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'''Serotonin syndrome''' is a potentially life-threatening drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs. | '''Serotonin syndrome''' is a potentially life-threatening drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs. | ||
Excess serotonin activity produces a spectrum of specific symptoms including cognitive, autonomic, and somatic effects.<ref>{{cite journal | vauthors=((Boyer, E. W.)), ((Shannon, M.)) | journal=New England Journal of Medicine | title=The Serotonin Syndrome | volume=352 | issue=11 | pages=1112–1120 | date=17 March 2005 | url=https://doi.org/10.1056/NEJMra041867 | issn=0028-4793 | doi=10.1056/NEJMra041867}}</ref> The symptoms may range from barely perceptible to fatal. | |||
Numerous drugs and drug combinations have been reported to produce serotonin syndrome. It is a medical emergency; if suspected, one should immediately seek emergency care. | |||
==Signs and symptoms== | ==Signs and symptoms== | ||
Symptom onset is usually rapid, often occurring within minutes and includes the following: | Symptom onset is usually rapid, often occurring within minutes, and includes the following: | ||
*'''Cognitive:''' Headache, agitation, hypomania, confusion, anxiety, hallucinations, coma | *'''Cognitive:''' Headache, agitation, hypomania, confusion, anxiety, hallucinations, coma | ||
*''' | *'''Autonomous:''' Shivering, sweating, hyperthermia, hypertension, tachycardia, nausea, diarrhea | ||
*''' | *'''Somatic:''' Twitching, tremors | ||
==Pathophysiology== | ==Pathophysiology== | ||
[[Serotonin]] is a [[neurotransmitter]] involved in | [[Serotonin]] is a [[neurotransmitter]] involved in many aspects of the body, including mood regulation (where it is believed to be involved in depression, anxiety, aggression, mania), appetite, digestion, sleeping, memory, libido, pain, and potentially migraines.<ref>{{cite journal | vauthors=((Jonnakuty, C.)), ((Gragnoli, C.)) | journal=Journal of Cellular Physiology | title=What do we know about serotonin? | volume=217 | issue=2 | pages=301–306 | date= November 2008 | url=https://onlinelibrary.wiley.com/doi/10.1002/jcp.21533 | issn=00219541 | doi=10.1002/jcp.21533}}</ref> In humans, the effects of excess serotonin were first noted in 1960 in patients receiving a [[MAOI]] and tryptophan in combination.<ref>{{cite journal | vauthors=((Oates, J. A.)), ((Sjoerdsma, A.)) | journal=Neurology | title=Neurologic effects of tryptophan in patients receiving a monoamine oxidase inhibitor | volume=10 | issue=12 | pages=1076–1076 | date=1 December 1960 | url=https://www.neurology.org/lookup/doi/10.1212/WNL.10.12.1076 | issn=0028-3878 | doi=10.1212/WNL.10.12.1076}}</ref> <p>The syndrome is caused by an unregulatable excess of serotonin in the central nervous system. Other [[neurotransmitters]] may also be affected as a result of serotonin syndrome; [[Cholinergics|cholinergic]], [[Dopamine|dopaminergic]], [[Glutamate|glutamatergic]], [[Noradrenaline|noradrenergic]], and [[GABA|GABA-]][[GABA|ergic]] receptors have all been shown to be influenced by [[serotonin]].<ref>{{cite journal | vauthors=((Brown, T. M.)), ((Skop, B. P.)), ((Mareth, T. R.)) | journal=Annals of Pharmacotherapy | title=Pathophysiology and Management of the Serotonin Syndrome | volume=30 | issue=5 | pages=527–533 | date= May 1996 | url=http://journals.sagepub.com/doi/10.1177/106002809603000517 | issn=1060-0280 | doi=10.1177/106002809603000517}}</ref> | ||
==Causes== | ==Causes== | ||
A large number of medications (either alone in high dose or in combination) can produce serotonin syndrome. In recent years, the serotonin system has become a target of many types of drugs such as painkillers (tramadol), anti-anxiety medications (buspirone) and anti-psychotics (aripiprazole) as well as the obvious anti-depressant medications (fluoxetine). With the increasing use of serotonin receptors as targets for a wide range of medication, it is becoming harder to predict medication's pharmacological profile and whether or not it has the potential to cause serotonin syndrome. | A large number of medications (either alone in high dose{{notetag|Several reports exist claiming serotonin syndrome to have been triggered by tramadol alone, at therapeutic or moderate doses.<ref name="VizcaychipiWalker2007">{{cite journal|last1=Vizcaychipi|first1=M.P.|last2=Walker|first2=S.|last3=Palazzo|first3=M.|title=Serotonin syndrome triggered by tramadol|journal=British Journal of Anaesthesia|volume=99|issue=6|year=2007|pages=919|issn=00070912|doi=10.1093/bja/aem325}}</ref><ref name="KitsonCarr2005">{{cite journal|last1=Kitson|first1=R.|last2=Carr|first2=B.|title=Tramadol and severe serotonin syndrome|journal=Anaesthesia|volume=60|issue=9|year=2005|pages=934–935|issn=0003-2409|doi=10.1111/j.1365-2044.2005.04345.x}}</ref><ref name="MousaviAminiahidashti2016">{{cite journal|last1=Mousavi|first1=SeyedJaber|last2=Aminiahidashti|first2=Hamed|last3=Shafiee|first3=Sajjad|last4=Hajiaghaei|first4=Gholamhossein|title=Tramadol Pill Alone May Cause Serotonin Syndrome|journal=Chinese Medical Journal|volume=129|issue=7|year=2016|pages=877|issn=0366-6999|doi=10.4103/0366-6999.178957}}</ref>}} or in combination) can produce serotonin syndrome. In recent years, the serotonin system has become a target of many types of drugs such as painkillers (tramadol), anti-anxiety medications (buspirone) and anti-psychotics (aripiprazole) as well as the obvious anti-depressant medications (fluoxetine). <p>Also, a common [[NMDA receptor antagonist]] in cough syrups, ([[dextromethorphan]]) has the risk of causing serotonin syndrome at high doses. With the increasing use of serotonin receptors as targets for a wide range of medication, it is becoming harder to predict medication's pharmacological profile and whether or not it has the potential to cause serotonin syndrome. | ||
{| class="wikitable" | {| class="wikitable" | ||
|- | |- | ||
| Line 22: | Line 26: | ||
|- | |- | ||
|[[Opioid]]s | |[[Opioid]]s | ||
|[[Tramadol]], tapentadol<ref>Grond, S., | |[[Tramadol]], tapentadol<ref>{{cite journal | vauthors=((Grond, S.)), ((Sablotzki, A.)) | journal=Clinical Pharmacokinetics | title=Clinical Pharmacology of Tramadol: | volume=43 | issue=13 | pages=879–923 | date= 2004 | url=http://link.springer.com/10.2165/00003088-200443130-00004 | issn=0312-5963 | doi=10.2165/00003088-200443130-00004}}</ref>, [[pethidine]], [[fentanyl]], pentazocine, [[buprenorphine]], [[oxycodone]]<ref>{{cite journal | vauthors=((Song, H.-K.)) | journal=Pain Physician | title=Serotonin syndrome with perioperative oxycodone and pregabalin | volume=16 | issue=5 | pages=E632-633 | date= October 2013 | issn=2150-1149}}</ref>, [[hydrocodone]], levorphanol, levopethorphan, propoxyphene, [[methadone]]<ref>{{cite journal | vauthors=((Codd, E. E.)), ((Shank, R. P.)), ((Schupsky, J. J.)), ((Raffa, R. B.)) | journal=Journal of Pharmacology and Experimental Therapeutics | title=Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception. | volume=274 | issue=3 | pages=1263–1270 | date=1 September 1995 | url=https://jpet.aspetjournals.org/content/274/3/1263 | issn=0022-3565}}</ref> | ||
</ref>, pethidine, [[fentanyl]], pentazocine, [[buprenorphine]], [[oxycodone]]<ref>Song, H.-K. | |||
</ref>, [[hydrocodone]], levorphanol, levopethorphan, propoxyphene, methadone<ref>Codd, E. E., Shank, R. P., Schupsky, J. J., | |||
|- | |- | ||
|CNS [[stimulant]]s | |CNS [[stimulant]]s | ||
|[[MDMA]], [[MDA]], phentermine, diethylpropion, [[amphetamine]] | |[[MDMA]], [[MDA]], phentermine, diethylpropion, [[amphetamine]], [[methamphetamine]], sibutramine, [[methylphenidate]], dexmethylphenidate, [[cocaine]], [[DXM|dextromethorphan]], [[aMT]] | ||
|- | |- | ||
|[[5-HT receptor|5-HT<sub>1</sub>]] agonists | |[[5-HT receptor|5-HT<sub>1</sub>]] agonists | ||
| Line 33: | Line 35: | ||
|- | |- | ||
|[[Psychedelics]] | |[[Psychedelics]] | ||
|[[5-MeO-DiPT | |[[5-MeO-DiPT]], [[2C-T-7]] | ||
|- | |- | ||
|[[Herbs]] | |[[Naturally occurring sources|Herbs]] | ||
|[[St. John's Wort]], [[Harmala alkaloids|syrian rue]], panax ginseng, [[nutmeg]], yohimbe | |[[St. John's Wort]], [[Harmala alkaloids|syrian rue]], panax ginseng, [[nutmeg]], yohimbe | ||
|- | |- | ||
|Others | |Others | ||
|[[Tryptophan]], L-Dopa, valproate, buspirone, lithium, linezolid, 5-hydroxytryptophan, chlorpheniramine, risperidone, olanzapine, ondansetron, granisetron, metoclopramide, ritonavir, [[gabapentin]], [[pregabalin]]<ref>Rao, M. L., Clarenbach, P., Vahlensieck, M., | |[[Tryptophan]], L-Dopa, valproate, buspirone, lithium, linezolid, 5-hydroxytryptophan, chlorpheniramine, risperidone, olanzapine, ondansetron, granisetron, metoclopramide, ritonavir, [[gabapentin]], [[pregabalin]]<ref>{{cite journal | vauthors=((Rao, M. L.)), ((Clarenbach, P.)), ((Vahlensieck, M.)), ((Krätzschmar, S.)) | journal=Journal of Neural Transmission | title=Gabapentin augments whole blood serotonin in healthy young men | volume=73 | issue=2 | pages=129–134 | date= June 1988 | url=http://link.springer.com/10.1007/BF01243384 | issn=0300-9564 | doi=10.1007/BF01243384}}</ref> | ||
|} | |} | ||
==Diagnosis and treatment== | ==Diagnosis and treatment== | ||
Diagnosis of serotonin syndrome includes observing the symptoms | Diagnosis of serotonin syndrome includes observing the symptoms exhibited and a thorough investigation of the patient's history. The syndrome has a characteristic picture but can be mistaken for other illnesses in some people, particularly those with neuroleptic malignant syndrome. No laboratory tests can currently confirm the diagnosis. | ||
Treatment consists of discontinuing medications which may contribute, and (in moderate to severe cases) administering a serotonin [[antagonist]]. An important side treatment includes controlling agitation with [[benzodiazepine]] [[sedation]]. | Treatment consists of discontinuing medications which may contribute, and (in moderate to severe cases) administering a serotonin [[antagonist]]. An important side treatment includes controlling agitation with [[benzodiazepine]] [[sedation]]. | ||
==See also== | ==See also== | ||
*[[Responsible use]] | *[[Responsible use]] | ||
*[[Serotonin]] | *[[Serotonin]] | ||
| Line 52: | Line 56: | ||
*[[Tramadol]] | *[[Tramadol]] | ||
*[[MDMA]] | *[[MDMA]] | ||
==Notes== | |||
{{notefoot}} | |||
==External links== | |||
*[https://en.wikipedia.org/wiki/Serotonin_syndrome Serotonin syndrome (Wikipedia)] | |||
==References== | ==References== | ||
<references /> | |||
{{Template:Responsible use2}} | |||
{{#set:Featured=true}} | |||
Latest revision as of 23:57, 2 May 2025
Serotonin syndrome is a potentially life-threatening drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, overdose of particular drugs, or the recreational use of certain drugs.
Excess serotonin activity produces a spectrum of specific symptoms including cognitive, autonomic, and somatic effects.[1] The symptoms may range from barely perceptible to fatal.
Numerous drugs and drug combinations have been reported to produce serotonin syndrome. It is a medical emergency; if suspected, one should immediately seek emergency care.
Signs and symptoms
Symptom onset is usually rapid, often occurring within minutes, and includes the following:
- Cognitive: Headache, agitation, hypomania, confusion, anxiety, hallucinations, coma
- Autonomous: Shivering, sweating, hyperthermia, hypertension, tachycardia, nausea, diarrhea
- Somatic: Twitching, tremors
Pathophysiology
Serotonin is a neurotransmitter involved in many aspects of the body, including mood regulation (where it is believed to be involved in depression, anxiety, aggression, mania), appetite, digestion, sleeping, memory, libido, pain, and potentially migraines.[2] In humans, the effects of excess serotonin were first noted in 1960 in patients receiving a MAOI and tryptophan in combination.[3]
The syndrome is caused by an unregulatable excess of serotonin in the central nervous system. Other neurotransmitters may also be affected as a result of serotonin syndrome; cholinergic, dopaminergic, glutamatergic, noradrenergic, and GABA-ergic receptors have all been shown to be influenced by serotonin.[4]
Causes
A large number of medications (either alone in high dose[note 1] or in combination) can produce serotonin syndrome. In recent years, the serotonin system has become a target of many types of drugs such as painkillers (tramadol), anti-anxiety medications (buspirone) and anti-psychotics (aripiprazole) as well as the obvious anti-depressant medications (fluoxetine).
Also, a common NMDA receptor antagonist in cough syrups, (dextromethorphan) has the risk of causing serotonin syndrome at high doses. With the increasing use of serotonin receptors as targets for a wide range of medication, it is becoming harder to predict medication's pharmacological profile and whether or not it has the potential to cause serotonin syndrome.
| Class | Drugs |
|---|---|
| Antidepressants | MAOIs, TCAs, SSRIs, SNRIs, bupropion, nefazodone, trazodone, mirtazapine |
| Opioids | Tramadol, tapentadol[8], pethidine, fentanyl, pentazocine, buprenorphine, oxycodone[9], hydrocodone, levorphanol, levopethorphan, propoxyphene, methadone[10] |
| CNS stimulants | MDMA, MDA, phentermine, diethylpropion, amphetamine, methamphetamine, sibutramine, methylphenidate, dexmethylphenidate, cocaine, dextromethorphan, aMT |
| 5-HT1 agonists | Triptans |
| Psychedelics | 5-MeO-DiPT, 2C-T-7 |
| Herbs | St. John's Wort, syrian rue, panax ginseng, nutmeg, yohimbe |
| Others | Tryptophan, L-Dopa, valproate, buspirone, lithium, linezolid, 5-hydroxytryptophan, chlorpheniramine, risperidone, olanzapine, ondansetron, granisetron, metoclopramide, ritonavir, gabapentin, pregabalin[11] |
Diagnosis and treatment
Diagnosis of serotonin syndrome includes observing the symptoms exhibited and a thorough investigation of the patient's history. The syndrome has a characteristic picture but can be mistaken for other illnesses in some people, particularly those with neuroleptic malignant syndrome. No laboratory tests can currently confirm the diagnosis.
Treatment consists of discontinuing medications which may contribute, and (in moderate to severe cases) administering a serotonin antagonist. An important side treatment includes controlling agitation with benzodiazepine sedation.
See also
Notes
External links
References
- ↑ Boyer, E. W., Shannon, M. (17 March 2005). "The Serotonin Syndrome". New England Journal of Medicine. 352 (11): 1112–1120. doi:10.1056/NEJMra041867. ISSN 0028-4793.
- ↑ Jonnakuty, C., Gragnoli, C. (November 2008). "What do we know about serotonin?". Journal of Cellular Physiology. 217 (2): 301–306. doi:10.1002/jcp.21533. ISSN 0021-9541.
- ↑ Oates, J. A., Sjoerdsma, A. (1 December 1960). "Neurologic effects of tryptophan in patients receiving a monoamine oxidase inhibitor". Neurology. 10 (12): 1076–1076. doi:10.1212/WNL.10.12.1076. ISSN 0028-3878.
- ↑ Brown, T. M., Skop, B. P., Mareth, T. R. (May 1996). "Pathophysiology and Management of the Serotonin Syndrome". Annals of Pharmacotherapy. 30 (5): 527–533. doi:10.1177/106002809603000517. ISSN 1060-0280.
- ↑ Vizcaychipi, M.P.; Walker, S.; Palazzo, M. (2007). "Serotonin syndrome triggered by tramadol". British Journal of Anaesthesia. 99 (6): 919. doi:10.1093/bja/aem325. ISSN 0007-0912.
- ↑ Kitson, R.; Carr, B. (2005). "Tramadol and severe serotonin syndrome". Anaesthesia. 60 (9): 934–935. doi:10.1111/j.1365-2044.2005.04345.x. ISSN 0003-2409.
- ↑ Mousavi, SeyedJaber; Aminiahidashti, Hamed; Shafiee, Sajjad; Hajiaghaei, Gholamhossein (2016). "Tramadol Pill Alone May Cause Serotonin Syndrome". Chinese Medical Journal. 129 (7): 877. doi:10.4103/0366-6999.178957. ISSN 0366-6999.
- ↑ Grond, S., Sablotzki, A. (2004). "Clinical Pharmacology of Tramadol:". Clinical Pharmacokinetics. 43 (13): 879–923. doi:10.2165/00003088-200443130-00004. ISSN 0312-5963.
- ↑ Song, H.-K. (October 2013). "Serotonin syndrome with perioperative oxycodone and pregabalin". Pain Physician. 16 (5): E632–633. ISSN 2150-1149.
- ↑ Codd, E. E., Shank, R. P., Schupsky, J. J., Raffa, R. B. (1 September 1995). "Serotonin and norepinephrine uptake inhibiting activity of centrally acting analgesics: structural determinants and role in antinociception". Journal of Pharmacology and Experimental Therapeutics. 274 (3): 1263–1270. ISSN 0022-3565.
- ↑ Rao, M. L., Clarenbach, P., Vahlensieck, M., Krätzschmar, S. (June 1988). "Gabapentin augments whole blood serotonin in healthy young men". Journal of Neural Transmission. 73 (2): 129–134. doi:10.1007/BF01243384. ISSN 0300-9564.
