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Serotonin Syndrome

By

David Tanen

, MD, David Geffen School of Medicine at UCLA

Last full review/revision Jul 2019| Content last modified Jul 2019

Serotonin syndrome is a potentially life-threatening drug reaction that tends to cause high body temperature, muscle spasms, and anxiety or delirium.

(See Overview of Heat Disorders.)

Serotonin is a chemical that transmits impulses between nerve cells. Serotonin syndrome results from increased stimulation of the brain's serotonin receptors, usually by drugs. Serotonin syndrome can result from therapeutic drug use, overdose of some drugs, or most commonly, from unintended drug interactions when two drugs that each stimulate serotonin receptors are taken at the same time. Serotonin syndrome can occur in all age groups.

Some Drugs That Can Cause Serotonin Syndrome

Class

Drugs

Antidepressants: Monoamine oxidase inhibitors

Phenelzine

Selegiline

Tranylcypromine

Antidepressants: Serotonin-norepinephrine reuptake inhibitors

Bupropion

Nefazodone

Trazodone

Venlafaxine

Antidepressants: Selective serotonin reuptake inhibitors

Citalopram

Escitalopram

Fluoxetine

Paroxetine

Sertraline

Antidepressants: Tricyclic antidepressants

Amitriptyline

Desipramine

Doxepin

Imipramine

Nortriptyline

Trimipramine

Central nervous system (CNS) stimulants

Amphetamine

Cocaine

Methamphetamine

3,4-Methylenedioxymethamphetamine (MDMA or Ecstasy)

Methylphenidate

Phentermine

Sibutramine

Hallucinogens

Lysergic acid diethylamide (LSD)

5-Methoxy-diisopropyltryptamine ("Foxy Methoxy")

Herbs

Nutmeg

Panax (Asian or American) ginseng

St. John’s wort

Syrian rue

5-Hydroxytryptamine (5-HT1) agonists (triptans)

Almotriptan

Eletriptan

Frovatriptan

Naratriptan

Rizatriptan

Sumatriptan

Zolmitriptan

Opioids

Buprenorphine

Fentanyl

Hydrocodone

Meperidine

Oxycodone

Pentazocine

Tramadol

Others

Buspirone

Chlorpheniramine

Dextromethorphan

Granisetron

5-Hydroxytryptophan

Levodopa

Lithium

Metoclopramide

Olanzapine

Ondansetron

Risperidone

Ritonavir

Tryptophan

Valproate

Symptoms

Symptoms often begin within 24 hours of drug ingestion. Symptom severity can vary widely. People may have anxiety, agitation and restlessness, easy startling, and delirium with confusion. Tremor or muscle spasms, muscle rigidity, rapid heart rate, high blood pressure, high body temperature, sweating, shivering, vomiting, and diarrhea may occur.

Symptoms usually resolve within 24 hours, but symptoms may last longer depending on the time required for the body to break down the drug.

Diagnosis

  • Typical symptoms developing in a person who is taking a drug known to cause serotonin syndrome

Diagnosis is based solely on the doctor's evaluation of a person's symptoms, physical examination findings (especially of the nervous system), and a history of taking a drug that affects serotonin receptors.

There are no tests to confirm the diagnosis, but testing of blood and urine may be needed to exclude other disorders that cause high fever and similar symptoms, and to identify complications.

Treatment

  • Stopping drugs that affect the serotonin receptors
  • Prescribing a sedative

When serotonin syndrome is recognized and treated promptly, the prognosis is usually good.

All drugs that affect the serotonin receptors should be stopped. Mild symptoms are often relieved with a sedative (such as a benzodiazepine). Symptoms usually resolve over about 24 to 72 hours, so most people require hospitalization for further testing, treatment, and monitoring.

In severe cases, admission to an intensive care unit is needed. The person is cooled as needed (for example, by misting the body with water and then blowing air across the body with a fan). The person's temperature may need to be measured frequently or continuously. Other measures to treat organ malfunction may also be needed. Sometimes, if symptoms do not resolve quickly, a serotonin blocker such as cyproheptadine may be given.

Drugs Mentioned In This Article

Generic Name Select Brand Names
Chlorpheniramine CHLOR-TRIMETON
Dextromethorphan DELSYM
Methamphetamine DESOXYN
Methylphenidate CONCERTA, RITALIN
Tranylcypromine PARNATE
cyproheptadine No US brand name
Metoclopramide REGLAN
Buprenorphine BUPRENEX
Nortriptyline AVENTYL
Frovatriptan FROVA
Zolmitriptan ZOMIG
Trimipramine Trimipramine
Escitalopram LEXAPRO
Sumatriptan IMITREX
Almotriptan AXERT
Pentazocine TALWIN
Phentermine ADIPEX-P
Ondansetron ZOFRAN
Desipramine NORPRAMIN
Venlafaxine EFFEXOR XR
Naratriptan AMERGE
Risperidone RISPERDAL
Granisetron SANCUSO
Rizatriptan MAXALT
Eletriptan RELPAX
Sertraline ZOLOFT
Selegiline ELDEPRYL
Imipramine TOFRANIL
Citalopram CELEXA
Olanzapine ZYPREXA
Phenelzine NARDIL
Meperidine DEMEROL
Paroxetine PAXIL
Fluoxetine PROZAC, SARAFEM
Ritonavir NORVIR
Trazodone OLEPTRO
Oxycodone OXYCONTIN
Bupropion WELLBUTRIN, ZYBAN
Fentanyl ACTIQ, DURAGESIC, SUBLIMAZE
Levodopa Levodopa
Tramadol ULTRAM
Lithium LITHOBID
Doxepin ZONALON

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