3.2.3 Neuroleptic malignant syndrome
Neuroleptic malignant syndrome is a rare but potentially extremely serious disorder. With a mortality rate possibly exceeding 10%, severe features constitute a medical emergency.
Neuroleptic malignant syndrome typically occurs within about two weeks of starting an antipsychotic or increasing its dose. It is characterised by:
- Raised temperature
- Muscle rigidity, which can be severe and interfere with speaking, eating and swallowing
- Altered mental status; mental status can fluctuate through the day, varying from confusion to coma
- Autonomic instability—irregular pulse rate, blood pressure fluctuation, excessive sweating, heart rhythm disturbances; urinary incontinence may be an early sign
- Raised creatine kinase1; excessive skeletal muscle breakdown can cause myoglobinuria and acute renal failure. The creatine kinase level in neuroleptic malignant syndrome is typically very much higher than that associated with exertion and physical contact (especially during restraint)
- Leucocytosis2
Neuroleptic malignant syndrome should be differentiated from serotonin syndrome — muscle rigidity, leucocytosis and raised creatine kinase may be absent in serotonin syndrome.
Factors which increase risk
Risk factors for neuroleptic malignant syndrome include high dose of an antipsychotic (or rapid increase of the dose), dehydration, catatonia, family history of the syndrome, and CNS disorders including tumour, encephalitis, delirium and dementia. Male gender and age under 40 years might be factors, but the seemingly increased risk may just be a reflection of higher use of antipsychotics in this group.
Concomitant use of the antipsychotic with drugs such as metoclopramide, lithium, and some antidepressants may increase the risk of neuroleptic malignant syndrome.
Risk-reduction measures
Starting treatment with a low dose of an antipsychotic and raising the dose slowly can help reduce the risk of neuroleptic malignant syndrome. Prolonged-release injections of antipsychotics should preferably be avoided in those at higher risk of the syndrome.
Treatment
Neuroleptic malignant syndrome is a medical emergency—emergency medical services should be consulted immediately in suspected cases. The antipsychotic should be discontinued immediately and other psychotropic3 medications such as antidepressants, lithium and antimuscarinics4 should also be stopped.
Supportive management, with close clinical and biochemical monitoring, should be instituted immediately including:
- hydration (intravenously if necessary), especially if creatine kinase5 is highly raised
- cooling the patient
- correction of metabolic abnormalities Other supportive care may be necessary according to individual circumstances and the patient may need to be managed on a medical ward. Specialists may use specific medicines for managing severe cases of neuroleptic malignant syndrome.
- An enzyme found in many body tissues. Raised concentration is a marker for muscle damage and disorders such as myocardial infarction, muscular dystrophy and renal failure. Creatine kinase (CK) is also referred to as creatine phosphokinase (CPK)↩
- An increase in the number of white cells in the blood, usually in response to inflammation. Leucocytosis can also be abnormally triggered by drugs↩
- The ability of a chemical substance to affect brain function, in particular those brain systems which subserve mental activity. The psychotropic action of a drug is usually (but not always) related to an ability to interact with neurotransmitter receptors in the brain↩
- Reduction or blocking of the effects of parasympathetic nerves; antimuscarinic effects include dry mouth, difficulty swallowing, blurred vision, confusion, palpitations, constipation, and urine retention↩
- An enzyme found in many body tissues. Raised concentration is a marker for muscle damage and disorders such as myocardial infarction, muscular dystrophy and renal failure. Creatine kinase (CK) is also referred to as creatine phosphokinase (CPK)↩