Neuroleptic-like Malignant Syndrome

Neuroleptic-like malignant syndrome is a serious but very rare adverse effect of some drugs, of e.g., neuroleptics, some anaesthetics and apparently tolca-pone. Symptoms include hyperthermia, muscle deterioration, even dissolution. 

There have been no fatalities attributable to ECT that have been described in young persons. There is an account of a 16-year-old girl who had eight ECTs and died of cardiac failure 10 days after the last treatment (Kish et ah, 1990). However, her death is likely to have been due to the continued administration of neuroleptic medication in spite of her neuroleptic malignant syndrome. 

Antipsychotic drugs include the older phenothiazines and butyrophenones, as well as newer atypical drugs. All of these can cause CNS depression, seizures, and hypotension. Some can cause QT prolongation. The potent dopamine D2 blockers are also associated with parkinsonian-like movement disorders (dystonic reactions) and in rare cases with the neuroleptic malignant syndrome, characterized by "lead-pipe" rigidity, hyperthermia, and autonomic instability (see Chapter 29 Antipsychotic Agents Lithium). 

In terms of clinical treatment and the public health, howevep TDAK [tardive akathisia] is a fact, not a question. It is one more serious side effect of neuroleptic treatment, like TD and the Neuroleptic Malignant Syndrome. Taken together, they define neuroleptic treatment as a necessary evil, a treatment that should be administered with care and caution, and reserved for patients who have no other recourse. 

Prozac and the other SSRIs, as well as any antidepressant that blocks the removal of serotonin from the synapse, can produce a well-documented, severe condition called the serotonin syndrome (Sternbach, 1991). This disorder includes the usual signs of overstimulation, such as euphoria and hypomania, agitation, confusion, and gastrointestinal upset, including diarrhea. However, the serotonin syndrome additionally involves overstimulation of the brain stem and spinal cord, producing fever and chills, severe incoordination, muscle spasms, and hyperactive reflexes. It bears some similarity to neuroleptic malignant syndrome, and like NMS it can also be lethal (chapter 4). 

Tiapride appears to be useful in alcohol withdrawal as an alternative to the benzodiazepines (2). It facilitates the management of ethanol withdrawal, but its use in patients at risk of severe reactions in acute withdrawal should be accompanied by adjunctive therapy for hallucinosis and seizures. Since it may prove difficult to identify such patients and since there is also a small risk of the neuroleptic malignant syndrome (particularly with parenteral administration), the usefulness of tiapride in this setting is likely to be limited. The potential risk of tardive dyskinesia at the dosage used in alcoholic patients following detoxification (300 mg/day) requires evaluation and necessitates medical supervision. It is unlikely to produce problems of dependence or abuse. 

Neuroleptic malignant syndrome (more likely when clozapine is used with another agent)... 

Tom M, Matsuda O, Makiguchi K, Sugano K. Neuroleptic malignant syndrome-like state following a withdrawal of antiparkinsonian drugs. J Nerv Ment Dis 1981 169(5) 324-7. 

Haioperidol +++ + + + kost likely cause of neuroleptic malignant syndrome (NMS) and TD... 

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. 

Additive dopaminergic effects would be expected. The serotonin syndrome is thought to occur because of increased stimulation of the 5-HT receptors in the brainstem and spinal cord. A syndrome resembling neuroleptic malignant syndrome (which has similar symptoms to the serotonin syndrome) can occur when a dopamine agonist like bromocriptine is... 

Cases cf Neurotoxicity Toxicity at therapeutic or subtherapeutic levels was reported in three cases. In two of these cases, the role of lithium is questionable. In one case of a rapidly fatal presentation of neuroleptic malignant syndrome (NMS) in a 72-year-old woman whose lithium level was 1.5 mM, the authors report a lithium-induced fatal NMS because she was not prescribed an antipsychotic [84 ]. However, her presentation is also consistent with fatal catatonia, sepsis, or unknown consumption of an antipsychotic, none of which were ruled out, and all of which are more likely than lithium-induced NMS. A second case in which a delirium with dyspraxia, but not ataxia in a 57-year-old man with a lithium level of 0.44 mM, that resolved after discontinuation of botii lithium and tricyclic antidepressant medication, was felt to be an interaction between the lithium and the antidepressant [85 ]. Lithium may have played a role, but he had been on lithium for years, and had developed anticholinergic problems with quetiapine previously, suggesting that the anticholinei c effects of the tricyclic antidepressant were more important in the delirium than the lithium. The third case of a 65-year-old man with multisystem atrophy becoming considerably worse with lithium at a level of 1.1 mM, is much more likely to represent lithium-related neurotoxicity at therapeutic levels [86 ]. 

Do not abruptly discontinue use of the antiparkinsonism drugs Neuroleptic malignant-like syndrome may occur when the antiparkinsonism drugs are discontinued or the dosage of levodopa is reduced abruptly. The nurse carefully observes the patient and reports the following symptoms muscular rigidity, elevated body temperature, and mental changes... 

A neuroleptic malignant-like syndrome occurred when norephedrine was combined with neuroleptic drugs (385). 

Turner MR, Gainsborough N. Neuroleptic malignant-like syndrome after abrupt rvithdrawal of baclofen. J Psychopharmacol 2001 15(l) 61-3. 

Friedman ]H, Feinberg SS, Feldman RG. A neuroleptics malignant like syndrome due to levodopa therapy withdrawal. JAMA. 

Bonnici A, Ruiner CE, St-Laurent L, Hornstein D. An interaction between levo-dopa and enteral nutrition resulting in neuroleptic malignant-like syndrome and prolonged ICU stay. Ann Pharmacother 2010 44(9) 1504-7. 

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