Key takeaways

Mixing certain medications, such as antidepressants and migraine or cough medications, can cause serotonin syndrome, a potentially life-threatening condition.
Symptoms of serotonin syndrome can develop quickly and include agitation, confusion, fever, and muscle rigidity, among others, and can range from mild to life-threatening.
Treatment for serotonin syndrome varies based on symptom severity but may include discontinuing the offending medication(s), hospitalization, and in some cases, medications to alleviate symptoms.
Prevention of serotonin syndrome involves careful medication management and consultation with healthcare providers to avoid dangerous drug interactions.

Let’s say you take a prescription antidepressant, such as Paxil (paroxetine), every day. You feel a migraine coming on, so you dig through the drawer in search of an Imitrex (sumatriptan) tablet.

Or, another common scenario—you take the antidepressant Cymbalta (duloxetine), and you feel a cold and cough coming on. You reach for a bottle of Robitussin-DM to treat your symptoms.

These medication combinations seem harmless, right? Think again. These scenarios of mixing medications can cause something called serotonin syndrome, which can be life-threatening.

Serotonin is a neurotransmitter. Depression is often associated with low levels of serotonin. Many treatments for depression help increase serotonin levels. Other medications (such as certain migraine medications, pain medications, cough suppressants, and even dietary supplements) can also increase serotonin levels.

If you take a medication that increases serotonin, you may feel just fine. But, too much serotonin from a dose that is too high, or from taking two or more medicines that increase serotonin levels, can cause serotonin syndrome (SS).

What is serotonin syndrome?

Serotonin syndrome occurs when there is too much serotonin in your system. How do you get too much serotonin in your body?

Serotonin syndrome can happen when someone:

Takes more than one medicine that affects serotonin levels
Starts or increases the dose of a medicine that increases serotonin
Takes too much medicine that increases serotonin (accidentally or on purpose)

When left untreated, the consequences can be severe.

Which medications can cause serotonin syndrome?

SSRI antidepressants: SSRIs (selective serotonin reuptake inhibitors) are the most common drugs involved in serotonin syndrome. They include Prozac (fluoxetine), Paxil (paroxetine), Zoloft (sertraline), Celexa (citalopram), Lexapro (escitalopram), Luvox (fluvoxamine), and Trintellix.
SNRI antidepressants: SNRIs (serotonin-norepinephrine reuptake inhibitors) include Cymbalta (duloxetine), Effexor (venlafaxine), and Pristiq (desvenlafaxine).
Other antidepressants: Tricyclic antidepressant medications (amitriptyline, nortriptyline), bupropion, trazodone, MAOIs (monoamine oxidase inhibitors)
Opioid painkillers: such as Percocet, oxycodone, OxyContin, Ultram (tramadol), Demerol (meperidine), fentanyl, Vicodin
Cough suppressants: Any cough/cold medication that contains dextromethorphan, such as Robitussin-DM, promethazine DM, Delsym, Mucinex-DM
Migraine medications: Triptans such as Amerge (naratriptan), Imitrex (sumatriptan), Relpax (eletriptan), Zomig (zolmitriptan), Axert (almotriptan)
Other prescription drugs: Metoclopramide, ondansetron, linezolid
Herbal supplements: Ginseng, St. John’s Wort
Illegal drugs: Ecstasy, LSD, cocaine

Talk to your pharmacist before starting on a new drug to avoid these potential interactions.

How common is serotonin syndrome?

Experts are not sure of the number of cases of serotonin syndrome. This is because mild cases may be overlooked or ignored. More severe cases may be attributed to another cause. We know that serotonin syndrome can occur in people of any age, and as antidepressant use is increasing, the cases of serotonin syndrome increase.

What are the symptoms of serotonin syndrome?

Serotonin syndrome symptoms develop quickly after taking the precipitating medicine—60% of cases occur within six hours. But symptoms may gradually get worse, becoming dangerous or life-threatening if not treated. Though most patients develop symptoms within 24 hours, there are case reports of people experiencing symptoms up to several weeks even after discontinuing the other drug known to increase serotonin levels, especially serotonergic agents with longer half-lives, such as fluoxetine (the longer the half life of a drug, the longer it lasts in your body).

So what are the symptoms of serotonin syndrome? They can vary from mild symptoms to life-threatening and may include:

Agitation
Anxiety
Restlessness
Mood changes/changes in mental status
Disorientation or confusion
Loss of muscle coordination
Sweating or shivering
Flushed skin
Fever
Hyperthermia (overheating)
Increased heart rate or high blood pressure
Nausea, vomiting, or diarrhea
Tremor
Muscle stiffness, muscle rigidity, or muscle jerks, especially in the legs
Hyperactive reflexes
Dilated pupils

More severe serotonin syndrome symptoms include high fever, seizures, irregular heartbeat, and unconsciousness. If you think you may be experiencing symptoms of serotonin syndrome, it’s important to seek emergency treatment from a doctor immediately.

Diagnosis

If you take a medicine that affects serotonin levels and experience any of the above symptoms, contact your doctor right away, or for more severe symptoms, seek immediate treatment in an urgent care center or emergency room. Severe cases are life-threatening and can quickly progress to death.

The healthcare provider you see can usually diagnose serotonin syndrome clinically, by evaluating your symptoms, reviewing the medicines you take (both prescription and over-the-counter), and, if necessary, conducting a physical examination. Some physicians use the Hunter Serotonin Toxicity Criteria to aid in the diagnosis of serotonin syndrome and to rule out conditions that exhibit similar signs such as neuroleptic malignant syndrome, malignant hyperthermia, and anticholinergic toxicity.

What is the treatment for serotonin syndrome?

Seek immediate treatment for symptoms of serotonin syndrome. Severe cases of serotonin syndrome can result in rhabdomyolysis (breakdown of muscle), myoglobinuria (muscle protein in the urine), metabolic acidosis, kidney failure, acute respiratory distress syndrome, respiratory failure, abnormal blood clotting, coma, and death.

For mild cases, your healthcare provider will likely advise you to discontinue the drug or drugs causing the reaction immediately. If you have more concerning or severe symptoms, you should be treated and monitored in the hospital. Treatment of serotonin syndrome depends on the symptoms and the severity of symptoms.

Some prescription medications used to treat symptoms include:

Benzodiazepines (such as diazepam) to help agitation, seizures, and stiffness
Cyproheptadine to block serotonin production
Medications to lower your heart rate or blood pressure (or raise your blood pressure if it is too low)

You may also need intravenous fluids for dehydration and fever, or supplemental oxygen.

Outlook

The length of time that you could experience serotonin syndrome varies. Those with milder forms of serotonin syndrome may feel better within one to three days. Some cases can take several weeks to go away, depending on which medication(s) caused the reaction and how long the medication(s) stay in your body.

American Family Physician explains that you can recover completely from serotonin syndrome, as long as it’s recognized quickly and complications are well-managed.

Can serotonin syndrome cause long-term damage?

The good news is that “in almost all cases, if the disease is caught early, there should be no long-term side effects,” according to hospitalist experts.

Because of the importance of treating serotonin syndrome early, it is critical to seek immediate treatment if you have symptoms.

Prevention

Anyone who takes medicine that increases serotonin is at risk of serotonin syndrome.

For your safety, get all of your medications at one pharmacy. This way, the pharmacist can get to know you and have your full medication list to screen for drug interactions.
If you have any changes in your medication regimen, such as starting a new medication, always consult your pharmacist to make sure you are not doubling up on serotonin. They can provide you with information to help minimize your risk.
If you take medications that increase serotonin, be aware of symptoms of serotonin syndrome. Seek immediate medical treatment if you have symptoms.
If you need a cold/cough medication and are already taking a drug that increases serotonin levels, check the ingredients, and avoid dextromethorphan. Your pharmacist can help you select an appropriate product.
Many different medications affect serotonin levels. A change in dosage or combination of two medicines that both increase serotonin can cause serotonin syndrome, which can be life-threatening.

Always check with your healthcare provider to make sure that the medications you take are compatible.