Serotonin Syndrome: Causes, Symptoms & Treatment

The hormone serotonin is popularly regarded as the happiness hormone par excellence: it lifts the mood and puts people in a good mood. But what happens when it is present in the body in a very large quantity? Then it not only damages our health, but in the worst case even puts our lives in danger. Serotonin syndrome is therefore a serious condition.

What is serotonin syndrome?

Serotonin syndrome is a syndrome that is associated with various symptoms. This disorder results from the accumulation of the hormone serotonin, which functions as both a tissue hormone and a neurotransmitter and has an influence on a wide variety of bodily functions. Serotonin is located as a neurotransmitter in the central as well as in the peripheral nervous system. There it takes on the task of activating many different receptors. As part of the central nervous system, it controls our attention and mood, for example, and is also responsible for regulating body heat. In the peripheral nervous system, it influences the movement of the gastrointestinal tract and the bronchial and skeletal muscles. In an appropriate amount, serotonin is therefore vital for the human organism. The term “serotonin syndrome” was coined by H. Sternbach, who first described the three typical symptoms of serotonin syndrome in 1991.

Causes

Serotonin syndrome is a disorder that develops as a result of a disruption of the central or peripheral serotonin receptors. According to Sternbach, the condition also occurs after administration of a drug that increases serotonin levels. For example, therapy with triptans or with antidepressants causes mild symptoms. And often, serotonin syndrome also results from the interaction of different drugs. If several serotonin-stimulating drugs are used in combination, the increased serotonin release can even have life-threatening effects. The interaction between serotonin-stimulating drugs and certain foods should also not be underestimated.

Symptoms, complaints, and signs

Serotonin syndrome can vary in severity in each patient. It can also occur in people of all ages. How bad the symptoms actually are may also be related to the drug that triggers it. There are a number of typical signs of serotonin syndrome. The symptoms are divided into three categories:

1. mental disturbances: Confusion, agitation, restlessness, disorientation and anxiety. 2. autonomic disorders: increased profuse sweating, chills, tachycardia (cardiac arrhythmia), hyperthermia (sharply rising body temperature), hypertension (high blood pressure), and diarrhea and vomiting. 3. neuromuscular disorders: involuntary and spasmodic muscle twitching, tremor (hyperactivity with tremor) and hyperreflexia. The above-mentioned signs of illness can appear just a few hours after taking a drug or a combination of drugs or increasing the dose. As a rule, serotonin syndrome becomes noticeable within 24 hours, and in about 60 percent of all patients even within six hours. And it is precisely this point that distinguishes serotonin syndrome from malignant neuroleptic syndrome, which is associated with very similar symptoms. However, in malignant neuroleptic syndrome, the first signs occur much more slowly and are not observed until a few days after taking the drug. In the worst case, serotonin syndrome can put the patient’s life in great danger: Severe cardiac arrhythmias, hyperthermia above 41 degrees Celsius, and hypertensive crises are life-threatening forms of serotonin syndrome that can cause cardiogenic shock.

Diagnosis and course of the disease

It is not uncommon for mild manifestations of serotonin syndrome to be overlooked – simply because the disease is not yet widely known and the symptoms are quite nonspecific. In addition, the symptoms are often not associated with the use of medication. Yet serotonin syndrome can be diagnosed quite well with the help of medication history. One method of identifying serotonin syndrome is called differential diagnosis, which involves ruling out malignant neuroleptic syndrome, malignant hyperthermia, poisoning, sepsis, meningitis, tetanus, and mental illnesses such as depression.

Complications

Serotonin syndrome can cause mental, autonomic, and neuromuscular disorders. For mental disorders, possible symptoms include anxiety and restlessness. The autonomic disorders include complications such as cardiac arrhythmias, gastrointestinal distress, and hypertension. Neuromuscular disorders are the most severe – spasmodic muscle twitching, tremor and hyperreflexia are among the complications. If the syndrome is not treated promptly, it can also lead to fever above 41 degrees Celsius, a sudden rise in blood pressure and other life-threatening complications. In extreme cases, the aforementioned symptoms trigger cardiogenic shock, which can lead to respiratory distress, pulmonary edema, and ultimately heart failure. As a result of severe symptoms, multiple organ failure may also occur, which is usually also life-threatening. Further complications can arise during treatment, either from surgical procedures such as percutaneous coronary intervention or the accompanying medications prescribed. Risks are mainly associated with thrombin inhibitors and anti-inflammatory drugs, which can cause additional damage to the already stressed cardiovascular system. When using a balloon pump, there is a risk of injuring the vessels. In addition, infections, wound healing problems and allergic reactions can occur, with further complications.

When should you see a doctor?

Serotonin syndrome should always be treated by a medical professional. As a rule, this disease cannot be cured on its own, so the affected person is always dependent on medical treatment. In order not to limit life expectancy, a doctor should be consulted at the first signs of this disease. A doctor should be consulted for serotonin syndrome if the affected person suffers from mental disorders. In this case, there are disturbances of orientation or inner restlessness. Furthermore, permanent vomiting or diarrhea can also indicate serotonin syndrome and must be examined by a doctor. Also permanent trembling in the hands often indicates the disease and requires a medical examination. In many cases, depression may also indicate serotonin syndrome. In the case of serotonin syndrome, the family doctor can be consulted. Further treatment is usually carried out by a specialist. Whether this will result in a complete cure cannot be universally predicted.

Treatment and therapy

To treat serotonin syndrome, the trigger must be addressed in the first place. That is, if a drug is to blame for the condition, then it must be discontinued immediately. Instead, the patient is prescribed another drug. At the same time, his state of health is closely monitored. This is the only way to stop the overproduction of serotonin. In mild cases, an improvement occurs within 24 hours. In addition, medication can also be administered to treat the symptoms. Thus, in a mild manifestation of the syndrome, lorazepam is mainly prescribed. This drug is used exclusively for general sedation. In moderate to severe disease, the physician administers cyproheptadine, for example, to inhibit the effect of serotonin in a non-specific manner. Autonomic disorders, however, are not easy to treat. This is the case, for example, when blood pressure suffers from severe fluctuations. And if even life-threatening symptoms such as hyperthermia, renal failure or aspiration occur, emergency measures are naturally used. Unlike fever, hyperthermia is not due to disturbed temperature regulation in the hypothalamus, but to uncontrolled increased activity of the muscles. Therefore, treatment with paracetamol makes no sense in this case. Agents with a long duration of action or a long half-life are particularly dangerous. They need several days to restore the full activity of the affected enzymes. Thus, the symptoms persist for several days to weeks after discontinuation of the trigger drug. Dangerous agents include fluoxetine, for example, which has a half-life of one week.

Prevention

If a patient tolerates an antidepressant particularly well, then the risk for serotonin syndrome is high. So it is advisable that he pay attention to any physical changes. In this way, the first signs of illness can be detected at an early stage and discussed with the doctor.The same also applies after increasing the dose of a drug. In addition, caution should also be exercised when self-medicating with preparations containing St. John’s wort extracts, dextromethorphan, or tryptophan, as these agents promote the production of serotonin.

Follow-up

Serotonin syndrome causes physical, neurologic, and psychological symptoms. Follow-up care is advisable to counteract symptoms even after treatment is completed. The syndrome should not occur again in the future. The quality of life of the affected person is the main focus. Serotonin syndrome can be caused by various factors. There is no generally valid trigger. The causative disease is treated with medication. During follow-up care, the physician reduces the dose until it is completely discontinued. He also checks to what extent the patient tolerates the medicine. The condition of the patient is recorded in regular check-ups. If the symptoms recur, treatment is resumed. Further examinations are necessary at the specialist’s discretion (differential diagnosis). Neurological symptoms are accompanied by convulsions or limb tremors. In severe cases, the respiratory muscles are affected. This situation is life-threatening for the affected person. Hospitalization is urgently required. Follow-up care takes place in the hospital. It is terminated when there is no longer any danger to life and the patient is allowed to leave the hospital again. There is a connection between serotonin syndrome and increased suicide risk. If there is an acute suicide risk, the rescue service must be called immediately. They provide first aid. If the danger persists, the affected person is admitted to hospital.

What you can do yourself

Since this disease can be fatal, it absolutely belongs to medical treatment. Spontaneous recovery is not possible. In addition, it is important to find out which medications triggered the syndrome in the patient. They must be discontinued or replaced. Only in this way can an improvement of the symptoms be achieved and a renewed increase in serotonin levels be prevented. For this purpose, it is necessary for the patient concerned to state which medications he or she has taken. This also applies if they were over-the-counter medications, such as St. John’s wort preparations. They also increase serotonin and may have contributed to a dangerous interaction. If patients with serotonin syndrome are not already undergoing psychotherapeutic treatment, they should start now at the latest. This can prevent future depression and thus enable patients to live without taking serotonin-increasing drugs. Lifestyle changes also have an antidepressant effect. Regular endurance sports, for example, regulates the metabolism and at the same time ensures a good mood. According to studies, a conscious, balanced diet also has a positive effect on existing depression and prevents it. Abstaining from stimulants such as nicotine and alcohol, as well as regular rest and sleep, also help patients to remain psychologically stable. Many people also benefit from self-help groups. Volunteer work also gives life new meaning.