Neuroleptic Malignant Syndrome NMS Sue Henderson Definition Rare

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 Muscle rigidity Fever

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 & Mc. Erlane, 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. , & Mc. Erlane, 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.