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Neuroleptic Malignant Syndrome Treatment & Management

  • Author: Theodore I Benzer, MD, PhD; Chief Editor: Asim Tarabar, MD  more...
 
Updated: Mar 24, 2016
 

Approach Considerations

Treatment of neuroleptic malignant syndrome (NMS) is mainly supportive; it is directed toward controlling the rigidity and hyperthermia and preventing complications (eg, respiratory failure, renal failure). Other interventions, such as dantrolene, bromocriptine, amantadine, lorazepam, and electroconvulsive therapy, have been advocated, but their value is controversial.[2, 39] Monitoring and management in an intensive care unit (ICU) is recommended.

The most important intervention is to discontinue all antipsychotics. Signs and symptoms should improve after the antipsychotic is stopped. No new focal neurologic deficits should develop, although cases of neurologic sequelae have been reported rarely. In most cases, symptoms will resolve in 1-2 weeks. Episodes precipitated by long-acting depot injections of antipsychotics can last as long as a month.

Patients should receive circulatory and ventilatory support as needed. Antipyretics, evaporative cooling, ice packs, and cooled intravenous (IV) fluids can be used to reduce hyperthermia. Consider prophylactic intubation for patients with excessive salivation, swallowing dysfunction, coma, hypoxemia, acidosis, and severe rigidity with hyperthermia. Aggressive fluid resuscitation and alkalization of urine can help prevent acute renal failure and enhance excretion of muscle breakdown products.

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Prehospital Care

Any patient being evaluated by prehospital personnel requires assessment of the airway, breathing, and circulation (ABCs). Any patient with altered mental status should receive thiamine, dextrose (or rapid glucose determination), and naloxone, to exclude alcohol withdrawal, hypoglycemia, and opioid overdose, respectively.

Prehospital personnel must assess the patient's safety and, if necessary, restrain the patient. Restraint use in agitated, hyperthermic patients can increase the risk of significant morbidity and mortality in neuroleptic malignant syndrome and other disease states (eg, cocaine intoxication, amphetamine abuse). Chemical restraints (eg, benzodiazepines), if available, may be preferable in such situations.

To identify possible precipitants of neuroleptic malignant syndrome, prehospital personnel should try to obtain an accurate medication list. If that is impossible, they should bring all the medication bottles found with the patient.

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Emergency Department Care

Treatment of patients with neuroleptic malignant syndrome may include the following:

  • Benzodiazepines for restraint may be useful
  • Stop all neuroleptics
  • Correct volume depletion and hypotension with intravenous fluids
  • Reduce hyperthermia

Methods to reduce the temperature include the following:

  • Cooling blankets
  • Antipyretics
  • Cooled intravenous fluids
  • Ice packs
  • Evaporative cooling
  • Pharmacologic therapies to reduce rigidity (see below)

When rhabdomyolysis occurs, maintain vigorous hydration and alkalinize the urine with intravenous sodium bicarbonate to prevent renal failure.

Additional evaluation and treatment should be in an inpatient setting, preferably an ICU.

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Electroconvulsive Therapy

In patients with neuroleptic malignant syndrome, electroconvulsive therapy (ECT) can help with the alteration of temperature, level of consciousness, and diaphoresis. It may also be useful in treating the underlying psychiatric disease in patients who are unable to take neuroleptics.[40, 41]

ECT with anesthesia has generally been safe, with no increased incidence of malignant hyperthermia from succinylcholine administration.[42, 43] However, serious treatment-related complications have occurred. Specifically, patients with neuroleptic malignant syndrome have developed cardiac arrest and ventricular fibrillation after ECT.

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Pharmacologic Therapy

A variety of medications have been used to provide symptomatic treatment of neuroleptic malignant syndrome. Dantrolene sodium directly relaxes muscles by inhibiting calcium release from the sarcoplasmic reticulum. Most patients respond to 400 mg/day or less.

Dantrolene therapy alone appears to shorten the duration of illness, but use is controversial. Reduction of fever and rigidity is not immediate but occurs over a mean of 1.7 days. A review of case reports concluded that combining dantrolene with other drugs prolongs the recovery period, and that using dantrolene as monotherapy seemed to be associated with increased mortality. The only benefit from dantrolene was in patients who had been on neuroleptic monotherapy.[44]

Bromocriptine is a dopamine agonist that overcomes neuroleptic-induced dopaminergic blockade. It has also been used in combination with dantrolene, but studies have questioned the benefit of this approach.[45, 44]

Other agents that have been tried include amantadine, which enhances presynaptic release of dopamine, and levodopa/carbidopa, which increase presynaptic dopamine stores. Dopaminergic medications can be especially useful if the NMS was caused by withdrawal of anti-Parkinson medication.[45, 46, 39]

Use of nondepolarizing neuromuscular blocking agents (eg, pancuronium, other newer agents) may be considered. These may achieve rapid, predictable, and effective control of rigidity and hyperthermia. However, such medications can be used only in patients who have been intubated and sedated and are receiving mechanical ventilation.

Antimuscarinic agents are not recommended. They are not only ineffective but also may worsen hyperthermia.

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Deterrence/Prevention

Clinicians should take a careful history before starting a new neuroleptic medication, to uncover any previous instances of neuroleptic malignant syndrome, as those patients are at risk for recurrence. Because neuroleptic malignant syndrome usually develops while the dose is being increased, the clinician, patient, and family members must be alert to this possibility until a steady dose is achieved.

Patient education should be provided regarding avoidance of factors that may increase the risk for development of neuroleptic malignant syndrome. These include dehydration, agitation, exhaustion, and malnutrition (see Patient Education).

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Consultations

Consultation with a neurologist may be needed if the diagnosis is in question. Consultation with a nephrologist is needed if the patient develops rhabdomyolysis and renal failure.

Consultation with a psychiatrist can be helpful to manage the underlying psychiatric disease once the neuroleptics have been withdrawn. On the other hand, if neuroleptic malignant syndrome is diagnosed in a psychiatric facility, the patient should be transferred to an acute care medical facility where intensive monitoring and treatment is available.

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Long-Term Monitoring

Neuroleptic malignant syndrome may be prolonged. If the patient is discharged, close follow-up care should be given to monitor residual symptoms. The patient's psychiatric disease must be evaluated and treated during withdrawal of the neuroleptic medication.

If neuroleptics are to be reinstituted, they should be administered at relatively low initial doses. Challenge with an atypical antipsychotic may be appropriate, since these drugs have a lower incidence of neuroleptic malignant syndrome.

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Contributor Information and Disclosures
Author

Theodore I Benzer, MD, PhD Assistant Professor in Medicine, Harvard Medical School; Director of the ED Observation Unit, Director of Toxicology, Chair of Quality and Safety, Department of Emergency Medicine, Massachusetts General Hospital

Theodore I Benzer, MD, PhD is a member of the following medical societies: Alpha Omega Alpha, American College of Emergency Physicians

Disclosure: Nothing to disclose.

Coauthor(s)

Mary C Mancini, MD, PhD, MMM Professor and Chief of Cardiothoracic Surgery, Department of Surgery, Louisiana State University School of Medicine in Shreveport

Mary C Mancini, MD, PhD, MMM is a member of the following medical societies: American Association for Thoracic Surgery, American College of Surgeons, American Surgical Association, Society of Thoracic Surgeons, Phi Beta Kappa

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.

Acknowledgements

Iqbal Ahmed, MBBS, FRCPsych (UK) Faculty, Department of Psychiatry, Tripler Army Medical Center; Clinical Professor of Psychiatry, Uniformed Services University of the Health Sciences; Clinical Professor of Psychiatry, Clinical Professor of Geriatric Medicine, University of Hawaii, John A Burns School of Medicine

Iqbal Ahmed, MBBS, FRCPsych (UK) is a member of the following medical societies: Academy of Psychosomatic Medicine, American Association for Geriatric Psychiatry, American Neuropsychiatric Association, American Psychiatric Association, American Society of Clinical Psychopharmacology, and Royal College of Psychiatrists

Disclosure: Nothing to disclose.

Michael J Burns, MD Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center

Michael J Burns, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

G Patricia Cantwell, MD, FCCM Professor of Clinical Pediatrics, Chief, Division of Pediatric Critical Care Medicine, University of Miami, Leonard M Miller School of Medicine; Medical Director, Palliative Care Team, Director, Pediatric Critical Care Transport, Holtz Children's Hospital, Jackson Memorial Medical Center; Medical Manager, FEMA, Urban Search and Rescue, South Florida, Task Force 2; Pediatric Medical Director, Tilli Kids – Pediatric Initiative, Division of Hospice Care Southeast Florida, Inc

G Patricia Cantwell, MD, FCCM is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Heart Association, American Trauma Society, National Association of EMS Physicians, Society of Critical Care Medicine, and Wilderness Medical Society

Disclosure: Nothing to disclose.

Timothy E Corden, MD Associate Professor of Pediatrics, Co-Director, Policy Core, Injury Research Center, Medical College of Wisconsin; Associate Director, PICU, Children's Hospital of Wisconsin

Timothy E Corden, MD is a member of the following medical societies: American Academy of Pediatrics, Phi Beta Kappa, Society of Critical Care Medicine, and Wisconsin Medical Society

Disclosure: Nothing to disclose.

Girish G Deshpande, MD, MBBS, FAAP Associate Professor of Pediatrics, Interim Director and Division Chief of Critical Care Medicine, Department of Pediatrics, University of Illinois College of Medicine at Peoria; Consulting Staff, Division of Critical Care Medicine, Children's Hospital of Illinois at OSF St Francis Medical Center

Girish G Deshpande, MD, MBBS, FAAP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Nothing to disclose.

Barry J Evans, MD Assistant Professor of Pediatrics, Temple University Medical School; Director of Pediatric Critical Care and Pulmonology, Associate Chair for Pediatric Education, Temple University Children's Medical Center

Barry J Evans, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Chest Physicians, American Thoracic Society, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Alan D Schmetzer, MD Professor Emeritus, Interim Chairman, Department of Psychiatry, Indiana University School of Medicine; Addiction Psychiatrist, Roudebush VA Medical Center

Alan D Schmetzer, MD is a member of the following medical societies: American Academy of Addiction Psychiatry, American Academy of Clinical Psychiatrists, American Academy of Psychiatry and the Law, American College of Physician Executives, American Medical Association, American Neuropsychiatric Association, American Psychiatric Association, and Association for Convulsive Therapy

Disclosure: Nothing to disclose.

Darius P Sholevar, MD Fellow, Cardiovascular Disease, Albert Einstein Medical Center

Disclosure: Nothing to disclose.

Mark S Slabinski, MD, FACEP, FAAEM Vice President, EMP Medical Group

Mark S Slabinski, MD, FACEP, FAAEM is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, and Ohio State Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Joseph Tonkonogy, MD, PhD Clinical Professor of Psychiatry, University of Massachusetts Medical School; Consulting Staff, Departments of Psychiatry, University of Massachusetts Medical School

Joseph Tonkonogy, MD, PhD is a member of the following medical societies: American Academy of Neurology, American Medical Association, American Neuropsychiatric Association, International Neuropsychological Society, Massachusetts Medical Society, Royal Society of Medicine, Society for Neuroscience, and United Council for Neurologic Subspecialties, Certification Behavioral Neurology and Neuropsychiatry

Disclosure: Nothing to disclose.

John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals

John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

References
  1. Rosebush PI, Mazurek MF. Serum iron and neuroleptic malignant syndrome. Lancet. 1991 Jul 20. 338(8760):149-51. [Medline].

  2. Tse L, Barr AM, Scarapicchia V, Vila-Rodriguez F. Neuroleptic Malignant Syndrome: A Review from a Clinically Oriented Perspective. Curr Neuropharmacol. 2015. 13 (3):395-406. [Medline].

  3. Chiou YJ, Lee Y, Lin CC, Huang TL. A Case Report of Catatonia and Neuroleptic Malignant Syndrome With Multiple Treatment Modalities: Short Communication and Literature Review. Medicine (Baltimore). 2015 Oct. 94 (43):e1752. [Medline].

  4. DELAY J, PICHOT P, LEMPERIERE T, ELISSALDE B, PEIGNE F. [A non-phenothiazine and non-reserpine major neuroleptic, haloperidol, in the treatment of psychoses]. Ann Med Psychol (Paris). 1960 Jan. 118(1):145-52. [Medline].

  5. Trollor JN, Chen X, Chitty K, Sachdev PS. Comparison of neuroleptic malignant syndrome induced by first- and second-generation antipsychotics. Br J Psychiatry. 2012 Jul. 201(1):52-6. [Medline].

  6. Trollor JN, Chen X, Sachdev PS. Neuroleptic malignant syndrome associated with atypical antipsychotic drugs. CNS Drugs. 2009. 23(6):477-92. [Medline].

  7. Gurrera RJ, Caroff SN, Cohen A, Carroll BT, DeRoos F, Francis A, et al. An international consensus study of neuroleptic malignant syndrome diagnostic criteria using the Delphi method. J Clin Psychiatry. 2011 Sep. 72(9):1222-8. [Medline].

  8. Jauss M, Krack P, Franz M, Klett R, Bauer R, Gallhofer B, et al. Imaging of dopamine receptors with [123I]iodobenzamide single-photon emission-computed tomography in neuroleptic malignant syndrome. Mov Disord. 1996 Nov. 11(6):726-8. [Medline].

  9. Gurrera RJ. Sympathoadrenal hyperactivity and the etiology of neuroleptic malignant syndrome. Am J Psychiatry. 1999 Feb. 156(2):169-80. [Medline].

  10. Ehara H, Maegaki Y, Takeshita K. Neuroleptic malignant syndrome and methylphenidate. Pediatr Neurol. 1998 Oct. 19(4):299-301. [Medline].

  11. Keck PE Jr, Pope HG Jr, Cohen BM, McElroy SL, Nierenberg AA. Risk factors for neuroleptic malignant syndrome. A case-control study. Arch Gen Psychiatry. 1989 Oct. 46(10):914-8. [Medline].

  12. Paparrigopoulos T, Tzavellas E, Ferentinos P, Mourikis I, Liappas J. Catatonia as a risk factor for the development of neuroleptic malignant syndrome: report of a case following treatment with clozapine. World J Biol Psychiatry. 2009. 10(1):70-3. [Medline].

  13. Sachdev P, Mason C, Hadzi-Pavlovic D. Case-control study of neuroleptic malignant syndrome. Am J Psychiatry. 1997 Aug. 154(8):1156-8. [Medline].

  14. Alexander PJ, Thomas RM, Das A. Is risk of neuroleptic malignant syndrome increased in the postpartum period?. J Clin Psychiatry. 1998 May. 59(5):254-5. [Medline].

  15. Otani K, Horiuchi M, Kondo T, Kaneko S, Fukushima Y. Is the predisposition to neuroleptic malignant syndrome genetically transmitted?. Br J Psychiatry. 1991 Jun. 158:850-3. [Medline].

  16. Rosebush PI, Stewart TD, Gelenberg AJ. Twenty neuroleptic rechallenges after neuroleptic malignant syndrome in 15 patients. J Clin Psychiatry. 1989 Aug. 50(8):295-8. [Medline].

  17. Berman BD. Neuroleptic malignant syndrome: a review for neurohospitalists. Neurohospitalist. 2011 Jan. 1 (1):41-7. [Medline]. [Full Text].

  18. Manu P, Sarpal D, Muir O, Kane JM, Correll CU. When can patients with potentially life-threatening adverse effects be rechallenged with clozapine? A systematic review of the published literature. Schizophr Res. 2012 Feb. 134(2-3):180-6. [Medline]. [Full Text].

  19. Gelenberg AJ, Bellinghausen B, Wojcik JD, Falk WE, Sachs GS. A prospective survey of neuroleptic malignant syndrome in a short-term psychiatric hospital. Am J Psychiatry. 1988 Apr. 145(4):517-8. [Medline].

  20. Strawn JR, Keck PE Jr, Caroff SN. Neuroleptic malignant syndrome. Am J Psychiatry. 2007 Jun. 164(6):870-6. [Medline].

  21. Deng MZ, Chen GQ, Phillips MR. Neuroleptic malignant syndrome in 12 of 9,792 Chinese inpatients exposed to neuroleptics: a prospective study. Am J Psychiatry. 1990 Sep. 147(9):1149-55. [Medline].

  22. Chopra MP, Prakash SS, Raguram R. The neuroleptic malignant syndrome: an Indian experience. Compr Psychiatry. 1999 Jan-Feb. 40(1):19-23. [Medline].

  23. Lazarus A. Neuroleptic malignant syndrome. Hosp Community Psychiatry. 1989 Dec. 40(12):1229-30. [Medline].

  24. Henderson T. Neuroleptic malignant syndrome in adolescents: four probable cases in the Western Cape. S Afr Med J. 2011 May 25. 101(6):405-7. [Medline].

  25. Croarkin PE, Emslie GJ, Mayes TL. Neuroleptic malignant syndrome associated with atypical antipsychotics in pediatric patients: a review of published cases. J Clin Psychiatry. 2008 Jul. 69(7):1157-65. [Medline].

  26. Modi S, Dharaiya D, Schultz L, Varelas P. Neuroleptic Malignant Syndrome: Complications, Outcomes, and Mortality. Neurocrit Care. 2016 Feb. 24 (1):97-103. [Medline].

  27. Rani FA, Byrne P, Cranswick N, Murray ML, Wong IC. Mortality in children and adolescents prescribed antipsychotic medication: a retrospective cohort study using the UK general practice research database. Drug Saf. 2011 Sep 1. 34(9):773-81. [Medline].

  28. Picard LS, Lindsay S, Strawn JR, Kaneria RM, Patel NC, Keck PE Jr. Atypical neuroleptic malignant syndrome: diagnostic controversies and considerations. Pharmacotherapy. 2008 Apr. 28(4):530-5. [Medline].

  29. Oomura M, Terai T, Sueyoshi K, Shigeno K. Reversible cardiomyopathy as the autonomic involvement of neuroleptic malignant syndrome. Intern Med. 2004 Dec. 43(12):1162-5. [Medline].

  30. Newman EJ, Grosset DG, Kennedy PG. The parkinsonism-hyperpyrexia syndrome. Neurocrit Care. 2009. 10(1):136-40. [Medline].

  31. Ward C. Neuroleptic malignant syndrome in a patient with Parkinson's disease: a case study. J Neurosci Nurs. 2005 Jun. 37(3):160-2. [Medline].

  32. Osman AA, Khurasani MH. Lethal catatonia and neuroleptic malignant syndrome. A dopamine receptor shut-down hypothesis. Br J Psychiatry. 1994 Oct. 165(4):548-50. [Medline].

  33. Martin TG. Serotonin syndrome. Ann Emerg Med. 1996 Nov. 28(5):520-6. [Medline].

  34. Dosi R, Ambaliya A, Joshi H, Patell R. Serotonin syndrome versus neuroleptic malignant syndrome: a challenging clinical quandary. BMJ Case Rep. 2014 Jun 23. 2014:[Medline].

  35. Perry PJ, Wilborn CA. Serotonin syndrome vs neuroleptic malignant syndrome: a contrast of causes, diagnoses, and management. Ann Clin Psychiatry. 2012 May. 24(2):155-62. [Medline].

  36. Odagaki Y. Atypical neuroleptic malignant syndrome or serotonin toxicity associated with atypical antipsychotics?. Curr Drug Saf. 2009 Jan. 4(1):84-93. [Medline].

  37. Heiman-Patterson TD. Neuroleptic malignant syndrome and malignant hyperthermia. Important issues for the medical consultant. Med Clin North Am. 1993 Mar. 77(2):477-92. [Medline].

  38. Vörös V, Osváth P, Fekete S, Tényi T. [Antipsychotics and rhabdomyolysis. Differential diagnosis and clinical significance of elevated serum creatine kinase levels in psychiatric practice]. Psychiatr Hung. 2009. 24(3):175-84. [Medline].

  39. Schneider SM. Neuroleptic malignant syndrome: controversies in treatment. Am J Emerg Med. 1991 Jul. 9(4):360-2. [Medline].

  40. Addonizio G, Susman VL. ECT as a treatment alternative for patients with symptoms of neuroleptic malignant syndrome. J Clin Psychiatry. 1987 Mar. 48(3):102-5. [Medline].

  41. Shoirah H, Hamoda HM. Electroconvulsive therapy in children and adolescents. Expert Rev Neurother. 2011 Jan. 11(1):127-37. [Medline].

  42. Ozer F, Meral H, Aydin B, Hanoglu L, Aydemir T, Oral T. Electroconvulsive therapy in drug-induced psychiatric states and neuroleptic malignant syndrome. J ECT. 2005 Jun. 21(2):125-7. [Medline].

  43. Hermesh H, Aizenberg D, Weizman A. A successful electroconvulsive treatment of neuroleptic malignant syndrome. Acta Psychiatr Scand. 1987 Mar. 75(3):237-9. [Medline].

  44. Reulbach U, Dütsch C, Biermann T, Sperling W, Thuerauf N, Kornhuber J, et al. Managing an effective treatment for neuroleptic malignant syndrome. Crit Care. 2007. 11(1):R4. [Medline]. [Full Text].

  45. Rosebush PI, Stewart T, Mazurek MF. The treatment of neuroleptic malignant syndrome. Are dantrolene and bromocriptine useful adjuncts to supportive care?. Br J Psychiatry. 1991 Nov. 159:709-12. [Medline].

  46. Sakkas P, Davis JM, Janicak PG, Wang ZY. Drug treatment of the neuroleptic malignant syndrome. Psychopharmacol Bull. 1991. 27(3):381-4. [Medline].

  47. Ghaziuddin N, Dhossche D, Marcotte K. Retrospective chart review of catatonia in child and adolescent psychiatric patients. Acta Psychiatr Scand. 2012 Jan. 125(1):33-8. [Medline].

 
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