How to Recognize the Signs and Symptoms of Serotonin Syndrome

Serotonin syndrome is a potentially life-threatening condition caused by elevated serotonin concentrations in your body from certain medications.

Serotonin is a type of chemical known as a neurotransmitter that communicates with nerve cells and has various functions throughout your body, primarily in your central nervous system and intestines.

In the right amounts, serotonin is necessary for important bodily functions, but when your body builds up too much, and your levels get too high, symptoms can range from unpleasant to severe. If it's left untreated, serotonin syndrome can potentially lead to death.

Serotonin Syndrome Symptoms

Symptoms of serotonin syndrome can be mild to severe indicating anything from a slight serotonin excess to a life-threatening imbalance. The most common symptoms include:

• Anxiety
• Confusion
• Dilated pupils
• Fever
• Flushing or paleness
• Headache
• High blood pressure
• Irregular heartbeat
• Muscle rigidity
• Poor coordination
• Profuse sweating
• Rapid breathing
• Restlessness
• Shivering
• Slow or fast pulse
• Sudden jerky or shock-like movements
• Tremor

If your condition becomes severe, it can turn into a life-threatening situation and may include signs like:

• High fever
• Losing consciousness
• Seizures
• Sudden swings in your blood pressure and/or pulse

SSRI Discontinuation Syndrome

It should be noted that some of the same symptoms listed above may also occur when you abruptly stop taking an antidepressant, or you taper it off too quickly. This is known as SSRI discontinuation syndrome.

Agitation, headaches, shock-like sensations, poor coordination, chills, and impaired concentration are characteristics common to both syndromes. Because of this risk, you must never stop taking your antidepressant abruptly without discussing it with your doctor.

Serotonin Syndrome Diagnosis

Because the symptoms are similar to many other issues, you won't be diagnosed with serotonin syndrome until every other possible diagnosis has been ruled out. This is mainly because serotonin syndrome has to be diagnosed purely on your symptoms, history, and your physical and neurological exam.

Other conditions that need to be ruled out include:

• Infections like meningitis and encephalitis
• Intoxication
• Neuroleptic malignant syndrome (NMS), is another drug-related disorder with some of the same symptoms as serotonin syndrome but results from antipsychotics (The biggest difference is that serotonin syndrome generally comes on quickly after starting the trigger medication.)
• Overdose of a substance like cocaine
• Reactions to other medications
• Withdrawal from alcohol or drugs

The tests your doctor may order to rule these conditions out include:

• Blood tests such as a complete blood count (CBC), blood cultures to test for infection, and other blood tests that check your electrolytes, screen for drugs and alcohol, and check your kidney, thyroid, and liver function
• Urine tests to screen for drugs and alcohol, as well as to look at your kidney function
• Computed tomography (CT) scan of your brain
• Electrocardiogram (ECT) to check your heart
• Lumbar puncture (spinal tap) to evaluate your spinal fluid
• Chest X-ray

While serotonin levels can be measured using a blood test, such tests cannot confirm whether or not a person has serotonin syndrome.

Serotonin Syndrome Causes

Serotonin syndrome, also known as serotonin toxicity, happens as the result of taking serotonergic drugs, which are medications that affect the level of serotonin in your body. It may be brought on by several different circumstances, including:

• Taking one serotonergic medication: It's unlikely that using one serotonergic medication by itself will cause serotonin syndrome, but it can happen in certain people who are sensitive to serotonin, especially when the dose is increased.
• Overdosing: You can end up with serotonin syndrome if you ingest too much of your serotonergic medication(s), whether an overdose is accidental or purposeful.
• Taking two serotonergic medications together: The most common cause of serotonin syndrome involves a person taking two (or more) serotonergic drugs at the same time, often without realizing it.

Medications Associated With Serotonin Syndrome

The medications that are most often associated with serotonin syndrome are antidepressants such as:

• Selective serotonin reuptake inhibitors (SSRIs) like Paxil (paroxetine), Prozac (fluoxetine), and Celexa (citalopram)
• Serotonin and norepinephrine reuptake inhibitors (SNRIs) like Cymbalta (duloxetine), Pristiq (desvenlafaxine), and Effexor (venlafaxine)
• Tricyclic antidepressants such as amitriptyline, Pamelor (nortriptyline), and Surmontil (trimipramine)
• Monoamine oxidase inhibitors (MAOIs) like Nardil (phenelzine) and Parnate (tranylcypromine)
• Atypical antidepressants like Wellbutrin (bupropion), which is also used for smoking cessation under the brand name Zyban

There are other medications that are also considered serotonergic drugs, though they may not be as well-known. Some examples of these include:

• Migraine medications called triptans such as Axert (almotriptan), Amerge (naratriptan), Imitrex (sumatriptan), and Maxalt (rizatriptan)
• Anticonvulsants like Tegretol (carbamazepine) and Depakene (valproic acid), which are used for migraines, epilepsy, and bipolar disorder
• Opioid pain medications such as codeine, Ultram (tramadol), Demerol (meperidine), Talwin (pentazocine), and Oxycontin (oxycodone)
• 5-HT3 receptor antagonists, which treat nausea, like Anzemet (dolasetron), granisetron, Zofran (ondansetron), and Aloxi (palonosetron)
• Reglan (metoclopramide), a prokinetic medication that's used to treat gastroesophageal reflux disease (GERD), diabetes, and sometimes to treat nausea in chemotherapy patients
• Over-the-counter cough and cold medications that contain dextromethorphan (DXM) like Children's Robitussin Cough Long-Acting, Vicks DayQuil Cough, Vicks Formula 44 Custom Care Dry Cough, Zicam Cough MAX, and many others
• Ergot derivatives, including Ergomar (ergotamine) for migraines and Methergine (methylergonovine) for uterine bleeding after childbirth
• A muscle relaxant called Amrix (cyclobenzaprine)
• Buspirone, a medication that's prescribed for anxiety disorders

Other substances and supplements that can contribute to serotonin syndrome include:

• St. John's Wort
• Illicit and recreational drugs such as cocaine, amphetamines, ecstasy, and LSD
• L-tryptophan, an over-the-counter amino acid supplement that people use to quit smoking, for mental health disorders, and to help athletic performance
• Lithobid (lithium), a mood stabilizer that's often used to treat bipolar disorder

All of these drugs and substances affect serotonin in some way. Some block nerve receptors; some block reuptake; some slow the breakdown of serotonin; and some increase the release of serotonin.

Risk Factors for Serotonin Syndrome

Your risk of developing serotonin syndrome goes up under the following circumstances.

You're Taking a New Medication or Dose

If you just started taking a serotonergic medication or you had your dose increased, you should watch for signs of serotonin syndrome. Some people's bodies are naturally slower than others at metabolizing serotonin, and this isn't something you or your doctor will know until you are on a drug that boosts serotonin.

You're Switching to a New Medication

If you're switching from an MAOI to another antidepressant or vice versa, be especially careful to follow your doctor's guidance. Almost all antidepressants contain a warning that you should wait for at least two weeks, and sometimes more, when you switch antidepressant types.

One of the main reasons for this is the danger that having both types of drugs in your system can lead to serotonin syndrome. Prozac (fluoxetine), in particular, takes several weeks to be flushed out of your body.

You're Taking More Than One Medication

Taking more than one serotonergic medication, supplement, or substance at the same time increases your risk of serotonin syndrome. For instance, you're on Wellbutrin for depression and you take an Imitrex (sumatriptan) for a migraine or you're taking Zoloft (sertraline) and you treat a cold with DayQuil (dextromethorphan).

Serotonin Syndrome Treatment

Once you've been diagnosed with serotonin syndrome, the first line of treatment is to discontinue all serotonergic drugs. Treatment may also include the use of medications to relieve symptoms or hospitalization to stabilize your condition.

Medication

Benzodiazepines like Valium (diazepam) or Ativan (lorazepam) may be helpful to relieve any muscular symptoms, and you may need supportive treatment like oxygen and intravenous (IV) fluids and stabilization of vital signs. Drugs that specifically act against serotonin, called serotonin antagonists, can potentially be useful.

Hospitalization

If your symptoms are worrisome, your doctor may have you hospitalized until you're stabilized. In cases where you're exhibiting signs of severe serotonin syndrome, you'll likely need to be hospitalized in the intensive care unit (ICU) until all your symptoms are gone.

For high fever, you may need to be sedated and given a medication that keeps you still (paralytic) to avoid any more damage to your muscles, in which case, you'll also have a breathing tube and ventilator.

How to Prevent Serotonin Syndrome

There are also steps you can take to prevent or minimize your risk of developing serotonin syndrome. 

• Be aware of the ingredients and actions of the medications and supplements you are taking
• Tell your doctor about all of the medications, supplements, and substances that you are taking
• Inform your doctor if you have a family member who has experienced serotonin syndrome
• Monitor your symptoms while taking serotonergic medication and alert your doctor if you experience sudden changes or any worrisome symptoms
• Seek medical attention if you think you are experiencing early symptoms of serotonin syndrome; getting help immediately may prevent symptoms from worsening
• Ensure that you are being monitored properly if you are taking an SSRI or SNRI along with migraine medication