Neuroleptic Malignant Syndrome

Question 1

A 60 year old woman is being managedt for a relapse of schizophrenia, for which she takes clozapine. She has history of HTN, T2DM, dyslipidaemia. On Day 7, she appears agitated, disorientated and febrile. Assess and manage.

Answer 1

Impression
Given sx of agitation, disorientation and fever in the setting of pharmacological treatment with clozapine, concerned about neuroleptic malignant syndrome in this patient. Usually will occur 1-2 weeks from starting/increasing doses.

All antipsychotic medications have been associated with NMS, however the high potency ones pose the greatest risk for this adverse effect.

Ddx to consider:

• sepsis (given fevers)
• intoxication/substance use disorder
• serotonin syndrome (unlikely in instance of no serotonergic meds)

Question 2

NMS - Classic tetrad of clinical manifestations

Answer 2

NMS - tetrad. -E-CAT

• Extrapyramidal symptoms: akathisia (inner restlessness), dystonia, tardive dyskinesia, rigidity (lead pipe)
• Temperature dysregulation (hyperthermia)
• Autonomic effects: tachycardia, hypertension, diaphoresis, tachypnoea
• CNS effects: drowsiness, confusion, coma

Question 3

NMS - History

Answer 3

History

• PC: ask about the tetrad of sx (E-CAT: EPSE, Cognitive, Autonomic, Temperature)
• Diagnostic criteria: exposure to dopamine agonist drug, severe muscle rigidity, hyperthermia, then other (tachycardia, HTN, diaphoresis, confusion, raised WCC, elevated serum CK-MB)
• PMHx
• Medications
• SNAP

Question 4

NMS - Examination

Answer 4

Examination

• General appearance + vital signs
• Neurological examination
• MSE

Question 5

NMS - Investigations

Answer 5

Investigations
- Key/diagnostic: serum CK-MB, WCC

• Bedside: vital signs, VBG (sepsis), urine tox screen
• Bloods: Ck-MB, UEC, LFT, FBC, ESR/CRP, Blood cultures
• Imaging: CT Brain,

Question 6

NMS - Management

Answer 6

Management
Acute setting
- cease clozapine/antipsychotic medication + any drugs that potentiate the syndrome (lithium, anticholinergics)
- Antidote: Bromocriptine (dopamine agonist)
- benzodiazepines in severe agitation and hyperthermia
- A to E assessment and any stabilising measures (IV fluids, BP management
- supportive: cooling, mx of rhabdomyolysis

After resolution of NMS
- consider restarting any withdrawn medications, switch antipsychotic medication