Definition
The serotonin syndrome, also called serotoninergic syndrome, is a life-threatening condition caused by an excess of the messenger substance serotonin. This life-threatening excess is caused by an overdose of medication or an unfavorable combination of different drugs. Serotonin syndrome leads to symptoms such as fever, muscular hyperactivity and psychiatric changes. The most important differential diagnosis is the malignant neuroleptic syndrome.
Causes
A serotonin syndrome does not develop by itself. It is the result of an overdose of medication, or an unfavorable combination of different drugs. The excess of serotonin may be intentional, for example with the intention of hurting yourself, or accidentally as part of a doctor’s prescription or self-medication.
In most cases, there is a risk of serotonin syndrome in therapy with antidepressants, as these increase the concentration of serotonin. If only one such drug (monotherapy) is taken, there is usually no risk of serotonin syndrome. However, if several drugs are taken at the same time, they can influence each other (drug interaction) and thus lead to a dangerous excess of serotonin.
The trigger is usually the combination of the drug trancylpromine, which belongs to the class of monoamine oxidase inhibitors, with other antidepressants (e.g. citalopram, venlafaxine, clomipramine etc.). The drug trancylpromine inhibits the breakdown of serotonin and also belongs to the class of antidepressants. A serotonin syndrome can also occur when switching from trancylpromine to another antidepressant if a two-week treatment break is not observed between the two drugs.
This is because it takes about two weeks until the effect of the trancylpromine has completely disappeared. Other medications that, in combination with each other, can pose a risk of serotonin syndrome are opioid analgesics (tramadol, pethidine, fentanyl, methadone), the cough suppressant dextrometorphan and medications for nausea, such as ondansetron and granisetron. What these drugs have in common is that they increase serotonin levels in some way.
This does not mean that they should never be used together, but they need to be carefully weighed and dosed precisely to minimize the risks. Furthermore, drugs like ecstasy, cocaine and LSD, especially in combination with antidepressants, can lead to a life-threatening serotonin syndrome. Also the combination of the reserve antibiotic Linezolid and antidepressants is considered dangerous and should be avoided.
For a long time there was also a warning against the combination of antidepressants with the triptans, which are often used for migraine. However, the risk is now considered to be rather low with good medical care. Citalopram is a very commonly prescribed antidepressant that is classified as a serotonin reuptake inhibitor (SSRI).
It increases serotonin levels by inhibiting the uptake of serotonin into the cell. Apart from depression, it is also used in other mental illnesses such as anxiety disorders and panic disorders. When taking citalopram it should be noted that the simultaneous intake of so-called monoamine oxidase inhibitors is strictly forbidden.
These include the active ingredients trancylpromine and moclobemide. Citalopram may be used at the earliest two weeks after stopping trancylpromine and at the earliest one day after treatment with moclobemide. Otherwise there is a risk of serotonin syndrome, as these active ingredients also increase the concentration of serotonin.
Triptans are drugs that are used to treat migraine. Although they do not increase the concentration of serotonin itself, they act on an important serotonin receptor. In this way they produce typical effects of serotonin.
They are also known as serotonin agonists. For a long time, a very cautious attitude prevailed when combining triptans with antidepressants. In the meantime, however, the risk of developing serotonin syndrome with this combination has been estimated to be rather low.
Patients taking a combination of triptans and antidepressants must regularly consult their treating physician about side effects and current dosage so that the therapy is well monitored. The consumption of alcohol per se cannot cause serotonin syndrome. However, regular consumption of alcohol increases the risk of drug interactions and side effects.Therefore, especially patients who take several drugs are advised not to consume alcohol.
Particularly in the case of psychological disorders, such as depression or anxiety disorders, alcohol worsens the condition of those affected and interferes with the success of the therapy. There is a high risk of interactions especially when several drugs are taken at the same time. Since the exact effects of alcohol in combination with medication cannot be predicted, consumption should be avoided.
The risk of serotonin syndrome only increases further with additional alcohol consumption. The main problem, however, is that doctors prescribe therapy with antidepressants and other drugs that affect serotonin levels, provided that no additional drugs, medication or alcohol is consumed on their own authority. If this is the case, however, the consequences cannot be accurately predicted and, above all, cannot be well absorbed.
The patient puts himself in incalculable danger. St. John’s wort is a herbal medicine that is used in the treatment of mild to moderate depression. Its effect is however very controversial in studies.
The main active ingredient of St. John’s wort is hyperforin, which probably leads to an increase in the norepinephrine and serotonin levels, among other things. Basically, the effect of St. John’s wort is very weak, so the risk of serotonin syndrome is low. It becomes problematic, however, if other drugs are taken apart from St. John’s wort, which increase the serotonin level.
These include in particular other antidepressants, but also certain opioid analgesics, migraine medication or some drugs for nausea. Since St. John’s wort is freely available and therefore does not need to be prescribed by a doctor, there is a risk that patients take it without consulting a doctor and are unaware of interactions with their medication. For this reason, St. John’s wort should always be taken only after consultation with a doctor who is familiar with the rest of the medication. This will enable him or her to assess the risk of serotonin syndrome. Information about side effects of St. John’s wort can be found in our article Side effects of St. John’s wort.
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