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 manifestations Sudden change in mental status Fever Muscle 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

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