What Is Serotonin Syndrome? Causes and Treatment

Updated on November 3, 2018
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Just your average apothecary (pharmacist), feet firmly planted behind the pharmacy counter, whose mortar and pestle are hitched to a star.

Increased blood pressure, visual disturbances, confusion, and vomiting are typical signs of serotonin syndrome.
Increased blood pressure, visual disturbances, confusion, and vomiting are typical signs of serotonin syndrome. | Source

What Is Serotonin Syndrome?

Serotonin syndrome is a serious and potentially life-threatening side-effect associated with certain medications or the combination of those medications. In this article, I will:

  • List the drugs most commonly associated with serotonin syndrome
  • Briefly present the symptoms typically associated with serotonin syndrome
  • Describe what causes serotonin syndrome
  • Explain how to avoid serotonin syndrome if you must take some of these medications

I hope this article will provide you with some relevant and useful information on this serious condition. I am a registered pharmacist with over 20 years of experience. This article is intended to explain in plain language (i.e. straight talk) on the serious risks and ways to prevent serotonin syndrome.

Serotonin syndrome is serious. Nevertheless, a 2002 article in the New England Journal of Medicine cited that "85% of physicians are unaware of it." It was the cause of the highly publicized and tragic death of 18-year old college student Libby Zion on March 5, 1984. In 2005, it was responsible for 118 deaths.

What Is Serotonin?

Serotonin, also sometimes abbreviated 5HT (5-hydroxytryptamine) is a chemical our body naturally produces from protein sources. Serotonin is a messanger molecule. It is especially located in our intestinal tract, although most pharmaceutical research is directed toward its effects on the CNS (Central Nervous System).

What is serotonin? Simply put, it is a messanger compound that is essential for both intestinal and mental health.

Who Should Be Concerned?

You should be aware of the risks of serotonin syndrome if you are taking one, or especially if taking more than one, of any of the following medications. Note: This list is NOT intended to be comprehensive:

Over-the-Counter (OTC) Medications or Supplements:

  • l-tryptophan
  • Chlorpheniramine (an antihistamine for allergies)
  • Dextromethorphan (a cough suppressant, like Delsym)
  • St. John's Wort (an herb, sometimes used for depression)

Prescription Medications:

  • Cyclobenzaprine (a muscle relaxer)
  • SSRI Antidepressants (e.g. citalopram, fluoxetine, sertraline, Lexapro, Luvox)
  • SNRI Antidepressants (e.g. Cymbalta, Effexor, Pristiq)
  • Clomipramine (an antidepressant)
  • Imipramine (an antidepressant)
  • Meperidine (for pain)
  • Methadone (for pain)
  • Tramadol (brand name Ultram, for pain)
  • Trazodone (an antidepressant, sometimes used for sleep)
  • MAO Inhibitors (e.g. isocarboxazid, phenelzine, selegiline)
  • Linezolid (an antibiotic, brand name Zyvox)
  • Migraine medications known as "triptans" (e.g. Imitrex, Amerge, Axert, Relpax, Zomig)

Illegal substances:

  • Lysergic Acid Diethylamine
  • methylenedioxymethamphetamine

I would emphasize that the likelihood of serotonin syndrome while taking just one of these at normal dosages if very rare. At inappropriately high doses, though, or in combination, the potential if far more likely.

Symptoms of Serotonin Syndrome

If you are taking any of the above medications and you begin to experience any of the following, it is advisable that you contact your doctor immediately:

  • Changes in blood pressure or body temperature (>100.4°F (38°C))
  • Confusion or visual disturbances, such as hallucinations
  • Muscle tremors, rapid pulse, unusual sweating
  • Restless or loss of coordination
  • Nausea, diarrhea or vomiting

What Causes Serotonin Syndrome?

To put it simply, serotonin syndrome is the result of overstimulation of the serotonin receptors in your body.

How does this happen?

Serotonin is a neurotransmitter; a normal, healthy chemical produced by your body. Neurotransmitters carry information from one nerve cell to the next. Certain medications cause serotonin levels to rise. Other medications directly stimulate serotonin receptors. Bad things happen when your body has too much serotonin, or when your serotonin receptors are over-stimulated. This is called serotonin syndrome.

Serotonin syndrome occurs when your dose of any of the previous medications is too high for you, or the combination of these medications is too high. It may begin within hours of a dangerous combination of the medications mentioned earlier.

Prevention and Treatment

Prevention

It would be nice if we could just avoid all medications that could cause serotonin syndrome. Nice, but for many, not practical. The medications that may contribute to serotonin syndrome are very useful for treating a variety of serious conditions and often significantly improve a patient's quality of life. Therefore, if you must take one of these medications, I suggest the following:

  • Be aware of the medications that can cause serotonin syndrome, and always take the lowest appropriate dosage.
  • Know the symptoms of serotonin syndrome so that you can identify them quickly and seek medical attention early if needed.
  • Unless absolutely necessary, avoid combining medications that may both contribute to serotonin syndrome.
  • Avoid OTC medications that may cause serotonin syndrome if you are already taking a prescription drug listed above. These include the cough suppressant "Dextromethorphan," the supplement "L-tryptophan" and the herbal product "St. John's Wort."

Treatment

The first thing you must do is seek medical help from a physician. If you have the symptoms described above and are taking one of these medications, immediately seek medical attention. The symptoms associated with serotonin syndrome are most likely to occur shortly after beginning therapy, or after combining therapies with these drugs. Medical treatment may involve several approaches including:

  1. Discontinuation of the drug(s)
  2. IV fluids
  3. Medication to treat muscle spasms
  4. Cyproheptadine (a serotonin antagonist which blocks the effects of serotonin on receptors)

For more information, a well-documented article on serotonin syndrome can be found here:

U.S. Pharmacist - SSRIs & Serotonin Syndrome

Questions & Answers

    Comments

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      • docashp profile image

        Hashp 

        15 months ago from india

        SSRI syndrome is a very important differential diagnosis of hyperthermic syndromes.Others being malignant hyperthermia, heat stroke, neurolept malignant syndrome.

        Nicely written article.

      • pharmacist profile imageAUTHOR

        Jason Poquette 

        5 years ago from Whitinsville, MA

        Hi Jessica,

        The SS would be unlikely from the Zanaflex alone, though not impossible. The combo with Ultram is more likely. Many people use this combination without issues. It appears you are especially sensitive. Or...it could have been something else altogether.

        Talk to your MD ASAP.

        Definitely tell your MD about your experience so that it can be factored in to any future recommendations.

        Glad you are okay now!

      • profile image

        Jessica Beauvais2 

        5 years ago

        I went to the hospital yesterday with what they told me was Seritonin Sydrome. It was worse than horrible! I had muscle twitching or spasms, vomiting, nausea, headache, eye twitching, weakness, diarrhea, loss of focus. I was told that it was because of a combination of Zanaflex, which I was prescribed at 4mg twice a day. I only usually take a half before bed, and 50mg of Tramadol which was prescribed to me just 4 days ago for swimmer's ear that I actually quit taking the day before because it wasn't helping.

        Background: I think I have experienced Serotonin Syndrome before with the Zanaflex just not as intensely and and pretty sure with Abilify and Trazadone but was not told what it was.

        I have three questions:

        • Was the SS set on by the combo of Zanaflex and Ultram or by the Zanaflex itself?

        • Should I quit taking Zanaflex?

        • should I tell my doc that I have a sensitivity to SS as I have experienced it serve real times with several different meds?

        Please help! I never want to experience this again!

      • pharmacist profile imageAUTHOR

        Jason Poquette 

        6 years ago from Whitinsville, MA

        Stewdowney,

        Sorry for the delayed reply. I was away for the weekend. Yes - there is reason to be at least mildly concerned about the potential for Pristiq and Tramadol to cause Serotonin Syndrome. Will they? It very much depends on the patient and on the dose. I would (1) discuss it with your doctor and (2) specifically ask about an alternative for pain to tramadol and (3) if you decide to use both drugs, read carefully the signs of serotonin syndrome, and watch for them. That is my advice. Please do let us know how this turns out. Best wishes.

      • profile image

        stewdowney 

        6 years ago

        I joined hubpages in hopes that I may receive a response as a member.

        My doctor has me on Prestiq for Depression and Anxiety, and on Tramadol (Ultram) for nerve pain in my thighs (Meralgia Paresthetica).

        I was originally prescribed Gabapentin (Neurontin) for the pain, but was taken off of it due to side effects and weight gain. I was then prescribed Topirimate (Topamax), but was taken off of that too due to side effects. I think the Gabapentin was the best drug for the pain, but the side effects were too great to deal with. The Tramadol has very short-lasting effects on the pain, and I fear that I am becoming "addicted" because I find myself watching the clock for time to take another one.

        In regards to the Prestiq, I have tried several different drugs for depression over the past few years, but ultimately had to stop taking them due to side effects and/or lack of results. Prestiq is the first drug to actually give results.

        My question to you is, should I be concerned about Serotonin Syndrome while taking both of these drugs? Isn't this something that my doctor should have considered before prescribing them? I am almost afraid to mention it to him for fear that his "pride" will keep him from acknowledging that he made a mistake.

      • profile image

        stew_downey 

        6 years ago

        My doctor has me on Pretiq for depression and Tramadol for pain from Meralgia Parasthetica. Should I be concerned about Serotonin Syndrome?

      • lucybell21 profile image

        Bonny OBrien 

        7 years ago from Troy, N.Y.

        Once again a well written hub. I work in a home for seniors, and I always wonder about all the different combo's of meds that they are taking. I really hope i will never have to depend on meds for anything. I don't even take asprin unless I really have to, just vitamins for me. All these different meds with all the side effects really make me nervous.

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