Serotonin is a neurotransmitter that acts as a hormone regulating emotions, sleep, appetite, and other functions. An increase in serotonin levels is often associated with a boost in mood, but with serotonin syndrome, you can have too much of a good thing.
A dangerous and serious drug reaction, serotonin syndrome can develop when you take too much of a medication containing serotonin or you take a combination of serotonergic drugs that allows for a buildup of serotonin in the body. However, you can prevent serotonin syndrome with careful medication management. Also, it can be treated, usually with the discontinuation of the problematic medications. Other medications, however, may be needed to treat certain complications of this uncommon, but potentially life-threatening, condition.
What Is Serotonin Syndrome?
Serotonin syndrome is caused by excessive serotonergic activity in the central nervous system, explains David Mischoulon, MD, PhD, from Massachusetts General Hospital. “It typically results from increased dose of a serotonergic drug, including by overdose, or combinations of serotonergic drugs. Sometimes other drug interactions can slow down the metabolism of serotonergic drugs and result in toxic levels in the blood. Both drug buildup and initiating or increasing the dose of a serotonergic agent can precipitate serotonin syndrome.”
Common offenders include most of the antidepressant medications, some pain medications (including opioids), dextromethorphan (a common cough medicine), some hallucinogens, and the herbal antidepressant St. John’s wort.
Serotonin Syndrome Symptoms
Usually, serotonin syndrome presents with three main symptoms, Dr. Mischoulon says.
Serotonin syndrome symptoms typically include autonomic instability, which is dysfunction of the autonomic nervous system, which controls involuntary bodily functions, such as heart rate, blood pressure, digestion, and temperature. Symptoms may include fever, elevated blood pressure, elevated heartbeat, and sweating.
Serotonin syndrome can also bring on neuromuscular abnormalities, such as stronger reflexes, tremors, and involuntary muscle contractions.
The third major symptom involves mental status changes, such as agitation, confusion, and anxiety. “Other signs may include dilated pupils, flushing, shivering, and diarrhea,” Dr. Mischoulon says. “In more extreme cases that can become a medical emergency, we might see temperatures above 38.5°C and 40.0°C, sustained muscle stiffness, seizures, unstable blood pressure, irregular heartbeat, and delirium, or even coma and death.”
If you suspect you may have serotonin syndrome after starting a new medication or increasing the dose of a drug you’re already taking, call your health-care provider. If you are experiencing serious symptoms or your symptoms are rapidly getting worse, get to an emergency room.
Serotonin Syndrome Treatment
Serotonin syndrome treatment usually involves discontinuation of the offending drug, and administration of supportive measures aimed at preventing complications.
“Clinicians often give medications such as benzodiazepines for agitation, tremors, and muscle stiffness,” Dr. Mischoulon says. “Cyproheptadine (an antihistamine) blocks serotonin receptors and can even be given orally in milder cases, though intravenous administration is preferred. If there is a very high body temperature, cooling measures may be needed. Intravenous fluids and oxygen are sometimes needed. In extreme cases, medication-induced paralysis and intubation may be required.”
Who Is Most at Risk for Serotonin Syndrome?
People at higher risk include those taking multiple serotonergic drugs and/or large numbers of drugs that can interact with each other, Dr. Mischoulon says.
“Also, some people who are poor metabolizers of drugs based on their pharmacogenetic profile are at higher risk,” he adds. “People who have trouble clearing drugs out of their system due to liver or kidney disease may be vulnerable. Recreational drug users, especially those using MDMA or related hallucinogens, are at risk. Interestingly, younger adults are at greater risk than older adults because younger people have stronger serotonergic activity in general.”
How Long Does Serotonin Syndrome Last?
Mild to moderate serotonin syndrome usually resolves spontaneously within 24 to 72 hours after discontinuation of the offending drug, Dr. Mischoulon says.
“If the drug has a short half-life, recovery may be faster,” he explains. “Severe cases may last longer, especially if monoamine oxidase inhibitor (MAOI) antidepressants are involved, since they produce irreversible enzyme changes that the body can take weeks to correct.”
Dr. Mischoulon also notes that mild cases may resolve spontaneously with discontinuation of the offending drug or drugs.
“Moderate-to-severe cases almost always require treatment, ranging from supportive care to pharmacologic interventions, such as sedation with benzodiazepines or administration of cyproheptadine,” he adds. “This is often done in an emergency room under physician supervision, because the syndrome can advance rapidly if left untreated.”
How to Prevent Serotonin Syndrome?
You can take precautions to prevent serotonin syndrome. “Avoiding combinations of serotonergic drugs, as well as checking for any drug interactions when starting a new medication can prevent serotonin syndrome,” Dr. Mischoulon says. “Starting low and increasing doses slowly when starting a new serotonergic drug is a good strategy. Never combine SSRIs or SNRIs with MAOIs, linezolid, or triptans. Avoidance of recreational drugs such as MDMA or cocaine while taking antidepressants is important.”
Clinicians should educate patients about these potential symptoms and their seriousness, he adds. Health-care providers should be alert for serotonin syndrome symptoms since they can be mistaken for other medical problems or drug side effects.
When starting any new medication or increasing the dose of a current medication, be sure to ask your doctor about any potential risks. It’s also critical that your health-care provider know all of the medications—prescription and over-the-counter—that you take, as well as any supplements.
