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What is Drug-Induced Serotonin Syndrome?

Serotonin syndrome is a potentially fatal condition in which too much serotonin overwhelms the brain and causes a physical chain reaction.

The neurotransmitter serotonin is vital in regulating mood and some physical functions — too little, and you will feel depressed and sluggish; too much, and you will become overexcited, manic, and potentially experience heart failure or a seizure.

CAUSES OF SEROTONIN SYNDROME

There are several potential causes of serotonin syndrome: taking too much of a drug like an antidepressant, adding a new drug to your regimen, or mixing drugs without a doctor’s supervision.

Mild symptoms of serotonin syndrome may not appear unusual, although they are uncomfortable. Severe symptoms can be fatal.

If you take antidepressants, it is crucial to follow your doctor’s instructions on safely managing your depression or anxiety with this treatment. Do not mix antidepressants with recreational drugs. Do not abuse other prescription substances. Tell your doctor about all the drugs you take, so they can manage your dose of antidepressants and help you avoid serotonin syndrome.

A magnifying glass over the word "Serotonin" in a book

This condition can also be caused by abusing recreational drugs like ecstasy, LSD, or amphetamines. If you struggle with addiction to a substance, get help.

HOW DOES SEROTONIN WORK IN THE BRAIN? 

Serotonin is an important neurotransmitter involved in mood regulation and other body functions. This neurotransmitter acts both peripherally and centrally, so it can impact nerve endings as well as receptors in the brain. 

Peripheral serotonin is produced in the gastrointestinal tract. Central serotonin is produced in the brainstem. 

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SEROTONIN IS INVOLVED WITH THE FOLLOWING:

  •  Wakefulness
  •  Attention
  •  Affective behavior like anxiety and depression
  •  Sexual interest
  •  Appetite
  •  Body temperature
  •  Motor tone
  •  Migraines
  •  Stomach problems like vomiting
  •  Aggression
  •  The experience of pain

Several drugs stimulate the release or prevent the reuptake of serotonin from managing mood or causing excitability. Prescription drugs like antidepressants can be an important component for managing serotonin when the brain needs this chemical to be regulated. However, both prescription and recreational substances can trigger serotonin syndrome by changing how the brain deals with this neurotransmitter.

ACTIONS IN THE BRAIN LEADING TO SEROTONIN SYNDROME INCLUDE:

  •  Inhibition of serotonin reuptake so that more is available to brain receptors
  •  Decreased serotonin metabolism
  •  Increased serotonin synthesis and release, so the brain makes more
  •  Activation of serotonergic receptors

There are several drugs that can trigger serotonin syndrome by causing the brain to make too much serotonin and by preventing the neurotransmitter from being metabolized out of the brain.

DRUGS THAT CAUSE SEROTONIN SYNDROME

A wide range of drugs can cause serotonin syndrome because they have different impacts on the serotonin receptors. 

Amphetamines like phentermine, antidepressants like bupropion, antiemetics like ondansetron, antihistamines like chlorpheniramine, some opioids like tramadol, cocaine, MDMA/ecstasy, herbal supplements like St. John’s wort, and over-the-counter medications with dextromethorphan can all inhibit the brain’s ability to absorb serotonin, meaning the neurotransmitter remains bioavailable to change signaling. 

At normal doses, and not mixed with other drugs, the above OTC and prescription medications are safe. When combined with other substances, including each other, these drugs can be dangerous.

Anxiolytics like buspirone, MAO inhibitors (antidepressants), triptans like eletriptan, and herbal supplements like St. John’s wort all prevent serotonin from being metabolized out of the brain.

Amphetamines, dietary supplements like L-tryptophan, and cocaine can all increase how much serotonin the brain produces, which may overwhelm the receptors.

Older antidepressants like mirtazapine, amphetamines (especially for weight loss), opioids like oxycodone or tramadol, MDMA/ecstasy, OTC drugs with dextromethorphan, and some treatments for Parkinson’s disease like L-dopa can all cause a flood of serotonin to be released into the brain and peripheral nervous system.

Buspirone, mirtazapine, triptans and other anti-migraine drugs, opioids including fentanyl, LSD, lithium, and prokinetic agents like metoclopramide can all cause serotonin receptors to become very active and take up a lot of serotonin in the brain.

Sources

(January 20, 2017) Serotonin Syndrome. Mayo Clinic. Retrieved March 2019 from https://www.mayoclinic.org/diseases-conditions/serotonin-syndrome/symptoms-causes/syc-20354758

(Winter 2013) Serotonin Syndrome. The Ochsner Journal. Retrieved March 2019 from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865832/

Serotonin Syndrome: Seven Things You Need to Know. Everyday Health. Retrieved March 2019 from https://www.everydayhealth.com/depression-pictures/serotonin-syndrome-things-you-need-to-know.aspx#serotonin-syndrome-symptoms

(April 5, 2018) Serotonin Syndrome. MedlinePlus. Retrieved March 2019 from https://medlineplus.gov/ency/article/007272.htm

(August 7, 2017) Serotonin Syndrome. Healthline. Retrieved March 2019 from https://www.healthline.com/health/serotonin-syndrome

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