A 32-year-old man from Delhi presents with a 3-month history of auditory hallucinations, paranoid delusions, and disorganized speech. He was started on risperidone 4 mg/day 2 weeks ago. Today he reports severe muscle rigidity, high fever (39.5°C), altered mental status, and profuse sweating. Laboratory investigations show CK 1200 U/L, creatinine 1.8 mg/dL (baseline 0.9), and WBC 12,500/μL. What is the most appropriate immediate management?

Explanation

## Clinical Diagnosis: Neuroleptic Malignant Syndrome (NMS) ### Pathophysiology NMS is a life-threatening idiosyncratic reaction to antipsychotics (both typical and atypical) characterized by dopamine antagonism in the hypothalamus and basal ganglia, leading to: - Severe muscle rigidity ("lead pipe" rigidity) - Hyperthermia (central thermoregulation failure) - Autonomic instability (diaphoresis, tachycardia) - Altered mental status ### Diagnostic Criteria (DSM-5) Presence of: 1. Exposure to antipsychotic within recent period 2. Hyperthermia (≥38.5°C) 3. Muscle rigidity 4. Mental status changes 5. Elevated CK (typically >1000 U/L, often >4000 U/L) **Key Point:** This patient meets all five criteria. The combination of fever, rigidity, altered mental status, and elevated CK within 2 weeks of risperidone initiation is pathognomonic. ### Immediate Management Algorithm ```mermaid flowchart TD A[Suspected NMS]:::outcome --> B[Discontinue antipsychotic immediately]:::action B --> C[Aggressive supportive care]:::action C --> D[Cooling measures, IV fluids]:::action D --> E{CK severely elevated or<br/>renal compromise?}:::decision E -->|Yes| F[Dantrolene 1 mg/kg IV q5-10min<br/>max 10 mg/kg/day]:::action E -->|No| G[Bromocriptine 2.5-5 mg TID<br/>or Amantadine 100 mg BID]:::action F --> H[Monitor CK, creatinine,<br/>urine myoglobin]:::action G --> H H --> I[Prevent rhabdomyolysis-induced<br/>acute kidney injury]:::action ``` ### Pharmacotherapy Details | Agent | Mechanism | Dosing | Use Case | |-------|-----------|--------|----------| | **Dantrolene** | Skeletal muscle relaxant; blocks Ca²⁺ release from SR | 1 mg/kg IV q5–10 min (max 10 mg/kg/day) | First-line if CK >4000 or renal dysfunction | | **Bromocriptine** | D₂ agonist; restores dopaminergic tone | 2.5–5 mg PO/NG TID | Alternative; slower onset | | **Amantadine** | NMDA antagonist + dopamine release | 100 mg PO BID | Adjunctive; less evidence | **High-Yield:** Dantrolene is the gold standard for severe/fulminant NMS because it acts directly on muscle, independent of dopamine restoration. ### Monitoring & Complications **Key Point:** Acute kidney injury from myoglobinuria is the leading cause of mortality in NMS. - Monitor urine colour (dark/cola-coloured = myoglobinuria) - Maintain urine output >200 mL/h with aggressive IV hydration - Alkalinize urine (sodium bicarbonate) to prevent myoglobin precipitation in renal tubules - Serial CK, creatinine, electrolytes q4–6h initially **Clinical Pearl:** NMS mortality is ~10% if untreated; <5% with prompt recognition and dantrolene. Most deaths are from renal failure or arrhythmias. ### Re-challenge After NMS - Wait ≥2 weeks after full recovery - Use lowest effective dose of a *different* antipsychotic (preferably atypical with lower NMS risk, e.g., aripiprazole, quetiapine) - Avoid the offending agent - Consider prophylactic benztropine during re-challenge **Warning:** Switching to haloperidol (a typical antipsychotic) after NMS is a common mistake — typical agents have *higher* NMS risk than atypicals.