Dantrolene neuroleptic malignant syndrome

A rare, but potentially fatal idiosyncratic adverse effect is neuroleptic malignant syndrome. This can occur with any antipsychotic drug. The symptoms are rigidity, hyperthermia, autonomic lability, and reduced level of consciousness. Massively elevated levels of creatinine kinase are usually found. Prior to 1984, the mortality rate was around 25% but improved early recognition has considerably reduced this. Management is cessation of antipsychotics, appropriate conservative measures and dantrolene if necessary for muscle rigidity. 

Coons, D. J., Hillman, F. J., Marshall, R. W. (1982). Treatment of neuroleptic malignant syndrome with dantrolene sodium A case report. American Journal of Psychiatry, 139, 943-945. 

Dantrolene may be effective in reducing muscle rigidity in neuroleptic malignant syndrome (388,389) (SEDA-20, 42), but a reliable regimen has not been established (390). 

Goekoop JG, Carbaat PA. Treatment of neuroleptic malignant syndrome with dantrolene. Lancet 1982 2(8288) 49-50. 

Tsujimoto S, Maeda K, Sugiyama T, Yokochi A, Chikusa H, Maruyama K. Efficacy of prolonged large-dose dantrolene for severe neuroleptic malignant syndrome. Anesth Analg 1998 86(5) 1143 1. 

Since the toxic effects of MDMA resemble certain features of both the serotonin syndrome and the neuroleptic malignant syndrome, some have suggested that MDMA may have combined actions on both the dopamine and serotonin systems (37). However, dantrolene (which may be helpful in cases of neuroleptic malignant syndrome) does not appear to be useful in dealing with MDMA toxicity (38). 

Concomitant treatment with donepezil and maprotiline in a 73-year-old patient with Alzheimer s disease and stroke produced a syndrome resembling the neuroleptic malignant syndrome (78). The patient responded to withdrawal of maprotiline and donepezil and intravenous fluids, and did not require dantrolene. 

Anaesthesia in MH-susceptible patients is achieved safely with total intravenous anaesthesia using propofol and opioids. Dantrolene for intravenous use must be available in every surgical theatre. The relation of malignant hyperthermia syndrome with neuroleptic malignant syndrome (for which dantrolene may be used as adjunctive treatment, see p. 388) is uncertain. 

In one patient who took 900 mg of phenelzine, there was a marked excess of nrinary and plasma catecholamines, analogous to pheochromocjdoma, and the patient was successfully managed with alpha-adrenoceptor antagonists (44). In another patient, who probably took about 2000 mg of phenelzine, hyperpyrexia was prominent and responded to dantrolene sodium (45). The authors noted clinical similarities to malignant hyperpyrexia and neuroleptic malignant syndrome. 

Ward A, Chaffman MO, Sorkin EM. Dantrolene. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in malignant hyperthermia, the neuroleptic malignant syndrome and an update of its use in muscle spasticity. Drugs 1986 32(2) 130-68. 

All basic and advanced life-support measures should be implemented. Gastric decontamination should be performed. Butyrophenones are readily absorbed by activated charcoal. Aggressive supportive care should be instituted. Dystonic reactions respond well to intravenous benztropine or diphenhydramine. Oral therapy with diphenhydramine or benztropine should be continued for 2 days to prevent recurrence of the dystonic reaction. For patients suffering from neuroleptic malignant syndrome, a potentially fatal condition associated with the administration of antipsychotic drugs, dantrolene sodium, and bromocriptine have been used in conjunction with cooling and other supportive measures. Arrhythmias should be treated with lidocaine or phenytoin. Diazepam is the drug of choice for seizures phenytoin is used to prevent recurrence. Hemodialysis and hemoperfu-sion have not been shown to be effective. 

The treatment of neuroleptic malignant syndrome consists of inunediately discontinuing the neuroleptic agent and administering dantrolene sodium and dopamine-functionenhancing substances such as levodopa-carbidopa, bromocriptine, or amantadine. 

Dantrolene acts directly on skeletal muscle to decrease contractility by blocking Ca release from the sarcoplasmic reticulum. It is used in states that include extreme muscle rigidity, such as malignant hyperthermia associated with inhaled anesthetic and skeletal muscle relaxants or neuroleptic malignant syndrome associated with antipsychotic. 

Temperature regulation problems (neuroleptic malignant syndrome [NMS], treated with dantrolene and bromocriptine)... 

Dantrolene is not likely to be effective for hyperthennia caused by conditions other than muscular hyperactivity, such as increased metabolic rate (eg, salicylate or dinitrophenol poisoning), neuroleptic malignant syndrome (NMS), impaired heat dissipation (eg, anticholinergic syndrome), or environment exposure (heat stroke). However, there is anecdotal evidence (case reports or case-control studies) of benefit for the management of NMS, MAO inhibitor (phenelzine poisoning)-induced hyperthermia, muscle rigidity from baclofen withdrawal, hypertonicity from carbon monoxide poisoning, tetanus, and black widow spider envenomation. 

A 64-year-old man developed periods of confusion and disorientation within 2 weeks of starting to take lithium 300 mg twice daily with doxepin 100 mg at bedtime. He was admitted to hospital because of urinary retention, and he was also lethargic and became confused, but despite the withdrawal of both drugs he developed a condition similar to the neuroleptic malignant syndrome (fever, muscle rigidity, changes in consciousness, autonomic dysfunction), which was successfully treated with dantrolene. ... 

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