Serotonin Syndrome Treatments and Medications

Drugs such as selective serotonin reuptake inhibitors (SSRIs) have saved countless lives simply by increasing serotonin levels in the brain. Serotonin-increasing drugs have proliferated in the last few decades. However, when two or more of these drugs get used at the same time, they can raise serotonin levels to toxic levels, sending people to the emergency room. What is serotonin syndrome and how can it be avoided? Read on to learn more.

What is serotonin syndrome?

A rare condition, serotonin syndrome (or serotonin toxicity) is excessive serotonin levels in the body caused by serotonin-raising drugs, such as antidepressants. Similar to an overdose, serotonin syndrome can result from an increase in the dose of a serotonin-raising drug by taking two or more serotonin-raising drugs or dietary supplements or from deliberate self-poisoning.

Symptoms can come on very rapidly, anywhere from a few hours to 24 hours after taking a serotonin-raising drug. Most cases are mild and resolve in one to three days after the drug has been discontinued. Severe cases, however, require hospitalization and could be fatal.

Serotonin is one of a family of substances called neurotransmitters, chemicals that pass nerve signals between nerve cells. In the brain, serotonin plays a role in regulating mood, attention, appetite, body temperature, and sleep. Serotonin also helps regulate muscle movements in the digestive system and tighten blood vessels. It is also one of the many substances responsible for blood clotting.

Drugs that increase serotonin in the body are called serotonergic drugs. All the major classes of antidepressants increase serotonin at nerve junctions, restoring the neurotransmitter balance to give patients more control over their moods and thoughts. Because these drugs are widely used, antidepressants are almost always implicated in serotonin syndrome.

SSRIs (selective serotonin reuptake inhibitors), such as Prozac (fluoxetine), Paxil (paroxetine), Celexa (citalopram), or Zoloft (sertraline) are the most common culprits because they are so widely used. However, SNRIs (serotonin-norepinephrine reuptake inhibitors), such as Effexor (venlafaxine) and Cymbalta (duloxetine), and tricyclic antidepressants such as amitriptyline and nortriptyline, are also common sources of serotonin toxicity. However, life-threatening or prolonged cases of serotonin syndrome are more often related to the use of a class of antidepressants called monoamine oxidase inhibitors (MAOIs), such as Selegiline or Nardil (phenelzine).

Antidepressant medications are safe drugs, so serotonin toxicity most often occurs when the dose is increased or they are combined with other serotonergic drugs such as:

• Opioids

• Amphetamines

• Certain migraine drugs (most often, triptans)

• Dextromethorphan, a common over-the-counter cough suppressant (found in various cough and cold medications)

• Some types of nausea drugs, anticonvulsants, smoking cessation drugs (bupropion), and antibiotics (linezolid)

• Illicit drugs such as Ecstacy, fentanyl, LSD, or amphetamines

• Dietary supplements with tryptophan

• Herbal supplements that increase serotonin levels such as St. John’s wort or ginseng.

Serotonin syndrome is a rare condition. Most cases are mild and are never reported. In 2016, the Toxic Exposure Surveillance System reported 102 patients died in emergency room visits with serotonin syndrome related to SSRIs.

How is serotonin syndrome diagnosed?

No test can diagnose serotonin syndrome. Instead, healthcare professionals must make a clinical diagnosis based on the symptoms and a medical history. Because serotonin syndrome resembles other adverse drug reactions such as neuroleptic malignant syndrome, a complete drug history is critical. Lab tests, such as blood tests or urinalysis, are only used to rule out other possible conditions.

The only significant risk factor for serotonin syndrome is the use of serotonergic drugs, so the healthcare provider will concentrate on prescription and other drug use when taking a medical history, including the type of drugs, dosages, prescription changes, and dietary supplements.

The symptoms of serotonin syndrome involve changes in mental status (such as euphoria, agitation, or delirium), neuromuscular issues (such as tremors or muscle tightness), or derangements in autonomic functions (such as high blood pressure or excessive sweating).

For mild serotonin syndrome, the most common symptoms include fast heartbeat, mildly high blood pressure, excessive sweating (diaphoresis), shivering, muscle rigidity, spontaneous or inducible involuntary muscle contractions, dilated pupils, and overactive reflexes (hyperreflexia). There may or may not be a fever (hyperthermia). In many mild cases, the only noticeable symptom might be a slight tremor.

Patients with moderate serotonin syndrome will have a serious fever—at least 104—on top of these other symptoms. They will also have noticeable changes in mental status such as anxiety, restlessness, agitation, and rapid speech. Involuntary eye movements (ocular clonus) and bowel movement sounds are also signs of moderate serotonin syndrome.

Severe serotonin syndrome will have many of these symptoms along with a dangerously high fever—106 or more. Vital signs are often erratic, with big swings in heart rate and blood pressure. Mental status has often deteriorated to delirium, confusion, or the possibility of coma. Rigid muscles, seizures, and blood clotting throughout the body are common.

Serotonin syndrome treatment options

Serotonin syndrome is treated by discontinuing serotonergic drugs, stabilizing vital signs, and managing complications. Patients with severe symptoms may require hospitalization or even admission to an intensive care unit.

Medications

Mild cases of serotonin syndrome typically resolve in one to three days only by discontinuing serotonergic medications. Symptoms such as anxiety, tremors, and fever are brought under control with a drug from a class of sedatives called benzodiazepines. If symptoms do not resolve, a doctor may use drugs that block the action of serotonin. Blood pressure will be brought under control by short-acting blood pressure medications.

Hospitalization

Even mild cases will require at least six hours of monitoring in an emergency room or clinic. Severe serotonin syndrome will require hospital care or admission to an ICU. Sedation, blood pressure medications, serotonin blockers, IV fluids, oxygen, cooling, and vital signs monitoring are the standard therapy. For extremely high fever, a patient may also need to be sedated, put on a mechanical ventilator, and given muscle-paralyzing drugs.

Medications

There is no cure for serotonin syndrome. Even the most dangerous incidents of serotonin syndrome resolve relatively quickly when serotonin medications are withdrawn. Medications are only used to manage the symptoms and stabilize vital signs.

Benzodiazepines

Benzodiazepines such as diazepam and lorazepam are sedatives. They are the first-line medication to reduce agitation and stabilize vital signs for mild to moderate serotonin syndrome. In addition to calming the patient, benzodiazepines lower blood pressure, slow down the heart, relax muscles, and help reduce fever caused by increased muscle activity.

Serotonin blockers

Serotonin blockers are used if benzodiazepines fail to calm a patient down. While several medications block serotonin, the most effective drug is cyproheptadine, an antihistamine used to relieve allergy symptoms. In this situation, the drug acts like a serotonin antidote by attaching to serotonin receptors and blocking the action of serotonin. In addition to calming the patient, cyproheptadine relaxes muscles and significantly lowers high fevers.

Blood pressure medications

Dangerously high blood pressure caused by serotonin syndrome will be treated with short-acting antihypertensives (drugs that lower blood pressure) such as esmolol or nitroprusside.

Sympathomimetic agents

Low blood pressure caused by serotonin syndrome will be treated with sympathomimetic agents such as norepinephrine, epinephrine, or phenylephrine. These drugs both speed up the heart and cause blood vessels to constrict, increasing blood pressure.

Paralytic agents

In severe cases of serotonin syndrome, dangerously high fever is caused by excessive muscle contractions rather than the brain’s “thermostat.” For this reason, traditional fever medications (antipyretics) will not work. Instead, the muscle contractions causing the fever must be stopped. Patients will be hospitalized, sedated, put on a mechanical ventilator, and partially paralyzed with a neuromuscular blocker such as vecuronium.

Choosing the best medication

Mild cases of serotonin syndrome resolve when serotonergic drugs are discontinued. No medication treats or cures serotonin syndrome. Instead, medications are used to treat symptoms and stabilize vital signs. There is, then, no “best” medication for serotonin syndrome, only medications that best fit the patient’s symptoms and vital signs.

Save big on your prescriptions

with the free SingleCare app.

4.8 average rating

Text a link to get the app

Send

Best medications for serotonin syndrome