1. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Neuroleptic Malignant Syndrome Recognition, Risk factors and Management

2. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Pathophysiology  Relative lack of dopamine –dopamine receptor blockade –inadequate dopamine production

3. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Pathophysiology  Supporting evidence –neuroleptic drugs block dopamine receptors –occurs with other dopamine blocking drugs –occurs on sudden withdrawal of antiparkinsonian therapy –responds to dopamine agonists

4. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Clinical features  Essential –recent or current therapy with dopamine blocking drug l neuroleptic l other drug eg metoclopramide –recently stopped a dopamine agonist eg L-dopa

5. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Clinical features  Major (all within 24 h) –fever > 37.5 o C (no other cause) –autonomic dysfunction –extrapyramidal features

6. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Autonomic dysfunction  2 or more of –hypertension or labile BP l systolic > 30 mmHg above baseline or l diastolic > 20 mmHg above baseline l variability of > 30 mmHg systolic or >20 mmHg diastolic between readings –tachycardia (pulse > 30 bpm above baseline) –diaphoresis (intense) –incontinence –tachypnoea (> 25 breaths/min)

7. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Extrapyramidal features  2 or more of –bradykinesia –lead-pipe or cogwheel rigidity –resting tremor –sialorrhoea –dysphagia –dysarthria/mutism

8. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Minor features  Support but are not required for diagnosis –rise in creatinine kinase –altered sensorium/delirium –leucocytosis > 15,000x10 9 /L –low serum iron  Help confirm diagnosis –therapeutic response to dopamine agonist

9. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Risk factors  Incidence 1% (0.02–3.23)  Pre-NMS –psychomotor agitation –dehydration

10. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Risk factors  Related to treatment –neuroleptic dose in first 24h > 600 mg of chlorpromazine –maximum dose in any 24h > 600 mg of chlorpromazine –required restraint or seclusion  Associated –past ECT

11. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Management  High risk patients –monitor temperature tds –monitor blood pressure tds –record episodes of diaphoresis  On suspicion –assess for other medical illness –FBC, MBA, CK, serum iron  On diagnosis –withdraw all dopamine blocking drugs

12. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Drug therapy  Bromocriptine –2.5 mg q8h up to 5 mg q4h –continue for 7–10 days after resolution then taper over 1–2 weeks (except depot preparations)  Dantrolene –2–3 mg/kg –extreme rigidity, very high fever (> 40 o C), unable to tolerate oral treatment

13. Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital Other therapy  Benzodiazepines –to control agitation/delirium  ECT –refractory to adequate trial of dopamine agonist/supportive care –after resolution of acute features l remain catatonic or l develop ECT-responsive psychotic features –suspected acute lethal catatonia