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Serotonin syndrome arises from an adverse reaction to medications that cause an excess of serotonin to build up in the body. Serotonin, a natural chemical vital for nerve cell and brain function, becomes problematic when its levels become too high, manifesting symptoms ranging from mild, like shivering and diarrhea, to severe, such as muscle rigidity, fever, and seizures. Left untreated, severe serotonin syndrome can be life-threatening.
This condition often occurs when medication dosages are increased or when a new drug is introduced. It frequently arises from combining medications containing serotonin, such as antidepressants and migraine medications. Serotonin syndrome can also be caused by the use of illicit drugs and specific dietary supplements.
Milder cases may resolve within a day or two after discontinuing the causative medications, sometimes with the aid of drugs that inhibit serotonin.
Symptoms
Symptoms of serotonin syndrome typically manifest within a few hours after taking a new medication or increasing the dosage of an existing one.
Common signs and symptoms include:
- Confusion
- Agitation or restlessness
- Inability to sleep
- Headache
- Dilated pupils
- High blood pressure
- Fast heartbeat
- Shivering
- Goose bumps
- Excessive perspiration
- Diarrhea
- Loss of muscle coordination or twitching of the muscles
Serotonin syndrome that is severe enough to be fatal. Symptoms include:
- Elevated body temperature
- Tremor
- Irregular heartbeat
- Seizures
- Unconsciousness
If you suspect you’re experiencing serotonin syndrome due to starting a new medication or adjusting the dosage of an existing one, it’s crucial to contact your doctor promptly or head to the emergency room. If symptoms are severe or rapidly worsening, seek emergency treatment without delay.
Causes
Serotonin syndrome is caused by an excessive accumulation of serotonin in the body. Typically, nerve cells in the brain and spinal cord produce serotonin, which helps regulate attention, behavior, and body temperature. Other nerve cells in the body, primarily in the intestines, also produce serotonin, which plays a role in regulating the digestive process, blood flow, and breathing.
While it’s possible for serotonin syndrome to occur with just one medication that increases serotonin levels, it most commonly happens when certain medications are combined. For example, serotonin syndrome may occur if you take an antidepressant with a migraine medication, or if you take an antidepressant with an opioid pain medication. Another cause of serotonin syndrome is intentional overdose of antidepressant medications.
Numerous over-the-counter and prescription drugs may be associated with serotonin syndrome, particularly antidepressants. Illicit drugs and dietary supplements may also be linked to the condition. Drugs and supplements that could potentially cause serotonin syndrome include:
- Selective Serotonin Reuptake Inhibitors (SSRIs), such as citalopram, fluoxetine, fluvoxamine, escitalopram, paroxetine, and sertraline
- Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs), including desvenlafaxine, levomilnacipran, milnacipran, duloxetine, and venlafaxine
- Bupropion, used for depression and tobacco addiction
- Tricyclic antidepressants, like amitriptyline and nortriptyline
- Monoamine Oxidase Inhibitors (MAOIs), such as isocarboxazid and phenelzine
- Lithium, used as a mood stabilizer
- Anti-migraine medications, including carbamazepine, valproic acid, and triptans such as almotriptan, naratriptan, and sumatriptan
- Opioid pain medications, such as codeine, fentanyl, hydrocodone, meperidine, oxycodone, and tramadol
- Illicit drugs, including LSD, ecstasy, cocaine, and amphetamines
- Over-the-counter cough and cold medications containing dextromethorphan
- Anti-nausea medications like granisetron, metoclopramide, droperidol, and ondansetron
- Linezolid, an antibiotic
- Ritonavir, an antiretroviral medication used to treat HIV
- Herbal supplements, such as St. John’s wort, ginseng, and nutmeg
Risk factors
Some individuals are more susceptible to the drugs and supplements that cause serotonin syndrome than others, but the condition can affect anyone.
You are at increased risk of serotonin syndrome if:
- You take multiple medications known to elevate serotonin levels.
- You recently began taking or upped the dosage of a drug that is known to raise serotonin levels.
- You consume herbal supplements that raise serotonin levels.
- You take an illegal substance that is known to raise serotonin.
Diagnosis
A definitive diagnosis of serotonin syndrome cannot be made with a single test. Instead, your doctor will diagnose the condition by ruling out other possible causes. They will typically begin by inquiring about your symptoms, medical background, and current medications. A physical examination will also be conducted as part of the diagnostic process.
To ensure that your symptoms are indeed caused by serotonin syndrome and not another condition, your doctor may use tests to:
- Assess any medication levels you may be taking
- Look for infection signs
- Examine bodily processes that serotonin syndrome may impact.
Several conditions can produce symptoms similar to those of serotonin syndrome. Minor symptoms may arise from various causes. However, moderate and severe symptoms resembling those of serotonin syndrome could be caused by:
- An overdose of illegal substances, antidepressants, or other drugs that raise serotonin levels
- A severe reaction to particular drugs, such as antipsychotics, anesthetics, and other substances known to cause these kinds of reactions
- Damage related to drug use
- Severe alcohol withdrawal
Your doctor may request additional tests to eliminate other potential causes of your symptoms. These tests may include:
- Chest X-ray
- Blood and urine tests
- Computed Tomography (CT) scan
- Lumbar puncture
Treatment
The intensity of your symptoms will determine how you are treated for serotonin syndrome.
- If your symptoms are mild, you might only need to see a doctor and cease taking the offending medicine.
- You might need to visit the hospital if your doctor is concerned about your symptoms. To ensure that your symptoms are getting better, your doctor could ask you to spend a few hours in the hospital.
- If you have severe serotonin syndrome, you will require hospitalization for intensive care.
The following treatments could be administered to you, depending on your symptoms:
- Muscle relaxants. Benzodiazepines can help manage agitation, seizures, and muscle rigidity. Examples of these drugs are lorazepam and diazepam.
- Serotonin-production blocking agents. Medication like cyproheptadine, which blocks the production of serotonin, can be helpful if other treatments aren’t working.
- Oxygen and intravenous fluids. The oxygen levels in your blood can be maintained by breathing through a mask, while fever and dehydration can be treated with intravenous fluids.
- Drugs that control heart rate and blood pressure. These could include nitroprusside or esmolol to lower elevated blood pressure or heart rate. Your doctor may prescribe phenylephrine or epinephrine if your blood pressure is too low.
- A machine, a breathing tube, and drugs to immobilize your muscles. If you have a high temperature, you could require this treatment.
Less severe forms of serotonin syndrome usually resolve within 24 to 72 hours after discontinuing medications that elevate serotonin levels. To alleviate the effects of excess serotonin already in your system, medication may be necessary. However, symptoms induced by certain antidepressants may persist for several weeks, as these medications have a longer duration of action compared to others that can cause serotonin syndrome.
