A timely diagnosis and discontinuation of antipsychotic therapy stand as first-line treatment for neuroleptic malignant syndrome (NMS), followed by supportive care and pharmacotherapy, a review conducted by University of Kentucky Chandler Medical Center researchers concluded. Findings from the review are published in the Annals of Pharmacotherapy.

Pharmacists Dominic J. Pileggi and Aaron M. Cook set out to review evidence for the treatment of NMS and to discus how to rechallenge patients with neuroleptics when ongoing pharmacotherapy for chronic psychological disorders is required. They conducted a literature search through March 2016 and a manual search of article reference sections. 

The review included case reports and case series that evaluated NMS and atypical NMS treatment as well as neuroleptic rechallenge. 

The data showed a reported incidence of NMS to be 0.02–0.03%, with a mortality rate of 5.6%. NMS most frequently resulted from administration of a new agent, use of high doses, or during rapid dose titration. Existing studies on NMS are primarily retrospective and highlight diagnostic criteria, causative agents, and potential pharmacotherapy. However, details on timing of administration, dose, and duration of pharmacotherapy appeared inconsistent. 

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Regarding supportive care, study authors include removing restraints, reducing elevated room temperature, using cooling blankets and antipyretics to reduce fever, initiating fluid resuscitation, correcting electrolytes, and maintaining a slightly alkalotic pH to prevent rhabdomyolysis and acute kidney injury. Calcium channel blockers have been suggested for labile hypertension, and deep vein thrombosis prophylaxis should be initiated if a patient is immobilized from rigidity. 

Regarding pharmacotherapy, the review highlights dantrolene sodium, bromocriptine, and benzodiazepines to have the “most compelling evidence for NMS resolution.” A step-wise approach based on NMS severity is also presented as a table with the most studied agents: lorazepam, diazepam, bromocriptine, amantadine, and dantrolene. Biperiden and other anticholinergics have limited data and are thought to possibly worsen hyperthermia; thus, these agents are not recommended to treat symptoms of NMS

Rechallenge was infrequently reported but demonstrated that recurrence could happen at any moment after NMS resolution. Rechallenge with antipsychotics is commonly needed and should be attempted only after a washout period of ≥2 weeks and with a different agent, slowly titrated with close monitoring. 

Case reports in the future should carefully document the precipitating cause(s), agents used to treat NMS symptoms, and the exact method of rechallenging (if applicable). Also, pharmaceutical companies should include analysis of cases of NMS in post-marketing surveillance as they arise. 

For more information visit aop.sagepub.com.