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Serotonin Syndrome: Causes, Symptoms, Diagnosis, Treatment, and Prevention

Serotonin regulates a number of functions in the body, including mood, sleep, appetite, and pain, and it is produced by nerve cells in the brain and other parts of the body. Normally, serotonin levels are balanced and stable, but sometimes they can become too high or too low. A condition called serotonin syndrome can be caused when serotonin levels are too high.

What causes serotonin syndrome?

Serotonin syndrome is usually caused by taking medications or drugs that increase the amount of serotonin in the body. These include:

• Antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), and tricyclic antidepressants (TCAs).

• Migraine medications, such as triptans, ergotamines, and dihydroergotamine.

• Pain medications, such as opioids, tramadol, and fentanyl.

• Anti-nausea medications, such as ondansetron and metoclopramide.

• Herbal or dietary supplements, such as St. John’s wort, ginseng, and 5-HTP.

• Illicit drugs, such as cocaine, ecstasy, LSD, and amphetamines.

Taking two or more of these medications or drugs at the same time, or increasing the dose of one of them, can also result in serotonin syndrome. Occasionally, even taking a normal dose of a single medication or drug can result in serotonin syndrome, especially if a person has a genetic variation that affects how serotonin is metabolized.

What are the symptoms of serotonin syndrome?

The symptoms of serotonin syndrome can vary from mild to severe, depending on the amount of serotonin in the body. They usually start within a few hours of taking the medication or drug that causes the condition. The symptoms may include:

• Nervousness, agitation, or restlessness.

• Confusion, disorientation, or hallucinations.

• Rapid heart rate, high blood pressure, or irregular heartbeat.

• Dilated pupils, blurred vision, or eye movements.

• Muscle twitching, spasms, rigidity, or tremors.

• Sweating, shivering, or goose bumps.

• Nausea, vomiting, or diarrhea.

• Headache, dizziness, or fainting.

• Seizures, coma, or death (in severe cases).

How is serotonin syndrome diagnosed?

Serotonin syndrome cannot be diagnosed by a specific test. The diagnosis is determined by a history of taking medications or drugs that affect serotonin, symptoms, and a physical examination. It may be necessary to perform blood tests, urine tests, or imaging tests to rule out other possible causes of the symptoms, including infection, poisoning, or stroke.

How is serotonin syndrome treated?

The main treatment for serotonin syndrome is to stop taking the medication or drug that causes the condition. This may require hospitalization and close monitoring of the vital signs and symptoms. In some cases, medications may be given to counteract the effects of serotonin, such as:

• Benzodiazepines, such as diazepam or lorazepam, to reduce agitation, seizures, and muscle stiffness.

• Serotonin antagonists, such as cyproheptadine or methysergide, to block the action of serotonin.

• Antihypertensive drugs, such as phenylephrine or epinephrine, to lower the blood pressure.

• Beta blockers, such as esmolol or propranolol, to slow down the heart rate and rhythm.

Other supportive treatments may include:

• Oxygen therapy, to maintain normal blood oxygen levels.

• Intravenous fluids, to prevent dehydration and electrolyte imbalance.

• Cooling measures, to lower the body temperature.

How can serotonin syndrome be prevented?

Using medications or drugs that increase serotonin levels with caution and under the guidance of a healthcare provider is the best way to prevent serotonin syndrome.

• Inform your healthcare provider about all the medications, supplements, and drugs that you are taking or planning to take, including over-the-counter, herbal, and illicit ones.

• Follow the instructions and dosages of your medications carefully, and do not change them without consulting your healthcare provider.

• Do not combine or switch medications or drugs that affect serotonin without checking with your healthcare provider first.

• Be aware of the signs and symptoms of serotonin syndrome, and seek medical attention immediately if you experience them.

• Do not self-medicate or use medications or drugs that are not prescribed for you.