Citizendia
Your Ad Here

Serotonin syndrome
Classification and external resources
Serotonin
ICD-9 333.99
DiseasesDB 30044
eMedicine ped/2786 
MeSH C21.613.276.720

Serotonin syndrome is a rare, but potentially life-threatening adverse drug reaction that results from intentional self-poisoning, therapeutic drug use, inadvertent interactions between drugs, or the recreational use of certain drugs. Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify Diseases The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. The Diseases Database is a free Website that provides information about the relationships between medical conditions Symptoms, and Medications. eMedicine is an online clinical medical knowledge base that was founded in 1996 by Scott Plantz and Richard Lavely two medical doctors Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books It is an iatrogenic (i. The terms iatrogenesis and iatrogenic artifact refer to adverse effects or complications caused by or resulting from medical treatment or advice e. caused by medical treatment) toxidrome (from toxic + syndrome). In Medicine, a toxidrome ( Portmanteau of Toxic and Syndrome) is a syndrome caused by a dangerous level of Toxins in the body Toxicity is the degree to which a substance is able to damage an exposed organism In Medicine and Psychology, the term syndrome refers to the association of several clinically recognizable features signs (observed by a physician It is most commonly referred to as serotonin syndrome, but the terms serotonin toxicity or serotonin toxidrome are more accurate as they reflect the fact that it is a form of poisoning. In the context of Biology, poisons are substances that can cause damage, Illness, or Death to Organisms usually by [1][2] Rarely it may also be called serotonin storm.

Serotonin syndrome is not a spontaneous drug reaction; it is a consequence of excess serotonergic activity at central nervous system (CNS) and peripheral serotonin receptors. In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges. In the field of Neurochemistry, 5-HT receptors are receptors for the Neurotransmitter and peripheral signal mediator Serotonin, also This excess serotonin activity produces a specific spectrum of clinical findings which may range from barely perceptible to fatal. [3]

Contents

Mechanism

Serotonin syndrome is caused by increased serotonin in the central nervous system. Serotonin (ˌsɛrəˈtoʊnən ( 5-hydroxytryptamine, or 5-HT) is a Monoamine Neurotransmitter synthesized in serotonergic Neurons In Vertebrates the central nervous system ( CNS) is the part of the Nervous system which is enclosed in the Meninges. It is the result of overstimulation of 5-HT1A receptors in central grey nuclei and the medulla and, perhaps, of overstimulation of 5-HT2 receptors. In the field of Neurochemistry, 5-HT receptors are receptors for the Neurotransmitter and peripheral signal mediator Serotonin, also In the field of Neurochemistry, 5-HT receptors are receptors for the Neurotransmitter and peripheral signal mediator Serotonin, also [3][4] These changes are more pronounced following supra-therapeutic doses and overdoses, and they merge in a continuum with the toxic effects. [5][6][7]

Drugs which may contribute

A large number of drugs and drug combinations have been associated with the serotonin syndrome.

Class Drugs
Herbs St John's Wort, Yohimbe, Boswellia
Antidepressants Monoamine oxidase inhibitors (MAOIs), TCAs, SSRIs, SNRIs, bupropion[8]
Opioids tramadol, pethidine
CNS stimulants phentermine, diethylpropion, amphetamines, substituted amphetamines, sibutramine, methylphenidate, methamphetamine, cocaine
5-HT1 agonists triptans
Phenethylamines MDMA, MDA, MDEA, PMA
Indoles Psilocybin, LSD
Others tryptophan, montelukast (Singulair), buspirone, kanna, lithium, linezolid, dextromethorphan (DXM), 5-Hydroxytryptophan, chlorpheniramine, risperidone[9]
Reference: Rossi, 2005;[10] National Prescribing Service, 2005[11]

The combination of MAOIs and other serotonin agonists or precursors poses a particularly severe risk of a life-threatening serotonin syndrome episode. A(n herb (ˈhɝb or /ˈɝb/ see pronunciation differences) is a plant that is valued for qualities such as medicinal properties flavor scent or the like St John's wort (pronounced) used alone refers to the species Hypericum perforatum, also known as Tipton's Weed or Klamath weed, but with qualifiers is Yohimbine, also known under the antiquated names quebrachin, aphrodin, corynine, yohimvetol and hydroergotocin, is a purported Boswellia is a Genus of Trees known for their fragrant Resin which has many Pharmacological uses particularly as anti-inflammatories An antidepressant is a Psychiatric medication used for alleviating major depression or Dysthymia ('milder' depression Monoamine oxidase inhibitors ( MAOIs) are a class of powerful antidepressant drugs prescribed for the treatment of depression. Tricyclic antidepressants (abbreviation TCAs) are a class of Antidepressant drugs first used in the 1950s Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders Serotonin-norepinephrine reuptake inhibitors (SNRIs are a class of Antidepressant used in the treatment of major depression and other mood disorders Bupropion ( INN, previously known as amfebutamone; sold as Wellbutrin, Zyban, and several other Trade names is an atypical Antidepressant An opioid is a chemical Substance that has a Morphine -like action in the body Tramadol ( INN) (ˈtræmədɒl is an atypical Opioid which is a centrally acting Analgesic, used for treating moderate to severe Pain. Pethidine ( INN) or meperidine ( USAN) (commonly referred to as Demerol but also referred to as isonipecaine lidol pethanol piridosal Algil Alodan Stimulant drugs are Drugs that temporarily increase alertness and awareness Phentermine, a contraction for " '''phen'''yl - '''ter'''tiary-butyl[[amine a' mine' ]]" is an Appetite suppressant of the Amphetamine Diethylcathinone (also called Diethylpropion and Amfepramone) is a Sympathomimetic Stimulant drug marketed as an appetite Amphetamine, and related drugs such as Methamphetamine are a group of drugs that act by increasing levels of Norepinephrine, Serotonin, and Dopamine The substituted Amphetamines are a family of amphetamine-based Stimulants, Hallucinogens, and other Recreational drugs. Sibutramine (trade name Meridia in the US and Canada Reductil in Europe and most other countries usually as sibutramine hydrochloride monohydrate is an orally Cocaine ( benzoylmethyl ecgonine) is a Crystalline Tropane Alkaloid that is obtained from the leaves of the Coca plant In the field of Neurochemistry, 5-HT receptors are receptors for the Neurotransmitter and peripheral signal mediator Serotonin, also Triptans are a family of Tryptamine based drugs used as Abortive medication in the treatment of Migraine and Cluster headaches They Phenethylamine, or β -phenylethylamine or 2-phenylethylamine is an Alkaloid and Monoamine. MDMA ( 34-methylenedioxy- N -methylamphetamine) most commonly known today by the street name Ecstasy (often abbreviated E, X, 34-Methylenedioxyamphetamine ( MDA or Tenamfetamine) is a Psychedelic hallucinogenic drug and empathogen/entactogen of the MDEA (also MDE) which stands for 34-methylenedioxy- N -ethylamphetamine is a Psychedelic hallucinogenic drug and Empathogen-entactogen PMA ( para Methoxy[[amphetamine]], p-methoxyamphetamine' or 4-methoxyamphetamine) is a synthetic Phenethylamine Indole is an Aromatic heterocyclic Organic compound. It has a bicyclic structure consisting of a six-membered Benzene ring fused to a five-membered Psilocybin (IPA /saɪləˈsaɪbɪn/ (also known as psilocybine) is a psychedelic Indole of the Tryptamine family found in Psilocybin Tryptophan (abbreviated as Trp or W) is one of the 20 standard amino acids, as well as an Essential amino acid in the Human diet Montelukast (trade name Singulair) is a Leukotriene receptor antagonist (LTRA used for the maintenance treatment of Asthma and to relieve symptoms of seasonal Buspirone (brand-names Ansial, Ansiced, Anxiron, Axoren, Bespar, BuSpar, Buspimen, Buspinol, Sceletium tortuosum is a Succulent herb commonly found in South Africa, which is also known as Kanna, Channa, Kougoed Lithium (ˈlɪθiəm is a Chemical element with the symbol Li and Atomic number 3 Linezolid ( INN) (lɪˈnɛzəlɪd is a synthetic Antibiotic of the Oxazolidinone class used for the treatment of infections caused by multi-resistant Dextromethorphan ( DXM or DM) is an Antitussive (cough suppressant drug found in many over-the-counter cold and Cough medicines 5-Hydroxytryptophan or 5-HTP is a naturally-occurring Amino acid, a precursor to the Neurotransmitter Serotonin and an intermediate Chlorphenamine ( INN) or chlorpheniramine ( USAN, former BAN) commonly marketed as its salt chlorphenamine Maleate (CPM Risperidone (pronounced Ris-PER-ǐ-dōn and sold under the trade name Risperdal in the Netherlands, United States, Canada, the Monoamine oxidase inhibitors ( MAOIs) are a class of powerful antidepressant drugs prescribed for the treatment of depression. 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. Monoamine oxidase inhibitors ( MAOIs) are a class of powerful antidepressant drugs prescribed for the treatment of depression. 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.

Spectrum concept

A recently postulated ‘spectrum concept’ of serotonin toxicity emphasises the role that progressively increasing serotonin levels play in mediating the clinical picture as side effects merge into toxicity. The dose effect relationship is the term used to describe the effects of progressive elevation of serotonin, either by raising the dose of one drug, or combining it with another serotonergic drug (which may produce large elevations in serotonin levels). [12]

Risk and severity

The relative risk and severity of serotonergic side effects and serotonin toxicity, with individual drugs and combinations, is complex. The serotonergic toxicity of SSRIs increases with dose, but even in over-dose it is insufficient to cause fatalities from serotonin syndrome in healthy adults. Selective serotonin reuptake inhibitors ( SSRIs) are a class of Antidepressants used in the treatment of depression, Anxiety disorders The syndrome occurs in approximately 14 to 16 percent of persons who overdose on SSRIs. [6] It is usually only when drugs with different mechanisms of action are mixed together that elevations of central nervous system serotonin reach potentially fatal levels. The most frequent (and perhaps the only) combination of therapeutic drugs likely to elevate serotonin to that degree is the combination of monoamine oxidase inhibitors with serotonin reuptake inhibitors (various drugs, other than SSRIs, have clinically significant potency as serotonin reuptake inhibitors, e. Monoamine oxidase inhibitors ( MAOIs) are a class of powerful antidepressant drugs prescribed for the treatment of depression. g. tramadol, amphetamine, and MDMA. Tramadol ( INN) (ˈtræmədɒl is an atypical Opioid which is a centrally acting Analgesic, used for treating moderate to severe Pain. Amphetamine, and related drugs such as Methamphetamine are a group of drugs that act by increasing levels of Norepinephrine, Serotonin, and Dopamine MDMA ( 34-methylenedioxy- N -methylamphetamine) most commonly known today by the street name Ecstasy (often abbreviated E, X, [13]

The relative risk of serotonin toxicity provides some clues and insights about the nature and extent of drugs’ serotonergic effects. For example, it suggests mirtazapine, which has no serotonergic toxicity, has no significant serotonergic effects at all, and is not in fact a dual action drug. Mirtazapine is an Antidepressant introduced by Organon International in 1994 used for the treatment of moderate to severe depression. [14]

Symptoms

Symptom onset is usually rapid, often occurring within minutes after self-poisoning or a change in medication. Serotonin syndrome encompasses a wide range of clinical findings. Mild symptoms may only consist of tachycardia, and shivering, diaphoresis (sweating commonly associated with shock), mydriasis (dilated pupils), myoclonus (intermittent tremor or twitching), as well as overactive or overresponsive reflexes. Diaphoresis is excessive sweating commonly associated with shock and other Medical emergency conditions "Dilated pupil" redirects here An Eye examination sometimes requires the dilation of the pupil Myoclonus (maɪˈɒklənəs is brief involuntary twitching of a Muscle or a group of muscles Hyperreflexia is defined as overactive or overresponsive Reflexes. In addition moderate intoxication includes abnormalities such as hyperactive bowel sounds, hypertension and hyperthermia; a temperature as high as 40 °C (104 °F) is common in moderate intoxication. Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the Blood pressure is chronically elevated Hyperthermia, in its advanced state referred to as heat stroke or sunstroke, is an acute condition which occurs when the Body produces or absorbs more The overactive reflexes and clonus in moderate cases may be greater in the lower limbs than in the upper limbs. Clonus (from the Greek for "violent confused motion" is a series of involuntary Muscular contractions due to sudden stretching of the muscle Mental status changes include hypervigilance and agitation. Hypervigilance is an "enhanced state of sensory sensitivity accompanied by an exaggerated intensity of behaviors whose purpose is to detect threats [3]

Severe symptoms include severe hypertension and tachycardia that may lead to shock. Severe case often have agitated delirium as well as muscular rigidity and high muscular tension. Temperature may rise to above 41. 1 °C (105. 98 °F) in life-threatening cases. Other abnormalities include metabolic acidosis, rhabdomyolysis, seizures, renal failure, and disseminated intravascular coagulation. In Medicine, metabolic acidosis is a process which if unchecked leads to acidemia (i Rhabdomyolysis is the rapid breakdown ( Lysis) of Skeletal muscle tissue ( rhabdomyo) due to injury to muscle tissue An epileptic seizure is caused by excessive and/or hypersynchronous electrical Neuronal activity and is usually self-limiting Renal failure or kidney Disseminated intravascular coagulation ( DIC) also known as consumptive coagulopathy, is a pathological activation of Coagulation (blood clotting mechanisms [3]

The symptoms are often described as a clinical triad of abnormalities:

Diagnosis

There is no lab test for serotonin syndrome, so diagnosis is by symptom observation and the patient's history. Serotonin toxicity has a characteristic picture which is generally hard to confuse with other medical conditions, but in some situations it may go unrecognized because it may be mistaken for a viral illness, anxiety, neurological disorder, or worsening psychiatric condition. A virus (from the Latin virus meaning Toxin or Poison) is a sub-microscopic infectious agent that is unable Anxiety is a physiological and psychological state characterized by Cognitive, Somatic, Emotional and Behavioral components [15] Much confusion has been produced by muddling it with side effects from serotonergic drugs. These rarely, if ever, become dangerous or fatal. Clinicians must also differentiate between serotonin syndrome and neuroleptic malignant syndrome, which has similar symptoms. Neuroleptic malignant syndrome (NMS is a life-threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs. [16]

Management

There is no antidote to the condition itself, and management involves the removal of the precipitating drugs, the initiation of supportive care, the control of agitation, the administration of serotonin antagonists (cyproheptadine or methysergide), the control of autonomic instability, and the control of hyperthermia. A receptor antagonist is a type of receptor ligand or Drug that does not provoke a biological response itself upon binding to a receptor, but blocks Cyproheptadine (usually as cyproheptadine hydrochloride, trade name Periactin) is an antihistaminic and Antiserotonergic agent Methysergide (UML-491 is a prescription drug used for prophylaxis of migraine headaches and is sold under the brand names Sansert and Deseril in 2mg dosages &trade The autonomic nervous system ( ANS) (or visceral nervous system) is the part of the Peripheral nervous system that acts as a Control [17][3]

The intensity of therapy depends on the severity of symptoms. If the symptoms are mild, treatment may only consist of discontinuation of the offending medication or medications, offering supportive measures, giving benzodiazepines, and waiting for the symptoms to resolve. The benzodiazepines (pronounced, often abbreviated to "benzos") are a class of Psychoactive drugs with varying Hypnotic If the offending medication is discontinued, the condition will often resolve on its own within 24 hours. [18][19] Moderate cases should have all thermal and cardiorespiratory abnormalities corrected and can benefit from serotonin antagonists (i. e. cyproheptadine). Critically ill patients should receive the above therapies as well as sedation, neuromuscular paralysis, and intubation. In Medicine, intubation refers to the placement of a tube into an external or internal orifice of the body [3]

Neuroleptic malignant syndrome and serotonergic syndrome

The clinical features of neuroleptic malignant syndrome (NMS) and serotonergic syndrome are very similar. Neuroleptic malignant syndrome (NMS is a life-threatening neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs. This can make differentiating them very difficult. [20]

Features, classically present in NMS, that are useful for differentiating the two syndromes are:[21]

Notable cases

The death of Libby Zion was due to serotonin syndrome caused by a combination of meperidine and phenelzine. In Medicine and Psychology, the term syndrome refers to the association of several clinically recognizable features signs (observed by a physician Libby Zion law or the Libby law refers to a regulation that limits the amount of residents work in hospitals Pethidine ( INN) or meperidine ( USAN) (commonly referred to as Demerol but also referred to as isonipecaine lidol pethanol piridosal Algil Alodan Phenelzine (sold as Nardil) is a Monoamine oxidase inhibitor (MAOI used as an Antidepressant drug. [3][22] This case had a profound impact on graduate medical education and residency work hour limitations. [23]

References

  1. ^ Gillman P (2004). "Comment on: Serotonin syndrome due to co-administration of linezolid and venlafaxine. ". J Antimicrob Chemother 54 (4): 844–5. doi:10.1093/jac/dkh404. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15317745.  
  2. ^ Gillman PK (2005). Serotonin toxicity, serotonin syndrome: 2005 update, overview and analysis. Retrieved on 10 January 2008.
  3. ^ a b c d e f g Boyer EW, Shannon M (2005). "The serotonin syndrome". N. Engl. J. Med. 352 (11): 1112–20. doi:10.1056/NEJMra041867. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15784664.  
  4. ^ Gillman PK (1999). "The serotonin syndrome and its treatment". J. Psychopharmacol. (Oxford) 13 (1): 100–9. PMID 10221364.  
  5. ^ Whyte IM, Serotonin Toxicity (Syndrome). in Medical Toxicology, Dart RC, Editor. 2004, Lippincott Williams & Wilkins: Baltimore. p. 103–6.
  6. ^ a b Isbister G, Bowe S, Dawson A, Whyte I (2004). "Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose". J Toxicol Clin Toxicol 42 (3): 277–85. doi:10.1081/CLT-120037428. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15362595.  
  7. ^ Whyte I, Dawson A, Buckley N (2003). "Relative toxicity of venlafaxine and selective serotonin reuptake inhibitors in overdose compared to tricyclic antidepressants". QJM 96 (5): 369–74. doi:10.1093/qjmed/hcg062. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12702786.  
  8. ^ Munhoz RP (2004). "Serotonin syndrome induced by a combination of bupropion and SSRIs". Clinical neuropharmacology 27 (5): 219–22. doi:10.1097/01.wnf.0000142754.46045.8c. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 15602102.  
  9. ^ Karki SD, Masood GR (2003). "Combination risperidone and SSRI-induced serotonin syndrome". The Annals of pharmacotherapy 37 (3): 388–91. doi:10.1345/aph.1C228. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12639169.  
  10. ^ Rossi S, editor. Australian Medicines Handbook 2005. The Australian Medicines Handbook or AMH is a medical reference text commonly used in practice by health professionals (particularly General practitioners Adelaide: Australian Medicines Handbook; 2005. ISBN 0-9578521-9-3
  11. ^ Prescribing Practice Review 32: Managing depression in primary care. National Prescribing Service Limited (2005). Retrieved on 16 July 2006.
  12. ^ Gillman PK (2006). Serotonin toxicity: 3 Spectrum concept. Retrieved on 17 November 2006.
  13. ^ Vuori E, Henry J, Ojanperä I, Nieminen R, Savolainen T, Wahlsten P, Jäntti M (2003). "Death following ingestion of MDMA (ecstasy) and moclobemide". Addiction 98 (3): 365–8. doi:10.1046/j.1360-0443.2003.00292.x. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 12603236.  
  14. ^ Gillman P (2006). "A systematic review of the serotonergic effects of mirtazapine in humans: implications for its dual action status". Hum Psychopharmacol 21 (2): 117–25. doi:10.1002/hup.750. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 16342227.  
  15. ^ Fennell J, Hussain M (2005). "Serotonin syndrome:case report and current concepts. ". Ir Med J 98 (5): 143–4. PMID 16010782.  
  16. ^ Nisijima K, Shioda K, Iwamura T (2007). "Neuroleptic malignant syndrome and serotonin syndrome". Prog. Brain Res. 162: 81–104. doi:10.1016/S0079-6123(06)62006-2. A digital object identifier ( DOI) is a permanent identifier given to an Electronic document. PMID 17645916.  
  17. ^ Sporer K (1995). "The serotonin syndrome. Implicated drugs, pathophysiology and management". Drug Saf 13 (2): 94–104. PMID 7576268.  
  18. ^ Prator B (2006). "Serotonin syndrome". J Neurosci Nurs 38 (2): 102–5. PMID 16681290.  
  19. ^ Jaunay E, Gaillac V, Guelfi J (2001). "[Serotonin syndrome. Which treatment and when?]". Presse Med 30 (34): 1695–700. PMID 11760601.  
  20. ^ Christensen V, Glenthøj B (2001). "[Malignant neuroleptic syndrome or serotonergic syndrome]". Ugeskr Laeger 163 (3): 301–2. PMID 11219110.  
  21. ^ Birmes P, Coppin D, Schmitt L, Lauque D (2003). "Serotonin syndrome: a brief review. ". CMAJ 168 (11): 1439–42. PMID 12771076.   Full Free Text.
  22. ^ Asch DA, Parker RM (March 1988). "The Libby Zion case. One step forward or two steps backward?". N. Engl. J. Med. 318 (12): 771–5. PMID 3347226.  
  23. ^ Brensilver JM, Smith L, Lyttle CS (1998). "Impact of the Libby Zion case on graduate medical education in internal medicine". Mt. Sinai J. Med. 65 (4): 296–300. PMID 9757752.  

External links

© 2009 citizendia.org; parts available under the terms of GNU Free Documentation License, from http://en.wikipedia.org
 Dapyx Software network: MP3 Explorer | Ebook Manager | Zenithic