23.2 Psychiatric Emergencies & Substance Misuse
Key Takeaways
- Serotonin syndrome has rapid onset with clonus, hyperreflexia and agitation; neuroleptic malignant syndrome develops over days with lead-pipe rigidity, hyporeflexia and a very high creatine kinase.
- Wernicke encephalopathy is the triad of confusion, ophthalmoplegia and ataxia, and requires parenteral thiamine before any glucose is given.
- Delirium tremens typically begins 48-72 hours after the last drink and is treated with a reducing benzodiazepine regimen, usually chlordiazepoxide.
3. Emergency Toxidromes: Serotonin Syndrome vs Neuroleptic Malignant Syndrome
Both conditions are life-threatening pharmacotoxic emergencies presenting with hyperthermia, autonomic instability, and altered mental status. Differentiating them is a classic, heavily tested MRCP Part 1 skill:
| Feature | Serotonin Syndrome (SS) | Neuroleptic Malignant Syndrome (NMS) |
|---|---|---|
| Primary Causative Agents | Serotonergic combinations: SSRIs, SNRIs, MAOIs (phenelzine, moclobemide), Tramadol, Linezolid, St John's Wort, MDMA, Lithium, Triptans, Fentanyl | Dopamine D2 receptor antagonists: Haloperidol, chlorpromazine, olanzapine, risperidone; OR abrupt cessation of dopaminergic agonists (levodopa, apomorphine) |
| Onset of Symptoms | Hyperacute: Rapid onset (<24 hours), often within hours of initiating or escalating dose | Subacute / Insidious: Evolves over 1 to 7 days (up to weeks) |
| Neuromuscular Manifestations | Neuromuscular excitation:<br>- Clonus (spontaneous, inducible, or ocular)<br>- Hyperreflexia (brisk jerks, especially lower limbs)<br>- Tremor, shivering, akathisia<br>- Hypertonia (predominantly lower extremities) | Severe muscular exhaustion / rigidity:<br>- "Lead-pipe" generalized rigidity<br>- Hyporeflexia or normal reflexes<br>- Bradykinesia, stupor, dystonic posturing |
| Pupils & Secretions | Mydriasis (dilated pupils), prominent diaphoresis, sialorrhoea | Normal pupils, marked diaphoresis, pallor |
| Gastrointestinal Signs | Hyperactive bowel sounds, abdominal cramps, diarrhoea | Hypoactive or normal bowel sounds; no diarrhoea |
| Diagnostic Criteria | Hunter Serotonin Toxicity Criteria: Serotonergic agent PLUS at least one of:<br>1. Spontaneous clonus<br>2. Inducible clonus AND agitation or diaphoresis<br>3. Ocular clonus AND agitation or diaphoresis<br>4. Tremor AND hyperreflexia<br>5. Hypertonia AND temperature >38°C AND ocular/inducible clonus | DSM-5 / Levenson Criteria: Neuroleptic exposure, severe muscle rigidity, fever, AND autonomic instability, altered consciousness, and elevated CK |
| Key Laboratory Findings | Mild leukocytosis, mild CK elevation, metabolic acidosis | Massive Creatine Kinase (CK) elevation (>1,000 to >50,000 IU/L) from rhabdomyolysis; marked leukocytosis (10–40 × 10^9/L); acute kidney injury |
| Specific Pharmacotherapy | 1. Discontinue all serotonergic agents.<br>2. IV Benzodiazepines (lorazepam/diazepam) for agitation and clonus.<br>3. Cyproheptadine (5-HT2A antagonist; 12 mg loading PO/NG, then 2 mg q2h).<br>4. Active cooling and ITU support. | 1. Discontinue all neuroleptics immediately.<br>2. Aggressive IV fluid resuscitation (target UOP >2 mL/kg/h) to prevent myoglobinuric renal failure.<br>3. Dantrolene (ryanodine receptor blocker; 1–2.5 mg/kg IV bolus, max 10 mg/kg/day).<br>4. Bromocriptine (D2 agonist; 2.5–5 mg PO/NG tds) or amantadine. |
4. Substance Misuse & Alcohol Withdrawal
Alcohol Withdrawal Syndrome
Chronic ethanol consumption enhances central inhibitory GABA-A transmission and downregulates excitatory NMDA glutamate receptors. Abrupt cessation unmasks a hyper-glutamatergic, hypo-GABAergic state, driving profound sympathetic overactivity.
Chronology of Alcohol Withdrawal Manifestations
│
├── 6–12 Hours: Autonomic Hyperactivity & Tremor
│ ├── Fine resting/postural tremor, diaphoresis, tachycardia, hypertension
│ └── Anxiety, agitation, nausea, insomnia, hyperreflexia
│
├── 12–24 Hours: Alcoholic Hallucinosis
│ ├── Perceptual disturbances (visual, tactile, auditory hallucinations)
│ └── Clear sensorium (intact orientation and insight; NOT delirium)
│
├── 24–48 Hours (Peak ~36 Hours): Withdrawal Seizures ("Rum Fits")
│ ├── Generalised tonic-clonic seizures, often multiple or clustered
│ └── High risk of progression to Delirium Tremens if untreated
│
└── 48–72 Hours: Delirium Tremens (DTs)
├── Coarse tremor, gross agitation, clouding of consciousness, disorientation
├── Vivid tactile (formication / insects crawling) & visual (zoopsia) hallucinations
└── Extreme autonomic instability (hyperpyrexia, drenching sweats, tachycardia, circulatory collapse)
*Medical emergency with up to 5% mortality without protocolised care*
- Management Protocol:
- Assess severity using the CIWA-Ar (Clinical Institute Withdrawal Assessment for Alcohol - Revised) score.
- First-Line Pharmacotherapy: Symptom-triggered reducing regimen of long-acting oral benzodiazepines: Chlordiazepoxide (e.g. 20–40 mg qds, tapered over 5–7 days) or Diazepam.
- Special Consideration in Hepatic Impairment: In decompensated liver disease, acute alcoholic hepatitis, or severe cirrhosis, long-acting benzodiazepines accumulate, precipitating hepatic encephalopathy. Use short- to intermediate-acting benzodiazepines without active metabolites that undergo direct glucuronidation: Lorazepam (or oxazepam).
Wernicke-Korsakoff Syndrome
Thiamine (vitamin B1) is an essential cofactor for carbohydrate metabolism, serving transketolase (pentose phosphate pathway), pyruvate dehydrogenase, and α-ketoglutarate dehydrogenase (Krebs cycle). Deficiency impairs cerebral cellular energy production, causing focal lactic acidosis and microvascular haemorrhagic necrosis within the mammillary bodies, periaqueductal gray matter, and thalamic nuclei.
- Wernicke's Encephalopathy (Acute & Reversible):
- Characterized by the classic triad:
- Encephalopathy / Acute Confusion: Apathy, disorientation, inattention, drowsiness.
- Ataxia: Broad-based, unsteady cerebellar gait, truncal ataxia.
- Ophthalmoplegia / Nystagmus: Bilateral abducens (CN VI) nerve palsies, horizontal and vertical nystagmus, conjugate gaze palsies.
- Exam Pearl: The complete triad is present in <20–30% of cases! Any malnourished or alcohol-dependent patient presenting with unexplained confusion must be treated empirically for Wernicke's.
- Characterized by the classic triad:
- Korsakoff's Psychosis (Chronic & Largely Irreversible):
- Consequence of untreated or inadequately treated Wernicke's encephalopathy.
- Cardinal features: Dense anterograde amnesia (inability to acquire new memories), retrograde amnesia with temporal gradient, and confabulation (spontaneous generation of false or fabricated memories to fill gaps, articulated without conscious intent to deceive), with preserved general intellectual capacity.
- CRITICAL EMERGENCY PRESCRIBING MANDATE:
- Intravenous Pabrinex (high-potency parenteral thiamine + vitamins B/C) must be administered immediately (2 pairs of ampoules IV TDS for 3–5 days, infused over 30 minutes in 100 mL 0.9% saline).
- PABRINEX MUST ALWAYS BE ADMINISTERED BEFORE ANY INTRAVENOUS GLUCOSE OR DEXTROSE INFUSION!
- Biochemical Rationale: Administering intravenous glucose loads thiamine-deficient neurons with pyruvate. Without thiamine pyrophosphate as a cofactor, pyruvate cannot be converted to acetyl-CoA, driving rapid, fulminant neuronal metabolic exhaustion, lactic acidosis, and immediate irreversible diencephalic brainstem necrosis.
A 52-year-old homeless man with a 25-year history of severe alcohol dependence is brought to the emergency department by paramedics after being found confused and disorientated outside a train station. On examination, he is malnourished, emaciated, and smells strongly of alcohol. He is disorientated to time and place, scoring 4/10 on the Abbreviated Mental Test. Neurological examination reveals a wide-based, unsteady, shuffling gait, prominent horizontal nystagmus on lateral gaze, and bilateral incomplete abducens (CN VI) nerve palsies. Vital signs show: heart rate 104 beats/min, blood pressure 112/68 mmHg, respiratory rate 16 breaths/min, temperature 36.1°C, and capillary blood glucose of 2.9 mmol/L. What is the most crucial next step in the emergency medical management of this patient?
A 38-year-old woman with a history of recurrent major depression managed with oral sertraline 150 mg once daily attends the acute medical unit with acute left flank pain secondary to an obstructing ureteric calculus. Five hours earlier, her general practitioner prescribed oral tramadol 100 mg four times daily for analgesia. On arrival, she is highly agitated, tremulous, and drenched in perspiration. Vital signs reveal a temperature of 38.6°C, heart rate of 126 beats/min, blood pressure of 168/98 mmHg, and respiratory rate of 22 breaths/min. Examination reveals bilateral dilated pupils with sluggish light reflexes, hyperactive bowel sounds with abdominal cramping, and generalized fine tremor. Neurological assessment demonstrates spontaneous horizontal ocular clonus, marked 4-beat inducible ankle clonus bilaterally, and 4+ hyperreflexia at the patellar and supinator reflexes with bilateral lower limb rigidity. Complete blood count shows a white cell count of 11.2 x 10^9/L, and serum creatine kinase is mildly elevated at 420 IU/L (reference <190). Which intervention represents the most appropriate specific medical therapy?