Recommendations

Key Recommendations

Prompt recognition and treatment is essential. Cessation of the offending medication and provision of supportive medical therapy are the cornerstones of treatment in any suspected case of NMS.[48] Get a toxicology consult or contact the Poison Center for advice. America's Poison Centers: poison help Opens in new window Supportive measures (hydration, external cooling if hyperthermia is severe and persistent) should start simultaneously with diagnostic evaluation.

Pharmacologic interventions and electroconvulsive therapy (ECT) are secondary measures, and their role in treating NMS is uncertain. Patients with NMS are usually severely ill and often need to be managed on an ICU or step-down unit.

Ratings scales are available for tracking the clinical course of NMS on the basis of factors such as severity of hyperthermia, rigidity, mental status alteration, and elevation in serum creatine kinase.[50][51]

Withdrawal of antipsychotic medication

If NMS is suspected, antipsychotics and dopamine antagonists must be stopped, and dopamine agonists must be restored or continued. Other drugs that may be contributory (e.g., lithium, metoclopramide) may need to be stopped.[3][9]​ If the patient’s psychiatric symptoms compel resumption of antipsychotic medication, a delay of at least 2 weeks following complete resolution of the NMS episode is advisable.[52]​ In practice, the class of drug that is suspected to be the cause of NMS is usually added to the patient’s medical records as an allergy.

Supportive therapy

Oxygen and airway management

  • Give supplemental oxygen by nasal cannula if needed; endotracheal intubation may be required for more severe cases.

Hydration

  • Most patients are dehydrated in the acute phase of the illness; therefore, administration of fluids, intravenously in severe cases, and prevention of volume depletion are essential.

  • When rhabdomyolysis occurs, vigorous hydration with intravenous fluids is recommended to prevent acute kidney injury.

Coolants

  • Hyperthermia can be treated with physical cooling measures. Antipyretics do not appear to be effective in NMS.

Patients with dysphagia may require a nasogastric tube for the administration of fluids, nutrition, and pharmacologic therapy.[3]

Pharmacologic therapy

Supportive medical management and prompt cessation of the antipsychotic medication are often sufficient to reverse the symptoms. In more extreme cases, pharmacotherapy can be used to reduce NMS-associated hyperthermia and rigidity. However, there is limited evidence on whether pharmacologic treatments ameliorate symptoms and improve recovery.

There are no specific recommendations regarding sequence or preference of one drug over the other, except that benzodiazepines are generally preferred as first-line treatment because of their lower risk in comparison with bromocriptine and dantrolene.

Benzodiazepines

  • Oral or intravenous lorazepam may be helpful to treat NMS-associated agitation and catatonia. It also works as a muscle relaxant. Adverse effects include respiratory depression and/or worsening delirium.[2]

Muscle relaxants

  • Dantrolene given orally or intravenously may aid resolution of NMS-associated muscular rigidity and hyperthermia.[48] However, some studies show that combination of dantrolene with other drugs for the treatment of NMS is associated with a prolongation of clinical recovery; therefore, use is somewhat controversial.[38][53]

Dopaminergic agents

  • Bromocriptine and amantadine are especially useful if the NMS was caused by withdrawal of anti-Parkinson medication. They are administered orally or by a nasogastric tube in patients with dysphagia.[2][3][18] However, like dantrolene, evidence for a beneficial effect in NMS is equivocal, and their use is also controversial.[38][53]

Dantrolene, bromocriptine, and amantadine are often used in the treatment of NMS despite the limited evidence of their effectiveness.[1][37][38] One systematic case series analysis suggests that dantrolene and bromocriptine may be more effective in the treatment of severe NMS than supportive care alone.[54]

Based on many anecdotal reports, it is generally advised that these treatments be continued until the NMS episode is fully resolved, and possibly longer (e.g., an additional 7-10 days) because NMS can return if effective treatments are terminated prematurely.

ECT

Case reports and one systematic case series analysis suggest that ECT may be effective in the treatment of NMS (particularly if severe), even after failed pharmacotherapy.[54][55][56][57][58] ECT is considered potentially useful in more extreme cases of NMS, but may often be impractical.

Recurrence and subsequent antipsychotic medication

Recurrence of NMS is managed in the same way as initial presentation: withdrawal of antipsychotic medication, supportive therapy, and adjunctive use of pharmacologic treatments if needed.

  • Recurrence of NMS may be less likely if resumption of antipsychotic medication is delayed until 2 or more weeks after resolution of NMS. In practice, this might be difficult to achieve, requiring extreme diligence and seeking additional peer consultation. Vigilance is required in all subsequent antipsychotic medication trials.

  • About 2 weeks after resolution of NMS, treatment with an antipsychotic (it is considered prudent to avoid the one that caused NMS) should be initiated at a low dose and slowly titrated in a monitored setting to assess for signs of recurrence.[1][52]

  • Some experts recommend a second-generation agent, with lower risk of extrapyramidal adverse effects, in preference to first-generation antipsychotic medications. However, there is no consensus on this view because no antipsychotic medication has been shown to have more or less risk than another.

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