Serotonin syndrome

Serotonin syndrome is a rare but potentially life-threatening condition ^[1]. Symptoms can occur when there is too much of the chemical serotonin in your body. This condition usually occurs as a consequence of taking too much of a serotonin-increasing drug, or a combination of drugs that increase serotonin levels.

What is serotonin syndrome?

An uncommon but potentially serious condition, serotonin syndrome occurs when the levels of serotonin in your brain become too high. This can happen if you overdose on one or more different types of psychiatric medication ^[2]. Symptoms can occur when people take too much of one, or a combination, of the following:

• Selective serotonin reuptake inhibitors (SSRIs)
• Serotonin and noradrenaline/norepinephrine reuptake inhibitors (SNRIs)
• Other antidepressantmedications, including monoamine oxidase inhibitors (MAOIs)
• A mood stabilizer such as lithium (often prescribed to people experiencing bipolar disorder)
• St John’s wort
• Migraine medications (‘triptans’)
• Street drugs such as cocaine and ecstasy

What are the symptoms of serotonin syndrome?

Serotonin syndrome symptoms range from milder to more severe. Some of the symptoms are similar to side effects or withdrawal effects that you might experience from taking or coming off antidepressants.

Symptoms include:

• Agitation
• Confusion
• Diarrhea
• Muscle twitching
• Shivering
• Sweating

If you experience these symptoms, seek immediate advice from your doctor.

Symptoms of severe serotonin syndrome include:

• A high temperature (38C or above)
• Seizures (fits)
• Irregular heartbeat (arrhythmia)
• Loss of consciousness

If you or someone you know experiences symptoms of severe serotonin syndrome, seek emergency medical treatment immediately by dialing 911. ^[2]

What causes serotonin syndrome?

Symptoms can occur as a result of having too much serotonin in the body, usually because of taking a combination of serotonin-increasing drugs.

SSRIs and SNRIs

SSRIs are widely prescribed to treat depression and other mental health problems because they are some of the best-tolerated and safest psychiatric medications available. SSRIs include fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa), escitalopram (Lexapro) and vilazodone (Viibryd).

SNRIs work in a similar way to SSRIs except that they also affect the amount of noradrenaline (also known as norepinephrine) available within the body, in addition to serotonin. Commonly prescribed SNRIs in the US include venlafaxine (Effexor), desvenlafaxine (Pristiq), duloxetine (Cymbalta), milnacipran (Savella) and sibutramine (Meridia)).

Both SSRIs and SNRIs have the potential to cause serotonin syndrome if not used correctly, as both types of medication can increase the levels of serotonin in the brain which can then trigger the condition.

MAOIs

Monamine oxidase inhibitors (MAOIs) were developed in the 1950s and are still used to treat depression and anxiety, but normally only if SSRIs and other antidepressants haven’t worked. Those prescribed MAOIs must consume a careful diet due to the potential for the drug to interact with certain foods ^[3].

In the US, the following four types of MAOIs have been approved by the Food and Drug Administration (FDA) to treat depression:

• Isocarboxazid (Marplan)
• Phenelzine (Nardil)
• Selegiline (Emsam)
• Tranylcypromine (Parnate)

Like SSRIs and SNRIs, MAOIs can sometimes cause levels of serotonin in the brain to become too high, which can result in serotonin syndrome.

Lithium

Lithium is a powerful mineral that occurs naturally in the environment. It is used as a mood stabilizer and is often prescribed to people experiencing symptoms of bipolar disorder. Normally it is prescribed in one of two forms:

• Lithium carbonate in tablet form (also known by trade names Camcolit, Liskonum and Priadel)
• Lithium citrate in liquid form (also known by trade names Li-liquid and Priadel).^[4]

Lithium is known to increase the release of serotonin in the brain, which could lead to serotonin syndrom in rare cases.

Causes of serotonin syndrome – St John’s wort

St John’s wort (‘Hibericum perforatum’) is an over-the-counter herbal supplement used to treat mental health problems, particularly mild to moderate depression. St John’s wort has significant drug interactions with many common prescription medicications. Like SSRIs and SNRIs, it is thought to increase the amount of serotonin available in the body, which can lead to serotonin syndrome, especially when used in conjunction with similar types of medication. ^[5]

Triptans

Triptans are a type of medication commonly prescribed for migraines and cluster headaches. They include the following drugs (with brand names in parentheses):

• Almotriptan (Axert)
• Eletriptan (Relpax)
• Frovatriptan (Frova)
• Naratriptan (Amerge)
• Rizatriptan (Maxalt)
• Sumatriptan (Imitrex)
• Zolmitriptan (Zomig)

Again, triptans are thought to interact with certain serotonin receptors in the brain, which could theoretically lead to serotonin syndrome.

Illegal drugs and other medications

Some research suggests a link between an increased risk of serotonin syndrome and recreational drugs including cocaine ^[6] and ecstasy. ^[7] In addition to these types of illicit drugs, there are some other drugs that can increase serotonin levels in the body, including appetite suppressants, analgesics, sedatives, antipsychotics, anxiolytics, and anti-nausea drugs. ^[8] 

Any drug that can cause the brain to produce higher levels of serotonin can potentially lead to serotonin syndrome, especially when used at the same time as other drugs or medications.

Can you prevent serotonin syndrome?

Serotonin syndrome is largely avoidable ^[6]. Speaking to your doctor thoroughly before starting any medication is always a good idea. This should include letting them know if you drink alcohol or use street drugs, if you are pregnant or planning to become pregnant, and what – if any – other medication you currently take – especially if this includes any of those mentioned above.

Always read the label and the enclosed patient information leaflet supplied with your medication before you begin taking it. If forgetting to take your medication is a problem for you, and could result in you taking more than your specified dose, think about using a system, such as a pill box with days of the week on it, or setting up a reminder on your phone or other device.

Serotonin syndrome diagnosis

Unfortunately, there is no single test available to diagnose serotonin syndrome. Clinicians usually diagnose the condition by ruling out other causes of your symptoms, given many other conditions have symptoms similar to those of serotonin syndrome.

Typically, your doctor will start by asking you about your symptoms, medical history, and what types of medication(s) you’re taking. Your doctor will also give you a physical examination, which normally involves:

• Measuring levels of any medications you’re taking
• Checking for signs of infection
• Checking body functions that may be affected by serotonin syndrome

Your doctor may conduct additional tests to rule out other possibilities, such as:

• Blood and urine tests to establish levels of serotonin in the body
• Chest X-ray to look at the effect on organs
• Computerized tomography (CT) scan
• Spinal tap (lumbar puncture)

Diagnosis of serotonin syndrome is clinical and will often be based on the Hunter Serotonin Toxicity Criteria (HSTC) which helps doctors identify symptoms, including by looking at serotonin levels and other physical manifestations, such as clonus (muscle reflexes). ^[8]

Serotonin syndrome treatment

Treatment will depend on the severity of symptoms and the levels and toxicity of serotonin present in the body.

If you have mild symptoms, treating serotonin syndrome will involve:

• Visiting the doctor and, with supportivecare, stopping taking the medication or medications associated with the increased serotonin

Severe symptoms could require a visit to the hospital for intensive treatment.

Depending on the type and severity of your symptoms, your doctor might offer:

• Serotonin receptor antagonists – drugs that reduce serotonin levels by blocking its production, such as cyproheptadine or chlorpromazine (severe cases only)
• Benzodiazepines, such as diazepam, to relieve anxiety, agitation, and muscle stiffness.
• Assessment of airways, breathing,and circulation. An oxygen mask may be used to help maintain oxygen levels in your
• Intravenous (IV) fluids to treat dehydration and fever.
• Esmolol (Brevibloc) or nitroprusside (Nitropress) to reduce a high heart rate or high blood pressure. Conversely phenylephrine (Vazculep) or epinephrine for low blood pressure
• Rapid cooling if you have hyperthermia (temperature of over 38.5 degrees C)

Milder forms of serotonin syndrome usually go away within 1-3 days of discontinuing medications that increase serotonin. You may need to take medications to block the effects of serotonin already in your system.

However, symptoms of serotonin syndrome caused by certain antidepressants could take several weeks to go away completely because they remain in your system longer than other medications that can cause serotonin syndrome. ^[9]

Serotonin syndrome complications

Unless recognized and treated early, serotonin syndrome can lead to seizures, shock, and even death. ^[10]

Given the potential severity of symptoms and the relative lack of awareness, it has been suggested that the public, and especially younger people, need to be better educated about the dangers of taking street drugs such as cocaine and ecstasy alongside commonly prescribed SSRI antidepressants ^[7].

It’s always worth talking to your doctor or healthcare provider whenever you are prescribed new medication about potential side effects and any potential interactions your new medication could have with existing drugs you are taking. Make sure you read the label and patient information leaflet and speak to your doctor if you’re concerned.