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Serotonin syndrome, also hyperserotonemia and serotonergic syndrome, is a hyperserotonergic state, that is an excess of 5-HT (serotonin) in the central nervous system. It is usually associated with high doses of serotonergic drugs, when combinations of serotonergic agents are used together, or when antidepressants are changed without an adequate washout period between drugs.
Less frequently it can also be caused by moderate dosage of a single serotonergeric drug,Gill M, LoVecchio F, Selden B. Serotonin syndrome in a child after a single dose of fluvoxamine. Ann Emerg Med. 1999 Apr;33(4):457-9.Tomaselli G, Modestin J. Repetition of serotonin syndrome after reexposure to SSRI--a case report. Pharmacopsychiatry. 2004 Sep;37(5):236-8. or in combination with non-serotonergeric drugs such as oxycodone,Karunatilake H, Buckley NA. Serotonin syndrome induced by fluvoxamine and oxycodone. Ann Pharmacother. 2006 Jan;40(1):155-7. Epub 2005 Dec 20. erythromycin,Lee DO, Lee CD. Serotonin Syndrome in a Child Associated with Erythromycin. Pharmacotherapy. 1999 Jul;19(7):894-6. or St. John's Wort.Dannawi M. Possible serotonin syndrome after combination of buspirone and St John's Wort. J Psychopharmacol. 2002 Dec;16(4):401.
Serotonin syndrome is rare, but it is a serious, potentially life-threatening medical condition. However there is no lab test for the condition, so diagnosis is by symptom observation. It may go unrecognized because it is often mistaken for a viral illness, anxiety, neurological disorder or worsening psychiatric condition.Fennell J, Hussain M. Serotonin syndrome:case report and current concepts. Ir Med J. 2005 May;98(5):143-4. Clinicians must differentiate between serotonin syndrome and neuroleptic malignant syndrome, which has similar symptoms. Patients taking serotonergic drugs and who have sudden onset of the below symptoms should immediately seek medical care.
Signs and symptoms
Symptoms may be classed into three groups:
- Cognitive effects: mental confusion, hypomania, agitation, headache, coma.
- Autonomic effects: shivering, sweating, fever, hypertension, tachycardia, nausea, diarrhea.
- Somatic effects: myoclonus/clonus (muscle twitching), hyperreflexia, tremor.
Insomnia, sleep disruption, and unrefreshing sleep are also reported symptoms, as well as itching and hives.
Drugs which may contribute
| Class | Drugs |
|---|---|
| antidepressants | MAOIs, TCAs, SSRIs, mirtazapine, venlafaxine, St John's Wort |
| opioids | tramadol, pethidine, |
| CNS stimulants | phentermine, diethylpropion, amphetamines, sibutramine |
| 5-HT1 agonists | triptans |
| illicit drugs | methylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (LSD), cocaine |
| others | selegiline, tryptophan, buspirone, lithium, linezolid, dextromethorphan (DXM), 5-HTP, chlorpheniramine |
| Reference: Rossi, 2005Rossi S, editor. Australian Medicines Handbook 2005. Adelaide: Australian Medicines Handbook; 2005. ISBN 0-9578521-9-3; National Prescribing Service, 2005http://www.nps.org.au/site.php?content=/html/ppr.php&ppr=/resources/Prescribing_Practice_Reviews/ppr32 accessed 16/jul/2006 | |
The combination of MAOIs and other serotonin agonists or precursors poses a particularly severe risk of a life-threatening serotonin syndrome episode. Many MAOIs inhibit monoamine oxidase irreversibly, so that the enzyme cannot function until it has been replaced by the body, which can take at least two weeks. A dangerous serotonin syndrome reaction can occur unless serotonin agonists and even serotonin precursors such as foods containing tryptophan are strictly avoided until the monoamine oxidase has been replaced.
Treatment
There is no antidote to the condition itself, but emergency medical clinicians can administer cyproheptadine or methysergide to control the symptoms.Sporer KA. The serotonin syndrome: implicated drugs, pathophysiology and management. Drug Saf 1995;13:94–104. Doing so is important as the symptoms can in severe cases be potentially life threatening.
If the symptoms are not severe or life threatening, optimal treatment consists of discontinuation of the offending medication or medications, offering supportive measures, and waiting for the symptoms to resolve. If the offending medication is discontinued, the condition will often resolve on its own within 24 hours.Prator KA. Serotonin syndrome. Journal of Neuroscience Nursing. 2006 Apr;38(2):102-5.Jaunay E, et al. Serotonin syndrome. Which treatment and when? Nouv Presse Med. 2001 Nov 17;30(34):1695-700
Neuroleptic malignant syndrome and serotonergic syndrome
The clinical features of neuroleptic malignant syndrome (NMS) and serotonergic syndrome are very similar. This can make differentiating them very difficult.
Features, classically present in NMS, that are useful for differentiating the two syndromes are Full Free Text.:
- Fever
- Muscle rigidity
References
Serotonin-Syndrom | Síndrome serotoninérgico | セロトニン症候群 | Serotnin-Syndromet | Zespół serotoninowy | Serotoniinisyndrooma
"Serotonin syndrome"