Neuroleptic Malignant Syndrome (NMS)

The following article, adapted from Medicines Information (the U.K.’s national drug information service), reviews the drugs that have been associated with the development of neuroleptic malignant syndrome (NMS).

Neuroleptic malignant syndrome (NMS) is a life-threatening neurological disorder most often caused by an adverse reaction to neuroleptic drugs (tranquilizers used to treat psychotic conditions). In most cases, NMS develops in a patient within the first two weeks of a drug treatment; however, the disorder may develop any time during a drug’s use.

The symptoms of NMS include:

• high fever
• sweating
• unstable blood pressure
• stupor
• muscular rigidity
• autonomic dysfunction (the autonomic nervous system regulates unconscious body functions, including heart rate, blood pressure, breathing, temperature regulation, gastrointestinal secretion, and metabolic and endocrine responses to stress)

The risk of developing NMS with particular drugs is unknown. The following information — based on published case reports in medical journals and adverse drug reaction reports to regulatory authorities — does not provide the basis necessary to calculate actual risk to patients using the drugs.

Drugs that have been associated with this disorder

1. First-generation or typical antipsychotics (see Table 1). The older or first-generation antipsychotics have been around since the 1950s. They are all now sold as generic drugs. Some of the old brand names that may be familiar to readers are THORAZINE (chlorpromazine), STELAZINE (trifluoperazine), HALDOL (haloperidol) and MELLARIL (thioridazine).
2. Atypical antipsychotics (see Table 2). The newer, second-generation antipsychotic drugs, called atypical antipsychotic agents, are among some of the most widely prescribed drugs in the U.S. For example, aripiprazole (ABILIFY), quetiapine (SEROQUEL) and olanzapine (ZYPREXA) were on the list of the most frequently prescribed drugs in 2009. None except clozapine (CLOZARIL, FAZACLO ODT) is available in a generic version.
3. Dopamine agonists (see Table 3). The most common uses for dopamine agonists are the treatment of Parkinson’s disease (in combination with levodopa [LARODOPA]) and restless leg syndrome. A number of case reports have been published of an NMS-like syndrome (NMLS) following withdrawal of levodopa preparations.
   NMS also can occur in people taking other anti-Parkinsonism drugs (dopaminergics) if the drugs are discontinued abruptly.
4. Antidepressants (see tables 4, 5 and 6). There have been a small number of case reports of NMS following antidepressant treatment. In some of these cases, the antidepressant was given in combination with antipsychotic drugs. Older antidepressants, tricyclic antidepressants (TCAs), appear to be more likely to cause NMS than the newer selective serotonin reuptake inhibitor (SSRI) antidepressants. SSRI antidepressants also are included in the group of the most frequently prescribed drugs in the country. Escitalopram (LEXAPRO) was the fifth most frequently prescribed drug in 2009.
5. Monoamine oxidase inhibitor (MAOI) antidepressants have been reported to produce a reaction similar to NMS when used in combination with TCAs or SSRIs. The symptoms may consist of agitation, delirium, elevated temperature and even death.
6. Metoclopramide (REGLAN). There have been case reports of NMS associated with the use of metoclopramide. One report describes a 6-month-old taking metoclopramide syrup and then experiencing NMS. This is the youngest person who has been reported to have NMS, confirming that children as well as adults are at risk of developing the syndrome.
7. Lithium carbonate (LITHOBID, LITHANE). Lithium carbonate taken in combination with antipsychotic drugs may increase the risk of NMS. It has been suggested that lithium toxicity may contribute to an increased risk of permanent brain damage following an NMS episode.
8. Abused substances. Cocaine, amphetamines and ecstasy may cause NMS-like symptoms. Also, alcohol and sedative drug withdrawal or hallucinogen intoxication may cause symptoms that are easily confused with the symptoms of NMS.

What You Can Do

You should contact your health care professional immediately if you develop the symptoms associated with NMS that are listed above.

Consumers may report serious adverse events from drugs to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online or by regular mail, fax or phone.

MedWatch

Consumers and health care professionals may report serious side effects to the FDA’s MedWatch Adverse Event Reporting Program either online or by regular mail, fax or phone.

Online: https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm
Regular mail: Use postage-paid, pre-addressed FDA form 3500 and mail to MedWatch, 5600 Fishers Lane, Rockville, MD 20852-9787
Fax: (800) FDA-0178
Phone: (800) FDA-1088

Table 1. First-Generation or Typical Antipsychotic Drugs

Table 2. Second-Generation or Atypical Antipsychotics

Table 3. Common Dopamine Agonists

Table 4. Common Tricyclic Antidepressants

Table 5. Selective Serotonin Reuptake Inhibitor (SSRI) Antidepressants

Table 6. Monoamine Oxidase Inhibitor (MAOI) Antidepressants

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