Serotonin syndrome

Definition

Serotonin syndrome occurs when you take medications that cause high levels of the chemical serotonin to accumulate in your body. Serotonin syndrome can occur when you increase the dose of such a drug or add a new drug to your regimen. Certain illicit drugs and dietary supplements are also associated with serotonin syndrome.

Serotonin is a chemical your body produces that's needed for your nerve cells and brain to function. But too much serotonin causes symptoms that can range from mild — shivering and diarrhea — to severe — muscle rigidity, fever and seizures. Severe serotonin syndrome can be fatal if not treated.

Milder forms of serotonin syndrome may go away within a day of stopping the medications causing symptoms and, sometimes, taking drugs that block serotonin.

Symptoms

Serotonin syndrome symptoms typically occur within several hours of taking a new drug or increasing the dose of a drug you're already taking. Signs and symptoms include:

• Agitation or restlessness
• Confusion
• Rapid heart rate and high blood pressure
• Dilated pupils
• Loss of muscle coordination or twitching muscles
• Heavy sweating
• Diarrhea
• Headache
• Shivering
• Goose bumps

Severe serotonin syndrome can be life-threatening. Signs and symptoms include:

• High fever
• Seizures
• Irregular heartbeat
• Unconsciousness

When to see a doctor
If you suspect you might have serotonin syndrome after starting a new drug or increasing the dose of a drug you're already taking, call your doctor right away or go to the emergency room. If you have severe or rapidly worsening symptoms, seek emergency treatment immediately.

Causes

Excessive accumulation of serotonin in your body creates the symptoms of serotonin syndrome. Under normal circumstances, nerve cells in your brain and spinal cord (central nervous system) produce serotonin that helps regulate your attention, behavior and body temperature. Other nerve cells in your body, primarily in your intestines, also produce serotonin. In these other areas, serotonin plays a role in regulating your digestive process, blood flow and breathing.

Although it's possible that taking just one drug that increases serotonin levels can cause serotonin syndrome in susceptible individuals, it occurs most often when you combine certain medications. For example, serotonin syndrome may occur if you take an antidepressant with a migraine medication. A common cause of serotonin syndrome is intentional overdose of antidepressant medications.

A number of over-the-counter and prescription drugs may be associated with serotonin syndrome, especially antidepressants. Illicit drugs and dietary supplements also may be associated with the condition. These drugs and supplements include:

• Selective serotonin reuptake inhibitors (SSRIs), antidepressants such as citalopram (Celexa), fluoxetine (Prozac, Sarafem), fluvoxamine, paroxetine (Paxil) and sertraline (Zoloft)
• Serotonin and norepinephrine reuptake inhibitors (SNRIs), antidepressants such as trazodone and venlafaxine (Effexor)
• Bupropion (Wellbutrin, Zyban), an antidepressant and tobacco-addiction medication
• Tricyclic antidepressants, such as amitriptyline and nortriptyline (Pamelor)
• Monoamine oxidase inhibitors (MAOIs), antidepressants such as isocarboxazid (Marplan) and phenelzine (Nardil)
• Anti-migraine medications such as triptans (Axert, Amerge, Imitrex), carbamazepine (Tegretol) and valproic acid (Depakene)
• Pain medications such as cyclobenzaprine (Flexeril), fentanyl (Duragesic), meperidine (Demerol) and tramadol (Ultram)
• Lithium (Lithobid), a mood stabilizer
• Illicit drugs, including LSD, Ecstasy, cocaine and amphetamines
• Herbal supplements, including St. John's wort and ginseng
• Over-the-counter cough and cold medications containing dextromethorphan (Delsym, Robitussin DM, others)
• Anti-nausea medications such as granisetron (Kytril), metoclopramide (Reglan) and ondansetron (Zofran)
• Linezolid (Zyvox), an antibiotic
• Ritonavir (Norvir), an anti-retroviral medication used to treat HIV/AIDS

Risk factors

Some people are more susceptible to the drugs and supplements that cause serotonin syndrome than are others, but the condition can occur in anyone.

You're at increased risk of serotonin syndrome if:

• You recently started taking or increased the dose of a medication known to increase serotonin levels
• You take more than one drug known to increase serotonin levels
• You take herbal supplements known to increase serotonin levels
• You use an illicit drug known to increase serotonin levels

Complications

Serotonin syndrome generally doesn't cause any problems once serotonin levels are back to normal. But if left untreated, severe serotonin syndrome can lead to unconsciousness and death.

Preparing for your appointment

Because serotonin syndrome can be a life-threatening condition, seek emergency treatment if you have worsening or severe symptoms.

If your symptoms aren't severe, you're likely to start by seeing your family doctor or a general practitioner. Here's some information to help you get ready for your appointment and to know what to expect from your doctor.

What you can do

• Be aware of any pre-appointment steps you need to take. When you make the appointment, be sure to ask if there's anything you need to do in advance, such as quitting any of the current medications or supplements you take.
• Write down any symptoms you're experiencing, including any that may seem unrelated to the reason for which you scheduled the appointment.
• Write down key personal information, including any major stresses or recent life changes.
• Make a list of all medications, as well as any vitamins or supplements you're taking.
• Take a family member or friend along, if possible. Sometimes it can be difficult to soak up all the information during an appointment. Someone who accompanies you may remember something that you missed or forgot.
• Write down questions to ask your doctor.

Preparing a list of questions will help you make the most of your time with your doctor. For symptoms you think may be caused by serotonin syndrome, some basic questions to ask your doctor include:

• Is serotonin syndrome most likely causing my symptoms, or could it be something else?
• Other than the most likely cause, what are other possible causes of my symptoms?
• What kinds of tests do I need?
• What is the best course of action?
• What are the alternatives to the primary approach that you're suggesting?
• I have other health conditions. How can I best manage them together?
• Can I still take the medications I've been prescribed, or will I need to change them or change the dose?
• Are there any restrictions that I need to follow, such as avoiding certain drugs or supplements?

Don't hesitate to ask your doctor any other questions you have.

What to expect from your doctor
Your doctor is likely to ask you a number of questions, such as:

• When did you begin experiencing symptoms?
• Have your symptoms been continuous or occasional?
• How severe are your symptoms?
• What prescription and over-the-counter medications do you take?
• Do you use any illicit drugs?
• Do you take any dietary supplements?

Tests and diagnosis

No single test can confirm a serotonin syndrome diagnosis. Your doctor will diagnose the condition by ruling out other possibilities.

Your doctor will likely begin by asking about your medical history and any medications you're taking. To make sure your symptoms are caused by serotonin syndrome and not something else, your doctor may use tests to:

• Measure levels of any drugs you're using
• Check your thyroid hormone level
• Check body functions that may be affected by serotonin syndrome

A number of conditions can cause symptoms similar to those of serotonin syndrome. Minor symptoms can be caused by numerous conditions. Causes of moderate and severe symptoms include:

• Anticholinergic syndrome, malignant hyperthermia and neuroleptic malignant syndrome, serious conditions caused by certain medications
• An overdose of cocaine, amphetamines or an MAOI, a type of drug for depression
• Certain thyroid conditions
• Withdrawal from alcohol or heroin

Treatments and drugs

Treatment of serotonin syndrome depends on the severity of your symptoms.

• If your symptoms are minor, a visit to the doctor and stopping the medication causing the problem may be enough.
• If you have symptoms that concern your doctor, you may need to go to the hospital. Your doctor may have you stay in the hospital for several hours to make sure you're OK.
• If you have severe serotonin syndrome, you'll need intensive treatment in a hospital.

Depending on your symptoms, you may receive the following treatments:

• Muscle relaxants. Benzodiazepines, such as diazepam (Valium) or lorazepam (Ativan), can help control agitation, seizures and muscle stiffness.
• Serotonin-production blocking agents. If other treatments aren't working, medications such as cyproheptadine can help by blocking serotonin production.
• Oxygen and intravenous (IV) fluids. Breathing oxygen through a mask helps maintain normal oxygen levels in your blood, and IV fluids are used to treat dehydration and fever.
• Drugs that control heart rate and blood pressure. These may include esmolol (Brevibloc) or nitroprusside (Nitropress), to reduce a high heart rate or high blood pressure. If your blood pressure is too low, your doctor may give you phenylephrine (Neo-Synephrine) or epinephrine.
• A breathing tube and machine and medication to paralyze your muscles. These may be necessary if you have a high fever.

Milder forms of serotonin syndrome usually go away within 24 hours of stopping medications that increase serotonin, and by taking medications to block the effects of serotonin already in your system if they're needed. However, symptoms of serotonin syndrome caused by some antidepressants could take several weeks to go away completely. These medications remain in your system longer than do other medications that can cause serotonin syndrome.

Prevention

Taking more than one serotonin-related medication may increase your risk of serotonin syndrome. This can be especially true if you're taking a serotonin reuptake inhibitor or a serotonin and norepinephrine reuptake inhibitor. Talk to your doctor about possible risks. Don't stop taking any such medications on your own. If your doctor prescribes a new medication, make sure he or she knows about all the other medications you're taking — especially if you receive prescriptions from more than one doctor.

If you and your doctor decide the benefits of combining certain serotonin-level-affecting drugs outweigh the risks, be alert to the possibility of serotonin syndrome.