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If you take antidepressants, you may have seen a warning that they can cause serotonin syndrome. Anything with the word “syndrome” at the end can sound pretty scary, but don’t worry. This syndrome is entirely preventable when you work closely with your healthcare provider.
This article will give you the tools to understand what causes serotonin syndrome and how you can prevent it. Plus, we’ll go over the treatments available if it happens to you or someone you love.
What is serotonin syndrome?
Serotonin is an important chemical or neurotransmitter that affects the brain. It helps balance your mood and impacts your sleep, bowel function, and blood clotting (Bakshi, 2020).
There is a link between low levels of serotonin in the brain and depression. Many antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), work by increasing serotonin levels in the brain.
Serotonin syndrome happens when your body has too much serotonin available to your brain cells. Serotonin syndrome can be mild, moderate, or severe. Some healthcare professionals choose to call it “serotonin toxicity” to reflect the danger of too much serotonin in the brain (Volpi-Abadie, 2013).
What causes serotonin syndrome?
Serotonin syndrome happens in two ways (Wang, 2016):
- The first is when you take too much of one serotonin medication.
- The second is when you take two or more medications, drugs, or supplements at the same time that increase serotonin levels in your body.
Serotonin levels can increase either by releasing more serotonin into the brain or preventing serotonin from getting reabsorbed (which keeps more serotonin in the brain). Serotonin syndrome occurs most often when you first start a new medication or increase your dose (Wang, 2016).
Medications that cause an increase and release of serotonin
Some substances increase serotonin precursors (the substance that helps boost serotonin). These include (Wang, 2016):
- Tryptophan (an amino acid found in high protein food like chicken, eggs, and tofu, or used as a supplement)
- Lithium (used to treat bipolar disorder)
- Fentanyl (used to treat pain)
- Lysergic acid diethylamide (LSD)
Other medications increase serotonin release in the brain. These include fenfluramine (used to treat seizures), amphetamines (used to treat attention deficit disorder), and MDMA (ecstasy).
SSRIs: everything you need to know
Medications that keep serotonin around in the brain
The medications that slow down the breakdown of serotonin include monoamine oxidase inhibitors (MAOIs), linezolid, methylene blue, Syrian rue, and procarbazine (Wang, 2016).
Several other medications slow down serotonin reuptake (reabsorption). These include (Wang, 2016):
- SSRIs like citalopram (Celexa), fluoxetine (Prozac; see Important Safety Information), paroxetine (Paxil), escitalopram (Lexapro; see Important Safety Information), fluvoxamine (Luvox), and sertraline (Zoloft; see Important Safety Information)
- Serotonin-norepinephrine reuptake inhibitors (SNRIs) like duloxetine (Cymbalta; see Important Safety Information), venlafaxine (Effexor; see Important Safety Information), Desvenlafaxine (Pristiq), Milnacipran (Savella), and Levomilnacipran (Fetzima)
- Tricyclic antidepressants like amitriptyline or nortriptyline
- Triptans used to treat migraine headaches like sumatriptan (Imitrex)
- Analgesics like meperidine (Demerol)
- Opioids like oxycodone or tramadol
- Anti-seizure medications like carbamazepine (Tegretol) and valproate (Depakote)
- Anti-nausea/anti-vomiting medications like ondansetron (Zofran) and metoclopramide (Reglan)
- Over-the-counter drug dextromethorphan (Robitussin DM)
- Herbal supplement St. John’s wort
Illicit drugs like cocaine, LSD, ecstasy, and amphetamines may cause serotonin syndrome when taken with an antidepressant (Simon, 2021).
Many prescription medications will list “serotonin syndrome” in the adverse effects on the packaging. Do not stop taking your medications or change the dose without discussing it with your healthcare provider.
What are the symptoms of serotonin syndrome?
Symptoms of serotonin syndrome can be mild, moderate, or severe. They can happen within minutes of taking your medication or at any time up to 24 hours after taking it. Serotonin syndrome can affect the nervous system, brain function, and other organs, such as the kidneys (Volpi-Abadie, 2013).
Watch out for any of the following symptoms after starting a new medication or upping your dose of a drug that impacts serotonin. Seek medical attention if you experience these symptoms, especially moderate or severe symptoms, as these can be quite dangerous.
St. John’s wort: uses, benefits, side effects
Mild serotonin syndrome
Mild symptoms include (Volpi-Abadie, 2013):
- Rapid heart rate (tachycardia)
- High blood pressure (hypertension)
- Sweating (diaphoresis)
- Dilated pupils (where the black circle in the eye gets much more prominent
- Shaking or shivering
- Muscle twitching or quick involuntary jerks (myoclonus)
- Feeling anxious and restless
Moderate serotonin syndrome
Moderate symptoms can include all of the symptoms of mild serotonin syndrome, plus (Volpi-Abadie, 2013):
- High fever
- Increased reflexes
- Tremors (shaking)
- Ocular clonus (where the eyes continuously move side to side)
- Muscle twitching
- Feeling agitated, easily startled, confused, or hypervigilant
Severe serotonin syndrome
Severe serotonin syndrome is a life-threatening medical event. Severe symptoms can lead to shock and potentially death. Severe serotonin symptoms include (Volpi-Abadie, 2013):
- Extremely high fevers (hyperthermia) with body temperatures of up to 106 degrees Fahrenheit (41 degrees Celsius)
- Delirium (feeling very confused and unaware of surroundings)
- Muscle rigidity
- Rhabdomyolysis (extensive muscle breakdown)
- Metabolic acidosis
- Disseminated intravascular coagulation (abnormal blood clotting throughout the body)
- Kidney failure
Antidepressants: types, side effects, uses, and risks
How do you diagnose serotonin syndrome?
Your healthcare provider can diagnose you with serotonin syndrome based on your symptoms and the medications, supplements, or other substances you’re taking. They may take some tests, such as blood and urine tests, CT scans, a chest x-ray, and possibly even a spinal tap (a test to check the fluid in your brain). This testing is to rule out other conditions or infections that might resemble serotonin syndrome. Your healthcare provider will want to confirm your diagnosis to provide the most appropriate treatment (Wang, 2016).
While these and other tests can rule out other conditions, there’s no specific test to confirm serotonin syndrome. So, we don’t know exactly how many people experience this condition. However, experts think the incidence is increasing as more people take antidepressants (Simon, 2021).
Many mild cases go untreated, and even severe cases may be attributed to other syndromes or conditions. Serotonin syndrome has been reported in people of all ages (Simon, 2021).
Can you prevent serotonin syndrome?
Serotonin syndrome is a serious condition that requires immediate medical attention. The good news? It’s preventable.
The most important step to prevent serotonin syndrome is to be open and honest with your healthcare provider. Let them know about anything else you are taking, including prescription or over-the-counter medications, supplements, and illicit drugs. Carefully monitor any side effects you have from your medications and supplements. Keep in contact with your healthcare provider if you notice anything unusual (Wang, 2016).
Remember that your risk of developing serotonin syndrome increases if you simultaneously take more than one substance that increases your serotonin levels, like an antidepressant and Robitussin DM or St. John’s wort. Your risk also goes up when you increase your antidepressant dose or take ecstasy, cocaine, LSD, or amphetamines. Take extra care if you are prescribed any other medications that impact serotonin (Wang, 2016).
How do you treat serotonin syndrome?
The treatment depends on how mild or severe your symptoms are. No matter how severe your serotonin syndrome symptoms are, the most crucial step is to stop the medications causing it. Most people improve rapidly just from stopping the medication (under medical supervision, of course) (Foong, 2018).
Some people require intravenous (IV) therapy, treatment with a benzodiazepine for muscle twitching (myoclonus), and cooling measures to bring down a fever. Moderate and severe cases may benefit from taking cyproheptadine, a serotonin antagonist that helps decrease serotonin (Wang, 2016).
Severe serotonin syndrome cases need significant help. The very high temperatures and muscle rigidity make it more difficult for people with severe symptoms to get enough oxygen flowing through their bodies. They need hospitalization and more extensive treatment, including placement on a ventilator to help them breathe. However, with swift treatment, people can recover from serotonin syndrome (Wang, 2016).
SNRIs: what are they, uses, side effects, and risks
What’s the prognosis of serotonin syndrome?
Most cases of serotonin syndrome clear up completely in one to three days with no lasting effects if you recognize and treat the symptoms immediately. Without swift treatment, however, serotonin syndrome can be fatal. Call your healthcare provider or 911 immediately if you experience symptoms of serotonin syndrome after starting or increasing a medication that acts on serotonin, or if you combine other substances with your medication. (Simon, 2021).
Work together with your healthcare provider and let them know which medications, drugs, and supplements you take and any reactions you have so that you can prevent serotonin syndrome altogether.
If you take several medications that raise your risk of serotonin syndrome, keep track of how you feel when taking them so you can alert your healthcare provider right away if you feel anything out of the ordinary.
- Bakshi, A. & Tadi, P. (2020). Biochemistry, serotonin. [Updated Jul 31, 2021]. In: StatPearls [Internet]. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK560856/
- Foong, A. L., Grindrod, K. A., Patel, T., & Kellar, J. (2018). Demystifying serotonin syndrome (or serotonin toxicity). Canadian Family Physician, 64(10), 720-727. Retrieved from https://pubmed.ncbi.nlm.nih.gov/30315014/
- Simon, L. V. & Keenaghan, M. (2021). Serotonin syndrome. [Updated Jul 22, 2021]. In: StatPearls [Internet]. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK482377/
- Volpi-Abadie, J., Kaye, A. M., & Kaye, A. D. (2013). Serotonin syndrome. The Ochsner Journal, 13(4), 533–540. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832/
- Wang, R. Z., Vashistha, V., Kaur, S., & Houchens, N. W. (2016). Serotonin syndrome: preventing, recognizing, and treating it. Cleveland Clinic Journal of Medicine, 83(11), 810-7. doi: 10.3949/ccjm.83a.15129. Retrieved from https://pubmed.ncbi.nlm.nih.gov/27824534/
Dr. Steve Silvestro is a board-certified pediatrician and Senior Manager, Medical Content & Education at Ro.