Serotonin Syndrome

Serotonin syndrome is a life-threatening condition caused by prescription medications, illicit drugs, herbs, and other substances. When used in combination, these substances increase serotonin levels in the body and cause symptoms like anxiety, high body temperature, and seizures.

Serotonin is a neurotransmitter your body produces naturally. Mental Health America says serotonin is involved in almost every human behavior. Your sleep/wake cycles, libido, appetite, and executive function are all tied to serotonin. 

The neurotransmitter also plays a role in regulating your temperature, constricting your blood vessels, and encouraging your gut to move. Too much can lead to serious health issues.

Serotonin syndrome requires medical intervention in many cases. If left untreated, serotonin syndrome can result in seizures, coma, or even death.

What Causes Serotonin Syndrome?

Your brain stem produces serotonin naturally and sends it throughout your central nervous system. Cells within your gut can produce serotonin too. 

Serotonin syndrome develops when medications increase serotonin production or keep your body from recycling the serotonin it makes. As the neurotransmitter builds within the body, symptoms develop.

People develop serotonin syndrome by taking one serotonin-boosting medication, combining drugs, or overdosing intentionally.

Researchers writing in the journal StatPearls say it’s unclear how many people develop serotonin syndrome. Some cases produce mild symptoms that are easy to ignore, and serious cases can be misattributed to something else. However, people who use medications that target the serotonin system and those who combine medications are at risk for this serious health condition.

Serotonin Syndrome Symptoms

Serotonin syndrome can manifest itself in a variety of symptoms. They can be categorized as mild, moderate, or severe.

Mild symptoms of serotonin syndrome include the following:

• Stiff or jerking muscles
• Shaking
• Anxiety
• Restlessness
• Insomnia
• Sweating
• Watery eyes
• Fast heartbeat

Moderate symptoms of serotonin syndrome include the following:

• Chaotic eye movements
• Rhythmic muscle contractions
• Agitation
• High blood pressure
• High body temperature
• Unusual bowel sounds
• Diarrhea, nausea, and vomiting

Serious symptoms of serotonin syndrome include the following:

• Rigid muscles
• Respiratory failure
• Seizures
• Coma
• Delirium
• Confusion
• Very high body temperature

Serotonin Syndrome: Medications & Drugs That Cause It

This table can help you understand the prescription medications, drugs, and herbs that could cause serotonin syndrome:

Sources: Merck Manual, StatPearls

When an individual takes certain types of medications to regulate serotonin levels, this can cause an excess amount of serotonin, which is a potentially life-threatening situation.

Medications affecting serotonin levels are potential causes of serotonin syndrome. Dietary supplements and cough suppressants are also commonly associated with contributing to serotonin syndrome.

SSRIs

Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that can deeply affect serotonin activity. Common SSRIs include the following:

• Celexa (citalopram)
• Lexapro (escitalopram)
• Prozac (fluoxetine)
• Paxil (paroxetine)
• Zoloft (sertraline)

Antidepressants & Painkillers

Other antidepressants like trazodone are also associated with serotonin syndrome as well as painkillers like tramadol and fentanyl. 

Over-the-Counter Remedies & Dietary Supplements

Many cough suppressants available at grocery stores have an ingredient called dextromethorphan, which affects serotonin activity. Common cough suppressants that have this ingredient include Robitussin DM and Coricidin HBP.

Some dietary supplements can also affect serotonin activity, including tryptophan and St. John’s wort.

Any over-the-counter serotonin booster will contribute to increased serotonin activity and increase the risk of developing serotonin syndrome.

Serotonin Syndrome Risk Factors 

While some individuals may be more susceptible to serotonin syndrome, this condition can affect anyone.

Factors that increase the risk of serotonin syndrome include the following:

• Experimenting with illicit drugs
• Taking herbal supplements that affect serotonin activity
• Increasing medication dosage
• Taking multiple medications or drugs that affect serotonin levels

Individuals who have low levels of serotonin due to diet, age-related brain conditions, chronic stress, or lack of natural light exposure may explore supplements and medication that affect serotonin levels, which may cause overcompensation. This can increase the risk of serotonin syndrome.

Complications

While serotonin syndrome will usually subside when serotonin reaches normal levels, serotonin syndrome can lead to a variety of complications if left untreated.

Untreated serotonin syndrome can result in seizures, respiratory issues, kidney failure, coma, and even death.

While pharmacologic management is often explored for lack of normal serotonin production, it is important to understand the risks of serotonin syndrome to avoid complications and health hazards.

What to Do When You Suspect Serotonin Syndrome

If you experience any of the symptoms of serotonin syndrome, even if they’re mild, get help. Go to a hospital or urgent care clinic, and bring the medications you’re taking. Explain the symptoms you’re experiencing, and ask for help.

If someone you love is experiencing severe serotonin syndrome symptoms like seizures, call 911. Tell the operator what you’re seeing and what the person took. Stay with the person until help arrives.

Diagnosis of Serotonin Syndrome

Currently, there is no test available to confirm cases of serotonin syndrome. Doctor diagnosis generally depends on ruling out other possibilities due to the fact that serotonin syndrome shares symptom similarities with a wide variety of health conditions. 

For instance, serotonin syndrome symptoms are similar to symptoms of meningitis, delirium tremens, heatstroke, sepsis, and tetanus. 

Most often, medical professionals will give an examination that explores the medical history of the individual as well as the symptoms experienced. A physical examination will also be performed. 

What to Expect at the Examination

During the physical examination, a doctor will screen for any other drugs in the individual’s system and check for any signs or symptoms of infection. The doctor will take a look at bodily processes to ensure everything is functioning properly.

A doctor might perform additional tests like blood and urine tests, a CT scan, or an x-ray (chest area). In some cases, a lumbar puncture procedure (spinal tap) may be performed. 

Serotonin syndrome symptoms often occur quickly, many times within minutes of taking medication or supplements. A majority of patients show symptoms within 6 to 24 hours after the overdose or adjustment to medication that caused the condition. 

In order to properly diagnose serotonin syndrome, a doctor must have access to complete and accurate medical information and medication use history.

Treatment for Serotonin Syndrome

Treatment for serotonin syndrome includes withdrawal of the serotonergic drug in question after identifying the cause of the overdose. The level of treatment will depend on the severity of the condition.

Mild cases of serotonin syndrome will subside within one to three days after detoxification. Mild cases generally do not warrant a hospital visit. 

Moderate and severe cases of serotonin syndrome do require medical intervention and potentially hospitalization. In such cases, benzodiazepines are often used to manage tremors and agitation. 

Other medications prescribed for the treatment of serotonin syndrome include the following:

• Cyproheptadine 
• Zyprexa (olanzapine)
• Chlorpromazine

Olanzapine and chlorpromazine are less commonly used because there is a potential for toxicity and adverse events. 

Cyproheptadine is classified as a serotonin 2A antagonist and is primarily recommended for treatment of serotonin syndrome. A 12 mg dose of cyproheptadine is usually administered followed by maintenance doses of 2 mg every 2 hours in the event that symptoms persist.

After stabilization, maintenance doses of 8 mg every 6 hours are often given to the individual. 

Prevention

There are a variety of ways to prevent serotonin syndrome. The primary way is to follow prescription guidelines when taking any sort of medication that affects serotonin levels. 

Avoiding the use of multiple medications and supplements that augment serotonin will also help individuals avoid serotonin toxicity.

Advances in technology are helping to prevent cases of serotonin syndrome, including computerized prescription ordering systems and medical software that can check for drug interactions when regiments require multiple medications. 

Although there are no established guidelines regarding how to prevent serotonin syndrome, being aware of ingredients of the supplements you take and increasing your own knowledge of how serotonin works in the body will be tremendously helpful for prevention. If you are on medication that affects serotonin levels, consult with your doctor about which supplements you can safely take in conjunction with your medication.