eMedicine Specialties > Psychiatry > Emergency

Neuroleptic Malignant Syndrome: Treatment & Medication

Author: Joseph Tonkonogy, MD, PhD, Clinical Professor of Psychiatry and Neurology, University of Massachusetts Medical School; Consulting Staff, Departments of Psychiatry and Neurology, University of Massachusetts Medical Center
Coauthor(s): Darius P Sholevar, MD, Fellow, Cardiovascular Disease, Albert Einstein Medical Center
Contributor Information and Disclosures

Updated: May 7, 2009

Treatment

Medical Care

The most important intervention is to discontinue all antipsychotics. In most cases, symptoms will resolve in 1-2 weeks. Neuroleptic malignant syndrome precipitated by long-acting depot injections of antipsychotics can last as long as a month. During the course of neuroleptic malignant syndrome, use supportive care aggressively. The value of other interventions, such as dantrolene, amantadine, bromocriptine, and electroconvulsive therapy, is uncertain.19

  • Supportive measures are aimed at preventing further complications and maintaining organ function.
    • Patients should receive circulatory and ventilatory support as needed.
    • Cooling blankets and antipyretics can be used to control temperature.
    • Aggressive fluid resuscitation and alkalization of urine can help prevent acute renal failure and enhance excretion of muscle breakdown products.
  • Electroconvulsive therapy has been proposed as a treatment based on its effectiveness in acute lethal catatonia. Some data suggest that electroconvulsive therapy is effective for neuroleptic malignant syndrome, but serious treatment-related complications have occurred (see Complications). Specifically, patients with neuroleptic malignant syndrome have developed cardiac arrest and ventricular fibrillation after electroconvulsive therapy.

Medication

Specific drug therapies, such as dantrolene, amantadine, bromocriptine, and electroconvulsive therapy, have an uncertain role in the treatment of neuroleptic malignant syndrome. While they generally are felt to be helpful, they have been found to be deleterious in some studies.

Skeletal muscle relaxants

Modulate contractions of muscle cells.


Dantrolene (Dantrium)

Stimulates muscle relaxation by modulating skeletal muscle contractions at a site beyond myoneural junction and by acting directly on the muscle itself.
Can be administered PO/IV. IV form is much more expensive and should be reserved for patients unable to take oral medications.

Adult

100-200 mg/d PO; not to exceed 400 mg/d
0.8-2.5 mg/kg IV q6h; not to exceed 10 mg/kg/d

Pediatric

0.5 mg/kg IV bid initially; increase to 0.5 mg/kg bid/qid; followed by increments of 0.5-3 mg/kg bid/qid prn; not to exceed 100 mg qid

Coadministration of clofibrate and warfarin can increase toxicity; coadministration with estrogen can increase hepatotoxicity in women >35 y

Documented hypersensitivity; active hepatic disease (hepatitis and cirrhosis)

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Might cause hepatotoxicity (use only for recommended indications); caution in impaired pulmonary function and severe cardiac insufficiency; might cause photosensitivity with exposure to sunlight

Dopaminergic agents

In order for a dopamine agonist to offer clinical benefit, it must stimulate D2 receptors. The role of other dopamine receptor subtypes currently is unclear.


Bromocriptine (Parlodel)

Strong dopamine D2 receptor agonist and partial dopamine D1 receptor agonist. Often administered with oral dantrolene.

Adult

5-10 mg PO bid, initial; not to exceed 40 mg/d

Pediatric

Not established

Ergot alkaloids can increase toxicity; amitriptyline, butyrophenones, imipramine, methyldopa, phenothiazines, and reserpine can decrease bromocriptine effects

Documented hypersensitivity; ischemic heart disease; peripheral vascular disorders

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Orthostatic hypotension, hypotension, and nausea are major adverse effects; psychosis might occur because bromocriptine effectively can antagonize effects of neuroleptics; caution in renal or hepatic disease


Amantadine (Symmetrel)

Antiviral agent effective against influenza A. Has a proposed role in altering the release and uptake of dopamine and has been used to treat Parkinson disease. Infrequently used to treat NMS.

Adult

100 mg PO bid; increase prn to 400 mg/d

Pediatric

<1 years: Not established
1-9 years: 5-9 mg/kg/d PO qd or divided bid
10-12 years: 100-200 mg/d PO qd or divided bid
>12 years: Administer as in adults

Drugs with anticholinergic or CNS stimulant activity increase toxicity; concurrent administration of hydrochlorothiazide plus triamterene with amantadine can increase plasma concentrations of amantadine

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in liver disease, uncontrolled psychosis, eczematoid dermatitis, seizures, and those receiving CNS stimulant drugs; reduce dose in renal disease when treating Parkinson disease; do not discontinue abruptly

Benzodiazepines

Used in a small number of patients unresponsive to above measures. In most cases, a continuous IV infusion of diazepam or lorazepam has been utilized.


Diazepam (Valium)

Depresses all levels of CNS (eg, limbic and reticular formation) possibly by increasing activity of GABA.
Individualize dosage and increase cautiously to avoid adverse effects.

Adult

5-10 mg PO/IV/IM q3-4h

Pediatric

0.05-0.3 mg/kg/dose IV/IM over 2-3 min q15-30min; repeat in 2-4 h prn; not to exceed 10 mg

Coadministration of other CNS depressants, including phenothiazines, barbiturates, alcohols, and MAOIs increases toxicity of benzodiazepines in CNS

Documented hypersensitivity; narrow-angle glaucoma; CNS depression

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Sedation, paradoxical agitation, anxiety, amnesia, mood lability, disinhibition, ataxia, dysarthria, and nystagmus are potential adverse effects; exercise caution in patients receiving other CNS depressants; use caution also in patients diagnosed with low albumin levels or hepatic failure because diazepam toxicity might increase


Lorazepam (Ativan)

Sedative hypnotic 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 limbic and reticular formation.

Adult

Continuous IV infusion starting at 0.5 mg/h; maximum rate of 10 mg/h

Pediatric

Adolescents: 0.07 mg/kg IV slowly over 2-5 min; repeat in 10-15 min prn; not to exceed 4 mg/dose

Concurrent use with alcohol, phenothiazines, barbiturates, and MAOIs increases toxicity of benzodiazepines in CNS

Documented hypersensitivity; preexisting CNS hypotension; depression; narrow-angle glaucoma

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Sedation, paradoxical agitation, anxiety, amnesia, mood lability, disinhibition, ataxia, and dysarthria are adverse effects; caution in renal or hepatic impairment, myasthenia gravis, cognitive impairment, or Parkinson disease

More on Neuroleptic Malignant Syndrome

Overview: Neuroleptic Malignant Syndrome
Differential Diagnoses & Workup: Neuroleptic Malignant Syndrome
Treatment & Medication: Neuroleptic Malignant Syndrome
Follow-up: Neuroleptic Malignant Syndrome
References
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Further Reading

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Keywords

neuroleptic malignant syndrome, antipsychotics, NMS, drug-induced movement disorder, lethal catatonia, neuroleptic-induced acute dystonia, neuroleptic-induced akathisia, neuroleptic-induced parkinsonism, neuroleptic-induced tardive dyskinesia, serotonin syndrome, hyperthermia, rigidity, autonomic dysregulation, 3, 4-methylenedioxymethamphetamine, MDMA, ecstasy, XTC

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Contributor Information and Disclosures

Author

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

Coauthor(s)

Darius P Sholevar, MD, Fellow, Cardiovascular Disease, Albert Einstein Medical Center
Disclosure: Nothing to disclose.

Medical Editor

Alan D Schmetzer, MD, Professor, Vice-Chair for Education, and Director of Residency Training in General and Addiction Psychiatry, Department of Psychiatry, Indiana University School of Medicine
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.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: Nothing to disclose.

Managing Editor

Iqbal Ahmed, MBBS, Professor, Department of Psychiatry, John A Burns School of Medicine, University of Hawaii
Iqbal Ahmed, MBBS is a member of the following medical societies: Academy of Psychosomatic Medicine, American Association for Geriatric Psychiatry, American Neuropsychiatric Association, and American Psychiatric Association
Disclosure: Nothing to disclose.

CME Editor

Harold H Harsch, MD, Program Director of Geropsychiatry, Department of Geriatrics/Gerontology, Associate Professor, Department of Psychiatry and Department of Medicine, Froedtert Hospital, Medical College of Wisconsin
Harold H Harsch, MD is a member of the following medical societies: American Psychiatric Association
Disclosure: lilly Honoraria Speaking and teaching; Forest Labs Honoraria Speaking and teaching; AstraZeneca Honoraria Speaking and teaching; Pfizer Grant/research funds Speaking and teaching; Northstar Grant/research funds Research; Novartis Grant/research funds research; Pfizer  Speaking and teaching; Sanofi-avetis Grant/research funds research; Otsuke Grant/research funds reseach; GlaxoSmithKline Grant/research funds research

Chief Editor

Stephen Soreff, MD, President of Education Initiatives, Nottingham, NH; Faculty, Metropolitan College of Boston University, Boston, MA
Stephen Soreff, MD is a member of the following medical societies: American College of Mental Health Administration and American Psychosomatic Society
Disclosure: Nothing to disclose.

 
 
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