Neuroleptic Malignant Syndrome Recognition Risk factors and Management

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

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

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

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

Clinical features N Major (all within 24 h) – fever > 37. 5 o. C (no other cause) – autonomic dysfunction – extrapyramidal features Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

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

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

Minor features N Support but are not required for diagnosis – rise in creatinine kinase – altered sensorium/delirium – leucocytosis > 15, 000 x 109/L – low serum iron N Help confirm diagnosis – therapeutic response to dopamine agonist Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

Risk factors N N Incidence 1% (0. 02– 3. 23) Pre-NMS – psychomotor agitation – dehydration Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

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

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

Drug therapy N Bromocriptine – 2. 5 mg q 8 h up to 5 mg q 4 h – continue for 7– 10 days after resolution then taper over 1– 2 weeks (except depot preparations) N Dantrolene – 2– 3 mg/kg – extreme rigidity, very high fever (> 40 o. C), unable to tolerate oral treatment Clinical Toxicology & Pharmacology, Newcastle Mater Misericordiae Hospital

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