A 38-year-old man with schizophrenia has been on risperidone 6 mg/day for 2 years with good symptom control. He now presents with tremor, rigidity, and hyperthermia (38.5°C). His creatine kinase is 1200 U/L, and serum creatinine is 1.8 mg/dL (baseline 0.9 mg/dL). What is the most appropriate immediate next step?

Explanation

## Clinical Diagnosis: Neuroleptic Malignant Syndrome (NMS) **Key Point:** The constellation of fever, rigidity, altered mental status (implied by schizophrenia presentation), and elevated CPK in a patient on an antipsychotic is pathognomonic for NMS — a life-threatening emergency. **High-Yield:** NMS is a medical emergency with mortality 5–20% if untreated. The classic tetrad is: 1. Hyperthermia (often >38.5°C) 2. Muscle rigidity ("lead pipe") 3. Altered mental status 4. Autonomic instability (tachycardia, hypertension, diaphoresis) ### Immediate Management Algorithm ```mermaid flowchart TD A[Suspected NMS: fever + rigidity + antipsychotic]:::outcome --> B{Confirm diagnosis}:::decision B -->|CPK elevated, renal dysfunction| C[Discontinue antipsychotic immediately]:::urgent C --> D[Supportive care: IV fluids, cooling]:::action D --> E[Dantrolene or bromocriptine if severe]:::action E --> F[Monitor CPK, renal function, electrolytes]:::action F --> G[Rechallenge only after 2 weeks symptom-free]:::action ``` **Clinical Pearl:** The elevated CPK (1200 U/L) and acute renal dysfunction (creatinine 1.8, baseline 0.9) indicate rhabdomyolysis — myoglobin precipitation in renal tubules. Aggressive IV hydration is critical to prevent acute kidney injury and hyperkalemia-induced arrhythmias. **Warning:** Continuing the antipsychotic or merely lowering the dose is catastrophic — NMS will progress to disseminated intravascular coagulation (DIC), acute renal failure, and death. Benztropine (anticholinergic) may worsen hyperthermia. **Mnemonic:** **FEVER** — **F**irst stop the drug, **E**levated CPK, **V**ery high mortality if untreated, **E**mergency supportive care, **R**echallenge only after recovery. ### Why Immediate Discontinuation? NMS is caused by dopamine blockade in the hypothalamus (thermoregulation) and basal ganglia (motor control). Continuing any dopamine antagonist perpetuates the cascade. Dantrolene (ryanodine receptor antagonist) and bromocriptine (dopamine agonist) are adjuncts in severe cases but are secondary to drug withdrawal and supportive care. [cite:Harrison 21e Ch 387]