Serotonin Syndrome: Causes, Symptoms, Treatment, Complications, Diagnosis

Serotonin is a neurotransmitter or chemical your body produces naturally. It is required for your brain and nerve cells to function correctly. However, having too much of serotonin can cause various signs and symptoms that can range from being mild to severe. Mild symptoms may include diarrhea and shivering, while severe symptoms can include fever, muscle rigidity, and seizures. Serotonin syndrome can happen when you take certain medications that cause high levels of serotonin to build up in the body.

Many types of dietary supplements and illegal drugs can also lead to serotonin syndrome. Severe serotonin syndrome can even be life-threatening. Here’s everything you need to know about serotonin syndrome.

What is Serotonin Syndrome?

Serotonin syndrome can be a potentially dangerous condition that leads to an accumulation of serotonin in the body as a result of adverse drug reactions. It happens when too much serotonin builds up in the body. (1,2,3,4) Normally, the nerve cells in the body produce serotonin, which is a neurotransmitter, a chemical present in the brain.

Serotonin plays many important roles in the body and helps regulate the following in the body: (5,6)

  • Blood flow
  • Breathing
  • Body temperature
  • Digestion

Serotonin also has a crucial role to play in ensuring the proper functioning of your brain and nerve cells and is also believed to have an effect on your mood.

If you are taking several prescribed medications together, there is a possibility of having too much accumulation of serotonin in the body. There are certain types of medications that can cause serotonin syndrome, including drugs used for the treatment of depression, migraine headaches, and pain management medications. Having too much serotonin in the body can lead to a variety of symptoms, which can range from mild to severe. These symptoms can affect your muscles, brain, and other parts of the body as well. (7,8)

Serotonin syndrome can happen when you start taking a new medication that interferes with the body’s natural serotonin levels. It can also occur if you increase the dosage of a current medication you are on. The condition is more likely to happen when two or more medicines are taken together. Serotonin syndrome can prove to be fatal if you do not get proper treatment.

Symptoms of Serotonin Syndrome

You may experience the symptoms of serotonin syndrome within hours or even minutes of taking a new drug or increasing the dosage of a current medication. The symptoms of serotonin syndrome include: (9,10)

In more severe cases of serotonin syndrome may include:

  • Seizures
  • Coma
  • Unresponsiveness
  • Irregular heartbeat

Causes of Serotonin Syndrome

Usually, serotonin syndrome occurs when you take two or more medications, nutritional supplements that increase the serotonin levels in the body, or illegal drugs. For example, if you are taking medicine to treat a migraine after already having taken an antidepressant, it can lead to serotonin syndrome. There are some types of prescription medications, including antibiotics, antivirals for treating AIDS and HIV, and some prescription drugs for pain and nausea are also known to increase the serotonin levels in the body.

Some examples of medications and supplements that can cause serotonin syndrome include:

Migraine Medications That Fall Under The Triptan Category

Migraine medications that belong to a class of drugs known as triptans are known to be associated with serotonin syndrome. These include: (11)

  • Naratriptan (brand name Amerge)
  • Almotriptan (brand name Axert)
  • Sumatriptan (brand name Imitrex)
  • Antidepressants

Antidepressants that are linked with serotonin syndrome include: (12)

  • Serotonin and norepinephrine reuptake inhibitors (SNRIs), such as Effexor
  • Selective serotonin reuptake inhibitors (SSRIs), such as Zoloft and Celexa
  • Tricyclic antidepressants, including amitriptyline and nortriptyline
  • Monoamine oxidase inhibitors (MAOIs), such as Marplan and Nardil
  • Several other antidepressants

Herbal Supplements

There are some herbal supplements that are known to cause serotonin syndrome. These include: (13)

  • Ginseng
  • St. John’s Wort

Cold And Cough Medications

There are some over-the-counter cold and cough medicines that contain dextromethorphan. These medications are linked with serotonin syndrome. Some of these include:

  • Delsym
  • Robitussin DM

Illegal Drugs

There are some illegal drugs that are associated with serotonin syndrome, including: (14)

Diagnosing Serotonin Syndrome

There is no specific diagnostic test available for serotonin syndrome. Your doctor will start by going over your medical history and reviewing your symptoms. It is essential you let your doctor know if you are taking any medications or use any illicit drugs over the last few weeks. Your doctor needs this information to make an accurate diagnosis.

Your doctor is likely to perform some other laboratory tests as well that will help them figure out if certain body functions or organs have been affected. These tests also help your doctor rule out any other conditions.

There are certain conditions that have similar symptoms to serotonin syndrome, including drug overdose, infections, and even hormonal problems. A medical condition known as neuroleptic malignant syndrome is also known to have similar symptoms to serotonin syndrome. It usually happens as a result of an adverse reaction to medications used in the treatment of psychotic diseases. (15,16)

Some of the other laboratory tests your doctor may order include:

  • A complete blood count
  • A blood culture
  • Kidney function tests
  • Liver function tests
  • Thyroid function tests
  • Drug screens

Treatments for Serotonin Syndrome

In cases of very mild serotonin syndrome, your doctor is likely to only recommend that you immediately stop taking the medication that is causing the problem. In cases of severe symptoms, you will need to be hospitalized, where your doctor will keep a close eye on your condition.

Some of the treatments for severe serotonin syndrome include: (17,18)

  • Immediate withdrawal of any medication that led to the condition
  • Intravenous fluids administered for fever and dehydration
  • Medications that block the body’s natural production of serotonin
  • Medications to help relieve muscle stiffness and any agitation

Are There Any Complications of Serotonin Syndrome?

In many cases, severe muscle spasms can cause a breakdown of muscle tissue, which can cause severe kidney damage. In such cases, your doctor might need to use medications to temporarily paralyze the muscles to prevent any further damage. A respirator and breathing tube might be inserted to help you breathe.

Conclusion

With timely treatment, the outlook for serotonin syndrome remains very good. There are usually no further issues once the serotonin levels get back to normal. If left untreated, though, serotonin syndrome can prove to be fatal.

It is not always possible to prevent serotonin syndrome. It is important that you let your doctor know about all the medications you are taking to help them determine which medicines might be causing your symptoms. Your doctor will continue to monitor you closely if you are hospitalized for the condition. The US Food and Drug Administration requires drug manufacturers to put warning labels on products to warn patients about the potential risk of serotonin syndrome.

References:

  1. Sternbach, H., 1991. The serotonin syndrome. Am J Psychiatry, 148(6), pp.705-713.
  2. Boyer, E.W. and Shannon, M., 2005. The serotonin syndrome. New England Journal of Medicine, 352(11), pp.1112-1120.
  3. Volpi-Abadie, J., Kaye, A.M. and Kaye, A.D., 2013. Serotonin syndrome. Ochsner Journal, 13(4), pp.533-540.
  4. Bodner, R.A., Lynch, T., Lewis, L. and Kahn, D., 1995. Serotonin syndrome. Neurology, 45(2), pp.219-223.
  5. Mohammad‐Zadeh, L.F., Moses, L. and Gwaltney‐Brant, S.M., 2008. Serotonin: a review. Journal of veterinary pharmacology and therapeutics, 31(3), pp.187-199.
  6. Berger, M., Gray, J.A. and Roth, B.L., 2009. The expanded biology of serotonin. Annual review of medicine, 60, pp.355-366.
  7. Keck, P.E. and Arnold, L.M., 2000. The serotonin syndrome. Psychiatric Annals, 30(5), pp.333-343.
  8. Bijl, D., 2004. The serotonin syndrome. Neth J Med, 62(9), pp.309-313.
  9. Ables, A.Z. and Nagubilli, R., 2010. Prevention, recognition, and management of serotonin syndrome. American family physician, 81(9), pp.1139-1142.
  10. Frank, C., 2008. Recognition and treatment of serotonin syndrome. Canadian Family Physician, 54(7), pp.988-992.
  11. Mathew, N.T., Tietjen, G.E. and Lucker, C., 1996. Serotonin syndrome complicating migraine pharmacotherapy. Cephalalgia, 16(5), pp.323-327.
  12. Mackay, F.J., Dunn, N.R. and Mann, R.D., 1999. Antidepressants and the serotonin syndrome in general practice. British Journal of General Practice, 49(448), pp.871-874.
  13. Warner, M.E., Naranjo, J., Pollard, E.M., Weingarten, T.N., Warner, M.A. and Sprung, J., 2017. Serotonergic medications, herbal supplements, and perioperative serotonin syndrome. Canadian Journal of Anesthesia/Journal canadien d’anesthésie, 64(9), pp.940-946.
  14. Parrott, A.C., 2002. Recreational Ecstasy/MDMA, the serotonin syndrome, and serotonergic neurotoxicity. Pharmacology Biochemistry and Behavior, 71(4), pp.837-844.
  15. Nisijima, K., Shioda, K. and Iwamura, T., 2007. Neuroleptic malignant syndrome and serotonin syndrome. Progress in brain research, 162, pp.81-104.
  16. Carbone, J.R., 2000. The neuroleptic malignant and serotonin syndromes. Emergency Medicine Clinics, 18(2), pp.317-325.
  17. Gillman, P.K., 1999. The serotonin syndrome and its treatment. Journal of Psychopharmacology, 13(1), pp.100-109.
  18. Frank, C., 2008. Recognition and treatment of serotonin syndrome. Canadian Family Physician, 54(7), pp.988-992.

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