Serotonin Syndrome: What It Is, Symptoms & Treatments

To understand serotonin syndrome, we'll need a brief idea about serotonin and its role in our body. Serotonin is a chemical messenger that aids in transferring messages between neurons (nerve cells) throughout the body. It is produced predominantly in the gut (90–95%), followed by the brain (5–10%). Serotonin performs an array of functions from mood regulation to improving appetite, bowel movements, learning and memory, sexual desire, and wound healing.

What is Serotonin Syndrome?

Serotonin syndrome is a serious drug reaction caused by excess serotonin in your body. Most often, it occurs when you take a new drug with serotonin-increasing properties or a combination of different medications that can affect serotonin levels. Sometimes, the use of herbal supplements and illegal drugs may also impact its levels.

How Common is Serotonin Syndrome?

Serotonin syndrome is not as common as one would think. It is relatively rare, but here's the catch: it can be fatal. Severe cases of serotonin syndrome resulting in hospitalisation or death are rare.

Mild cases, however, are most likely to be overlooked, misdiagnosed, or confused with other similar medical conditions. In a study conducted on 112045 hospitalised patients, each taking at least one serotonin level-affecting medication, six were diagnosed with serotonin syndrome. It's also suggested that a few cases, especially milder ones, may have been overlooked.

What Causes Serotonin Syndrome?

There may be a rise in the level of serotonin in the following cases:

Intake of a recently started medication or an increased dose of the same ongoing medication. For example, antidepressants, such as SSRIs (the most common), help maintain higher levels of serotonin.
Taking a combination of medications affecting serotonin levels, for example, migraine medications or pain medications
Accidental or intentional overconsumption of such medications beyond the prescribed dose
Over-the-counter medications such as medicines for coughs and nausea

Although the exact mechanism behind serotonin syndrome is not clear because of limited research, it is largely thought to be due to disrupted receptor activity, leading to an imbalance between serotonin production and utilisation (impaired reuptake by nerve cells).

Here are 6 categories of medications that have the potential to cause serotonin syndrome:

1. Antidepressants:

taking a higher dose or a combination of antidepressants can pose a higher risk

SSRIs (Fluoxetine)
SNRIs (Desvenlafaxine)
TCA (tricyclic Antidepressants) (Amitriptyline)
Monoamine oxidase inhibitors (Marplan)
Bupropion (Antidepressant and smoking cessation)

2. Severe Pain (Tramadol, Fentanyl)

Migraine (Triptans, carbamazepine)
Mood stabilizer (Lithium)
Over-the-counter medications
- cough medication (Dextromethorphan)
- nausea medication (Ondansetron)

3. Antiviral medication used in the treatment of HIV (Ritonavir)

Apart from medications, other potential causes include:

Usage of illicit drugs (Cocaine, LSD, ecstasy)
Dietary supplement: Tryptophan
Herbal supplements: ginseng, nutmeg, St.John’s Wort.

What Does Serotonin Syndrome Feel Like?

What are Serotonin Syndrome Symptoms?

Serotonin syndrome usually presents as a triad of symptoms, showing:

Altered mental status (affecting cognition)
Overactive nervous system
Hyperactive muscular system

The symptoms shown are a combination of each system that can be mild, moderate, or severe in intensity.

A. Mild symptoms of Serotonin Syndrome

Nausea and vomiting
Diarrhoea
Nervousness/ restlessness
Pupil dilation
Mild tremors
Headache

B. Moderate symptoms of Serotonin Syndrome

Muscle twitching, stiffness and tightness
Agitation
Confusion
Abnormal eye movements
Shivering
Sweating ( not due to any physical activity)
Fluctuations in blood pressure and body temperature

C. Severe symptoms of Serotonin Syndrome

Feeling confused and disoriented
Seizures
High fever (more than 38.5°C)
Rapid and uneven heartbeat
High blood pressure
Tremors
Uncoordinated body movements
loss of consciousness (fainting)

Serotonin syndrome can be life-threatening in severe cases. If you or your loved ones experience any severe symptoms, call the emergency health line number or visit the hospital immediately.

How Do I Know If I Have Serotonin Syndrome?

To be diagnosed with serotonin syndrome, an individual should have a history of consuming medications that possess the ability to alter the body's serotonin levels and must have at least three of the following signs and symptoms:

Exaggerated muscle reflexes (hyperreflexia)
Muscle spasms
Fever with temperature above38°C
Agitation
Sweating
Abnormal eye movements
Altered mental status such as confusion and disorientation
Tremors

As there's no single test to diagnose serotonin syndrome, your doctor may ask you for relevant medical history and do a detailed examination to rule out any other medical conditions such as infections, hormone issues, ongoing medications (prescribed as well as over-the-counter) health supplements, etc. Some medical conditions similar to serotonin syndrome include:

Neuroleptic malignant syndrome (NMS)
Infections like meningitis, encephalitis
alcohol withdrawal
adverse reaction to other medications
illegal substance abuse (cocaine)

Remember to be honest with your doctor, even if it comes to the use of illegal drugs, as they are here to help you, not judge you. The doctor may also write for a few lab tests such as:

Blood and urine tests - to analyse the level of drugs, infections
Organ function tests - kidney, liver, thyroid
Additional tests (if needed) to identify any complications or conditions similar to serotonin syndrome as mentioned above - X-ray, CT scan
Lumbar puncture - to analyse spinal fluid (to check for inflexions)

If left untreated, serotonin syndrome can be life-threatening. Hence, it's imperative to seek help promptly for medical intervention.

How Fast Does Serotonin Syndrome Occur?

In general, most individuals may experience the symptoms within the first 24 hours. For some people, the symptoms of serotonin syndrome may appear the first few hours of taking a new medication, or a higher dose of the same ongoing medication or a combination of medications may alter the serotonin levels.

How Long Does Serotonin Syndrome Last?

Usually, milder forms of serotonin syndrome wear off within 24-72 hours with proper medical intervention. If the serotonin syndrome is due to some medications, for example, antidepressants, it might take several weeks for the symptoms to fully resolve. The risk of death is higher in cases of multiple medications and can happen within 24 hours.

How to Treat Serotonin Syndrome?

The treatment plan depends on the severity of your symptoms:

1. In cases of mild symptoms: Your doctor may advise stopping the causative medications. If the symptoms don't reduce quickly, they may prescribe a serotonin blocker.

2. In cases of moderate symptoms: A moderate form of serotonin syndrome may require hospitalisation for at least 24 hours to observe the improvement of your symptoms with treatment.

3. In cases of severe symptoms: A severe form may require admission to an intensive care unit (ICU), where the doctors can closely monitor the functioning of your vital organs.

You might be put on the following medications by your doctor depending on the symptoms:

Muscle relaxants - medicines like benzodiazepine, and lorazepam can help with muscle stiffness, agitation and seizures.
Serotonin blockers - medication such as cyproheptadine helps block the production of serotonin.
Drugs to control blood pressure and heart rate - Medicines like esmolol and nitroprusside can help to lower elevated blood pressure and heart rate.

In cases of significantly low blood pressure, your doctor might prescribe epinephrine or phenylephrine.

Oxygen and intravenous fluids - Providing oxygen through a breathing mask can help maintain oxygen levels in the blood. I.V. fluids help treat dehydration and fever.
A breathing tube with a machine containing muscle-paralyzing medications - may be required if you have a high fever.

FAQs About Serotonin Syndrome

1. How to ease serotonin syndrome?

Receiving prompt medical care is the ultimate method by which the symptoms of serotonin syndrome can be relieved. This may include medications such as serotonin blockers, muscle relaxants, etc., under the supervision of a doctor.

2. Does serotonin syndrome go away?

Yes. Serotonin syndrome usually goes away within the first 24-72 hours, followed by proper medications. Severe forms may require hospitalisation and may carry the risk of death if not intervened at the earliest.

Prevention Strategies for Serotonin Syndrome

Here are five ways by which you can prevent the chances of getting serotonin syndrome:

1. Ensure your doctor is informed about all the medications that you take, be they prescription-based or over-the-counter medicines. Maintain a list of these medications and share it with your doctor or pharmacist, especially if you're taking prescriptions from more than one doctor.

2. Be well informed about the role of each medication in your body, and make sure to read the warning labels that are mentioned in the tiny pamphlets that come along with the medications.

3. Discuss with your doctor if you or any of your family members have experienced serotonin syndrome before.

4.Do not stop or change any medications without your doctor's approval.

5. Be informed about serotonin syndrome, especially if you're taking combination medicines or higher doses of the same medication. Look out for the symptoms, and if you think you're developing serotonin syndrome, inform your doctor at the earliest.

Myths and Misconceptions

Here are the 2 common myths revolving around serotonin syndrome:

Myth 1: Combining two serotonin altering drugs always results in serotonin syndrome.

Fact: Just combining two drugs that are capable of increasing serotonin levels does not always result in serotonin syndrome, as it mainly depends on the type of serotonin receptor involved. Among many different serotonin receptors, only some are involved in serotonin syndrome.

Myth 2: Most of the serotonin altering drugs cause severe serotonin syndrome.

Fact: Only very few medications, such as monoamine oxidase inhibitors (MAOs), are capable of inflicting severe serotonin syndrome. A larger number of medicines can only cause mild to moderate serotonin syndrome and are relatively safe.

For example, in July 2006, the FDA released a warning stating that combining triptans (migraine medications) with SSRIs (antidepressants) can result in severe and life-threatening serotonin syndrome. Later in November 2006, it was suggested that the above-mentioned combination was safe for the majority of the patients.

Conclusion

Serotonin syndrome is a rare but potentially fatal condition caused by medication(s) or a combination of medications that have serotonin-increasing properties. Fortunately, it can be treated effectively with timely medical intervention. As the old saying goes, “Prevention is better than cure”. It is possible to reduce the chances of getting serotonin syndrome by adopting simple strategies.

References

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Cleveland Clinic. (2018). Serotonin Syndrome | Cleveland Clinic. Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/17687-serotonin-syndrome
Cleveland Clinic. (2022, November 29). St. John’s Wort (Hypericum Perforatum): Risks & Potential Benefits. Cleveland Clinic. https://my.clevelandclinic.org/health/drugs/9304-st--johns-wort
How Serotonin Syndrome Is Diagnosed and Treated. (n.d.). Verywell Mind. Retrieved August 1, 2024
‌John R. Horn, P., & Philip D. Hansten, P. (2014). Serotonin Syndrome: Myths and Misconceptions. www.pharmacytimes.com, 80. https://www.pharmacytimes.com/view/serotonin-syndrome-myths-and-misconceptions
Mayo Clinic. (2022, January 22). Serotonin Syndrome - Symptoms and Causes. Mayo Clinic. https://www.mayoclinic.org/diseases-conditions/serotonin-syndrome/symptoms-causes/syc-20354758
Serotonin syndrome. (2024, July 29). Wikipedia. https://en.m.wikipedia.org/wiki/Serotonin_syndrome