Introduction 

“Too much of a good thing” - is too much happiness dangerous to our health? 

Serotonin: commonly known as the ‘happiness hormone’, is a chemical in the brain which plays a role in regulating our mood, sleep, perception, aggression and attention.¹ It can be released when we laugh at a movie, socialise, or exercise.

However, some individuals don’t produce enough serotonin.² This can be because of genetic or lifestyle factors which cause a chemical imbalance in the brain. If a continuous low mood and loss of interest/pleasure persist for a couple of weeks, this may lead to a diagnosis of depression.³ 

Although it is widely recognised that low serotonin causes depression, anxiety and panic disorder, not many people are aware too much serotonin can also be detrimental to us. 

Read this article to find out more about serotonin syndrome, how it can occur, signs to watch out for, and how to prevent this condition from happening to you. 

What is serotonin syndrome?

Serotonin syndrome, also referred to as serotonin toxicity is a potentially life-threatening drug-induced condition caused by too much serotonin accumulating in the brain. 

This condition can arise when taking two different types of drugs that increase serotonin, such as taking an antidepressant alongside a migraine medication or overdosing on one serotonin-elevating drug. There are also some lesser-known causes of serotonin syndrome, such as illicit drug use.⁴ 

The condition usually occurs within hours of taking a new drug or increasing the dose. In milder forms, symptoms can subside in a couple of days after stopping the suspected medication. 

However, if untreated, serotonin syndrome can cause multi-organ failure and subsequently death, either due to high fever or seizure. Most symptoms present themselves within 24 hours of taking a drug. Nevertheless, symptoms can often go unnoticed.

Below are the symptoms to watch out for when taking serotonin-elevating medication.

Mild symptoms

• High blood pressure
• Confusion 
• Rapid heart rate 
• Headache 
• Shivering
• Insomnia 
• Restlessness 
• Dilated pupils 
• Twitching muscles 
• Diarrhoea 

Severe symptoms

• Loss of consciousness 
• Seizure 
• High fever (above 38℃)
• Irregular heartbeat 
• Tremor 

Causes of serotonin syndrome

Antidepressant medication

The most commonly prescribed antidepressants are SSRIs (selective serotonin reuptake inhibitors). Other drugs include SNRIs (selective noradrenaline reuptake inhibitors) and MAOIs (monoamine oxidase reuptake inhibitors). 

SSRIs work by increasing levels of serotonin in the brain. Serotonin transmits signals between brain cells, so when it's unavailable in the required amount, the drug blocks its reabsorption (reuptake) into the neuron. This keeps more serotonin available in the brain for further transmission between cells.⁵ 

The most common SSRIs are Citalopram and Fluoxetine (Prozac). SNRIs act the same way but act on the hormone noradrenaline with serotonin.

On the other hand, MAOIs block an enzyme called monoamine oxidase which removes serotonin from the brain, keeping more serotonin around for transmission. Researchers estimate that 15% of SSRI overdoses lead to mild symptoms, and SSRIs used in conjunction with MAOIs pose the greatest risk for serotonin syndrome.⁶ 

Migraine medication

Medications used to treat/prevent migraines are called ‘triptans’ (e.g. Sumatriptan). These can interact directly with some serotonin receptors. Taking these medications together can particularly increase the risk of serotonin syndrome.

As migraines are more common in people with anxiety and depression than in the general population, those who use antidepressants must treat both conditions with care and may need more education and awareness of serotonin syndrome.⁷ 

Other medications to treat migraines such as anticonvulsants can also stimulate an increase of serotonin. However, developing serotonin syndrome from the use of migraine medication is quite rare. 

Herbal supplements 

Although perceived as harmless and beneficial to our health, some herbal supplements can increase the risk of serotonin syndrome. For example, the supplement St. John’s wort a yellow flower used in traditional European medicine, teas and tablets contains an active ingredient called hyperforin. Hyperforin inhibits serotonin uptake, meaning more serotonin remains in the brain for transmission. 

People use St. John’s wort to treat depression and menopausal symptoms (although its effectiveness remains unclear). If it is used alongside antidepressants, serotonin may become too elevated and the individual may develop mild symptoms of serotonin syndrome. 

Another herbal supplement associated with an increased risk of serotonin syndrome is ginseng. Ginseng is a Korean plant sold in capsule form and can be found in local health stores and pharmacies. 

It is traditionally used to protect the nervous system and is believed to be useful for preventing depression by boosting energy and reducing stress.⁸ Similarly to St. John’s wort, ginseng increases serotonin levels in multiple areas of the brain and should not be casually used in individuals on antidepressant medication. 

Illicit drugs 

Street drugs that many of us may have heard of are known to increase serotonin levels. MDMA (a central nervous system stimulant) is most closely associated with serotonin syndrome. Moreover, recreational drugs have recently been linked to the condition; for example, LSD (a hallucinogenic drug) and the stimulant cocaine. MDMA causes a greater release of serotonin than normal and causes mood-elevating effects.⁹ 

Serotonin syndrome can occur when taking illicit drugs as mild symptoms like dilated pupils and hyperactivity can mask themselves as ‘part of the experience’ of taking such substances recreationally. Symptoms typically occur within a few hours of taking the drug. Medical attention should be sought immediately if the more severe symptoms are apparent. 

Typically not deemed a ‘drug’, alcohol has been suggested in recent studies to interact with antidepressants when used together. This can result in serotonin syndrome in those who usually feel energetic and happy when drinking, rather than calm and sleepy.¹⁰ 

How to prevent serotonin syndrome 

Medication management 

Taking multiple medications which elevate serotonin can be a major risk factor for serotonin syndrome. Knowing what medications you are taking and their individual effects is essential, especially with substances like herbal supplements and any other remedies which are not prescribed. 

Additionally, be sure to check with your GP or healthcare provider what is suitable to use when taking antidepressants, and be honest about the at-home medications or supplements used. 

How to treat serotonin syndrome 

There is no specific test used to diagnose serotonin syndrome. However, if the condition is suspected, assessments such as blood counts, electrolyte counts, drug screening, CT scans, and checking symptoms and bodily functions can help to rule out other possibilities. 

The treatment of serotonin syndrome is dependent on the severity of symptoms. Most mild cases of serotonin syndrome resolve in 24-72 hours simply by stopping the medication which is causing the problem, but a visit to a doctor is nevertheless recommended. In the case of severe serotonin syndrome, intensive treatment in the hospital is required to see if symptoms will alleviate over time.

When severe, serotonin syndrome can be treated by using muscle relaxants like benzodiazepines (Valium) to control seizures and muscle stiffness. Moreover, oxygen and intravenous fluids can support recovery, and drugs controlling heart rate and blood pressure can also be administered. If symptoms do not subside, serotonin-production-blocking agents can be administered.¹³ 

Summary 

Serotonin syndrome is not widely known among the general population despite the early intervention and management required for this potentially life-threatening disorder. 

Especially for those taking antidepressants, any additional medicines and remedies taken should be carefully examined. However, any drug altering the levels of serotonin in the brain should be used with caution to mitigate the potential risks. 

Serotonin syndrome especially affects those taking antidepressant medication because antidepressants remain in our system longer than other medications. As research into serotonin syndrome continues advancing, increased awareness is needed about the warning symptoms and prevention strategies.