How Long Does Serotonin Syndrome Last?

Medically reviewed by Lindsay Cook, PharmD

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are common antidepressants that boost the availability of serotonin.

Having too much serotonin in your body can cause a condition called serotonin syndrome (SS). SS is dangerous and can be life-threatening.

SS often requires medical intervention within six to 24 hours of symptoms appearing; however, the timeline can vary.

Once offending medications are stopped, SS typically resolves within one day, though this timeline depends on several variables and the specific medications involved. In mild cases, symptoms may go away within six hours.

Keep reading to learn more about the timeline of developing SS, its symptoms, causes, potential health risks, prognosis, and treatment options.

What Is Serotonin?

While varying different types of antidepressants exist, all are generally thought to work by changing the activity of certain neurotransmitters (chemical messengers) in the brain.

One such neurotransmitter that antidepressants target is serotonin.

Serotonin plays a vital role in maintaining numerous body functions. Serotonin helps with mood regulation and stabilization, memory, sleep, and learning through its action in the central nervous system (CNS).

SS can be life-threatening and is caused by medications that increase serotonin levels, like SSRIs and SNRIs.

What Causes SS?

SS occurs when your serotonin receptors are overstimulated, which can cause severe neurological problems and become life-threatening.

Medication changes, dose adjustments, or drug interactions can affect SS. It should be treated promptly to prevent serious consequences.

Medications or other substances that boost serotonin levels are called serotonergic. SS can occur when serotonin receptors in the brain and body are overstimulated.

In recent years, there has been a noticeable uptick in SS cases. This is partly due to the increasing use of prescription medications that affect serotonin levels and the growing awareness and education about SS.

Symptoms of SS

SS can look different in each person. It can start with mild symptoms and sometimes get very serious, with various symptoms.

SS symptoms fall into two different categories: autonomic dysfunction and neuromuscular excitation.

Symptoms of neuromuscular excitation involve overactivity of the signaling between nerves and muscles, causing unpredictable movements. This may present as seizures, muscle cramps, or tremors.

Symptoms of autonomic dysfunction involve hyperactivity of the autonomic nervous system.

The autonomic nervous system is responsible for maintaining your body’s vital functions; dysfunction of this system can lead to high blood pressure, irregular heartbeats, and fever.

Mild Symptoms

Mild symptoms of SS may include:

• Excessive sweating

• Diarrhea

• Headache

• Shivering or goosebumps

• Insomnia

Moderate Symptoms

Moderate symptoms of SS may include:

• Hypertension (high blood pressure)

• Overheating

• Tachycardia (rapid heartbeat)

• Muscle twitching

• Confusion

• Increased bowel sounds

• Dilated pupils

• Agitation

• Extreme alertness

Severe Symptoms

Severe symptoms can develop.

If not treated promptly, symptoms of SS can be life-threatening, such as:

• Fever

• Tremor

• Seizures

• Delirium

• Irregular heartbeat

• Severe muscle cramps

• Kidney failure

• Blood clots

• Loss of consciousness or coma

At-Risk Population(s)

SS develops because of medication changes, interactions between drugs, or overdose.

SS can affect anyone of any age taking a serotonergic medication, such as an antidepressant. SS may develop in people taking monoamine oxidase inhibitor (MAOI) drugs.

In addition, adults 65 years and older may be at an increased risk of developing SS because, on average, older adults take more medications.

Taking more medications increases the risk of drug interactions that affect the level of serotonin in the body, increasing the risk of SS.

If you think you might have symptoms of SS, it's crucial to see a healthcare provider immediately. In mild cases, stopping the medication causing the issue and receiving supportive care can help you recover quickly and easily.

If not addressed, continuing serotonergic medications can quickly turn a mild case into a severe one. In any case, you should consult a healthcare provider before stopping or changing your medications.

How Long Does SS Last?

SS typically begins within 24 hours of an increased exposure to a serotonergic agent, whether from a medication change, dose change, drug interaction, or overdose.

Most people feel the need to seek medical attention within six hours of symptom onset. In milder cases, however, it can take longer for symptoms to become concerning because they start slowly and aren't very severe at first.

In many cases, SS goes away 24 to 72 hours after the causative medication is stopped, but the timeline of SS will vary based on what medication you are taking.

Some medications may have an onset quicker than others, and some higher doses may be more likely to cause SS than lower doses. Some drug interactions may also be more severe than others, leading to significant variability in the timeline of symptoms.

SS may sometimes occur after a serotonergic medication is stopped.

One medication that may cause this is fluoxetine since this medication has a long half-life and is likely to remain in the body for weeks after the last dose.

Role of Medications in Causing SS

Many medications can change serotonin levels in your body, not just antidepressants.

Below is a table describing different drug classes that may lead to the development of SS. Note that this is not a complete list of medications that can contribute to SS:

Some over-the-counter (OTC) medications contain ingredients that can boost serotonin levels. For example, cough and cold medications, like Adult Tussin Cough (dextromethorphan/guaifenesin), a cough suppressant, can increase serotonin levels in the body.

Taking this medicine alongside serotonin-modulating drugs like antidepressants can cause elevated serotonin in the body and potentially SS.

Herbal supplements may also contribute to the development of SS. Some examples of herbal medicines that can be serotonergic include nutmeg, ginseng, Saint-John’s-wort, and Syrian rue.

Because of herb-drug interaction risks, it’s best to consult a pharmacist or provider before trying over-the-counter herbal remedies.

Treating SS

SS is treated in three key ways, which are:

• Stopping all serotonergic medications or supplements

• Supportive care to maintain stable blood pressure and heart rate, such as intravenous (IV) fluids, blood pressure-lowering medications, and medications to maintain normal heart rhythm

• Sedation with benzodiazepines (CNS depressants, used to treat various mood disorders)

More severe cases may require treatment with serotonin antagonists, which help reverse the serotonin overload.

Furthermore, cyproheptadine is a first-generation antihistamine commonly used to reverse SS. However, more evidence is needed to support its effectiveness for this purpose.

Severe fever and critical illness cases may require treatment with neuromuscular blocker medications and intubation to breathe and remain stable.

It is essential to seek medical attention when experiencing SS to prevent reaching higher or life-threatening severity.

Diagnosing SS

For someone to be diagnosed with SS, healthcare providers use a system called Hunter's criteria, in which people must present with at least one of the symptom descriptions listed in the criteria, along with taking a serotonergic medication.

Hunter Criteria include the following:

• Spontaneous clonus, which refers to involuntary muscle contractions

• Inducible clonus (muscle contractions) plus agitation or sweating

• Ocular clonus (rapid, side-to-side eye movements) plus agitation or sweating

• Tremor plus hyperreflexia (overactive reflexes)

• Hypertonia (stiff muscles) plus fever with ocular or inducible clonus

SS-Related Complications

Fortunately, SS generally has no long-term or lasting effects after it resolves. However, a mild case can become severe if you are not treated promptly.

Not treating SS, however, can cause severe complications, including seizures and difficulty breathing, which can lead to coma or death.

Likewise, irreversible organ damage may occur if not treated appropriately or promptly.

Prognosis & Prevention

Symptoms of SS often develop within six hours of an overdose (or other cause of increased serotonin exposure).

Early, milder symptoms may include excessive sweating, diarrhea, headache, shivering, or shaking.

These symptoms may worsen within the next few hours, leading to irregular heartbeat, high blood pressure, muscle twitching, uncontrollable eye movements, and fever.

If not treated promptly, symptoms can worsen, leading to coma, seizures, or even death. For best results, seek treatment as soon as you think you may be experiencing SS to avoid progressing to severe complications.

To help prevent SS from drug interactions, be sure to tell your healthcare provider about all medications you use, including prescription drugs, OTC medicines, and supplements, so they can check for drug interactions that may be harmful.

Be aware anytime your healthcare provider increases the dosage of your antidepressant or other serotonin-modulating medication.

If you think you may be developing SS, seek medical attention immediately.

Summary

SS is a potentially life-threatening complication resulting from increased serotonin levels from serotonin-modulating medications.

While this complication is rare, it is essential to seek immediate medical attention if you believe you are experiencing SS.

SS can be caused by changing a dose or medication of a serotonin-modulating drug, resulting from interactions between medications or an overdose.

SS often requires medical intervention within six to 24 hours of symptoms appearing; however, the timeline can vary. If treated promptly, most cases of SS resolve within 24 hours of diagnosis.

To protect yourself or your loved one, be aware of any unusual side effects that occur soon after a new medication is started or after an antidepressant dosage is increased.

Read the original article on Verywell Health.