2. CASE
• 81 year old male with history of schizoaffective disorder
presents to the hospital with increasing auditory
hallucinations, persecutory delusions and depressive
symptoms. Current meds include levothyroxine, procyclidine,
and venlafaxine (started 2wks ago)
• Pt was admitted and started on loxapine 10mg qAM and
50mg qPM for psychotic symptoms and methotrimeprazine
10mg qD for sleep disturbance.
• 3 Days Later: Methotrimeprazine discontinued due to
somnolence and loxapine increased to 65mg/d at bedtime.
3. RISK FACTORS
• 0.02 to 3% of those on Neuroleptics
• Certain psychiatric conditions
• i.e. acute catatonia and extreme agitation
• Recent or rapid dose escalation
• Switching medications
• Parenteral administration
• Higher doses
Innocent until proven guilty
• Concomitant use of Lithium or other
psychotropic drugs
• Higher potency agents
• Depot formulations
• Comorbid substance abuse or neurological
disease
• Acute medical illness
4. CASE: 12 HOURS LATER
• Pt has diaphoresis, tremulousness, urinary incontinence, and
some cognitive impairment with tremor, rigidity, and unsteady
gate
• Temperature 38.3ºC
• Blood Pressure 124/84
• Pulse 128
5. DIAGNOSIS
• Neuroleptic or Antiemetic Use
• Tetrad
• Fever
• Rigidity
• Mental Status Change
• Autonomic instability
7. PHYSICAL
• Hyperthermia
• > 38º C
• Autonomic Instability
• Tachycardia
• Labile of high blood pressure
• Tachypnea
• Diaphoresis
• Dysrhythmias
Mental Status Change
Initial symptom
Agitates delirium with confusion
Catatonic signs & mutism
Stupor and eventual Coma
Muscular Rigidity
Generalized
“Lead Pipe Rigidity” with passive motion
testing
Stable resistance through all ranges
of movement
Tremor
Dysarthria or dysphagia
8. CASE: DIAGNOSTIC TEST
• EKG: No acute ischemic changes
• Mild Leukocytosis (11.7) with a left shift (ANC 9.9)
• AST Elevated (82)
• Elevated CK (1145) with a Normal CK-MB
• Normal Electrolytes
9. DIAGNOSTIC TESTING CHANGES
• Elevated Serum CK (>1000)
• Leukocytosis (10,000 to 40,000)
• Mildly Elevated LDH, Alkaline Phosphates, AST, ALT
• Electrolyte abnormalities
• Azotemia
• Low Serum Iron Concentrations (Sensitivity 92-100%)
• MRI & CT may show diffuse cerebral edema with severe metabolic
derangements
• EEG with generalized slow wave activity
11. PATHOPHYSIOLOGY
• Theories:
• Dopamine receptor blockade
• hypothalamus → hyperthermia and
dysautonomia
• Nigrostrital pathway → rigidity and tremor
• Possible direct toxic effect of neuroleptics to
muscle.
• Familial clusters suggest genetic component
12. CASE
• The next morning patient was found to have bilateral hyporeflexia, CK increase(2574),
temperature increase (39.3) and myoglobinuria
• Neuroleptic Syndrome was suspected and Loxapine was discontinued
• Dantrolene 70mg IV and changed 24 hours later to Bromocriptine 2.5mg TID
13. TREATMENT
• STOP the causative agent!
• Supportive Care
• Lower Fever
• (Tylenol not effective)
• Benzodiazepines for agitation
• Electroconvulsive Therapy
• Dantrolene, Bromocriptine, Amantadine
• No clinical studies to support use
15. CASE: 10 DAYS AFTER ADMISSION
• NMS Symptoms subsided and the patients CK level returned to normal and the
bromocriptine was tapered.
• Patient had continued psychotic symptoms and was then started on Olanzapine 2.5mg
daily and Sertraline 25mg daily for depressive symptoms.
CASE: 5 WEEKS LATER
• The patients depressive and psychotic symptoms improved considerably and he was
discharged from the hospital without further complications.
16. RESTARTING NEUROLEPTICS
• Relapse Rate 10-90%
• If required the following guidelines MAY minimize risk of NMS recurrence
• Wait at least 2 weeks before resuming therapy
• Use lower rather than higher potency agents
• Avoid concomitant lithium
• Avoid dehydration
• Carefully monitor for symptoms of NMS
17. PROGNOSIS
• Most episodes resolve in 2 weeks (>70%)
• Mortality rates 10-20%
• Decreased if associated with higher
potency agents compared to lower potency
agents
• Cause of Death
• Cardiac arrhythmias
• Myocardial infarction
• Seizures
• Pulmonary edema
• Bronchopneumonia
• Renal failure
18. REFERENCES
• Wijdicks, E, Up to Date: Neuroleptic Malignant Syndrome, Dec 2nd, 2011
• Chandran, G, Mikler, D, Keegan, D. Neuroleptic Malignant Syndrome: Case report and
discussion
• Stern, Massachusetts General Hospital Comprehensive Clinical Psychiatry, 1 st ed. ,
Neuroleptic Malignant Syndrome
