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. It is an iatrogenic (i.e. caused by medical treatment) toxidrome (from toxic + syndrome). 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.^[1][2] Rarely it may also be called serotonin storm. Image File history File links Download high resolution version (2000x1431, 33 KB) File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Serotonin ... For the professional wrestling stable, see Ravens Nest#Serotonin. ... The International Statistical Classification of Diseases and Related Health Problems (most commonly known by the abbreviation ICD) provides codes to classify diseases and a wide variety of signs, symptoms, abnormal findings, complaints, social circumstances and external causes of injury or disease. ... The following is a list of codes for International Statistical Classification of Diseases and Related Health Problems. ... The Disease Bold textDatabase 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. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... Ancient Greek painting in a vase, showing a physician (iatros) bleeding a patient. ... Categories: Move to Wiktionary | Stub ... Toxic redirects here, but this is also the name of a song by Britney Spears; see Toxic (song) Look up toxic and toxicity in Wiktionary, the free dictionary. ... In medicine, the term syndrome is the association of several clinically recognizable features, signs, symptoms, phenomena or characteristics which often occur together, so that the presence of one feature alerts the physician to the presence of the others. ... For other uses, see Poison (disambiguation). ...

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. This excess serotonin activity produces a specific spectrum of clinical findings which may range from barely perceptible to fatal.^[3] A diagram showing the CNS: 1. ... In the field of neurochemistry, 5-HT receptors are receptors for the neurotransmitter and peripheral signal mediator serotonin, also known as 5-hydroxytryptamine or 5-HT. 5-HT receptors are located on the cell membrane of nerve cells and other cell types in animals and mediate the effects of serotonin...

Mechanism

Serotonin syndrome is caused by increased serotonin in the central nervous system. 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.^[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] For the professional wrestling stable, see Ravens Nest#Serotonin. ... A diagram showing the CNS: 1. ... In the field of neurochemistry, 5-HT receptors are receptors for the neurotransmitter and peripheral signal mediator serotonin, also known as 5-hydroxytryptamine or 5-HT. 5-HT receptors are located on the cell membrane of nerve cells and other cell types in animals and mediate the effects of serotonin... In the field of neurochemistry, 5-HT receptors are receptors for the neurotransmitter and peripheral signal mediator serotonin, also known as 5-hydroxytryptamine or 5-HT. 5-HT receptors are located on the cell membrane of nerve cells and other cell types in animals and mediate the effects of serotonin...

Drugs which may contribute

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

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. This article is about the plants used in cooking and medicine. ... Binomial name Hypericum perforatum L. St Johns wort (IPA pronunciation: , rhyming with hurt, or ) used alone refers to the species Hypericum perforatum, also known as Klamath weed or Goat weed, but, with qualifiers, is used to refer to any species of the genus Hypericum. ... Yohimbine, also known under the outdated names quebrachin, aphrodin, corynine, yohimvetol, and hydroergotocin, is the principal alkaloid of the bark of the West-African tree Pausinystalia yohimbe Pierre (formerly Corynanthe yohimbe), family Rubiaceae (Madder family). ... Species Boswellia sacra (aka or )Boswellia frereana Boswellia papyrifera Boswellia serrata Boswellia is a genus of trees known for their fragrant resin which has many pharmacological uses particularly as anti-inflamatories. ... Prozac, a selective serotonin reuptake inhibitor (SSRI) Serotonin-norepinephrine reuptake inhibitor, Venlafaxine An antidepressant is a psychiatric medication or other substance (nutrient or herb) used for alleviating depression or dysthymia (milder depression). ... MAOI redirects here. ... Chemical structure of the tricyclic antidepressant amitriptyline. ... SSRI is an acronym that stands for several things: It is a class of antidepressants called selective serotonin reuptake inhibitor SSRI also is used as the stock symbol for Silver Standard Resources Inc. ... Serotonin Norepinephrine Serotonin-norepinephrine reuptake inhibitors (SNRIs) are a class of antidepressant used in the treatment of clinical depression and other affective disorders. ... Bupropion (INN; also amfebutamone,[1] brand names Wellbutrin, Zyban, Budeprion and Buproban) is an atypical antidepressant, which acts as a norepinephrine reuptake inhibitor and dopamine reuptake inhibitor,[2] and a nicotinic antagonist. ... An opioid is a chemical substance that has a morphine-like action in the body. ... Tramadol (INN) (IPA: ) is an atypical opioid which is a centrally acting analgesic, used for treating moderate to severe pain. ... Pethidine (INN) or meperidine (USAN) (also referred to as: isonipecaine; lidol; pethanol; piridosal; Algil®; Alodan®; Centralgin®; Demerol®; Dispadol®; Dolantin®; Dolargan® (in Poland);[1] Dolestine®; Dolosal®; Dolsin®; Mefedina®) is a fast-acting opioid analgesic drug. ... Sustained-Release 15mg Dexedrine Spansules. ... Phentermine is an appetite suppressant of the amphetamine and phenethylamine class. ... Diethylpropion (Tenuate®) is a sympathomimetic stimulant drug marketed as an appetite suppressant. ... Amphetamine or Amfetamine(Alpha-Methyl-PHenEThylAMINE), also known as beta-phenyl-isopropylamine and benzedrine, is a prescription stimulant commonly used to treat Attention-deficit hyperactivity disorder (ADHD) in adults and children. ... The substituted amphetamines are a family of amphetamine-based stimulants, hallucinogens, and other recreational drugs. ... Sibutramine (Meridia® in the USA, Reductil® in Europe), usually as sibutramide hydrochloride monohydrate, is an orally administered agent for the treatment of obesity. ... Vitamin R redirects here. ... This article is about the psychostimulant, d-methamphetamine. ... In the field of neurochemistry, 5-HT receptors are receptors for the neurotransmitter and peripheral signal mediator serotonin, also known as 5-hydroxytryptamine or 5-HT. 5-HT receptors are located on the cell membrane of nerve cells and other cell types in animals and mediate the effects of serotonin... Triptans are a family of tryptamine drugs used as abortive medication in the treatment of migraine and cluster headaches. ... Phenethylamine is an alkaloid and monoamine. ... ecstasy and religious ecstasy MDMA, most commonly known today by the street name ecstasy, is a synthetic entactogen of the phenethylamine family whose primary effect is to stimulate the brain to rapidly secrete large amounts of serotonin, causing a general sense of openness, empathy, energy, euphoria, and well-being. ... MDA is an abbreviation for Moldova (its ISO 3166-1 three-letter country code); two organizations in the U.S.: the Muscular Dystrophy Association; the Missile Defense Agency, an agency of the Department of Defense; various computing terms: the OMGs model-driven architecture; Monochrome Display Adapter, a computer display... MDEA (also MDE), which stands for 3,4-methylenedioxy-N-ethylamphetamine, is a psychedelic hallucinogenic drug and empathogen-entactogen of the phenethylamine family. ... For other uses, see PMA (disambiguation). ... Indole is an aromatic heterocyclic organic compound. ... Psilocybin (also known as psilocybine) is a psychedelic alkaloid of the tryptamine family, found in psilocybin mushrooms. ... For other uses, see Cocaine (disambiguation). ... Tryptophan (abbreviated as Trp or W)[1] is one of the 20 standard amino acids, which are the building blocks of proteins, and an essential amino acid in the human diet. ... Montelukast is a leukotriene receptor antagonist (LTRA) used for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies. ... Buspirone (brand-names Ansial, Ansiced, Anxiron, Axoren, Bespar, BuSpar, Buspimen, Buspinol, Buspisal, Narol, Spitomin, Sorbon) is an anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. ... This article is about the chemical element. ... Linezolid (INN) (IPA: ) is a synthetic antibiotic, the first of the oxazolidinone class, used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA). ... 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 in tryptophan metabolism. ... Chlorphenamine (INN) or chlorpheniramine (USAN, former BAN), commonly marketed as its salt chlorphenamine maleate (CPM), is first-generation antihistamine used in the prevention of the symptoms of allergic conditions such as rhinitis and urticaria. ... Bupropion (INN; also amfebutamone,[1] brand names Wellbutrin, Zyban, Budeprion and Buproban) is an atypical antidepressant, which acts as a norepinephrine reuptake inhibitor and dopamine reuptake inhibitor,[2] and a nicotinic antagonist. ... Risperdal tablets Risperidone (pronounced Ris-PER-ǐ-dōn and sold under the trade name Risperdal in the United States, Canada, the United Kingdom, Portugal and several other countries, Risperdal or Ridal in New Zealand, Rispolept in Eastern Europe, and Belivon, or Rispen elsewhere) is an atypical antipsychotic medication developed by... MAOI redirects here. ... MAOI redirects here. ... Monoamine oxidase Monoamine oxidases (singular abbreviation MAO) (EC 1. ...

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. 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.g. tramadol, amphetamine, and MDMA.^[13] SSRI is an acronym that stands for several things: It is a class of antidepressants called selective serotonin reuptake inhibitor SSRI also is used as the stock symbol for Silver Standard Resources Inc. ... Monoamine oxidase inhibitors (MAOIs) are a class of antidepressant drugs prescribed for the treatment of depression. ... Tramadol (INN) (IPA: ) is an atypical opioid which is a centrally acting analgesic, used for treating moderate to severe pain. ... Amphetamine or Amfetamine(Alpha-Methyl-PHenEThylAMINE), also known as beta-phenyl-isopropylamine and benzedrine, is a prescription stimulant commonly used to treat Attention-deficit hyperactivity disorder (ADHD) in adults and children. ... ecstasy and religious ecstasy MDMA, most commonly known today by the street name ecstasy, is a synthetic entactogen of the phenethylamine family whose primary effect is to stimulate the brain to rapidly secrete large amounts of serotonin, causing a general sense of openness, empathy, energy, euphoria, and well-being. ...

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.^[14] Mirtazapine is an antidepressant introduced by Organon International in 1994 used for the treatment of moderate to severe depression. ...

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. 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. The overactive reflexes and clonus in moderate cases may be greater in the lower limbs than in the upper limbs. Mental status changes include hypervigilance and agitation.^[3] This article or section does not cite any references or sources. ... Diaphoresis is excessive sweating commonly associated with shock and other medical emergency conditions. ... Mydriasis is an excessive dilation of the pupil due to disease or drugs. ... Myoclonus is brief, involuntary twitching of a muscle or a group of muscles. ... Hyperreflexia is defined as overactive or overresponsive reflexes. ... For other forms of hypertension, see Hypertension (disambiguation). ... 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 heat than it can dissipate. ... Clonus (from the Greek for violent, confused motion) is a series of involuntary muscular contractions due to sudden stretching of the muscle. ... Hypervigilance is an enhanced state of sensory sensitivity accompanied by an exaggerated intensity of behaviors whose purpose is to detect threats. ... This page is a candidate to be moved to Wiktionary. ...

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.^[3] In medicine, metabolic acidosis is a state in which the blood pH is low (under 7. ... Rhabdomyolysis is the rapid breakdown of skeletal muscle tissue due to traumatic injury, either mechanical, physical or chemical. ... This article is about the medical condition. ... Renal failure or kidney failure is a situation in which the kidneys fail to function adequately. ... Disseminated intravascular coagulation (DIC) is a pathological process in the body where the blood starts to coagulate throughout the whole body. ...

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

• Cognitive effects: mental confusion, hypomania, hallucinations, agitation, headache, coma.
• Autonomic effects: shivering, sweating, fever, hypertension, tachycardia, nausea, diarrhea.
• Somatic effects: myoclonus/clonus (muscle twitching), hyperreflexia, tremor.

Cognitive The scientific study of how people obtain, retrieve, store and manipulate information. ... Severe confusion of a degree considered pathological usually refers to loss of orientation (ability to place oneself correctly in the world by time, location, and personal identity), and often memory (ability to correctly recall previous events or learn new materal). ... Hypomania is a mood state characterized by persistent and pervasive elated or irritable mood, and thoughts and behaviors that are consistent with such a mood state. ... A hallucination is a false sensory perception in the absence of an external stimulus, as distinct from an illusion, which is a misperception of an external stimulus. ... This page is a candidate to be moved to Wiktionary. ... A headache (cephalgia in medical terminology) is a condition of pain in the head; sometimes neck or upper back pain may also be interpreted as a headache. ... For other uses, see Coma (disambiguation). ... This article or section is in need of attention from an expert on the subject. ... Shivering is a human bodily function in response to cold. ... Perspiration (also called sweating or sometimes transpiration) is the production and evaporation of a fluid, consisting primarily of water as well as a smaller amount of sodium chloride (the main constituent of table salt), that is excreted by the sweat glands in the skin of mammals. ... An analogue medical thermometer showing the temperature of 38. ... For other forms of hypertension, see Hypertension (disambiguation). ... This article or section does not cite any references or sources. ... For other uses, see Nausea (disambiguation). ... In medicine, diarrhea, also spelled diarrhoea (see spelling differences), refers to frequent loose or liquid bowel movements. ... The somatic nervous system is that part of the peripheral nervous system associated with the voluntary control of body movements through the action of skeletal muscles, and also reception of external stimuli. ... Myoclonus is brief, involuntary twitching of a muscle or a group of muscles. ... Clonus (from the Greek for violent, confused motion) is a series of involuntary muscular contractions due to sudden stretching of the muscle. ... Hyperreflexia is defined as overactive or overresponsive reflexes. ... For the film, see Tremors (film). ...

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.^[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. Patients taking serotonergic drugs and who have sudden onset of symptoms should immediately seek medical care. This article is about biological infectious particles. ... This article is about state anxiety. ... Neurology is a branch of medicine dealing with disorders of the central and peripheral nervous systems. ... Neuroleptic malignant syndrome (NMS) is a life-threatening, neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs. ...

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.^[16][3] Antagonists will block the binding of an agonist at a receptor molecule, inhibiting the signal produced by a receptor-agonist coupling. ... 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. ... This article or section is in need of attention from an expert on the subject. ...

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. If the offending medication is discontinued, the condition will often resolve on its own within 24 hours.^[17][18] 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.^[3] Alprazolam 2 mg tablets The benzodiazepines (pronounced , often abbreviated to benzos) are a class of sedative hypnotic psychoactive drugs with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are mediated by slowing down the central nervous system. ... This article or section needs copy editing for grammar, style, cohesion, tone and/or spelling. ...

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.^[19] Neuroleptic malignant syndrome (NMS) is a life-threatening, neurological disorder most often caused by an adverse reaction to neuroleptic or antipsychotic drugs. ...

Features, classically present in NMS, that are useful for differentiating the two syndromes are:^[20] In medicine, the term syndrome is the association of several clinically recognizable features, signs, symptoms, phenomena or characteristics which often occur together, so that the presence of one feature alerts the physician to the presence of the others. ...

• Fever
• Muscle rigidity
• Laboratory values (increased WBC and CK)

Notable cases

The death of Libby Zion was due to serotonin syndrome caused by a combination of meperidine and phenelzine.^[3] This case had a profound impact on graduate medical education and residency work hour limitations.^[21] Please wikify (format) this article or section as suggested in the Guide to layout and the Manual of Style. ... Pethidine (INN) or meperidine (USAN) (also referred to as: isonipecaine; lidol; operidine; pethanol; piridosal; Algil®; Alodan®; Centralgin®; Demerol®; Dispadol®; Dolantin®; Dolestine®; Dolosal®; Dolsin®; Mefedina®) is a fast-acting opioid analgesic drug. ... Phenelzine (brand name Nardil) is an antidepressant drug that belongs to the monoamine oxidase inhibitor (MAOI) class of drugs. ...

References

A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... 2008 (MMVIII) is the current year, a leap year that started on Tuesday of the Anno Domini (or common era), in accordance to the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ... The Australian Medicines Handbook or AMH is a medical reference text commonly used in practice by health professionals (particularly general practitioners and pharmacists) in Australia. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... Year 2006 (MMVI) was a common year starting on Sunday of the Gregorian calendar. ... A digital object identifier (or DOI) is a standard for persistently identifying a piece of intellectual property on a digital network and associating it with related data, the metadata, in a structured extensible way. ...

External links

• Dr P K Gillman's site, 'PsychoTropicalResearch', devoted to Serotonin and 'Serotonin Syndrome' research.
• PSY184 at FPnotebook
• Great article with a plethora of information on the toxidrome; its causes and statistics involving the subsidiation of the toxidrome.