Serotonin syndrome is a life-threatening drug reaction caused by medications that increase levels of the neurotransmitter serotonin in the brain. Serotonin is needed for the brain and nervous system to function, playing a key role in functions such as mood, sleep, and appetite.
However, too much serotonin causes symptoms that range from mild shivering and diarrhea to high fever and seizures. This is known as serotonin syndrome.
Serotonin syndrome can occur when you start taking a new medication that contains serotonin or when you increase the dose of one you’re currently taking, or by combining medications that contain serotonin, such as a migraine medication and an antidepressant.
Read on to learn more about what causes serotonin syndrome, how to recognize early warning signs, and how to prevent it by speaking with your healthcare provider.
What Is Serotonin?
Serotonin is a chemical messenger, or neurotransmitter, produced by nerve cells primarily in the brain and spinal cord. It plays a role in regulating functions such as mood, attention, appetite, and body temperature. By transmitting signals between nerve cells, serotonin contributes significantly to emotional well-being and cognitive processes, helping to maintain balance in the nervous system.
Serotonin also has important functions in the digestive system. It helps control bowel movements and the functioning of the gut, influencing motility and secretion. Because serotonin impacts both the central nervous system and the digestive tract, it serves as a chemical bridge between mental and physical health [1].
What Causes Serotonin Syndrome?
Excessive amounts of serotonin in the body, typically caused by medication use, lead to serotonin syndrome. The following medications may increase the risk of serotonin syndrome, but are generally safe when taken under medical supervision: [2][3]:
Antidepressants
- Selective serotonin reuptake inhibitors (SSRIs): Celexa, Prozac, Luvox, Lexapro, Zoloft.
- Serotonin and norepinephrine reuptake inhibitors (SNRIs): Fetzima, Savella, Cymbalta, Effexor XR, Wellbutrin.
- Tricyclic antidepressants: Amitriptyline and nortriptyline
- Monoamine oxidase inhibitors (MAOIs): Marplan and Nardil.
Other medications or supplements that can lead to serotonin syndrome, particularly when combined with a serotonergic medication such as those listed above, include:
Migraine Medications
- Carbamazepine (Tegretol, Carbatrol)
- Valproic acid
- Triptans, including:
- Almotriptan
- Naratriptan (Amerge)
- Sumatriptan (Imitrex, Tosymra)
Opioid Pain Medications
- Codeine
- Fentanyl
- Hydrocodone
- Meperidine (Demerol)
- Oxycodone
- Tramadol
Anti-Nausea Medications
- Granisetron (Sancuso, Sustol)
- Metoclopramide (Reglan)
- Droperidol (Inapsine)
- Ondansetron (Zofran)
Other Drug-Induced Causes of Serotonin Syndrome:
- Lithium: A mood stabilizer often used to treat bipolar disorder
- Illicit Drugs: LSD, ecstasy, cocaine, methamphetamine
- OTC Medications: Containing dextromethorphan
- Herbal Supplements: St.John’s Wort or Ginseng
Symptoms of Serotonin Syndrome
Serotonin syndrome symptoms typically begin within several hours of taking a new drug or increasing the dose of a drug you’re already taking. Signs and symptoms of serotonin syndrome include [3]:
- Physical: Rapid heart rate, increased blood pressure, muscle twitching, locked jaw, sweating/shaking, dilated pupils, diarrhea, headache, goosebumps
- Behavioral: Restlessness, agitation, confusion, inability to focus, mood swings or aggression
- Life-Threatening (require immediate support): High fever, tremor, seizures, irregular heartbeat, unconsciousness
If you notice any of the signs of serotonin syndrome after starting a new drug or increasing the dose of one you’re already on, speak with your health care provider right away. If you have severe or rapidly worsening symptoms, seek emergency medical care immediately.
Risk Factors of Serotonin Syndrome
The condition can occur in anyone, especially if they are taking any of the medications listed above. However, some individuals may be at a higher risk:
- You recently started one of the medications known to increase serotonin levels, or recently upped your dose
- You take more than one drug to increase serotonin levels (e.g, anti-migraine and anti-nausea pills combined)
- You take an herbal supplement such as Nutmeg, Ginseng, or SAMe to increase serotonin naturally
- You take illicit drugs such as cocaine or MDMA
Can You Die from Serotonin Syndrome?
Yes, serotonin syndrome can kill you, although deadly cases are rare. Serotonin syndrome has a mortality rate of 2% to 12%, with nearly 50% of fatal cases occurring within 24 hours of symptom onset [2].
Out of roughly 7,300 diagnosed cases of serotonin syndrome in the US, around 100 patients die, often linked to SSRI overdoses or interactions with other medications or alcohol. Death often stems from hyperthermia (extreme fever, often exceeding 102°F), seizures, rhabdomyolysis (muscle breakdown), and complications like organ failure or coma [4].
Preventing Serotonin Syndrome
Taking more than one serotonin-related medication or increasing your dose can increase the risk of serotonin syndrome. Always know what medications you take and share a list with your doctor, psychiatrist, or pharmacist.
If you or an immediate family member has struggled with symptoms of serotonin syndrome after taking certain medications in the past, be sure to let your medical provider know this. A few other ways to prevent serotonin syndrome include:
- Read warnings on drug or supplement packaging for “serotonin-boosting effects.”
- Avoid combining multiple serotonergic drugs or supplements.
- Follow prescribed doses, never take extra or reduce your dose without speaking to your doctor.
- Ask providers or pharmacists about serotonin risks before starting new meds.
- Disclose all OTC, herbal, or illicit substances to your doctor.
- Consider genetic testing (pharmacogenomics) to check compatibility with serotonin-affecting. medications like SSRIs, as variants in genes like CYP2D6 can predict poor metabolism and a higher risk. Some insurance plans may cover this (e.g, Medicare covers some of Myriad Genetics’ GeneSight) [5].
Treating Depression Without SSRI Antidepressants
If you have a higher risk of serotonin syndrome and struggle with chronic depression, alternative treatments such as ketamine and TMS may offer hope without the risk of complications sometimes seen with medication.
These therapies work differently from traditional antidepressants and can be effective for those who do not respond well to or cannot tolerate SSRIs.
Ketamine Therapy
Ketamine is a fast-acting therapy delivered either intravenously, as lozenges, or as a nasal spray that targets glutamate receptors in the brain, leading to rapid improvement in mood. It has shown promise in treatment-resistant depression, often providing relief within hours or days, unlike SSRIs, which can take weeks.
TMS
TMS is a non-invasive procedure that uses magnetic pulses to stimulate specific areas of the brain involved in mood regulation. It is FDA-approved for treating depression, especially when other treatments have failed or caused adverse effects. TMS sessions are usually done daily over several weeks and carry a low risk of side effects, making it a valuable option for those avoiding medication.
Alternative Medical Treatments for Depression: Ketamine Therapy and TMS in Utah
Harper Clinic is a state-of-the-art functional medicine clinic in Utah, providing evidence-based TMS and Ketamine therapy for treatment-resistant depression. Our consultation team is happy to evaluate you to see if you meet the criteria for advanced mental health treatments and help you move forward on your healing journey.
If you have already tried two or more conventional antidepressant medications with complications, or are at risk of serotonin syndrome, you may be a good candidate for TMS or ketamine. We also offer these for off-label use in treatment-resistant cases of OCD, PTSD, and anxiety.
Speak with a clinician to review candidacy, verify insurance, and schedule your treatment today at Harper Clinic.
Sources
[1] Bamalan, O. et al. 2023. Physiology, Serotonin. StatsPearl.
[2] Simon, L. et al. 2024. Serotonin Syndrome. StatsPearl.
[3] Mayo Clinic. 2024. Serotonin Syndrome.
[4] Spadaro, A. et al. 2022. High-risk and low-prevalence diseases: Serotonin syndrome. Science Direct.
[5] Saguin, E. et al. (2024). Pharmacogenetics testing for poor response to antidepressants: a transnosographic case series. Frontiers in pharmacology, 15, 1440523.