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Neuroleptic Malignant Syndrome Medication

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

Medication Summary

Specific drug therapies, such as dantrolene, amantadine, and bromocriptine, have an uncertain role in the treatment of neuroleptic malignant syndrome. Recommendations for the use of these drugs are from noncontrolled prospective and retrospective studies and case reports; no controlled studies exist. While the drugs generally are felt to be helpful, they have been found to have deleterious effects in some studies.

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Skeletal Muscle Relaxants

Class Summary

These agents stimulate muscle relaxation by modulating skeletal muscle contractions at sites beyond the myoneural junction and by acting directly on muscle itself. Benzodiazepines are used in a small number of patients with neuroleptic malignant syndrome unresponsive to other measures. In most cases, a continuous IV infusion of diazepam or lorazepam has been utilized.

Dantrolene (Dantrium, Revonto)

 

Dantrolene interferes with the release of calcium from sarcoplasmic reticulum, thus directly inhibiting muscle contraction. It also prevents or reduces the increase in myoplasmic calcium ion concentration that activates acute catabolic process associated with malignant hyperthermia. It is used to treat muscular rigidity and hyperthermia associated with neuroleptic malignant syndrome.

Dantrolene is available as a sodium salt in 25-mg, 50-mg, and 100-mg capsules and in 20-mg vial for intravenous (IV) administration. The IV form is much more expensive and should be reserved for patients unable to take oral medications.

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Benzodiazepine-Antispasmodic Agents

Class Summary

By binding to specific receptor sites, benzodiazepines appear to potentiate the effects of gamma-aminobutyric acid (GABA) and facilitate inhibitory GABA neurotransmission and the action of other inhibitory transmitters.

Diazepam

 

Diazepam modulates postsynaptic effects of gamma amino-butyric acid A (GABA-A) transmission, resulting in an increase in presynaptic inhibition. It appears to act on part of the limbic system, as well as on the thalamus and hypothalamus, to induce a calming effect. Individualize dosage and increase cautiously to avoid adverse effects.

Lorazepam (Ativan)

 

Lorazepam is a benzodiazepine with short onset of effects and intermediate-long half-life.

By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, it might depress all levels of CNS, including the limbic and reticular formation.

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Dopamine Agonists

Class Summary

A dopamine agonist must stimulate D2 receptors if it is to offer clinical benefit in neuroleptic malignant syndrome. D2 receptor blockade might cause neuroleptic malignant syndrome by removing tonic inhibition from the sympathetic nervous system or more directly by neuroleptic agents (eg, phenothiazines).

Bromocriptine (Parlodel)

 

Bromocriptine is a semisynthetic, ergot alkaloid derivative that is a strong dopamine D2-receptor agonist and a partial dopamine, D1-receptor agonist. It stimulates dopamine receptors in the corpus striatum. Bromocriptine may relieve akinesia, rigidity, and tremor associated with Parkinson disease. Initiate at low dosage. Slowly increase dosage to individualize therapy. Assess dosage titration every 2 weeks. Gradually reduce dose in 2.5-mg decrements if severe adverse reactions occur.

Amantadine

 

Amantadine has been used to treat Parkinson disease and has been tried in neuroleptic malignant syndrome because it increases synaptic dopamine activity. Its antiparkinsonian activity results from blocking reuptake of dopamine into presynaptic neurons and causing direct stimulation of postsynaptic receptors.

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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.

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