonal degeneration (length-dependent) | Distal symmetric sensorimotor polyneuropathy — "glove and stocking" numbness/pain, ↓ankle reflexes |
| B₁₂ deficiency | Poor nutrition associated with chronic alcoholism [2] | Subacute combined degeneration of cord, peripheral neuropathy, ataxia, optic atrophy, dementia, depression, psychosis, delirium. Classically: loss of ankle jerk (peripheral neuropathy) with ↑knee jerk (corticospinal tract involvement) [2] |
| B₃ deficiency (pellagra) | Poor nutrition [2] | 3Ds: dementia, dermatitis, diarrhoea; + peripheral neuropathy, psychiatric changes [2] |
| Risk of stroke | Light/moderate drinking → ↓ risk of ischaemic stroke; heavy drinking → ↑ risk of haemorrhagic stroke [2] | Moderate alcohol raises HDL (protective); heavy use → hypertension, coagulopathy, AF → haemorrhagic stroke |
Wernicke's — Give Thiamine BEFORE Glucose
This is hammered home in every exam. Glucose loading in a thiamine-depleted patient consumes the last remaining thiamine (needed as a cofactor for glucose metabolism), precipitating or worsening Wernicke's encephalopathy. Always give parenteral thiamine first (or simultaneously with glucose), NEVER glucose alone in a suspected alcoholic patient.
| Complication | Mechanism |
|---|---|
| Fatal overdose (respiratory depression) | μ-receptor agonism at brainstem respiratory centre → ↓ respiratory drive → apnoea → death. This is the #1 cause of death in opioid dependence |
| Constipation (chronic) | μ-receptors in myenteric plexus → ↓ peristalsis → chronic constipation → bowel obstruction, faecal impaction |
| Endocrinopathy | Chronic opioids → hypothalamic-pituitary suppression → ↓ GnRH → ↓ testosterone/oestrogen → hypogonadism, ↓ libido, amenorrhoea, osteoporosis |
| Immune suppression | Opioids modulate immune cell function → ↑ susceptibility to infections |
| Neonatal abstinence syndrome | Maternal opioid use → transplacental transfer → fetal dependence → neonatal withdrawal after delivery (tremor, irritability, poor feeding, seizures) |
| Complication | Mechanism |
|---|---|
| MI, cardiomyopathy, sudden CVS collapse [2] | Massive catecholamine surge → coronary vasospasm (cocaine), direct myocardial toxicity, accelerated atherosclerosis. Cocaine specifically: ↑ platelet aggregation + vasoconstriction + ↑ myocardial O₂ demand |
| Stroke [2] | Hypertensive crisis → haemorrhagic stroke; cocaine → vasospasm → ischaemic stroke |
| Choreiform movement disorder [2] | Chronic dopamine excess → dopaminergic sensitisation in basal ganglia → dyskinesias |
| Psychosis (persecutory delusions, AH, VH) [2] | ↑↑ DA in mesolimbic pathway → positive psychotic symptoms. Usually subside ≤ 1 week but may persist > 1 month [2] |
| Obstetric: miscarriage, premature labour, placental abruption [2] | Vasoconstriction of uterine arteries → placental ischaemia → abruption. Sympathomimetic effects → uterine contractions |
| Severe depression, suicidal ideation during crash [2] | DA store depletion → profound dopaminergic deficit post-binge → anhedonia, psychomotor retardation |
- Ketamine-induced ulcerative cystitis/uropathy: haematuria, frequency, urge incontinence, ↓ bladder volume with detrusor overactivity [2]. This is characteristic of chronic ketamine users in HK. The mechanism is direct chemical toxicity of ketamine metabolites on the urothelium → chronic inflammation → fibrosis → contracted bladder. Can be irreversible in severe cases.
- Biliary dilatation and abnormal LFTs (ketamine is excreted in bile → cholangiopathy)
- Hyponatraemia [2]: SIADH + excessive water intake → dilutional hypoNa → cerebral oedema, seizures
- Hyperthermia [2]: Vigorous physical activity (dancing) + impaired thermoregulation (5-HT effect) + warm environment → potentially fatal hyperthermia → rhabdomyolysis → AKI
- Serotonin syndrome [2]: Especially dangerous when combined with SSRIs or MAOIs
- Hepatotoxicity [2]: Direct hepatotoxic effect of MDMA metabolites
- Chronic: degeneration of 5-HT nerve terminals → long-term psychiatric sequelae (depression, anxiety, depersonalisation, memory impairment) [2]
- Chronic use → downregulation of GABA receptors → ↓ inhibition on DA release → ↑ risk of schizophrenia [2]. This is one of the best-established psychiatric consequences — cannabis is an independent risk factor for psychosis, especially in genetically predisposed individuals, with a dose-response relationship (higher THC content and earlier age of onset = higher risk)
- Cannabinoid hyperemesis syndrome: cyclic vomiting + abdominal pain + compulsive hot bathing in chronic heavy users. Mechanism not fully understood (paradoxical — cannabis is usually anti-emetic)
- Amotivational syndrome: apathy, ↓ goal-directed behaviour, ↓ productivity (controversial — may reflect pre-existing traits)
B. Psychiatric Complications
Alcohol use can be a cause or effect of other psychiatric disorders [2]. This bidirectional relationship applies to all substances.
| Disorder | Substances | Key Features |
|---|---|---|
| Substance-induced depression | Alcohol (most common), stimulant withdrawal, cannabis, opioids | Temporal link to substance use; usually resolves with sustained abstinence (weeks-months). Chronic alcohol use is the most common cause |
| Substance-induced psychosis | Methamphetamine, cocaine, cannabis, alcohol (withdrawal — DT), ketamine, LSD | Visual hallucinations more common than auditory; resolves with abstinence in most cases; cannabis can trigger persistent psychosis in vulnerable individuals |
| Substance-induced anxiety | Stimulant intoxication, alcohol/BDZ/opioid withdrawal, caffeine, cannabis | Withdrawal anxiety from GABAergic substances can be indistinguishable from primary anxiety disorders |
| Substance-induced delirium | Alcohol withdrawal (DT), BDZ withdrawal, anticholinergic intoxication | Fluctuating consciousness is the hallmark — this is an acute medical emergency |
| Substance-induced amnestic syndrome | Alcohol (Korsakoff syndrome), BDZs (anterograde amnesia) | Korsakoff: irreversible anterograde + retrograde amnesia with confabulation |
Alcohol comorbid psychiatric disorders [3]:
-
Schizophrenia: 30% of patients with schizophrenia have comorbid alcohol problems [3]
- Alcohol decreases feelings of isolation
- Temporarily reduces symptoms of anxiety/depression/insomnia
- But increases psychotic symptoms and mood swings
- Leads to disruptive behaviour, suicide, treatment non-compliance, drug abuse, poor clinical outcome
- Drug accumulation due to hepatic damage [3] — liver impairment → ↓ metabolism of antipsychotics → toxicity
-
20% of drug abusers are alcoholic; alcoholics are 6 times more prone to become drug abusers [3] — polysubstance use is the rule, not the exception
This is critically important:
7% of alcohol abusers die of suicide [3]
Alcoholism is a factor in 30% of all completed suicides [3]
50% of suicide attempts have consumed alcohol at the time of the attempt [3]
96% of alcoholics who die by suicide continue alcohol use up to the end of their lives [3]
Why is the link so strong? Multiple mechanisms converge:
- Alcohol causes and exacerbates depression (direct neurotoxic effect on serotonergic pathways)
- Alcohol causes disinhibition → lowers the threshold for acting on suicidal thoughts
- Chronic alcoholism leads to social losses (relationships, employment, housing) → hopelessness
- Withdrawal states include severe anxiety and agitation → impulsive self-harm
- Comorbid psychiatric disorders (depression, personality disorders) are both risk factors for alcoholism and suicide
Medical comorbidity in bipolar disorder — risk factors include [4]:
- Alcohol and substance use
- Unhealthy diet, physical inactivity
- Social isolation, unemployment
- Side effects of pharmacotherapy (e.g., sodium valproate, atypical antipsychotics)
These factors collectively explain the significantly ↑ mortality and ↓ life expectancy by ~13 years (M) and 9 years (F) in bipolar disorder [2], with suicide (1/3 of mortality): ~8% (M) and 5% (F) hospitalised patients die by suicide over 40 years [2].
| Domain | Complications | Mechanism |
|---|---|---|
| Occupational | Absenteeism (esp Mondays — "St Monday's syndrome"), ↓ productivity, job loss, occupational decline | Intoxication → inability to work; withdrawal → too unwell; cognitive decline → ↓ performance |
| Financial | Debt, poverty, bankruptcy | Expenditure on substances; loss of income from unemployment; financial exploitation |
| Interpersonal | Marital breakdown, domestic violence, child neglect/abuse, social isolation | Intoxication → disinhibition → aggression; neglect of relationships as substance becomes priority |
| Legal/Forensic | Minor criminal offences (esp for cash, e.g., theft, prostitution) [2]; DUI, drug possession charges | Need to fund habit; disinhibited behaviour while intoxicated; possession of illicit substances |
| Housing | Homelessness | Loss of income + interpersonal breakdown → eviction |
| Self-care | ↓ Self-care [1][2] — poor hygiene, malnutrition, dental decay | Substance use takes priority over basic needs; anorexia (stimulants); malnutrition (alcohol) |
| Driving | Road traffic accidents | Impaired coordination, judgment, reaction time |
| Treatment | Complication | Mechanism |
|---|---|---|
| Methadone maintenance | QTc prolongation → torsades de pointes; respiratory depression (esp with BDZ co-use); constipation; weight gain | Methadone blocks hERG potassium channels → prolonged repolarisation → arrhythmia risk. Full μ-agonist → respiratory depression dose-dependent |
| Disulfiram | Disulfiram-ethanol reaction (flushing, nausea, vomiting, tachycardia, hypotension); hepatotoxicity; psychosis (rare) | ALDH inhibition → acetaldehyde accumulation → toxic reaction. Direct hepatotoxicity (monitor LFTs). Inhibits dopamine-β-hydroxylase → ↑ DA → psychosis in vulnerable patients |
| Naltrexone/Nalmefene | Hepatotoxicity (high doses); precipitated withdrawal if opioids present; nausea, headache | μ-receptor blockade → abrupt loss of agonist effect if opioids on board; direct hepatotoxicity mechanism unclear |
| Acamprosate | GI side effects (diarrhoea); headache | Generally well-tolerated; renally excreted (avoid in renal impairment) |
| Flumazenil | Precipitated withdrawal seizures in BDZ-dependent patients | Competitive antagonism at BDZ site → sudden loss of GABA enhancement → excitatory rebound |
| Naloxone | Precipitated withdrawal in opioid-dependent patients; re-sedation (short half-life) | Competitive μ-antagonism; heroin/methadone outlast naloxone → re-sedation after naloxone wears off |
The prognosis of substance use disorders is variable and depends heavily on the substance, severity, comorbidities, social support, and treatment engagement:
| Factor | Better prognosis | Worse prognosis |
|---|---|---|
| Substance | Cannabis, BDZs | Opioids, methamphetamine, alcohol |
| Severity | Harmful use / mild SUD | Severe dependence / addiction |
| Comorbidity | No psychiatric comorbidity | Comorbid substance abuse is consistently listed as a poor prognostic factor across all psychiatric disorders — schizophrenia, bipolar disorder, depression [2][4] |
| Treatment | Early engagement, good adherence | Treatment resistance, poor insight |
| Social | Stable housing, employment, supportive relationships | Homelessness, social isolation, ongoing exposure to drug-using peers |
| BDZ dependence | After attaining abstinence, 73% and 59% maintain abstinence at 3 and 10 years respectively [2] | Prolonged withdrawal symptoms for months to years |
High Yield Summary
Route-related complications: IVDU → cellulitis, abscesses, hepatitis B/C, HIV, right-sided endocarditis, DVT/PE. Smoking → COPD, aspiration pneumonia. Snorting → nasal septal perforation.
Alcohol neurological complications (highest yield):
- Wernicke's encephalopathy: triad of encephalopathy + ophthalmoplegia/nystagmus + truncal ataxia. Thiamine deficiency. Caine criteria (≥2/4). Give parenteral thiamine IMMEDIATELY (before glucose!). 84% → irreversible Korsakoff syndrome
- Korsakoff syndrome: anterograde/retrograde amnesia + confabulation. Irreversible.
- Cerebellar degeneration: Purkinje cell loss → vermis atrophy → truncal ataxia
- Alcohol-related dementia: frontal lobe pattern; 50-70% of abusers have some cognitive deficits
- Central pontine myelinolysis: rapid hypoNa correction → pontine demyelination. Prevent: correct Na < 10 mmol/24h
Alcohol and suicide: 7% of alcohol abusers die by suicide; alcoholism is a factor in 30% of all completed suicides; 50% of suicide attempters consumed alcohol at the time
Alcohol comorbid with schizophrenia: 30% prevalence; temporarily reduces isolation/anxiety but worsens psychosis, mood, compliance, outcomes; drug accumulation from hepatic damage
Substance-specific: Ketamine → ulcerative cystitis (HK-relevant, potentially irreversible). MDMA → hyponatraemia + hyperthermia + serotonin syndrome + 5-HT neurotoxicity. Stimulants → MI/stroke/psychosis/obstetric complications. Cannabis → schizophrenia risk (dose-response).
Comorbid substance abuse is a poor prognostic factor across schizophrenia, bipolar disorder, and depression.
Active Recall - Complications of Substance Misuse
References
[1] Lecture slides: GC 166. I cannot help myself, taking these pills just feels good Substance abuse and addiction.pdf [2] Senior notes: ryanho-psych.md (Chapter 5.2 Misuse of Substance; Chapter 5.1 Alcohol-related Disorders) [3] Lecture slides: GC 161. Alcohol and the Brain From Psychiatric to Neuropsychiatric Perspectives.pdf [4] Lecture slides: GC 163. I am a superman Bipolar disorder.pdf
High Yield Summary
Definition: Substance misuse = use for pleasure with disregard of personal/social dangers; dependence = physical + psychological withdrawal; addiction = extreme end with social decline
ICD-10 Dependence: ≥3 of 6 — Compulsion, Control difficulty, Withdrawal, Tolerance, Neglect of alternatives, Persisting despite harm (CANT Control Withdraw)
Neurobiology: All drugs → ↑ DA in NAc via mesolimbic pathway. Three stages: Binge/Intoxication (VTA, NAc) → Withdrawal/Negative affect (tolerance, DA deficit) → Craving/Preoccupation (hippocampus, amygdala, PFC loss of control) → shift from DA/reward to glutamate/habit circuitry
Route matters: Faster onset = more reinforcing (IV > smoking > snorting > oral)
Only ~10% who experiment develop dependence — determined by biopsychosocial factors
HK epidemiology: Heroin #1 (ageing cohort), methamphetamine #2 (younger users), ketamine declining, cannabis rising
Life-threatening withdrawals: Alcohol and BDZs (GABAergic — seizures, DTs). Opioid withdrawal is NOT typically fatal.
Key drug-specific features:
- Opioids: miosis + respiratory depression + constipation (intox); mydriasis + piloerection + diarrhoea (withdrawal)
- BDZs: slurred speech, ataxia, nystagmus; withdrawal mimics anxiety relapse; 1/3 dependent after ≥6mo use
- Methamphetamine: sympathomimetic toxidrome + psychosis; post-use crash with severe depression
- Cocaine: DA reuptake blockade; NO β-blockers (unopposed alpha)
- MDMA: serotonin syndrome + hyponatraemia; Rx cyproheptadine
- Ketamine: dissociative; ketamine-induced cystitis (HK-relevant); role in treatment-resistant depression
- Cannabis: CB1 agonism; ↑ schizophrenia risk with chronic use
High Yield Summary
Levels of use: Experimental → Problem use/misuse → Harmful use → Dependence (≥3/6 ICD-10) → Addiction
Identify the substance: Use toxidrome pattern — vital signs + pupil size + mental state. Key: miosis = opioids; mydriasis + sympathomimetic = stimulants; nystagmus + dissociation = ketamine/PCP
Always rule out medical mimics: Hypoglycaemia, head injury, hepatic encephalopathy, DKA, sepsis, thyrotoxicosis, Wernicke's encephalopathy. NEVER assume "just intoxicated"
Psychiatric comorbidity is the rule, not the exception: Determine whether psychiatric symptoms are substance-INDUCED (resolve with abstinence) or a PRIMARY disorder with secondary substance misuse (self-medication). Temporal relationship is the key differentiator
Bipolar disorder: OR 5.2 for drug abuse/dependence vs general population; commonly misdiagnosed; 5-7 year delay to correct diagnosis
Assessment aims: Differentiate the problem (diagnosis), formulate (what/why/how), facilitate treatment plan (stage of change). Lab confirmation with urine drug screen is standard
Cannabis detection: Up to 20 days in daily users (lipophilic storage in fat)
High Yield Summary
ICD-10 Dependence: ≥3/6 criteria (CANT Control Withdraw) present for some time in past year. Harmful use is diagnosed ONLY if dependence criteria are NOT met.
DSM-5 SUD: ≥2/11 criteria within 12 months. Severity: Mild (2-3), Moderate (4-5), Severe (≥6). Includes craving as explicit criterion (ICD-10 does not).
Diagnosis is based on: (1) Diagnostic criteria — tolerance, withdrawal, compulsion; (2) Drug screening/testing; (3) Screening tools (CAGE, AUDIT)
Key screening tools: CAGE (sensitive, modest specificity), AUDIT (sensitive + specific, best overall). SADQ > 30 = inpatient detox. CIWA-Ar guides severity of alcohol withdrawal ( > 20 = severe).
Urine drug screen: Most common confirmatory test. Cannabis detectable for 20 days in daily users. Positive UDS ≠ dependence; negative UDS ≠ no use.
Blood markers of chronic alcoholism: ↑GGT (70%, sensitive but non-specific), ↑MCV (60%), ↑CDT (most specific). BAC with no intoxication = tolerance.
Alcohol withdrawal timeline: Tremor (6-12h) → Hallucinations (12-24h) → Seizures (12-48h) → Delirium tremens (48-96h). DT: delirium + vivid hallucinations + autonomic hyperactivity + paranoid delusions. Mortality < 5% if treated.
Must-do baseline investigations: UDS, CBC, LFT, RFT + electrolytes, glucose, Hep B/C + HIV (if IVDU), ECG.
High Yield Summary
Treatment aims: Complete abstinence ideally; harm reduction if not possible. Match intervention to stage of change.
Treatment must be biopsychosocial: Pharmacotherapy alone is insufficient.
Acute intoxication: Stabilise (ABC) → Identify substance → Specific antidote if available (naloxone for opioids, flumazenil for BDZs — both with cautions) → Supportive care.
Alcohol withdrawal: CIWA-Ar guided BDZ dosing (symptom-triggered preferred); long-acting BDZ (diazepam/chlordiazepoxide); oxazepam if liver failure; thiamine BEFORE glucose; barbiturates/propofol for refractory DT.
Opioid withdrawal: Symptomatic (clonidine/lofexidine + supportive) OR substitution (methadone/buprenorphine). Buprenorphine must wait for moderate withdrawal (COWS ≥ 12) or it precipitates withdrawal.
BDZ withdrawal: Switch to long-acting (diazepam), taper ≥ 8 weeks (1/8 Q2w).
Stimulant intoxication: BDZ first-line for agitation/seizures/hyperthermia. NO β-blockers alone for cocaine. Antipsychotics for persistent psychosis. Hyperthermia: BDZ → NMB + GA if severe.
Relapse prevention: Alcohol — acamprosate + naltrexone (first-line); disulfiram (supervised aversion). Opioids — methadone/buprenorphine maintenance; naltrexone. Stimulants — psychosocial only (no established pharmacotherapy).
Key psychosocial therapies: Motivational interviewing (all substances, all stages), CBT (moderate evidence), contingency management (esp stimulants), mutual help groups (AA/NA), brief intervention (non-dependent at-risk drinkers).
Harm reduction: Needle exchange, take-home naloxone, opioid substitution, supervised consumption, MDMA harm reduction education.
High Yield Summary
Route-related complications: IVDU → cellulitis, abscesses, hepatitis B/C, HIV, right-sided endocarditis, DVT/PE. Smoking → COPD, aspiration pneumonia. Snorting → nasal septal perforation.
Alcohol neurological complications (highest yield):
- Wernicke's encephalopathy: triad of encephalopathy + ophthalmoplegia/nystagmus + truncal ataxia. Thiamine deficiency. Caine criteria (≥2/4). Give parenteral thiamine IMMEDIATELY (before glucose!). 84% → irreversible Korsakoff syndrome
- Korsakoff syndrome: anterograde/retrograde amnesia + confabulation. Irreversible.
- Cerebellar degeneration: Purkinje cell loss → vermis atrophy → truncal ataxia
- Alcohol-related dementia: frontal lobe pattern; 50-70% of abusers have some cognitive deficits
- Central pontine myelinolysis: rapid hypoNa correction → pontine demyelination. Prevent: correct Na < 10 mmol/24h
Alcohol and suicide: 7% of alcohol abusers die by suicide; alcoholism is a factor in 30% of all completed suicides; 50% of suicide attempters consumed alcohol at the time
Alcohol comorbid with schizophrenia: 30% prevalence; temporarily reduces isolation/anxiety but worsens psychosis, mood, compliance, outcomes; drug accumulation from hepatic damage
Substance-specific: Ketamine → ulcerative cystitis (HK-relevant, potentially irreversible). MDMA → hyponatraemia + hyperthermia + serotonin syndrome + 5-HT neurotoxicity. Stimulants → MI/stroke/psychosis/obstetric complications. Cannabis → schizophrenia risk (dose-response).
Comorbid substance abuse is a poor prognostic factor across schizophrenia, bipolar disorder, and depression.