• 65 year old NH resident• Assisted with ADL, limited mobility• Decreased oral intake• Staring straight ahead for long periods x 3 days • Muscular rigidity, ↓mobility• Diaphoretic

• Schizoaffective disorder (Clozapine)• Previous self harm, drug overdose• Drug-induced parkinsonism• Epilepsy• Mild/moderate COPD• Past pneumonia• GORD

• Clozapine (6 years)• Escitalopram• Sodium valproate• Lamotrigine• Omeprazole• Spiriva, PRN salbutamol• Vitamin D

• T 38.2oC• Alert• GCS 14/15• Confused• Symmetrical limb

rigidity• Tremor R>L hand• Diaphoretic• P 125/min SR• BP 155/92

• Lungs clear• Abdo soft, non-

tender, absent bowel sounds

• No meningism/ focal neurology

• Normal pupils• No clonus• Reflexes normal

• Sepsis• Non-convulsive status epilepticus• Neuroleptic Malignant Syndrome• Serotonin syndrome• Progression of psychotic illness with catatonia

• CRP 5 mg/l• Hb 118 g/l• WBC 6.7 10^9/L• PLT 185 10^9/L• Cr 111 µmol/l, EGFR

43ml/min• Na+ 146 mmol/l• K+ 3.5 mmol/l• CK 3260 U/l• AST/ALT 38/29 U/l• ALP 120 U/l• Bilirubin 6 µmol/l

• pO2 65mmHg, pCO2 28, pH 7.47

• Lactate 1.3 mmol/l• TSH 0.79 IU/l• CXR NAD• ECG sinus tachycardia• Valropate (98 µmol/l)• Blood & urine cultures

-ve• CT Brain cerebral

atrophy• EEG normal

• Idiosyncratic, life-threatening complication of antipsychotic drug treatment

• Characterized by fever, severe muscle rigidity, and autonomic and mental status changes

• Incidence of 0.01%–0.02%• Insidious onset• 66% within the first week of starting

antipsychotics

Criteria A• Fever• Muscular rigidity

Criteria B• Altered sensorium• Mutism• Tachycardia• Hypertension/ Labile BP• Diaphoresis• Tremor• Dysphagia• Leucocytosis• Lab evidence of Muscle

injuryBoth major criteria and 2 minor criteria AND not due to other cause e.g. viral encephalitis or psychiatric cause

• AntipsychoticsConventional•Phenothiazines (e.g. chlorpromazine, fluphenazine, thioridazine)•Butyrophenone (e.g. haloperidol)Atypical•Benzisoxazoles : risperidone•Theinobenzodiazepine: olanzapine•Dibenzazepines: clozapine, quetiapine

• Antiemetics•Phenothiazines: prochlorperazine, promethazine•Dopamine antagonist: metoclopramide, domperidone

• High potency conventional antipsychotics• Parenteral route• Higher titration rate• Previous NMS• CNS disorders of dopamine (e.g., Parkinson's)• Abrupt withdrawal of dopaminergic drugs (e.g.,

levodopa, bromocriptine).• Intercurrent illness

• Withdraw offending medication• Fluid resuscitation• Correction of electrolytes• Physical cooling• Anticipate and manage complications:• Cardiorespiratory failure• Acute renal failure• Aspiration pneumonia

• Consider Intensive Care

• Limited evidence (efficacy, outcome?)• No consensus • Not consistently effective• Dopaminergic agents : bromocriptine 2.5-5 mg

Q8H PO/NG, Amantadine 100-400mg NG• Muscle relaxants: dantrolene 1-2.5mg/kg BWT

Q6H IV• Benzodiazepines (Lorazepam 1-2mg Q4-6H)

• ECT is effective even after failed pharmaco-therapy (6-8 bilateral treatments)

• High recurrence rate up to 30%• Wait for at least 2 weeks before rechallenge• Informed consent from patient and family• Start low dose, atypical agent, and titrate slowly• Monitor carefully for development of early signs of

NMS

• Treated with bromocriptine along with supportive care in a ward setting

• Good functional recovery• Liaison with psychiatrist, rechallenge?• Discharged back to nursing home on Day 7• Remained well at 4 weeks’ clinic follow up,

without clozapine

• Widespread adoption of atypical antipsychotics has markedly reduced the incidence, but NMS remains a risk for susceptible patients receiving these drugs.

• Hyperthermia, muscular rigidity, autonomic instability and altered mental state are salient clinical features.

• Early diagnosis and prompt discontinuation of offending medications are crucial.

• In the absence of randomized controlled trials, it is difficult to recommend one single intervention over another or over supportive management.

• For mild cases, supportive care and careful clinical monitoring may be sufficient.

• Strawn JR, Keck PE, Caroff SN. Neuroleptic Malignant Syndrome Am J Psychiatry 2007; 164, 6: 870-76

• Hall RCW, Hall RCW, Chapman M. Neuroleptic Malignant Syndrome in the Elderly: Diagnostic Criteria, Incidence, Risk Factors, Pathophysiology, and Treatment. Clinical Geriatrics 2006; 14, 5: 39-46

• Boyer EW, Shannon M. The Serotonin Syndrome. N Engl J Med 2005;352:1112-20.