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Serotonin syndrome

Serotonin syndrome is a potentially life threatening drug reaction that causes the body to have
too much serotonin, a chemical produced by nerve cells.
Causes

Serotonin syndrome most often occurs when two drugs that affect the body's level of serotonin
are taken together at the same time. The drugs cause too much serotonin to be released or to
remain in the brain area.
For example, you can develop this syndrome if you take migraine medicines called triptans
together with antidepressants called selective serotonin reuptake inhibitors (SSRIs) and selective
serotonin/norepinephrine reuptake inhibitors (SSNRIs). Popular SSRIs include citalopram
(Celexa), sertraline (Zoloft), fluoxetine (Prozac), paroxetine (Paxil), and escitalopram (Lexapro).
SNRIs include duloxetine (Cymbalta) and venlafaxine (Effexor). Brand names of triptans include
sumatriptan (Imitrex), zolmitriptan (Zomig), frovatriptan (Frova), rizatriptan (Maxalt),
almotriptan (Axert), naratriptan (Amerge), and eletriptan (Relpax).
The FDA recently asked the manufacturers of these types of drugs to include warning labels on
their products that tell you about the potential risk of serotonin syndrome. Talk to your doctor
before stopping any medication.
Serotonin syndrome is more likely to occur when you first start or increase the medicine.
Older antidepressants called monoamine oxidase inhibitors (MAOIs) can also cause serotonin
syndrome with the medicines described above, as well as meperidine (Demerol, a painkiller) or
dextromethorphan (cough medicine).
Drugs of abuse, such as ecstasy and LSD have also been associated with serotonin syndrome.
Symptoms

Symptoms occur within minutes to hours, and may include:

Agitation or restlessness

Diarrhea

Fast heartbeat and high blood pressure

Hallucinations

Increased body temperature

Loss of coordination

Nausea

Overactive reflexes

Rapid changes in blood pressure

Vomiting

Exams and Tests

The diagnosis is usually made by asking questions about your medical history, including the
types of drugs you take.
To be diagnosed with serotonin syndrome, you must have been taking a drug that changes the
body's serotonin levels (serotonergic drug) and have at least three of the following signs or
symptoms:

Agitation

Diarrhea

Heavy sweating not due to activity

Fever

Mental status changes such as confusion or hypomania

Muscle spasms (myoclonus)

Overactive reflexes (hyperreflexia)

Shivering

Tremor

Uncoordinated movements (ataxia)

Serotonin syndrome is not diagnosed until all other possible causes have been ruled out,
including infections, intoxication, metabolic and hormone problems, and drug withdrawal. Some

symptoms of serotonin syndrome can mimic those due to an overdose of cocaine, lithium, or an
MAOI.
If you have just start taking or increased the dosage of a tranquilizer (neuroleptic drug), other
conditions such as neuroleptic malignant syndrome will be considered.
Tests may include:

Blood cultures (to check for infection)

Complete blood count (CBC)

CT scan of the brain

Drug (toxicology) and alcohol screen

Electrolyte levels

Electrocardiogram (ECG)

Kidney and liver function tests

Thyroid function tests

Treatment

People with serotonin syndrome should stay in the hospital for at least 24 hours for close
observation.
Treatment may include:

Benzodiazepines such as diazepam (Valium) or lorazepam (Ativan) to


decrease agitation, seizure-like movements, and muscle stiffness

Cyproheptadine (Periactin), a drug that blocks serotonin production

Intravenous (through the vein) fluids

Withdrawal of medicines that caused the syndrome

In life-threatening cases, medicines that keep your muscles still (paralyze them) and a temporary
breathing tube and breathing machine will be needed to prevent further muscle damage.
Outlook (Prognosis)

People may get slowly worse and can become severely ill if not quickly treated. Untreated
serotonin syndrome can be deadly. However, with treatment, symptoms can usually go away in
less than 24 hours.
Possible Complications

Uncontrolled muscle spasms can cause severe muscle breakdown. The products produced when
the muscles break down are released into your blood and eventually go through the kidneys. This
can cause severe kidney damage if not recognized and treated appropriately. With appropriate
treatment, the condition is reversible.
When to Contact a Medical Professional

Call your health care provider right away if you have symptoms of serotonin syndrome.
Prevention

Always tell all of your providers what medicines you take. People who take triptans with SSRIs
or SNRIs should be closely followed, especially right after starting a medicine or increasing its
dosage.
Alternative Names

Hyperserotonemia; Serotonergic syndrome


References

Brent J, Palmer R. Monoamine oxidase inhibitors and serotonin syndrome. In: Shannon MW,
Borron SW, Burns MJ, eds. Haddad and Winchester's Clinical Management of Poisoning and
Drug Overdose. 4th ed. Philadelphia, PA: Elsevier Saunders; 2007:chap 29.
Ford MD, Clinical Toxicology. 1st ed. Philadelphia, PA: WB Saunders; 2001:150, 522, 547, 550.
Levine M, Ruha AM. Antidepressants. In: Marx J, ed. Rosen's Emergency Medicine: Concepts
and Clinical Practice. 8th ed. Philadelphia, PA: Elsevier Saunders; 2013: chap 151.
Parrot AC. Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic
neurotoxicity. Pharmacol Biochem Behav. 2002 Apr;71(4):837-44. Review.
Prator BC. Serotonin syndrome. J Neurosci Nurs. 2006 Apr;38(2):102-5.
Sternbach H. The Serotonin Syndrome. Am J Psychiatry. 1991: 148:705.

US Food and Drug Administration. FDA Public Health Advisory: Combined Use of 5Hydroxytryptamine Receptor Agonists (Triptans), Selective Serotonin Reuptake Inhibitors
(SSRIs) or Selective Serotonin/Norepinephrine Reuptake Inhibitors (SNRIs) May Result in Lifethreatening Serotonin Syndrome. Rockville, MD: Center for Drug Evaluation and Research; July
19, 2006.
Update Date 7/22/2014

Updated by: Jacob L. Heller, MD, MHA, Emergency Medicine, Virginia Mason Medical Center,
Seattle, WA. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M.
Editorial team.
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