Neuroleptic Malignant Syndrome (NMS)

Sue Henderson

Definition

• Rare adverse reaction to dopamine receptor antagonists (blockers)

• Leading to autonomic dysfunction

• Can be fatal if not recognized early

Commonly associated with:

• haloperidol (Serenace)

• fluphenazine (Prolixin)

• chlorpromazine (Largactil)

Less commonly associated with:

atypicals:• quetiapine (Seroquel)• risperidone (Risperdal)• olanzapine (Zyprexa)dopamine receptor antagonists:• prochlorperazine (Stemetil)• metoclopramide (Maxalon)• promethazine (Phenergan)

Pathophysiology

• Not fully understood

• Probably dopaminergic blockade or depletion in CNS

• May be a drug induced malignant catatonia (? same underlying pathophysiology) (Fink, 1996, as cited in Strawn, Keck & Caroff, 2007).

• Genetics may be involved

Incidence

• 0.5% to 3% of all patients treated with traditional antipsychotics

• Recent 0.01% to 0.02% (Stubner, 2004, as cited in Strawn, Keck

& Caroff, 2007). (? Due to atypical use)• Haloperidol implicated in ½ cases

(potency, widespread use)Death in 10% of cases (Strawn, Keck & Caroff, 2007).

Risk Factors

• previous history of NMS/EPSE

• dehydration

• discontinuation of antiparkinsonian

• withdrawal of benzodiazepines

• history of organic brain syndrome

• use of high potency agents

• iron deficiency

Onset

At any time - can develop rapidly

Most cases when:• drug started• dosage increased • rapidly titrated

Mild to severe - depending on individual

Clinical manifestationsSudden change in mental status

FeverMuscle rigidity

Sudden change in mental status

Mental state changes precede other signs in 80% of cases

Clouding of consciousness ranging from:• confusion to stupor or coma • agitation, • delirium, and • catatonia

Fever

• Hyperpyrexia > 38 °C of unknown origin (? caused by dopamine blockade in hypothalamus causing temperature dysregulation and profuse sweating)

Muscle Rigidity

• Dystonia abrupt onset stiffening and rigidity in large muscles (especially head & neck)

• Severe muscle rigidity produces excess body heat contributing to hyperpyrexia

• Sometimes difficulty swallowing or a sensation of tongue thickening that rapidly worsens

Rigidity

As the syndrome progresses:• increasing muscle rigidity can lead to diminished

chest wall compliance, hypoventilation, and even respiratory failure.

Other• EPSEs: parkinsonian tremors, akathisia• elevated or labile blood pressure• tachycardia, tachypnea, tremor, and urinary

incontinence

Laboratory

• Raised Creatine kinase (muscle enzyme)• Raise Myoglobinuria (muscle protein)• Creatine kinase rises 2 – 4 hours after muscle

injury (indicator degree muscle damage), continued rise may indicate onset :

• Rhabdomyolysis (skeletal muscle break down) releases myoglobin into circulation.

• Once myoglobin in kidneys, it precipitates in renal tubules causing kidney damage and subsequent renal failure.

Lab: other

• proteinuria secondary to stress/tissue damage

• elevated white blood cell count• Arterial blood gas analysis - assess for

adequate oxygenation and metabolic acidosis (Harrison & McErlane, 2008).

Prevention

• Conservative use of antipsychotics

• Reduction of risk factors

• Early diagnosis

• Prompt discontinuation of offending medications

Medical Management

Depending on symptom severity and complications:

• See table in handout (Woodbury & Woodbury, 1992 cited in Strawn,

Keck & Caroff, 2007).

• See video Brvar and Bunc (2007) pre and post Dantrolene

Re-challenge Anti-psychotics

• 30% risk of developing again• Check reports on previous episodes for accuracy• Clearly documented indications for antipsychotics• Consider alternative medications• Reduce risk factors• Rechallenge at least 2/52 after recovery from NMS• Use low doses of low-potency conventional

antipsychotics or atypical antipsychotics• Titrate gradually after a test dose• Monitor for early signs of NMS• Obtain informed consent from patients/family regarding

benefits of antipsychotic versus risk recurrence (Strawn, Keck, & Caroff, 2007).

Resources

Neuroleptic Malignant Syndrome Information Service

www.nmsis.org

References

Brvar, M., & Bunc, M. (2007). Video of dantrolene effectiveness on neuroleptic malignant syndrome associated muscular rigidity and tremor. Critical Care 11(3), 415.

Fink, M. (1996). Neuroleptic malignant syndrome and catatonia: One entity or two? . Biological Psychiatry, 39, 1-4.

Harrison, P. A., & McErlane, K. S. (2008 ). Neuroleptic malignant syndrome American Journal of Nursing, 108(7), 35-38.

Strawn, J. R., Keck, P. E., & Caroff, S. N. (2007). Neuroleptic malignant syndrome. American Journal of Psychiatry, 164(6), 870-876.