Serotonin syndrome

from Wikipedia, the free encyclopedia
Classification according to ICD-10
T88.7 Unspecified undesirable side effect of a drug or drug
ICD-10 online (WHO version 2019)

The serotonin syndrome , also known as serotonergic syndrome , a complex of symptoms ('s symptoms ) caused by an accumulation of tissue hormone and neurotransmitter serotonin acting or serotonin-like substances are produced in parts of the body. Autonomous, neuromotor and cognitive disorders as well as behavioral changes are characteristic of this syndrome . It includes symptoms such as changes in mental state, restlessness, rapid involuntary muscle twitches, increased reflex readiness, sweating, chills and tremors . The serotonin syndrome is often the result of a drug interaction that can lead to an increase in serotonin activity and is observed in particular with the combined use of serotonergic drugs with MAO inhibitors .

Definition and diagnosis

The criteria for defining serotonin syndrome were first described by Sternbach in 1991. According to this, the diagnosis of serotonin syndrome requires the occurrence of at least three of the symptoms described by the author: either the symptoms occur as a result of the primary administration of a drug that can increase the serotonin level in the brain, then as a result of a further increase in the dose of such a drug or finally as a Result of the additional combination with another drug (of a different substance class), from which an increase in the serotonin level is also to be expected.

Symptoms of Serotonin Syndrome
autonomous vegetative symptoms
Pulse rise Increase in blood pressure
sweat "Feeling flu"
nausea (acute) vomiting
diarrhea a headache
rapid breathing Dilated pupil
Symptoms of central nervous excitation
Restlessness Akathisia
Hallucinations Hypomania
Disorders of consciousness Incoordination
neuromuscular symptoms
tremor increased reflexes
Myoclonus pathological reflexes
cramps Seizures

The symptoms described by Sternbach are now grouped into three groups of symptoms (see table on the right).

The serotonin syndrome z. B. explain paradoxical restlessness or even anxiety ( akathisia ), which sometimes at the beginning z. B. therapy with an antidepressant from the group of SSRIs , especially if such a drug is added too quickly. The appearance of suicidal thoughts has also been linked to serotonin syndrome.

Due to the frequent prescription of drugs from the SSRI group, there is a high likelihood of developing serotonin syndrome as a result of problematic interactions when combining these drugs with other drugs that can also affect serotonin levels. Such drugs include, for example, certain pain relievers such as tramadol , but also remedies for migraines or headaches such as triptans , i.e. drugs that are relatively often taken in addition to an SSRI by those affected with depressive symptoms.

Differential diagnosis

Diagnostically, the differentiation from the so-called neuroleptic malignant syndrome can be difficult. Because of the flu-like symptoms, the serotonin syndrome can also be misunderstood as a viral infection and, if central nervous symptoms occur, in particular as meningoencephalitis.

Mental illnesses - in particular depression with symptoms of anxiety - are also often associated with restlessness (agitation), which can manifest itself as vegetative-physical symptoms. The differentiation between a serotonin syndrome and such syndromes is therefore not always easy, even for the doctor.

In order to diagnose serotonin syndrome, in addition to a careful medical history, neuromuscular symptoms such as tremors and pathologically increased reflexes are the most important factors. The general increase in excitation of the muscles can ultimately lead to life-threatening conditions and even death by including the respiratory muscles.

causes

Serotonin syndrome is mostly a result of an interaction between drugs that affect the serotonin system. Symptoms of serotonin syndrome, which are mostly still relatively mild, can, however, be observed in individual cases under monotherapy with triptans , tricyclic and tetracyclic antidepressants , selective serotonin reuptake inhibitors or serotonin-noradrenaline reuptake inhibitors . The combined use of various medicinal substances, which synergistically increase their effect on the serotonin system , can lead to a life-threatening increase in these symptoms. These include, for example, interactions between drugs that block the re-uptake of serotonin from the synaptic cleft and those that inhibit the breakdown of serotonin via the enzyme monoamine oxidase type A. Another possible cause of serotonin syndrome is the combined use of serotoninergic drugs with drugs that inhibit the breakdown of serotonininergic drugs. These include interactions between some selective serotonin reuptake inhibitors and substances that inhibit the cytochrome P450 enzyme system responsible for their metabolism . Interactions between drugs and foods can also be causes of serotonin syndrome. Genetically, the active levels of drugs can also be increased in poor metabolizers of CYP2C19 and C2D6. As a result, the risk of developing serotonin syndrome is increased when using antidepressants.

At the molecular level, the serotonin syndrome is attributed to an uncalculated strong activation of central or peripheral serotonin receptors , in particular 5-HT 1 and 5-HT 2 .

Pharmacological mechanisms as possible causes of serotonin syndrome
mechanism Active ingredients
Increase in serotonin synthesis Tryptophan , 5-hydroxytryptophan
Increase in serotonin release MDMA , amphetamines , tramadol , nicotine
Inhibition of the reuptake of serotonin from the synaptic cleft Selective serotonin reuptake inhibitors (eg. As fluoxetine , fluvoxamine , sertraline , citalopram , escitalopram and paroxetine ), serotonin-norepinephrine reuptake inhibitor (z. B. venlafaxine ), tricyclic antidepressants (eg. As amitriptyline , clomipramine ), trazodone , nefazodone , Amphetamines, cocaine , dextromethorphan , pethidine and St. John's wort
Inhibition of the breakdown of serotonin MAO-A inhibitors (e.g. tranylcypromine and moclobemide ), linezolid
Stimulation of serotonin receptors Buspirone , triptans (e.g. sumatriptan )
Enhancement of the serotonin effects lithium
Inhibition of the breakdown of the above drugs CYP2D6 inhibitors (e.g. ritonavir ), CYP3A4 inhibitors (e.g. saquinavir , efavirenz , erythromycin , grapefruit juice )

treatment

When treating patients who develop serotonin syndrome, the focus is on eliminating its causes. The causative drugs are discontinued and the patients are monitored.

In mild cases, lorazepam is recommended for calming down. In moderate to severe cases, non-specific drugs that inhibit serotonin effects , such as cyproheptadine , can be used.

If signs of hyperthermia , disseminated intravascular coagulopathy , rhabdomyolysis , kidney failure or inhalation of the body's secretions ( aspiration ) occur, the patient must be closely monitored with additional emergency measures.

literature

  • S. Rossi (Ed.): Australian Medicines Handbook 2005 . Australian Medicines Handbook, Adelaide 2005, ISBN 0-9578521-9-3 .
  • P. Birmes, D. Coppin, L. Schmitt, D. Lauque: Serotonin syndrome: a brief review. In: CMAJ. Volume 168, No. 11, May 27, 2003, pp. 1439-1442. Review PMID 12771076 .
  • P. Schweikert-Wehner: Side effects of antidepressants Serotonin in excess. In: Pharmaceutical newspaper. Volume 106, No. 9, 2015, pp. 22-23.

Individual evidence

  1. ↑ Alphabetical directory for the ICD-10-WHO version 2019, volume 3. German Institute for Medical Documentation and Information (DIMDI), Cologne, 2019, p. 801
  2. ^ H. Sternbach: The serotonin syndrome . In: Am J Psychiatry . tape 148 , no. 6 , June 1991, pp. 705-713 , PMID 2035713 .
  3. ↑ Serotonin syndrome with mirtazapine monotherapy . (PDF; 138 kB). In: Switzerland Med Forum. 5, 2005, pp. 859-861.
  4. ^ OP Soldin, JM Tonning: Serotonin syndrome associated with triptan monotherapy . In: N. Engl. J. Med. Band 358 , no. May 20 , 2008, pp. 2185-2186 , doi : 10.1056 / NEJMc0706410 , PMID 18480219 .
  5. ^ PI Rosebush, P. Margetts, MF Mazurek: Serotonin syndrome as a result of clomipramine monotherapy . In: J Clin Psychopharmacol . tape 19 , no. 3 , June 1999, p. 285-287 , PMID 10350043 .
  6. ↑ JL Hernández, FJ Ramos, J. Infante, M. Rebollo, J. González-Macías: Severe serotonin syndrome induced by mirtazapine monotherapy . In: Ann Pharmacother . tape 36 , no. 4 , April 2002, p. 641-643 , PMID 11918514 .
  7. ↑ EE Ubogu, B. Katirji: Mirtazapine-induced serotonin syndrome . In: Clin Neuropharmacol . tape 26 , no. 2 , 2003, p. 54-57 , PMID 12671522 .
  8. ↑ V. Chechani: Serotonin syndrome presenting as hypotonic coma and apnea: potentially fatal complications of selective serotonin receptor inhibitor therapy . In: Crit. Care Med. Volume 30 , no. 2 , February 2002, p. 473-476 , PMID 11889332 .
  9. ↑ S. Ozdemir, I. Yalug, AT Aker: Serotonin syndrome associated with sertraline monotherapy at therapeutic doses . In: Prog. Neuropsychopharmacol. Biol. Psychiatry . tape 32 , no. 3 , April 2008, p. 897-898 , doi : 10.1016 / j.pnpbp.2007.11.018 .
  10. ↑ JJ Pan, WW Shen: Serotonin syndrome induced by low-dose venlafaxine . In: Ann Pharmacother . tape 37 , no. 2 , February 2003, p. 209-211 , PMID 12549949 .
  11. ↑ a b K. E. DeSilva, DB Le Flore, BJ Marston, D. Rimland: Serotonin syndrome in HIV-infected individuals receiving antiretroviral therapy and fluoxetine . In: AIDS . tape 15 , no. 10 , July 2001, p. 1281-1285 , PMID 11426073 .
  12. ↑ P. Schweikert-Wehner: Serotonin in excess . Ed .: Pharmaceutical newspaper. tape 160 , no. 9 . Govi Verlag, Eschborn February 26, 2015, p. 22-23 .
  13. ↑ a b c H, Sternbach: Serotonin syndrome: How to avoid, identify, & treat dangerous drug interactions . In: Current Psychiatry . tape 2 , no. 5 , 2003 ( mdedge.com ).
  14. ↑ Rahul R. Bhalsinge, Anita A. Barde, Pratibha S. Worlikar, Manasi V. Limaye, Mrunal P. Dhole: Effect of nicotine on serotonin (5-HT) levels in brain of depressed rats . In: International Journal of Basic & Clinical Pharmacology . tape 6 , no. 4 , March 25, 2017, ISSN  2279-0780 , p. 938-941 , doi : 10.18203 / 2319-2003.ijbcp20171108 ( ijbcp.com [accessed April 26, 2020]).
  15. ↑ Mutschler et al .: drug effects. 10th edition, p. 768.
  16. ^ TM Brown, BP Skop, TR Mareth: Pathophysiology and management of the serotonin syndrome . In: Ann Pharmacother . tape 30 , no. 5 , May 1996, pp. 527-533 , PMID 8740336 .