Serotonin Syndrome (Toxicity)

Updated on December 29, 2019
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Kim is licensed in mental health and addiction counseling. Her education is in business, counseling, and health administration.

What is Serotonin Syndrome/Toxicity?

This article uses case studies, video and research to explain serotonin syndrome, which is also called serotonin toxicity. The article lists mild and severe signs and symptoms of serotonin syndrome. A list of drugs associated with serotonin syndrome is given, which includes prescribed and over the counter medications, herbal and dietary supplements and illicit drugs. A look at the risk and prevalence rates will show a rising risk for serotonin syndrome that is going unrecognized and unreported. While serotonin syndrome is preventable, it can only be prevented by educating providers and patients. Legal considerations and medical malpractice cases related to serotonin syndrome are included.

St. John's Wort
St. John's Wort | Source

Responding to Severe Symptoms

It is important to seek immediate emergency medical attention for severe symptoms and to report all prescribed, over the counter, supplements and illicit drug use to treatment providers.

Case Studies: Mack, Reena and Mr JW

Mack, age 29, was confused and saying things that didn’t make sense. He went to the Emergency Room. Test results all came back normal and he was sent home. The next day he was found collapsed face down on the pavement outside his apartment. He was taken to the Emergency Room and admitted to the Intensive Care Unit (ICU) with a 109-degrees temperature. It was unlikely that he would survive.

Reena, age 63, was confused and alone. She called a friend and confided that she was seeing people in her living room that she had known in the past, and that people were crawling on her walls. She wasn’t sure when she last ate or took her medications. She was bedridden and awaiting hip surgery. She was taken to the Emergency Room and admitted to the hospital.

Surprisingly, Mack did survive. He was treated for serotonin syndrome and double pneumonia. Most of his medications were discontinued. Reena was discharged and reports, “They took me off all those antidepressants.” Both showed signs of serotonin syndrome.

A research article in Canadian Family Physician (Frank, 2008), shared about Mr. JW who was admitted to the hospital for pneumonia at age 80. His condition worsened and he was admitted to ICU. He had been taking Prozac for 10 years. He was taken off Prozac and improved. A week later his depression returned, and he was started on Paxil. Within 24 hours of starting Paxil, he became confused, agitated and unresponsive at times. His temperature was 101.3 and his pulse was 115. He had muscle jerks. His doctor recognized serotonin syndrome and discontinued Paxil. He improved.

Serotonin Syndrome Can Happen to Anyone

Serotonin syndrome occurs when taking medications that cause too much serotonin to accumulate in the body.

Causes

Serotonin syndrome occurs when taking medications that cause too much serotonin to accumulate in the body. Serotonin is a chemical the body produces to help the nervous system work properly. Too much serotonin occurs when increasing the dose of a medication that increases serotonin or combining medications that increase serotonin. While some people are more susceptible, serotonin syndrome can happen to anyone.

Drugs that increase serotonin include prescription drugs, over the counter drugs, herbal supplements and illegal street drugs. Mayo Clinic identifies the following medications that could potentially cause serotonin syndrome (Hall-Flavin, 2019):

Drugs Associated With Serotonin Syndrome

Drug Type
Description/Examples
Selective serotonin reuptake inhibitors (SSRIs)
antidepressants such as citalopram (Celexa), fluoxetine (Prozac, Sarafem), fluvoxamine, paroxetine (Paxil) and sertraline (Zoloft)
Serotonin and norepinephrine reuptake inhibitors (SNRIs)
antidepressants such as trazodone, duloxetine (Cymbalta) and venlafaxine (Effexor)
Bupropion (Wellbutrin, Zyban)
an antidepressant and tobacco-addiction medication
Tricyclic antidepressants
such as amitriptyline and nortriptyline (Pamelor)
Monoamine oxidase inhibitors (MAOIs),
antidepressants such as isocarboxazid (Marplan) and phenelzine (Nardil)
Anti-migraine medications
such as triptans (Axert, Amerge, Imitrex), carbamazepine (Tegretol) and valproic acid (Depakene)
Pain medications
such as opioid pain medications including codeine (Tylenol with codeine), fentanyl (Duragesic), hydrocodone meperidine (Demerol), oxycodone (Oxycontin, Percocet, Percodan) and tramadol (Ultram).
Lithium
(Lithobid), a mood stabilizer
Illicit drugs
including LSD, Ecstasy, cocaine and amphetamines
Herbal supplements
including St. John's wort, ginseng and nutmeg
Over-the-counter cough and cold medications
containing dextromethorphan (Delsym, Mucinex DM, others)
Anti-nausea medications
such as granisetron, metoclopramide (Reglan), droperidol (Inapsine) and ondansetron (Zofran)
Linezolid
(Zyvox), an antibiotic
Ritonavir
(Norvir), an anti-retroviral medication used to treat HIV/AIDS
Drugs that increase serotonin include prescription drugs, over the counter drugs, herbal supplements and illegal street drugs.

Symptoms

Symptoms of serotonin syndrome can range from mild to severe. Mild symptoms can go away within 24 hours of stopping medications. Severe symptoms require immediate emergency medical attention and can be fatal (Hall-Flavin, 2019).

Mild Symptoms

 
 
 
Agitation or restlessness
Heavy sweating
Confusion
Diarrhea
Rapid heart rate and high Blood Pressure
Headache
Diluted Pupils
Shivering
Loss of muscle coordination or twitching muscles
goose bumps
muscle rigidity
 
Mild symptoms can go away within 24 hours of stopping medication.

Severe Symptoms

 
 
High Fever
Irregular heartbeat
Seizures
Unconsciousness
 
 
. Severe symptoms require immediate emergency medical attention and can be fatal.

Be Careful of Serotonin Syndrome

Increasing Cause for Concern

While serotonin syndrome is potentially life threatening, serious cases that require hospitalization are rare and mild cases are unlikely to result in death. In the United States, 93 deaths from serotonin syndrome were reported in 2002 (Frank, 2008).

However, it is believed that deaths from serotonin syndrome are under reported for several reasons (Uddin, et al, 2017). Milder cases are not being counted. Clinicians are not aware of the syndrome and don’t recognize it when it occurs. Some deaths are wrongly believed to be caused by something else.

Serotonin syndrome is becoming an increasing concern because adult antidepressant use has increased (Uddin, et al, 2017). In the United States, adult use of antidepressants increased from 6% in 1999 to 10.4% in 2010 to 11.11% in 2014. Use of antidepressants by adults age 65 and older increased from 3% in 1998 to 19% in 2014 (Yan, 2017).

Increased Use of Antidepressants in US

Increased concern for serotonin syndrome as adult antidepressant use increases.
Increased concern for serotonin syndrome as adult antidepressant use increases. | Source

Serotonin Syndrome is Preventable

only by educating providers and patients.

(Foong, et al, 2018)

Prevention

To prevent serotonin syndrome from occurring and to prevent fatalities from serotonin syndrome it is important to:

  • recognize signs and symptoms.
  • be familiar with drugs associated with serotonin syndrome.
  • seek emergency medical attention for severe symptoms
  • report all prescribed, over the counter, supplements and illicit drug use to treatment providers.
  • Check with prescribers and pharmacists before starting a new drug.

Serotonin Syndrome Made Simple

Legal Considerations

Seek consultation, but generally a malpractice lawsuit for serotonin syndrome would cost more than could be recovered (Lassen & Andriotis, 2013).
Seek consultation, but generally a malpractice lawsuit for serotonin syndrome would cost more than could be recovered (Lassen & Andriotis, 2013). | Source

Legal Cases Related to Serotonin Syndrome

A legal consultation for malpractice claims against providers can be considered, but generally the injuries sustained in a case of serotonin syndrome would need to be severe enough to justify the expense and risk of a malpractice lawsuit. Damages awarded would not likely cover the expenses of taking a case to trial. The lawsuit would cost more than could be recovered (Lassen & Andriotis, 2013).

In Miami, a twelve-year old boy died from serotonin syndrome. Her mother filed a wrongful death and medical malpractice lawsuit against the child’s psychiatrist and the group home where her autistic son lived. The child was taking Seroquel, Zyprexa, Depakote, and Clonazepam. The doctor hadn’t seen the child in a year and the child was showing signs of a poor reaction to medications. It is unknown if the case had legal merit or if there was enough evidence to proceed with the case (Miller, 2009).

A Houston jury awarded $20.5 million in damages against a pharmaceutical company, Akorn, Inc. The company manufactures methylene blue, which is used to dye tissue during surgical procedures. Akorn, Inc. failed to include in its prescription warning labeling that methylene blue would react adversely to Effexor XR, an antidepressant. The patient in this case was given methylene blue during her surgery and was taking Effexor XR. She developed serotonin syndrome and suffers from permanent cognitive injuries as a result of the drug interactions (Purser, 2017).

References

Foong, A. L., Grindrod, K. A., Patel, T., & Kellar, J. (2018). Demystifying serotonin syndrome (or serotonin toxicity). Canadian family physician Medecin de famille canadien, 64(10), 720–727

Frank C. (2008). Recognition and treatment of serotonin syndrome. Canadian family physician Medecin de famille canadien, 54(7), 988–992.

Hall-Flavin DK (expert opinion). Mayo Clinic. Oct. 17, 2019. Retrieved from https://www.mayoclinic.org/diseases-conditions/serotonin-syndrome/symptoms-causes/syc-20354758

Lassen II, C & Andriotis, G (2013). Is serotonin syndrome a likely malpractice case? Avvo legal answers. Retrieved from https://www.avvo.com/legal-answers/is-serotonin-syndrome-a-likely-malpractice-case--1185424.html

Miller, R. (2009). Serotonin syndrome malpractice lawsuit. Maryland medical malpractice attorney blog. Retrieved from https://www.marylandmedicalmalpracticeattorneyblog.com/serotonin-syndrome-malpractice-lawsuit/

Purser, B. (2017) Houston jury awards more than $20.5 million in damages against pharmaceutical company. The Telegraph, Retrieved from https://www.macon.com/news/local/community/houston-peach/article143301309.html

Teeple, R. C., Caplan, J. P., & Stern, T. A. (2009). Visual hallucinations: differential diagnosis and treatment. Primary care companion to the Journal of clinical psychiatry, 11(1), 26–32. doi:10.4088/pcc.08r00673

Uddin, M. F., Alweis, R., Shah, S. R., Lateef, N., Shahnawaz, W., Ochani, R. K., … Shah, S. A. (2017). Controversies in Serotonin Syndrome Diagnosis and Management: A Review. Journal of clinical and diagnostic research : JCDR, 11(9), OE05–OE07. doi:10.7860/JCDR/2017/29473.10696

Yan, J. (2017). Percentage of Americans Taking Antidepressants Climbs. Psychiatric News, 52(20), 1–1. doi: 10.1176/appi.pn.2017.pp9b2

This content is accurate and true to the best of the author’s knowledge and does not substitute for diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed health professional. Drugs, supplements, and natural remedies may have dangerous side effects. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.

Questions & Answers

    © 2019 Kim Harris

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      • kimh039 profile imageAUTHOR

        Kim Harris 

        7 weeks ago

        Thanks so much, Bob. I appreciate your taking the time to read it.

      • profile image

        diogenes 

        7 weeks ago

        Hi: I thoroughly enjoyed your concise, well-written and informative article on this (to me) obscure ailment.

        It would pay any of us to check our medication against the list you include and to pay attention to any present or future symptoms you describe.

        Well done!

        Bob

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