AKT · Psychiatry/Psychotic

Neuroleptic malignant syndrome (NMS)

Abrupt central D2 dopamine blockade (or withdrawal of dopaminergic drugs)

Overview

A rare, life-threatening reaction to dopamine antagonism: rigidity, hyperthermia, autonomic instability and altered consciousness, with a markedly raised creatine kinase. It follows antipsychotics — typical more than atypical — but equally follows abrupt withdrawal of levodopa or a dopamine agonist in Parkinson disease.

Recognise

Onset over DAYS to two weeks — usually within 2 weeks of starting or increasing the drug
Generalised "lead-pipe" rigidity with bradykinesia and HYPOreflexia
Hyperthermia, often >38.5 °C, with profuse sweating
Autonomic instability: labile blood pressure, tachycardia, tachypnoea
Fluctuating consciousness, from confusion to coma
Raised CK (often >1000 U/L), leukocytosis, raised transaminases

Red flags

Temperature >40 °C, CK rising steeply, oliguria or dark urine → rhabdomyolysis with AKI; this is a critical-care emergency

Differentials & how to tell them apart

Serotonin syndromeHOURS not days; clonus and HYPERreflexia; follows a serotonergic drug

Sepsis / meningoencephalitisSource of infection, no dopamine-antagonist exposure, rigidity is not lead-pipe

Malignant catatoniaCan be indistinguishable; psychiatric prodrome with waxy flexibility and echophenomena — responds to benzodiazepines/ECT

Malignant hyperthermiaMinutes after a volatile anaesthetic or suxamethonium, not days after an antipsychotic

Anticholinergic deliriumDry, flushed, no rigidity, normal CK

Investigations

Clinical diagnosis supported by CK (the single most useful test — typically markedly raised), FBC (leukocytosis), U&E and creatinine (AKI from rhabdomyolysis), LFT, calcium/phosphate, CRP, clotting/DIC screen, ABG/lactate, urinary myoglobin. Exclude infection with cultures and consider CT head/LP where meningoencephalitis is plausible — do not let that delay treatment.

Management

Stop the antipsychotic (or restart the withdrawn dopaminergic), resuscitate, cool actively and give IV fluids

1STOP the causative antipsychotic immediately — or, if the trigger was withdrawal of levodopa/a dopamine agonist in Parkinson disease, RESTART it. ABCDE, IV crystalloid, active cooling, benzodiazepines.
2Aggressive IV fluids for rhabdomyolysis with close renal monitoring; VTE prophylaxis (these patients are immobile and hypercoagulable).Gate: Severe rigidity, temperature >40 °C or renal impairment → critical care for dantrolene ± bromocriptine
3Re-challenge, when the illness needs it, is at least 2 weeks after full recovery, with a different — preferably atypical, lower-potency — antipsychotic, started low and titrated slowly under specialist supervision.Gate: Any recurrence of rigidity or pyrexia on re-challenge → stop again and rethink the whole regimen

Benzodiazepines (lorazepam) — Supportive first-line for agitation and rigidity; also treats malignant catatonia if that turns out to be the diagnosis

Dantrolene — Direct muscle relaxant for severe rigidity/hyperthermia — critical care and specialist advice

Bromocriptine or amantadine — Dopamine agonists to reverse the blockade; specialist use

Key points

Two traps. First, NMS is not only an antipsychotic reaction — abruptly stopping levodopa in Parkinson disease produces the identical picture, and the treatment is the opposite (restart the drug). Second, antipsychotics are frequently the first thing reached for in an agitated, confused, febrile patient — which is precisely how NMS gets made worse.

Monitor & prognosis

Continuous temperature, cardiac monitoring and GCS; CK, U&E and urine output at least daily until falling.

Mortality around 10% untreated, much lower with early recognition. Most recover in 1–2 weeks; depot preparations prolong it.

Source: BNF · NICE CKS · Maudsley Prescribing Guidelines