What Is Serotonin Syndrome?

Sick man with flu

GregorBister / Getty Images

In This Article

What Is Serotonin Syndrome?

Serotonin syndrome is a potentially life-threatening condition that's caused by elevated serotonin concentrations in your body from certain medications. Serotonin is a type of chemical known as a neurotransmitter that communicates with nerve cells and has a wide variety of functions throughout your body, primarily in your central nervous system and intestines.

In the right amounts, serotonin is necessary for important bodily functions, but when your body builds up too much and your levels get too high, symptoms can range from unpleasant to severe. If it's left untreated, serotonin syndrome can potentially lead to death.

Symptoms

Symptoms of serotonin syndrome can be mild to severe indicating anything from a slight serotonin excess to a life-threatening imbalance. The most common symptoms include:

  • Anxiety
  • Confusion
  • Dilated pupils
  • Fever
  • Flushing or paleness
  • Headache
  • High blood pressure
  • Irregular heartbeat
  • Muscle rigidity
  • Poor coordination
  • Profuse sweating
  • Rapid breathing
  • Restlessness
  • Shivering
  • Slow or fast pulse
  • Sudden jerky or shock-like movements
  • Tremor

If your condition becomes severe, it can turn into a life-threatening situation and may include signs like:

  • High fever
  • Losing consciousness
  • Seizures
  • Sudden swings in your blood pressure and/or pulse

If you suspect you or a loved one is showing signs of serotonin syndrome, contact your doctor immediately. If your symptoms are getting worse or they're severe, head to the emergency room or call 911. Immediate treatment is important because you can become seriously ill and your condition can become fatal the longer you go untreated.

SSRI Discontinuation Syndrome

It should be noted that some of the same symptoms listed above may also occur when you abruptly stop taking an antidepressant or you taper it off too quickly, known as SSRI discontinuation syndrome. Agitation, headaches, shock-like sensations, poor coordination, chills, and impaired concentration are some of the characteristics common to both syndromes. Because of this risk, it's vital that you never stop taking your antidepressant abruptly without discussing it with your doctor.

Diagnosis

Because the symptoms are similar to many other issues, you won't be diagnosed with serotonin syndrome until every other possible diagnosis has been ruled out. This is mainly because serotonin syndrome has to be diagnosed purely on your symptoms, history, and your physical and neurological exam.

Other conditions that need to be ruled out include:

  • Infections like meningitis and encephalitis
  • Intoxication
  • Neuroleptic malignant syndrome (NMS), another drug-related disorder that has some of the same symptoms as serotonin syndrome but results from antipsychotics (The biggest difference is that serotonin syndrome generally comes on quickly after starting the trigger medication.)
  • Overdose of a substance like cocaine
  • Reactions to other medications
  • Withdrawal from alcohol or drugs

The tests your doctor may order to rule these conditions out include:

  • Blood tests such as a complete blood count (CBC), blood cultures to test for infection, and other blood tests that check your electrolytes, screen for drugs and alcohol, and check your kidney, thyroid, and liver function
  • Urine tests to screen for drugs and alcohol, as well as to look at your kidney function
  • Computed tomography (CT) scan of your brain
  • Electrocardiogram (ECT) to check your heart
  • Lumbar puncture (spinal tap) to evaluate your spinal fluid
  • Chest X-ray

Causes

Serotonin syndrome, also known as serotonin toxicity, happens as the result of taking serotonergic drugs, which are medications that affect the level of serotonin in your body. It may be brought on by several different circumstances including:

  • Taking one serotonergic medication: It's unlikely that using one serotonergic medication by itself will cause serotonin syndrome, but it can happen in certain people who are sensitive to serotonin, especially when the dose is increased.
  • Overdosing: You can end up with serotonin syndrome if you ingest too much of your serotonergic medication(s), whether or not overdose is an accident or purposeful.
  • Taking two serotonergic medications together: The majority of cases of serotonin syndrome involve a person taking two (or more) serotonergic drugs at the same time, often without realizing it.

Medications Associated With Serotonin Syndrome

The medications that are most often associated with serotonin syndrome are antidepressants such as:

  • Selective serotonin reuptake inhibitors (SSRIs) like Paxil (paroxetine), Prozac (fluoxetine), and Celexa (citalopram)
  • Serotonin and norepinephrine reuptake inhibitors (SNRIs) like Cymbalta (duloxetine), Pristiq (desvenlafaxine), and Effexor (venlafaxine)
  • Tricyclic antidepressants such as amitriptyline, Pamelor (nortriptyline), and Surmontil (trimipramine)
  • Monoamine oxidase inhibitors (MAOIs) like Nardil (phenelzine) and Parnate (tranylcypromine)
  • Atypical antidepressants like Wellbutrin (bupropion), which is also used for smoking cessation under the brand name Zyban

There are other medications that are also considered serotonergic drugs, though they may not be as well-known. Some examples of these include:

  • Migraine medications called triptans such as Axert (almotriptan), Amerge (naratriptan), Imitrex (sumatriptan), and Maxalt (rizatriptan)
  • Anticonvulsants like Tegretol (carbamazepine) and Depakene (valproic acid), which are used for migraines, epilepsy, and bipolar disorder
  • Opioid pain medications such as codeine, Ultram (tramadol), Demerol (meperidine), Talwin (pentazocine), and Oxycontin (oxycodone)
  • 5-HT3 receptor antagonists, which treat nausea, like Anzemet (dolasetron), granisetron, Zofran (ondansetron), and Aloxi (palonosetron)
  • Reglan (metoclopramide), a prokinetic medication that's used to treat gastroesophageal reflux disease (GERD), diabetes, and sometimes to treat nausea in chemotherapy patients
  • Over-the-counter cough and cold medications that contain dextromethorphan (DXM) like Children's Robitussin Cough Long-Acting, Vicks DayQuil Cough, Vicks Formula 44 Custom Care Dry Cough, Zicam Cough MAX, and many others
  • Ergot derivatives, including Ergomar (ergotamine) for migraines and Methergine (methylergonovine) for uterine bleeding after childbirth
  • A muscle relaxant called Amrix (cyclobenzaprine)
  • Buspirone, a medication that's prescribed for anxiety disorders

Other substances and supplements that can contribute to serotonin syndrome include:

  • St. John's Wort
  • Illicit and recreational drugs such as cocaine, amphetamines, ecstasy, and LSD
  • L-tryptophan, an over-the-counter amino acid supplement that people use to quit smoking, for mental health disorders, and to help athletic performance
  • Lithobid (lithium), a mood stabilizer that's often used to treat bipolar disorder

All of these drugs and substances affect serotonin in some way. Some block nerve receptors; some block reuptake; some slow the breakdown of serotonin; and some increase the release of serotonin.

Because so many medications can contribute to serotonin syndrome, it's essential that any doctors you see who prescribe you medication always know about all the over-the-counter and prescription medications and supplements you're currently taking.

Risk Factors

Your risk of developing serotonin syndrome goes up under the following circumstances.

You're Taking a New Medication or Dose

If you just started taking a serotonergic medication or you had your dose increased, you should watch for signs of serotonin syndrome. Some people's bodies are naturally slower than others at metabolizing serotonin, and this isn't something you or your doctor will know until you are on a drug that boosts serotonin.

Most cases of serotonin syndrome start within 24 hours after starting or increasing a serotonergic medication and the majority of those start within six hours.

You're Switching to a New Medication

If you're switching from an MAOI to another antidepressant or vice versa, be especially careful to follow your doctor's guidance. Almost all antidepressants contain a warning that you should wait for at least two weeks, and sometimes more, when you switch antidepressant types.

One of the main reasons for this is the danger that having both types of drugs in your system can lead to serotonin syndrome. Prozac (fluoxetine), in particular, takes several weeks to be flushed out of your body.

You're Taking More Than One Medication

Taking more than one serotonergic medication, supplement, or substance at the same time increases your risk of serotonin syndrome. For instance, you're on Wellbutrin for depression and you take an Imitrex (sumatriptan) for a migraine or you're taking Zoloft (sertraline) and you treat a cold with DayQuil (dextromethorphan).

Treatment

Once you've been diagnosed with serotonin syndrome, the first line of treatment is to discontinue all serotonergic drugs. Treatment may also include the use of medications to relieve symptoms or hospitalization to stabilize your condition.

Medication

Benzodiazepines like Valium (diazepam) or Ativan (lorazepam) may be helpful to relieve any muscular symptoms, and you may need supportive treatment like oxygen and intravenous (IV) fluids and stabilization of vital signs. Drugs that specifically act against serotonin, called serotonin antagonists, can potentially be useful.

For mild to moderate cases, your symptoms should subside within 24 to 72 hours once you've discontinued taking the serotonergic drug and you can expect to fully recover.

Hospitalization

If your symptoms are worrisome, your doctor may have you hospitalized until you're stabilized. In cases where you're exhibiting signs of severe serotonin syndrome, you'll likely need to be hospitalized in the intensive care unit (ICU) until all your symptoms are gone.

For high fever, you may need to be sedated and given a medication that keeps you still (paralytic) to avoid any more damage to your muscles, in which case, you'll also have a breathing tube and ventilator.

Was this page helpful?
Article Sources
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Ochsner J. 2013;13(4):533-540.

  2. Foong AL, Grindrod KA, Patel T, Kellar J. Demystifying serotonin syndrome (or serotonin toxicity). Can Fam Physician. 2018;64(10):720-727.

  3. Renoir T. Selective serotonin reuptake inhibitor antidepressant treatment discontinuation syndrome: A review of the clinical evidence and the possible mechanisms involved. Front Pharmacol. 2013;4:45. doi:10.3389/fphar.2013.00045

  4. Isbister GK, Buckley NA, Whyte IM. Serotonin toxicity: A practical approach to diagnosis and treatment. Med J Aust. 2007;187(6):361-365.

Additional Reading