Serotonin syndrome
Hyperserotonemia; Serotonergic syndrome; Serotonin toxicity; SSRI - serotonin syndrome; MAO - serotonin syndrome
Serotonin syndrome (SS) is a potentially life-threatening drug reaction. It causes the body to have too much serotonin, a chemical produced by nerve cells.
Causes
SS most often occurs when two medicines that affect the body's level of serotonin are taken together at the same time. The medicines 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).
Migraine
A migraine is a type of headache. It may occur with symptoms such as nausea, vomiting, or sensitivity to light and sound. In many people, a throbbi...
Common SSRIs include citalopram (Celexa), sertraline (Zoloft), fluoxetine (Prozac), paroxetine (Paxil), and escitalopram (Lexapro). SSNRIs include duloxetine (Cymbalta) and venlafaxine (Effexor). Common triptans include sumatriptan (Imitrex), zolmitriptan (Zomig), frovatriptan (Frova), rizatriptan (Maxalt), almotriptan (Axert), naratriptan (Amerge), and eletriptan (Relpax).
If you take these medicines, be sure to read the warning on the packaging. It tells you about the potential risk of serotonin syndrome. However, do not stop taking your medicine. Talk to your doctor about your concerns first.
SS is more likely to occur on starting or increasing the medicine.
Older antidepressants called monoamine oxidase inhibitors (MAOIs) can also cause SS with the medicines described above, as well as meperidine (Demerol, a painkiller) or dextromethorphan (cough medicine).
Drugs of abuse, such as ecstasy, LSD , cocaine , and amphetamines have also been associated with SS.
LSD
Substance abuse - LSD; Drug abuse - LSD; Drug use - LSD; Lysergic acid diethylamide; Hallucinogen - LSD
Cocaine
Substance abuse - cocaine; Drug abuse - cocaine; Drug use - cocaine
Amphetamines
Substance abuse - amphetamines; Drug abuse - amphetamines; Drug use - amphetamines
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 and vomiting
- Overactive reflexes
- Rapid changes in blood pressure
Exams and Tests
The diagnosis is usually made by asking the person questions about medical history, including the types of drugs.
To be diagnosed with SS, the person must have been taking a drug that changes the body's serotonin level (serotonergic drug) and have at least 3 of the following signs or symptoms:
-
Agitation
Agitation
Agitation is an unpleasant state of extreme arousal. An agitated person may feel stirred up, excited, tense, confused, or irritable.
- Diarrhea
- Heavy sweating not due to activity
- Fever
-
Mental status changes, such as
confusion
or hypomania
Confusion
Confusion is the inability to think as clearly or quickly as you normally do. You may feel disoriented and have difficulty paying attention, remembe...
- Muscle spasms (myoclonus)
-
Overactive reflexes (
hyperreflexia
)
Hyperreflexia
Autonomic dysreflexia is an abnormal, overreaction of the involuntary (autonomic) nervous system to stimulation. This reaction may include: Change i...
- Shivering
- Tremor
- Uncoordinated movements (ataxia)
SS is not diagnosed until all other possible causes have been ruled out. This may include infections, intoxication, metabolic and hormone problems, and drug or alcohol withdrawal. Some symptoms of SS can mimic those due to an overdose of cocaine, lithium, or an MAOI.
If a person has just started taking or increased the dosage of a tranquilizer (neuroleptic drug), other conditions such as neuroleptic malignant syndrome (NMS) will be considered.
Tests may include:
- Blood cultures (to check for infection)
-
Complete blood count
(CBC)
Complete blood count
A complete blood count (CBC) test measures the following:The number of red blood cells (RBC count)The number of white blood cells (WBC count)The tota...
-
CT scan of the brain
CT scan of the brain
A head computed tomography (CT) scan uses many x-rays to create pictures of the head, including the skull, brain, eye sockets, and sinuses.
-
Drug (toxicology) and alcohol screen
Drug (toxicology) and alcohol screen
A toxicology screen refers to various tests that determine the type and approximate amount of legal and illegal drugs a person has taken.
-
Electrolyte levels
Electrolyte levels
Electrolytes are minerals in your blood and other body fluids that carry an electric charge. Electrolytes affect how your body functions in many ways...
-
Electrocardiogram (ECG)
Electrocardiogram (ECG)
An electrocardiogram (ECG) is a test that records the electrical activity of the heart.
- Kidney and liver function tests
-
Thyroid function tests
Thyroid function tests
Thyroid function tests are used to tell whether your thyroid is working normally. The most common thyroid function tests are:Total, or free T4 (the m...
Treatment
People with SS will likely stay in the hospital for at least 24 hours for close observation.
Treatment may include:
- Benzodiazepine medicines, 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 the 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, SS can be deadly. With treatment, symptoms 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 the blood and eventually go through the kidneys. This can cause severe kidney damage if SS isn't recognized and treated properly.
When to Contact a Medical Professional
Call your health care provider right away if you have symptoms of serotonin syndrome.
Prevention
Always tell your providers which medicines you take. People who take triptans with SSRIs or SSNRIs should be closely followed, especially right after starting a medicine or increasing its dosage.
References
Brady MF. Serotonin syndrome. In: Ferri FF, ed. Ferri's Clinical Advisor 2017 . Philadelphia, PA: Elsevier; 2017:1154-1155.
Fricchione GL, Beach SR, Huffman JC, Bush G, Stern TA. Life-threatening conditions in psychiatry: catatonia, neuroleptic malignant syndrome, and serotonin syndrome. In: Stern TA, Fava M, Wilens TE, Rosenbaum JF, eds. Massachusetts General Hospital Comprehensive Clinical Psychiatry . 2nd ed. Philadelphia, PA: Elsevier; 2016:chap 55.
Levine M, Ruha AM. Antidepressants. In: Marx JA, Hockberger RS, Walls RM, eds. Rosen's Emergency Medicine . 8th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 151.
Review Date: 5/14/2016
Reviewed By: Jesse Borke, MD, FACEP, FAAEM, Attending Physician at FDR Medical Services / Millard Fillmore Suburban Hospital, Buffalo, NY. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the A.D.A.M. Editorial team.