Serotonin Syndrome

If you’ve never heard of serotonin syndrome, you’re not alone. This potentially serious condition occurs when a person has too much serotonin in their body, often due to a buildup of certain medications that increase serotonin activity in the central nervous system. Doctors and researchers aren’t exactly sure how common it is—as symptoms are often attributed to another condition or merely overlooked—though cases have apparently increased over the last couple decades. But, what exactly is serotonin syndrome?

Below, we cover the signs of serotonin syndrome, specific drugs that can cause serotonin syndrome and treatment options.

What Is Serotonin Syndrome?

Serotonin is a neurotransmitter made naturally by our bodies. It’s often referred to as a “happy hormone” and helps regulate our behavior, mood, memory and more. When there’s too much of the happy hormone at one time, a person can experience serotonin syndrome—a dangerous condition if left untreated. When a person experiences depression, anxiety or other issues, doctors may prescribe a patient one or more medications to help increase serotonin activity.

“While normal serotonin function is important for our well-being, too much serotonin activity in our bodies can be dangerous,” says Kelly Johnson-Arbor, M.D., a medical toxicologist and co-medical director of the National Capital Poison Center. “Excessive serotonin activity commonly occurs when people take medications that affect serotonin function.”

Serotonin syndrome can be a life-threatening condition, and severe cases can lead to seizures, renal failure and coma.

Causes of Serotonin Syndrome:

Serotonin syndrome is caused by exposure to drugs or other substances that lead to increases in serotonin in the central nervous system, says Nima Majlesi, D.O., a double board-certified physician in emergency medicine and medical toxicology based in Staten Island, New York.

“Oftentimes, this can occur in therapeutic use of medication, intentional overdose of a single agent or the addition of more than one drug resulting in an interaction that promotes increases in serotonin,” he adds.

Drugs That Can Cause Serotonin Syndrome:

Antidepressant and antianxiety medications most commonly lead to serotonin syndrome, says Craig Beach, M.D., a double board-certified general and forensic psychiatrist and founder of Open Mind Health, based in San Diego. However, several other drugs can also affect the body’s metabolism of serotonin.

Drugs that can cause serotonin syndrome include the following, according to experts:

-Antidepressant and antianxiety medications, including monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and tricyclics

-Analgesics, such as meperidine and tramadol

-Antiemetics, such as ondansetron and metoclopramide

-Antibiotics, such as linezolid

-Pain medications, such as tramadol and fentanyl

-Dextromethorphan, an ingredient in some over-the-counter cough suppressants

-Dietary supplements, such as St. John’s wort and tryptophan

-Stimulants, such as amphetamines, cocaine and ecstasy

Serotonin Syndrome Symptoms:

Signs and symptoms of serotonin syndrome frequently occur within hours after a person takes a medication—or medications—that increases the amount of serotonin in their body. “Most cases occur within 24 hours, and 60% of cases occur within six hours after starting a new medication or increasing the dose of a medication,” says Dr. Beach.

“The widely held belief is that serotonin syndrome involves a triad of symptoms, which includes delirium, elevated body temperature and muscular stiffness,” says Dr. Majlesi. “However, the fact is that this syndrome includes a much larger range of symptoms.”

These symptoms can include:shivering, heavy sweating, restlessness, muscle stiffness, muscle twitching, irregular heartbeat, dilated pupils, headache, dry mouth, diarrhea, high blood pressure, elevated body temperature, changes in mood/mental state, including confusion or agitation, hallucinations, seizures, unconsciousness.

Dr. Majlesi notes it would be more appropriate to use the term “serotonin toxicity” to describe serotonin syndrome, due to the range and degree of symptoms that can occur. “What makes serotonin toxicity unique is its unusual ability to affect our legs more often than other parts of the body,” he says. “This often can lead to a range of symptoms, which includes mild difficulty walking, to severe stiffness and increased tone.”

When to See a Doctor?

“​If you are able to recognize serotonin toxicity it would be impressive,” Dr. Majlesi says, adding that the most common scenario is when a family member recognizes their loved one is acting unusually.

If you notice symptoms of serotonin syndrome and have taken one or more of the drugs listed above, contact your health care provider for an evaluation.

How Is Serotonin Syndrome Diagnosed?

There’s no lab test to determine if a person has serotonin syndrome, meaning they need a clinical diagnosis from a doctor instead. “Patients with possible signs or symptoms of serotonin syndrome should be evaluated by a doctor who will often make the diagnosis based on the history of medication use in addition to the patient’s clinical signs and symptoms,” says Dr. Johnson-Arbor.

When determining a diagnosis, Dr. Majlesi says the first question asked is often: “Has the patient taken a serotonergic agent in the past few weeks?” A doctor will then typically look for the following symptoms:tremor, excessive sweating, increased reflexes, stiffness of muscles, elevated body temperature (greater than 100.4 degrees), elevated heart rate, unusual rapid beating of the eyes to the sides, agitation.

“If these are present, then the diagnosis of serotonin syndrome or toxicity is likely,” he says.

Risks of Serotonin Syndrome:

The risks of serotonin syndrome are difficult to pinpoint considering the relatively low rate of proper diagnosis and recognition, says Dr. Majlesi.

Serotonin syndrome can occur in tandem with a different syndrome–especially if a person takes a combination of antidepressant and antipsychotic drugs. “Serotonin syndrome has significant overlap with another potentially life-threatening condition called neuroleptic malignant syndrome (NMS),” says Dr. Beach. NMS and serotonin syndrome have many overlapping symptoms, including muscle rigidity, tremor, abnormal reflexes and seizures.

The biggest risk of serotonin syndrome is not addressing it soon enough. If a person is not diagnosed quickly, serotonin syndrome can be fatal. “Fortunately, when the diagnosis of serotonin syndrome is recognized and promptly treated, most patients survive without complication,” says Dr. Johnson-Arbor.

As researchers better understand serotonin syndrome, the medical community has made several positive changes to help reduce risk. “Drugs such as MAOIs were so commonly associated with serotonin syndrome that they have been almost completely replaced by SSRIs and other much safer antidepressants,” Dr. Majlesi says. Additionally, most hospitals have stopped using meperidine–a pain-relieving drug that has been linked to high risk for serotonin syndrome–in favor of safer alternatives.

Treatment for Serotonin Syndrome:

Treatment for mild serotonin syndrome may be as simple as refraining from taking medications that cause symptoms. Depending on the level of severity, a person with serotonin syndrome can receive symptomatic and supportive care, says Dr. Beach. “In moderate to severe cases, there are medications to help the body stop producing serotonin,” he adds.

For people with severely elevated body temperature, serotonin syndrome treatment may also include external cooling, mechanical ventilation and/or drugs that cause temporary paralysis (to ensure muscles stop generating heat), says Dr. Majlesi.

“Many patients will require hospitalization, and some may even need to be monitored in an intensive care unit,” says Dr. Johnson-Arbor. Once treated, most cases of serotonin syndrome resolve within 24 to 72 hours.

“If you experience unwanted signs or symptoms after taking medications and are concerned about serotonin syndrome, do not try to manage this condition yourself,” she says. Instead, call your doctor or contact Poison Control immediately.