Serotonin Syndrome

Serotonin syndrome occurs when medications that increase the level of serotonin (a chemical mediator) accumulate in the body. This syndrome usually happens when dosage is increased or new supplements are added to the diet. Certain illegal drugs can also increase the levels of serotonin.

Serotonin is a chemical mediator in the body needed for nerve cells and the brain. However, too much serotonin causes symptoms such as shivering and diarrhea. Severe serotonin syndrome can be fatal if not treated. A milder syndrome may go away within a day of stopping the medications that caused the symptoms and, sometimes, taking drugs that block serotonin. 

The nerve cells are known to produce serotonin in the body. It is a neurotransmitter, which is a chemical that helps regulate body temperature, blood flow, breathing, and digestion. Serotonin is also known to play an important role in the accurate functioning of brain and nerve cells. If an individual consumes different medicines prescribed for treating migraine, depression, or to manage pain together, they may end up increasing serotonin levels in the body. Too much serotonin causes various symptoms, which can range from mild to severe. These symptoms are also known to affect the brain, muscles, and other parts of the body.

Usually, when an individual starts taking a new medicine, there are chances of developing serotonin syndrome. It would usually occur if there is an increase in dosage, especially when two or more different medications are being taken together. If the individual does not receive prompt treatment, there is a chance the serotonin syndrome could be fatal.           

Serotonin is made up of the essential amino acid tryptophan. This type of amino acid needs to enter the body through diet and is known to be commonly found in foods such as red meat, cheese, eggs, and nuts. A deficiency in tryptophan can lead to lower levels of serotonin, which in turn leads to other medical conditions, such as anxiety, mood swings, and depression. Serotonin is one of the most important chemicals in the body; it impacts each and every part of the body in some way or another. From enhancing the emotions of an individual to fine-tuning motor skills, serotonin is required for all of these to function smoothly. One can also consider serotonin a natural mood stabilizer. It helps with eating, sleeping, and digestion. Apart from these, serotonin is also known to maintain healthy bones, decrease the level of depression, normalize anxiety, stimulate nausea, and heal wounds quickly. Since serotonin is known to naturally regulate an individual’s mood, one may feel happier, more focused, less anxious, and more stable and calmer when serotonin levels are normal. A slight deficiency can lead to problems such as lack of sleep and anxiety attacks. The normal range of serotonin in the blood should be 101 to 283 nanograms per milliliter, however, this benchmark may vary.

Serotonin syndrome symptoms usually occur within several hours of taking a new drug or increasing the dose of a drug. Signs and symptoms of serotonin syndrome include: 

• Agitation or restlessness
• Confusion
• Tachycardia and high blood pressure
• Dilated pupils
• Loss of muscle coordination
• Twitching muscles
• Muscle rigidity
• Heavy sweating
• Headache
• Diarrhea
• Shivering
• Goose bumps

Severe serotonin syndrome can be life-threatening. Signs and symptoms include:

• High fever
• Seizures
• Irregular heartbeat
• Unconsciousness

Excessive accumulation of serotonin is the main cause of serotonin syndrome. Under normal conditions, the body produces serotonin to help regulate attention, behavior, and body temperature.

Enterochromaffin cells of the intestines also produce serotonin. Serotonin syndrome may occur if migraine medicine is taken with anti-depressant medication. Some of the drugs that can cause serotonin syndrome are:

• Selective serotonin reuptake inhibitors (SSRIs): Anti-depressants such as citalopram, fluoxetine, fluvoxamine, paroxetine, Zoloft, Celexa, and sertraline
• Norepinephrine reuptake inhibitors (SNRIs): Anti-depressants such as trazodone, duloxetine, venlafaxine, and bupropion (an antidepressant and tobacco-addiction medication)
• Tricyclic anti-depressants: These include amitriptyline and nortriptyline.
• Monoamine oxidase inhibitors (MAOIs): Anti-depressants such as isocarboxazid, Marplan, Nardil, and phenelzine.
• Anti-migraine medications: These include triptans, carbamazepine, Imitrex, Axert, Amerge, and valproic acid.
• Pain medications: These include cyclobenzaprine, fentanyl, meperidine, and tramadol.
• Lithium, a mood stabilizer
• Herbal supplements: Such as ginseng and nutmeg
• Anti-nausea medications: Such as granisetron, metoclopramide, droperidol, and ondansetron
• Linezolid, an antibiotic
• Ritonavir, antiretroviral medication used to treat HIV/AIDS
• Other types of antidepressants: Such as Wellbutrin, which is given to control tobacco addiction
• Certain other illegal drugs, which are also known to be associated with serotonin syndrome, including cocaine, ecstasy, LSD, and amphetamines.
• Medications for cold and cough, such as Delsym and Robitussin DM.

A single test alone cannot diagnose serotonin syndrome.

The tests for serotonin syndrome starts with a physical examination. The doctor will begin by checking your medical history and symptoms. Inform the doctor of any medications being taken or if any illegal drugs were taken in the past few days or week. The doctor will perform several tests to find out if any organs or body parts have been affected. By doing so, it will also help rule out the possibility of other medical conditions.

To make sure the serotonin syndrome is caused by excess serotonin and not by any other condition, the doctor will perform tests to:

• Measure drug levels in the blood
• Check for signs of infection
• Check body functions which may be affected by serotonin

A number of conditions which can cause symptoms similar to serotonin syndrome are:

• Anticholinergic syndrome
• Drug overdose
• Withdrawal from illegal drugs

Some tests may be suggested to rule out similar conditions, including:

• Blood and urine tests
• Chest X-ray
• Computerized tomography
• Spinal tap (lumbar puncture)
• Complete blood count
• Kidney function test
• Blood culture
• Drug screening
• Thyroid function test
• Liver function test

Treatment for serotonin syndrome depends on the severity of symptoms. The following treatments are available:

• Muscle relaxants: Benzodiazepines, such as Diazepam or lorazepam, can help control agitation, seizures, and muscle stiffness.
• Blocking serotonin production: Cyproheptadine can block the production of serotonin and provide relief from the symptoms of serotonin syndrome.
• Oxygen and intravenous (IV) fluids: Breathing oxygen through an oxygen mask helps maintain adequate levels of oxygen in the blood, and IV fluids help fight dehydration and hyperthermia.
• Drugs to control heart rate and blood pressure: These include esmolol and nitroprusside to reduce high heart rate or high blood pressure. If the blood pressure is low, the doctor might administer adrenaline. Milder forms of serotonin syndromes usually fade away within one to three days. However, symptoms of serotonin syndrome caused by ingesting anti-depressants take several weeks to cease completely. 

Three things to help treat serotonin syndrome are:

• Identify the cause of the syndrome and stop medication: If an individual has started a new course of medication or is using a new combination of medicine and begins experiencing any of the symptoms related to serotonin syndrome, that person should contact the doctor and ask if the medication should be stopped. If one is unable to reach out to a doctor, it is best to hold off on consuming the medicine. If the symptoms of serotonin syndrome are mild, it will go away within a day or two. The doctor can prescribe a different medication and stop the existing one. Note that medication should be stopped only if you have recently started it (less than a week) and then experienced symptoms. If the medicine is being consumed for a longer duration, it is best to talk to the doctor before stopping the medicine, since it can be related to a different condition altogether.
• For longer duration, check with a physician: If the individual has been taking medications for a longer period (more than a few weeks), it is best to first contact the doctor before completely stopping the medicine. Many anti-depressants or other types of medication can cause serotonin syndrome as well as serious withdrawal symptoms if stopped suddenly. The doctor can guide you on other options available so you will know the best course to take.
• Anti-serotonin medicine: You will need to seek immediate medical attention if the symptoms caused by serotonin syndrome do not go away in a few days, if you have been consuming the medication which has caused the syndrome for a longer period of time, or if the symptoms are severe, such as changes in mental status or high blood pressure. The doctor can also prescribe anti-serotonin medication to treat the condition, such as cyproheptadine.

If the serotonin syndrome is appropriately treated, the symptoms usually take twenty-four hours to resolve.

In the meantime, the doctor will keep a watch on the status of the symptoms to ensure you are getting better.

To prevent serotonin syndrome, monitor all medications closely in cooperation with your doctor.

Taking more than one serotonin-related medication or increasing the dosage more than required will predispose you to developing serotonin syndrome.

Do not stop taking any such medications without the advice of a doctor.

If the doctor prescribes new medications, make sure he/she knows about any other drugs that are already in use. While using combination therapy, one must be aware of possible outcomes, like serotonin syndrome. 

Dietary changes also influence the levels of serotonin in the body. Foods that tend to increase serotonin levels are those rich in omega-3, such as tuna, and those high in tryptophan, an amino acid found in many food items, including eggs, pumpkin seeds, soy and any beverages related to soy, peanuts, cheese, and chicken. Another contributing factor which could lead to an increase in serotonin levels is a diet rich in folate, such as legumes, nuts, cereals, beans, and green vegetables.

No alternative or homeopathic remedies exist for serotonin syndrome.

There are no known ways to reduce the levels of serotonin in the body; the only way to treat it is through pharmacotherapy, which includes the consumption of muscle relaxants and serotonin blockers.

Lifestyle modifications are necessary in order to cope with serotonin syndrome.

People with serotonin syndrome can meet other people who have suffered the same condition and share their experiences. You can ask your doctor about support groups in the area and join them.

There are also many online forums where people share their experiences of serotonin syndrome.

There are several risks and complications associated with serotonin syndrome.

Risk factors of serotonin syndrome include:

• Improper doses of medications
• Consumption of more than one drug known to increase serotonin levels
• Herbal supplements that can increase the levels of serotonin
• Illicit drugs

Serotonin syndrome does not cause any severe complications, because serotonin levels can decrease and come back to normal in a short period of time. However, if left untreated, a severe form of serotonin syndrome can lead to unconsciousness and death.