Materiały źródłowe

• #1 Serotonin Syndrome – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK482377/

  Serotonin syndrome, also known as serotonin toxicity, poses a significant clinical challenge due to its potentially life-threatening nature and diverse etiology. Resulting of excessive serotonergic activity in the central nervous system, this condition arises from various sources, including therapeutic medication use, drug interactions, and intentional overdoses. […] Serotonin syndrome may be a consequence of therapeutic medication use, accidental interactions between medications and recreational drugs, or an intentional overdose. […] The etiology of serotonin syndrome results from cellular toxicity of excess target post-synaptic 5-HT stimulation.

• #2 The Serotonin Syndrome: From Molecular Mechanisms to Clinical Practice

  https://www.mdpi.com/1422-0067/20/9/2288

  The combination of an MAOI with an SSRI, and SNRI or another MAOI is the most dangerous combination and the most likely to result in SS. […] Increased production of serotonin (through an overabundance of the precursor molecule L-tryptophan) as well as decreased metabolism of serotonin (by the administration of MAOI), may each cause receptor overstimulation and SS. […] Several discrete mechanisms have been hypothesized to explain how drugs cause SS, although it is likely that more than one of these mechanisms may need to be simultaneously triggered in order to result in clinically significant SS. […] It appears that certain individuals with known polymorphisms at the T102C site of the 5-HT2A receptor gene may be predisposed to developing SS. […] Individual variations in serotonin metabolism by CYPs have also been proposed to contribute to SS susceptibility. […] SERT proteins are critical to the termination of synaptic serotonergic activity.

• #3 Serotonin syndrome (serotonin toxicity) – UpToDate

  https://www.uptodate.com/contents/serotonin-syndrome-serotonin-toxicity

  Serotonin syndrome, also referred to as serotonin toxicity, is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. It is seen with therapeutic medication use, inadvertent interactions between drugs, and intentional self-poisoning. […] Serotonin syndrome may involve a spectrum of clinical findings, which often include mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. […] The selective serotonin reuptake inhibitors (SSRIs) are perhaps the most commonly implicated group of medications associated with serotonin syndrome. […] The syndrome has been described following intentional overdose, and even in post-cardiac arrest patients treated with therapeutic hypothermia. […] However, the true incidence of serotonin syndrome may be under-represented in data such as the NPDS for a number of reasons.

• #4 Serotonin syndrome (serotonin toxicity) – UpToDate

  https://www.uptodate.com/contents/serotonin-syndrome-serotonin-toxicity

  Serotonin syndrome, also referred to as serotonin toxicity, is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. It is seen with therapeutic medication use, inadvertent interactions between drugs, and intentional self-poisoning. […] Serotonin syndrome may involve a spectrum of clinical findings, which often include mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. […] The selective serotonin reuptake inhibitors (SSRIs) are perhaps the most commonly implicated group of medications associated with serotonin syndrome. […] The syndrome has been described following intentional overdose, and even in post-cardiac arrest patients treated with therapeutic hypothermia. […] However, the true incidence of serotonin syndrome may be under-represented in data such as the NPDS for a number of reasons.

• #5 Serotonin syndrome: a spectrum of toxicity | BJPsych Advances | Cambridge Core

  https://www.cambridge.org/core/journals/bjpsych-advances/article/serotonin-syndrome-a-spectrum-of-toxicity/BB07FCAF5DC69DF5FFC0AEB113147A9E

  Serotonin syndrome can present as a spectrum of different symptoms and signs and in varying degrees of severity. […] In practice, serotonin syndrome usually results from drug interactions, classically secondary to the combined overdose of an SSRI with an (irreversible) monoamine oxidase inhibitor (MAOI), which in around 50% of cases is believed to result in severe serotonin syndrome. […] Severe serotonin toxicity can have a rapid onset and deterioration; death can ensue within 24 h. […] In some cases symptoms may be misattributed to deterioration in mental state, with the risk of increasing or additional medication. […] There appears to be a sequential stimulatory effect in the presence of excess serotonin, which corresponds roughly to the spectrum of increasing toxicity. […] There is support for the theory that a particular concentration of serotonin is a prerequisite for the development of serotonin syndrome. However, there is considerable inter-individual variation and this variability has its basis in genetic factors, which include polymorphisms of CYP2D6, SERT or the serotonin receptors themselves.

• #6 Serotonin syndrome (serotonin toxicity) – UpToDate

  https://www.uptodate.com/contents/serotonin-syndrome-serotonin-toxicity

  Serotonin syndrome, also referred to as serotonin toxicity, is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. It is seen with therapeutic medication use, inadvertent interactions between drugs, and intentional self-poisoning. […] Serotonin syndrome may involve a spectrum of clinical findings, which often include mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. […] The selective serotonin reuptake inhibitors (SSRIs) are perhaps the most commonly implicated group of medications associated with serotonin syndrome. […] The syndrome has been described following intentional overdose, and even in post-cardiac arrest patients treated with therapeutic hypothermia. […] However, the true incidence of serotonin syndrome may be under-represented in data such as the NPDS for a number of reasons.

• #7 Detecting and Managing Serotonin Syndrome – Psychiatry Advisor

  https://www.psychiatryadvisor.com/features/detecting-and-managing-serotonin-syndrome/

  Serotonin syndrome is caused by drugs that either affect serotonin metabolism or act as direct serotonin receptor agonists, or both, and takes place in the setting of excess stimulation of central and peripheral serotonin receptors. […] Drugs that can cause serotonin syndrome do so by inhibiting serotonin reuptake, increasing serotonin synthesis, decreasing serotonin metabolism, increasing serotonin release, or activating serotonergic receptors. […] The actual incidence of serotonin syndrome and associated morbidity is likely underestimated, as serotonin syndrome is frequently underdiagnosed and underreported and can easily be overlooked, especially when mild. […] It has been suggested that more than 85% of physicians are not familiar with the existence of serotonin syndrome or which drugs or drug combinations may cause it.

• #8 Drug-Induced Serotonin Syndrome

  https://www.uspharmacist.com/article/drug-induced-serotonin-syndrome

  SS typically occurs when a patient takes two or more drugs that elevate serotonin levels through different mechanisms, but the syndrome can occur with the use of individual agents. […] Mechanisms that cause SS include increased serotonin production, inhibition of serotonin reuptake, inhibition of serotonin metabolism, increased serotonin release, and stimulation of serotonin receptors. […] Two serotonergic drugs do not need to be administered concurrently to cause SS; the syndrome can occur up to 6 weeks after discontinuation of just one such drug with a long-acting dosage form, like fluoxetine (Prozac, Sarafem) or an MAOI (e.g., isocarboxazid, phenelzine). […] Concurrent use of medications that interact with serotonergic drugs, thereby resulting in inhibition of the CYP450 metabolic pathway, can also contribute to SS.

• #9 The Serotonin Syndrome: From Molecular Mechanisms to Clinical Practice

  https://www.mdpi.com/1422-0067/20/9/2288

  The combination of an MAOI with an SSRI, and SNRI or another MAOI is the most dangerous combination and the most likely to result in SS. […] Increased production of serotonin (through an overabundance of the precursor molecule L-tryptophan) as well as decreased metabolism of serotonin (by the administration of MAOI), may each cause receptor overstimulation and SS. […] Several discrete mechanisms have been hypothesized to explain how drugs cause SS, although it is likely that more than one of these mechanisms may need to be simultaneously triggered in order to result in clinically significant SS. […] It appears that certain individuals with known polymorphisms at the T102C site of the 5-HT2A receptor gene may be predisposed to developing SS. […] Individual variations in serotonin metabolism by CYPs have also been proposed to contribute to SS susceptibility. […] SERT proteins are critical to the termination of synaptic serotonergic activity.

• #10 Pulsenotes | Serotonin syndrome

  https://app.pulsenotes.com/specialities/psychiatry/notes/serotonin-syndrome

  A range of agents can induce SS by a variety of mechanisms that ultimately increase serotonergic transmission in the CNS: Increased release of serotonin: Amphetamines, MDMA (ecstasy), cocaine; Impaired serotonin reuptake: SSRIs, SNRIs, MDMA, tricycle antidepressants, serotonin modulators; Inhibit serotonin metabolism: Monoamine oxidase inhibitors; Serotonin receptor agonists: Buspirone, Triptans; Increased sensitivity of serotonin receptor: Lithium. […] SS may occur due to exposure to a single agent that affects serotonergic transmission or a combination of drugs that collectively cause a net increase in serotonergic transmission.

• #11 The Serotonin Syndrome: From Molecular Mechanisms to Clinical Practice

  https://www.mdpi.com/1422-0067/20/9/2288

  The combination of an MAOI with an SSRI, and SNRI or another MAOI is the most dangerous combination and the most likely to result in SS. […] Increased production of serotonin (through an overabundance of the precursor molecule L-tryptophan) as well as decreased metabolism of serotonin (by the administration of MAOI), may each cause receptor overstimulation and SS. […] Several discrete mechanisms have been hypothesized to explain how drugs cause SS, although it is likely that more than one of these mechanisms may need to be simultaneously triggered in order to result in clinically significant SS. […] It appears that certain individuals with known polymorphisms at the T102C site of the 5-HT2A receptor gene may be predisposed to developing SS. […] Individual variations in serotonin metabolism by CYPs have also been proposed to contribute to SS susceptibility. […] SERT proteins are critical to the termination of synaptic serotonergic activity.

• #12 Pulsenotes | Serotonin syndrome

  https://app.pulsenotes.com/specialities/psychiatry/notes/serotonin-syndrome

  A range of agents can induce SS by a variety of mechanisms that ultimately increase serotonergic transmission in the CNS: Increased release of serotonin: Amphetamines, MDMA (ecstasy), cocaine; Impaired serotonin reuptake: SSRIs, SNRIs, MDMA, tricycle antidepressants, serotonin modulators; Inhibit serotonin metabolism: Monoamine oxidase inhibitors; Serotonin receptor agonists: Buspirone, Triptans; Increased sensitivity of serotonin receptor: Lithium. […] SS may occur due to exposure to a single agent that affects serotonergic transmission or a combination of drugs that collectively cause a net increase in serotonergic transmission.

• #13 Serotonin Syndrome | 5-Minute Clinical Consult

  https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116962/all/Serotonin_Syndrome

  A potentially life-threatening drug-induced syndrome that results from synaptic increase in serotonin (5-hydroxytryptamine [5-HT]) concentrations and stimulation of peripheral and CNS serotonergic receptors. […] Increased synaptic 5-HT or agonist concentration as a result of one or more of the following mechanisms: (i) decreased 5-HT breakdown (e.g., MAOI), (ii) decreased 5-HT reuptake (e.g., SSRI), (iii) increased 5-HT agonists (e.g., tryptophan), (iv) increased 5-HT release (e.g., amphetamines), and (v) CYP2D6 and CYP3A4 inhibitors (e.g., erythromycin). […] A number of drugs are associated with serotonin syndrome, which usually involves combination with an SSRI. These include SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline); MAOIs; SNRIs (duloxetine, venlafaxine, desvenlafaxine); tricyclic antidepressants (e.g., amitriptyline, clomipramine); other antidepressants (nefazodone, trazodone, mirtazapine); anxiolytic (buspirone); lithium; triptans; anticonvulsants (divalproex [Depakote]); analgesics (fentanyl, meperidine, pentazocine, tramadol); antibiotics/antivirals (linezolid, tedizolid [weak MAOI], ritonavir); over-the-counter (OTC) cough medications (dextromethorphan); some antipsychotics (risperidone, olanzapine); antiemetics (ondansetron, granisetron); other medications, such as metoclopramide, cyclobenzaprine, L-dopa; dietary supplements (tryptophan); herbal supplements (St. John wort, nutmeg); methylene blue; and drugs of abuse (e.g., methylenedioxymethamphetamine [MDMA], cocaine, D-lysergic acid diethylamide [LSD], amphetamine). […] The greatest number of adverse events are associated with SSRIs in combination with other substances, and the combination of SSRIs and MAOIs carries the greatest risk of developing serotonin toxicity.

• #14 Serotonin Syndrome

  https://www.uspharmacist.com/article/serotonin-syndrome

  Serotonin syndrome, also referred to as serotonin toxicity, is one such condition that, in some cases, may be fatal. Medications with serotonergic activity, some even available OTC, are the culprits of this potentially preventable complex of symptoms. The incidence of serotonin syndrome is increasing with the expanded use of serotonergic agents and, specifically, with polypharmacy. The most common drug combinations associated with serotonin syndrome involve the monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and the tricyclic antidepressants (TCAs). While there are several mechanisms that result in excess serotonin, severe, life-threatening serotonin toxicity occurs only with combinations of medications acting at different sites, most frequently including an MAOI and an SSRI. This condition is more likely to occur when a medication is initially introduced into the regimen or when the dosage is increased. Serotonin syndrome is a potentially preventable, drug-related complication that occurs from increased serotonin activity in the central nervous system through a variety of mechanisms including an increase in serotonin synthesis, a decrease in serotonin metabolism, an increase in serotonin release, inhibition of serotonin uptake, direct serotonin receptor stimulation, and a nonspecific increase in serotonin activity. The toxicity is characterized by an altered mental status, neuromuscular excitation, and autonomic stimulation. The patient’s medication history is positive for serotonergic drugs. Serotonin syndrome is diagnosed only after all other potential causes of symptoms have been ruled out. Published case reports warn that clinicians treating patients with a combination of serotonergic antidepressants and atypical antipsychotics for psychotic depression should be aware of the potential for serotonin syndrome. It is the combination of serotonergic drugs, acting by different mechanisms, that is capable of raising intrasynaptic serotonin to a level that is life threatening. Complications can occur, such as uncontrolled muscle spasms causing severe muscle breakdown and resulting in renal damage, if not recognized and treated appropriately. The combination that most commonly does this is an MAOI drug combined with any serotonin reuptake inhibitor (SRI). Treatment involves removal of the causative agents and may also include the use of serotonin antagonists. Symptoms typically resolve within 24 hours after withdrawal of the serotonergic medication. Clinicians should obtain complete medication histories to identify patients at risk, strictly monitor medication therapy including concomitant agents, and receive education about serotonin syndrome.

• #15 Serotonin Syndrome

  https://www.uspharmacist.com/article/serotonin-syndrome

  Serotonin syndrome, also referred to as serotonin toxicity, is one such condition that, in some cases, may be fatal. Medications with serotonergic activity, some even available OTC, are the culprits of this potentially preventable complex of symptoms. The incidence of serotonin syndrome is increasing with the expanded use of serotonergic agents and, specifically, with polypharmacy. The most common drug combinations associated with serotonin syndrome involve the monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and the tricyclic antidepressants (TCAs). While there are several mechanisms that result in excess serotonin, severe, life-threatening serotonin toxicity occurs only with combinations of medications acting at different sites, most frequently including an MAOI and an SSRI. This condition is more likely to occur when a medication is initially introduced into the regimen or when the dosage is increased. Serotonin syndrome is a potentially preventable, drug-related complication that occurs from increased serotonin activity in the central nervous system through a variety of mechanisms including an increase in serotonin synthesis, a decrease in serotonin metabolism, an increase in serotonin release, inhibition of serotonin uptake, direct serotonin receptor stimulation, and a nonspecific increase in serotonin activity. The toxicity is characterized by an altered mental status, neuromuscular excitation, and autonomic stimulation. The patient’s medication history is positive for serotonergic drugs. Serotonin syndrome is diagnosed only after all other potential causes of symptoms have been ruled out. Published case reports warn that clinicians treating patients with a combination of serotonergic antidepressants and atypical antipsychotics for psychotic depression should be aware of the potential for serotonin syndrome. It is the combination of serotonergic drugs, acting by different mechanisms, that is capable of raising intrasynaptic serotonin to a level that is life threatening. Complications can occur, such as uncontrolled muscle spasms causing severe muscle breakdown and resulting in renal damage, if not recognized and treated appropriately. The combination that most commonly does this is an MAOI drug combined with any serotonin reuptake inhibitor (SRI). Treatment involves removal of the causative agents and may also include the use of serotonin antagonists. Symptoms typically resolve within 24 hours after withdrawal of the serotonergic medication. Clinicians should obtain complete medication histories to identify patients at risk, strictly monitor medication therapy including concomitant agents, and receive education about serotonin syndrome.

• #16 The Serotonin Syndrome: From Molecular Mechanisms to Clinical Practice

  https://www.mdpi.com/1422-0067/20/9/2288

  The combination of an MAOI with an SSRI, and SNRI or another MAOI is the most dangerous combination and the most likely to result in SS. […] Increased production of serotonin (through an overabundance of the precursor molecule L-tryptophan) as well as decreased metabolism of serotonin (by the administration of MAOI), may each cause receptor overstimulation and SS. […] Several discrete mechanisms have been hypothesized to explain how drugs cause SS, although it is likely that more than one of these mechanisms may need to be simultaneously triggered in order to result in clinically significant SS. […] It appears that certain individuals with known polymorphisms at the T102C site of the 5-HT2A receptor gene may be predisposed to developing SS. […] Individual variations in serotonin metabolism by CYPs have also been proposed to contribute to SS susceptibility. […] SERT proteins are critical to the termination of synaptic serotonergic activity.

• #17 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  Serotonin syndrome is typically caused by the use of two or more serotonergic medications or drugs. […] This may include selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), amphetamines, pethidine (meperidine), tramadol, dextromethorphan, buspirone, L-tryptophan, 5-hydroxytryptophan, St. John’s wort, triptans, MDMA, ondansetron, metoclopramide, or cocaine. […] It occurs in about 15% of SSRI overdoses. […] It is a predictable consequence of excess serotonin on the central nervous system. […] Many cases of serotonin toxicity occur in people who have ingested drug combinations that synergistically increase synaptic serotonin. […] It may also occur due to an overdose of a single serotonergic agent.

• #18 Drug-Induced Serotonin Syndrome

  https://www.uspharmacist.com/article/drug-induced-serotonin-syndrome

  SS typically occurs when a patient takes two or more drugs that elevate serotonin levels through different mechanisms, but the syndrome can occur with the use of individual agents. […] Mechanisms that cause SS include increased serotonin production, inhibition of serotonin reuptake, inhibition of serotonin metabolism, increased serotonin release, and stimulation of serotonin receptors. […] Two serotonergic drugs do not need to be administered concurrently to cause SS; the syndrome can occur up to 6 weeks after discontinuation of just one such drug with a long-acting dosage form, like fluoxetine (Prozac, Sarafem) or an MAOI (e.g., isocarboxazid, phenelzine). […] Concurrent use of medications that interact with serotonergic drugs, thereby resulting in inhibition of the CYP450 metabolic pathway, can also contribute to SS.

• #19 Serotonin Syndrome: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17687-serotonin-syndrome

  Use certain illegal drugs or herbal products or over-the-counter drugs that affect serotonin levels. […] Antidepressants are the most commonly used medications that affect serotonin levels. […] Antidepressant drug classes and medication examples that can increase serotonin levels include: […] Selective serotonin reuptake inhibitors (SSRIs): […] This drug class is the most common antidepressant class involved in serotonin syndrome due to its widespread use. […] Other medications can also affect your bodys serotonin level, especially when combined with other drugs that affect serotonin. […] Other herbal and dietary supplements and illegal substances that affect serotonin levels and could cause serotonin syndrome include: […] Medical experts still have much to learn about serotonin syndrome.

• #20 Serotonin syndrome (serotonin toxicity) – UpToDate

  https://www.uptodate.com/contents/serotonin-syndrome-serotonin-toxicity

  Serotonin syndrome, also referred to as serotonin toxicity, is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. It is seen with therapeutic medication use, inadvertent interactions between drugs, and intentional self-poisoning. […] Serotonin syndrome may involve a spectrum of clinical findings, which often include mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. […] The selective serotonin reuptake inhibitors (SSRIs) are perhaps the most commonly implicated group of medications associated with serotonin syndrome. […] The syndrome has been described following intentional overdose, and even in post-cardiac arrest patients treated with therapeutic hypothermia. […] However, the true incidence of serotonin syndrome may be under-represented in data such as the NPDS for a number of reasons.

• #21 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  Serotonin syndrome is typically caused by the use of two or more serotonergic medications or drugs. […] This may include selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), amphetamines, pethidine (meperidine), tramadol, dextromethorphan, buspirone, L-tryptophan, 5-hydroxytryptophan, St. John’s wort, triptans, MDMA, ondansetron, metoclopramide, or cocaine. […] It occurs in about 15% of SSRI overdoses. […] It is a predictable consequence of excess serotonin on the central nervous system. […] Many cases of serotonin toxicity occur in people who have ingested drug combinations that synergistically increase synaptic serotonin. […] It may also occur due to an overdose of a single serotonergic agent.

• #22 Serotonin syndrome: Preventing, recognizing, and treating it | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/83/11/810

  Serotonin syndrome is caused by elevated serotonin levels in the central and peripheral nervous systems. […] Conditions that can alter the regulation of serotonin include therapeutic doses, drug interactions, intentional or unintentional overdoses, and overlapping transitions between medications. […] The only drugs that have been reliably confirmed to precipitate serotonin syndrome are MAOIs, SSRIs, SNRIs, and serotonin releasers. […] An estimated 15% of SSRI overdoses lead to mild or moderate serotonin toxicity. […] The combination of age and comorbidities may increase the risk for this condition. […] Serotonin syndrome characteristically presents as the triad of autonomic dysfunction, neuromuscular excitation, and altered mental status. […] Symptoms of serotonin toxicity arise within an hour of a precipitating event (eg, ingestion) in approximately 28% of patients, and within 6 hours in 61%.

• #23

  https://www.pulsus.com/scholarly-articles/a-brief-report-on-serotonin-syndrome-causes-diagnosis-andprevention-9254.html

  Serotonin Syndrome (SS) is the side effects that might happen with the utilization of certain serotonergic prescriptions or drugs. […] An enormous number of meds and street medications can cause serotonin disorder when taken alone at high dosages or in mix z innymi serotonergic drugs. Common Selective Serotonin reuptake inhibitors are: citalopram (Celexa), sertraline (Zoloft), fluoxetine (Prozac), paroxetine (Paxil) and escitalopram (Lexapro). SSNRIS include duloxetine (Cymbalta), venlafaxine (Effexor), Desvenlafaxine (Pristiq), Milnacipram (Savella). Common triptans include Sumatriptan (Imitrex), Zolmitriptan (Zolmig), Frovatriptan (frova), Rizatriptan (Maxalt), Almotriptan (Axert).

• #24 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  Serotonin syndrome is typically caused by the use of two or more serotonergic medications or drugs. […] This may include selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), amphetamines, pethidine (meperidine), tramadol, dextromethorphan, buspirone, L-tryptophan, 5-hydroxytryptophan, St. John’s wort, triptans, MDMA, ondansetron, metoclopramide, or cocaine. […] It occurs in about 15% of SSRI overdoses. […] It is a predictable consequence of excess serotonin on the central nervous system. […] Many cases of serotonin toxicity occur in people who have ingested drug combinations that synergistically increase synaptic serotonin. […] It may also occur due to an overdose of a single serotonergic agent.

• #25

  https://www.pulsus.com/scholarly-articles/a-brief-report-on-serotonin-syndrome-causes-diagnosis-andprevention-9254.html

  Serotonin Syndrome (SS) is the side effects that might happen with the utilization of certain serotonergic prescriptions or drugs. […] An enormous number of meds and street medications can cause serotonin disorder when taken alone at high dosages or in mix z innymi serotonergic drugs. Common Selective Serotonin reuptake inhibitors are: citalopram (Celexa), sertraline (Zoloft), fluoxetine (Prozac), paroxetine (Paxil) and escitalopram (Lexapro). SSNRIS include duloxetine (Cymbalta), venlafaxine (Effexor), Desvenlafaxine (Pristiq), Milnacipram (Savella). Common triptans include Sumatriptan (Imitrex), Zolmitriptan (Zolmig), Frovatriptan (frova), Rizatriptan (Maxalt), Almotriptan (Axert).

• #26 Serotonin Syndrome

  https://www.uspharmacist.com/article/serotonin-syndrome

  Serotonin syndrome, also referred to as serotonin toxicity, is one such condition that, in some cases, may be fatal. Medications with serotonergic activity, some even available OTC, are the culprits of this potentially preventable complex of symptoms. The incidence of serotonin syndrome is increasing with the expanded use of serotonergic agents and, specifically, with polypharmacy. The most common drug combinations associated with serotonin syndrome involve the monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and the tricyclic antidepressants (TCAs). While there are several mechanisms that result in excess serotonin, severe, life-threatening serotonin toxicity occurs only with combinations of medications acting at different sites, most frequently including an MAOI and an SSRI. This condition is more likely to occur when a medication is initially introduced into the regimen or when the dosage is increased. Serotonin syndrome is a potentially preventable, drug-related complication that occurs from increased serotonin activity in the central nervous system through a variety of mechanisms including an increase in serotonin synthesis, a decrease in serotonin metabolism, an increase in serotonin release, inhibition of serotonin uptake, direct serotonin receptor stimulation, and a nonspecific increase in serotonin activity. The toxicity is characterized by an altered mental status, neuromuscular excitation, and autonomic stimulation. The patient’s medication history is positive for serotonergic drugs. Serotonin syndrome is diagnosed only after all other potential causes of symptoms have been ruled out. Published case reports warn that clinicians treating patients with a combination of serotonergic antidepressants and atypical antipsychotics for psychotic depression should be aware of the potential for serotonin syndrome. It is the combination of serotonergic drugs, acting by different mechanisms, that is capable of raising intrasynaptic serotonin to a level that is life threatening. Complications can occur, such as uncontrolled muscle spasms causing severe muscle breakdown and resulting in renal damage, if not recognized and treated appropriately. The combination that most commonly does this is an MAOI drug combined with any serotonin reuptake inhibitor (SRI). Treatment involves removal of the causative agents and may also include the use of serotonin antagonists. Symptoms typically resolve within 24 hours after withdrawal of the serotonergic medication. Clinicians should obtain complete medication histories to identify patients at risk, strictly monitor medication therapy including concomitant agents, and receive education about serotonin syndrome.

• #27 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  Serotonin syndrome is typically caused by the use of two or more serotonergic medications or drugs. […] This may include selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), amphetamines, pethidine (meperidine), tramadol, dextromethorphan, buspirone, L-tryptophan, 5-hydroxytryptophan, St. John’s wort, triptans, MDMA, ondansetron, metoclopramide, or cocaine. […] It occurs in about 15% of SSRI overdoses. […] It is a predictable consequence of excess serotonin on the central nervous system. […] Many cases of serotonin toxicity occur in people who have ingested drug combinations that synergistically increase synaptic serotonin. […] It may also occur due to an overdose of a single serotonergic agent.

• #28 Orphanet: Serotonin syndrome

  https://www.orpha.net/en/disease/detail/43116

  A rare neurologic disease characterized by an excess of serotonin in the central nervous system, associated with the use of various agents, including selective serotonin reuptake inhibitors (SSRIs) and recreational stimulants. […] SSRIs and monoamine oxidase inhibitors (MAOIs) may be responsible for this syndrome at toxic but also at therapeutic concentrations. The syndrome may appear: a few hours to a few days after the initiation of the treatment; following simultaneous combination (counter-indication) of MAOIs-A (toloxatone, moclobemide) and SSRIs or successive combination with an excessively short pill-free interval; as the result of drug-drug interactions; or in some cases of acute poisoning. Individual susceptibility and severity of clinical effects may be explained by interindividual pharmacokinetic and pharmacodynamic differences. Various recreational stimulants including amphetamines (especially MDMA), synthetic cathinones, and cannabinoids are also increasingly involved.

• #29 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  The combination of monoamine oxidase inhibitors (MAOIs) with precursors such as L-tryptophan or 5-hydroxytryptophan pose a particularly acute risk of life-threatening serotonin syndrome. […] The case of combination of MAOIs with tryptamine agonists (commonly known as ayahuasca) can present similar dangers as their combination with precursors, but this phenomenon has been described in general terms as the cheese effect. […] Many MAOIs irreversibly inhibit monoamine oxidase. […] With respect to tricyclic antidepressants, only clomipramine and imipramine have a risk of causing SS. […] The relative risk and severity of serotonergic side effects and serotonin toxicity, with individual drugs and combinations, is complex. […] SS has been reported in patients of all ages, including the elderly, children, and even newborn infants due to in utero exposure.

• #30 Serotonin Syndrome | 5-Minute Clinical Consult

  https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116962/all/Serotonin_Syndrome

  A potentially life-threatening drug-induced syndrome that results from synaptic increase in serotonin (5-hydroxytryptamine [5-HT]) concentrations and stimulation of peripheral and CNS serotonergic receptors. […] Increased synaptic 5-HT or agonist concentration as a result of one or more of the following mechanisms: (i) decreased 5-HT breakdown (e.g., MAOI), (ii) decreased 5-HT reuptake (e.g., SSRI), (iii) increased 5-HT agonists (e.g., tryptophan), (iv) increased 5-HT release (e.g., amphetamines), and (v) CYP2D6 and CYP3A4 inhibitors (e.g., erythromycin). […] A number of drugs are associated with serotonin syndrome, which usually involves combination with an SSRI. These include SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline); MAOIs; SNRIs (duloxetine, venlafaxine, desvenlafaxine); tricyclic antidepressants (e.g., amitriptyline, clomipramine); other antidepressants (nefazodone, trazodone, mirtazapine); anxiolytic (buspirone); lithium; triptans; anticonvulsants (divalproex [Depakote]); analgesics (fentanyl, meperidine, pentazocine, tramadol); antibiotics/antivirals (linezolid, tedizolid [weak MAOI], ritonavir); over-the-counter (OTC) cough medications (dextromethorphan); some antipsychotics (risperidone, olanzapine); antiemetics (ondansetron, granisetron); other medications, such as metoclopramide, cyclobenzaprine, L-dopa; dietary supplements (tryptophan); herbal supplements (St. John wort, nutmeg); methylene blue; and drugs of abuse (e.g., methylenedioxymethamphetamine [MDMA], cocaine, D-lysergic acid diethylamide [LSD], amphetamine). […] The greatest number of adverse events are associated with SSRIs in combination with other substances, and the combination of SSRIs and MAOIs carries the greatest risk of developing serotonin toxicity.

• #31 Serotonin Syndrome | 5-Minute Clinical Consult

  https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116962/all/Serotonin_Syndrome

  A potentially life-threatening drug-induced syndrome that results from synaptic increase in serotonin (5-hydroxytryptamine [5-HT]) concentrations and stimulation of peripheral and CNS serotonergic receptors. […] Increased synaptic 5-HT or agonist concentration as a result of one or more of the following mechanisms: (i) decreased 5-HT breakdown (e.g., MAOI), (ii) decreased 5-HT reuptake (e.g., SSRI), (iii) increased 5-HT agonists (e.g., tryptophan), (iv) increased 5-HT release (e.g., amphetamines), and (v) CYP2D6 and CYP3A4 inhibitors (e.g., erythromycin). […] A number of drugs are associated with serotonin syndrome, which usually involves combination with an SSRI. These include SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline); MAOIs; SNRIs (duloxetine, venlafaxine, desvenlafaxine); tricyclic antidepressants (e.g., amitriptyline, clomipramine); other antidepressants (nefazodone, trazodone, mirtazapine); anxiolytic (buspirone); lithium; triptans; anticonvulsants (divalproex [Depakote]); analgesics (fentanyl, meperidine, pentazocine, tramadol); antibiotics/antivirals (linezolid, tedizolid [weak MAOI], ritonavir); over-the-counter (OTC) cough medications (dextromethorphan); some antipsychotics (risperidone, olanzapine); antiemetics (ondansetron, granisetron); other medications, such as metoclopramide, cyclobenzaprine, L-dopa; dietary supplements (tryptophan); herbal supplements (St. John wort, nutmeg); methylene blue; and drugs of abuse (e.g., methylenedioxymethamphetamine [MDMA], cocaine, D-lysergic acid diethylamide [LSD], amphetamine). […] The greatest number of adverse events are associated with SSRIs in combination with other substances, and the combination of SSRIs and MAOIs carries the greatest risk of developing serotonin toxicity.

• #32

  https://www.pulsus.com/scholarly-articles/a-brief-report-on-serotonin-syndrome-causes-diagnosis-andprevention-9254.html

  Serotonin Syndrome (SS) is the side effects that might happen with the utilization of certain serotonergic prescriptions or drugs. […] An enormous number of meds and street medications can cause serotonin disorder when taken alone at high dosages or in mix z innymi serotonergic drugs. Common Selective Serotonin reuptake inhibitors are: citalopram (Celexa), sertraline (Zoloft), fluoxetine (Prozac), paroxetine (Paxil) and escitalopram (Lexapro). SSNRIS include duloxetine (Cymbalta), venlafaxine (Effexor), Desvenlafaxine (Pristiq), Milnacipram (Savella). Common triptans include Sumatriptan (Imitrex), Zolmitriptan (Zolmig), Frovatriptan (frova), Rizatriptan (Maxalt), Almotriptan (Axert).

• #33 Serotonin Syndrome

  https://emed.ie/Toxicology/Serotonin_Syndrome.php

  A toxic drug effect characterised by mental state changes and a variety of autonomic and neuromuscular manifestations. […] Causes are usually intentional self-poisoning with serotonergic agents or when drugs that inhibit the cytochrome P450 are added to therapeutic regimens of SSRIs. […] Specific agents that may be implicated in serotonin syndrome include: amphetamines and their derivatives (ecstasy, dextroamphetamine, methamphetamine, and sibutramine), analgesics (cyclobenzaprine, fentanyl, meperidine, tramadol), antidepressants/mood stabilizers (buspirone, lithium), MAOIs (such as phenelzine), SSRIs (such as fluoxetine) serotonin-norepinephrine reuptake inhibitors (e.g. venlafaxine), St. John’s wort, TCADs, antiemetics (metoclopramide, ondansetron), antimigraine drugs (carbamazepine, ergot alkaloids, triptans, valproic acid).

• #34 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  Various drugs, other than SSRIs, also have clinically significant potency as serotonin reuptake inhibitors, (such as tramadol, amphetamine, and MDMA) and are associated with severe cases of the syndrome. […] Cases where opioids alone are the cause of SS are typically seen with tramadol, because of its dual mechanism as a serotonin-norepinephrine reuptake inhibitor. […] SS caused by tramadol can be particularly problematic if an individual taking the drug is unaware of the risks associated with it and attempts to self-medicate symptoms such as headache, agitation, and tremors with more opioids, further exacerbating the condition.

• #35 Surprising Drugs That Can Cause Serotonin Syndrome

  https://www.pharmacytimes.com/view/surprising-drugs-that-can-cause-serotonin-syndrome

  Serotonin syndrome usually occurs because of a combination of 2 or more serotonergic medicines. […] Causative agents typically include monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants. […] The stimulants dexmethylphenidate and methylphenidate are known to increase the release of serotonin when used concurrently with SSRIs or SNRIs, but the clinical significance of this is unclear, and data to evaluate the overall impact are lacking. […] The opioids meperidine and methadone as well as the muscle relaxant cyclobenzaprine impair serotonin reuptake from the synaptic cleft into the presynaptic neuron. […] Fentanyl and metaxalone are direct serotonin receptor agonists. […] The risk of serotonin syndrome increases when 2 of these 3 opioids are used concurrently, and all these medications raise the risk of serotonin syndrome when used with other serotonergic medications.

• #36 Serotonin Syndrome: Risk Factors and Prevention Strategies | Clean Recovery Centers

  https://www.cleanrecoverycenters.com/serotonin-syndrome-risk-factors-and-prevention-strategies/

  Overdosing on illegal drugs or combining them with prescription medications may also lead to developing serotonin syndrome. […] Taking herbal supplements while also taking various prescriptions may be problematic. […] Nausea medications are sometimes temporarily prescribed for illnesses and conditions.

• #37 Surprising Drugs That Can Cause Serotonin Syndrome

  https://www.pharmacytimes.com/view/surprising-drugs-that-can-cause-serotonin-syndrome

  Serotonin syndrome usually occurs because of a combination of 2 or more serotonergic medicines. […] Causative agents typically include monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants. […] The stimulants dexmethylphenidate and methylphenidate are known to increase the release of serotonin when used concurrently with SSRIs or SNRIs, but the clinical significance of this is unclear, and data to evaluate the overall impact are lacking. […] The opioids meperidine and methadone as well as the muscle relaxant cyclobenzaprine impair serotonin reuptake from the synaptic cleft into the presynaptic neuron. […] Fentanyl and metaxalone are direct serotonin receptor agonists. […] The risk of serotonin syndrome increases when 2 of these 3 opioids are used concurrently, and all these medications raise the risk of serotonin syndrome when used with other serotonergic medications.

• #38 Drug-Induced Serotonin Syndrome

  https://www.uspharmacist.com/article/drug-induced-serotonin-syndrome

  A potentially lethal condition, serotonin syndrome (SS) is caused most often when certain antidepressant agents are taken concurrently with other drugs that modulate synaptic serotonin levels. […] SS may occur when central and peripheral serotonin receptors are overstimulated through the action of antidepressant medications or drugs of abuse. […] Drug classes implicated include antimigraine agents; triptans (e.g., sumatriptan); antidepressants (e.g., SSRIs, serotonin norepinephrine reuptake inhibitors [SNRIs], buspirone, tricyclic antidepressants, monoamine oxidase inhibitors [MAOIs]); antipsychotics; anticonvulsants; antiparkinsonian agents; analgesics (e.g., meperidine, tramadol); OTC products (e.g., cough and cold medication containing dextromethorphan); herbal products (e.g., St. John’s wort [Hypericum perforatum]; and the antibiotic linezolid.

• #39 Serotonin Syndrome | 5-Minute Clinical Consult

  https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116962/all/Serotonin_Syndrome

  A potentially life-threatening drug-induced syndrome that results from synaptic increase in serotonin (5-hydroxytryptamine [5-HT]) concentrations and stimulation of peripheral and CNS serotonergic receptors. […] Increased synaptic 5-HT or agonist concentration as a result of one or more of the following mechanisms: (i) decreased 5-HT breakdown (e.g., MAOI), (ii) decreased 5-HT reuptake (e.g., SSRI), (iii) increased 5-HT agonists (e.g., tryptophan), (iv) increased 5-HT release (e.g., amphetamines), and (v) CYP2D6 and CYP3A4 inhibitors (e.g., erythromycin). […] A number of drugs are associated with serotonin syndrome, which usually involves combination with an SSRI. These include SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline); MAOIs; SNRIs (duloxetine, venlafaxine, desvenlafaxine); tricyclic antidepressants (e.g., amitriptyline, clomipramine); other antidepressants (nefazodone, trazodone, mirtazapine); anxiolytic (buspirone); lithium; triptans; anticonvulsants (divalproex [Depakote]); analgesics (fentanyl, meperidine, pentazocine, tramadol); antibiotics/antivirals (linezolid, tedizolid [weak MAOI], ritonavir); over-the-counter (OTC) cough medications (dextromethorphan); some antipsychotics (risperidone, olanzapine); antiemetics (ondansetron, granisetron); other medications, such as metoclopramide, cyclobenzaprine, L-dopa; dietary supplements (tryptophan); herbal supplements (St. John wort, nutmeg); methylene blue; and drugs of abuse (e.g., methylenedioxymethamphetamine [MDMA], cocaine, D-lysergic acid diethylamide [LSD], amphetamine). […] The greatest number of adverse events are associated with SSRIs in combination with other substances, and the combination of SSRIs and MAOIs carries the greatest risk of developing serotonin toxicity.

• #40 Drug-Induced Serotonin Syndrome

  https://www.uspharmacist.com/article/drug-induced-serotonin-syndrome

  A potentially lethal condition, serotonin syndrome (SS) is caused most often when certain antidepressant agents are taken concurrently with other drugs that modulate synaptic serotonin levels. […] SS may occur when central and peripheral serotonin receptors are overstimulated through the action of antidepressant medications or drugs of abuse. […] Drug classes implicated include antimigraine agents; triptans (e.g., sumatriptan); antidepressants (e.g., SSRIs, serotonin norepinephrine reuptake inhibitors [SNRIs], buspirone, tricyclic antidepressants, monoamine oxidase inhibitors [MAOIs]); antipsychotics; anticonvulsants; antiparkinsonian agents; analgesics (e.g., meperidine, tramadol); OTC products (e.g., cough and cold medication containing dextromethorphan); herbal products (e.g., St. John’s wort [Hypericum perforatum]; and the antibiotic linezolid.

• #41 Serotonin syndrome: Symptoms, Causes & Treatment

  https://www.mentalhealth.com/library/serotonin-syndrome

  Lithium is known to increase the release of serotonin in the brain, which could lead to serotonin syndrome in rare cases. […] St John’s wort has significant drug interactions with many common prescription medications. Like SSRIs and SNRIs, it is thought to increase the amount of serotonin available in the body, which can lead to serotonin syndrome, especially when used in conjunction with similar types of medication. […] Any drug that can cause the brain to produce higher levels of serotonin can potentially lead to serotonin syndrome, especially when used at the same time as other drugs or medications.

• #42 Serotonin Syndrome | 5-Minute Clinical Consult

  https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116962/all/Serotonin_Syndrome

  A potentially life-threatening drug-induced syndrome that results from synaptic increase in serotonin (5-hydroxytryptamine [5-HT]) concentrations and stimulation of peripheral and CNS serotonergic receptors. […] Increased synaptic 5-HT or agonist concentration as a result of one or more of the following mechanisms: (i) decreased 5-HT breakdown (e.g., MAOI), (ii) decreased 5-HT reuptake (e.g., SSRI), (iii) increased 5-HT agonists (e.g., tryptophan), (iv) increased 5-HT release (e.g., amphetamines), and (v) CYP2D6 and CYP3A4 inhibitors (e.g., erythromycin). […] A number of drugs are associated with serotonin syndrome, which usually involves combination with an SSRI. These include SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline); MAOIs; SNRIs (duloxetine, venlafaxine, desvenlafaxine); tricyclic antidepressants (e.g., amitriptyline, clomipramine); other antidepressants (nefazodone, trazodone, mirtazapine); anxiolytic (buspirone); lithium; triptans; anticonvulsants (divalproex [Depakote]); analgesics (fentanyl, meperidine, pentazocine, tramadol); antibiotics/antivirals (linezolid, tedizolid [weak MAOI], ritonavir); over-the-counter (OTC) cough medications (dextromethorphan); some antipsychotics (risperidone, olanzapine); antiemetics (ondansetron, granisetron); other medications, such as metoclopramide, cyclobenzaprine, L-dopa; dietary supplements (tryptophan); herbal supplements (St. John wort, nutmeg); methylene blue; and drugs of abuse (e.g., methylenedioxymethamphetamine [MDMA], cocaine, D-lysergic acid diethylamide [LSD], amphetamine). […] The greatest number of adverse events are associated with SSRIs in combination with other substances, and the combination of SSRIs and MAOIs carries the greatest risk of developing serotonin toxicity.

• #43 Serotonin Syndrome | 5-Minute Clinical Consult

  https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116962/all/Serotonin_Syndrome

  A potentially life-threatening drug-induced syndrome that results from synaptic increase in serotonin (5-hydroxytryptamine [5-HT]) concentrations and stimulation of peripheral and CNS serotonergic receptors. […] Increased synaptic 5-HT or agonist concentration as a result of one or more of the following mechanisms: (i) decreased 5-HT breakdown (e.g., MAOI), (ii) decreased 5-HT reuptake (e.g., SSRI), (iii) increased 5-HT agonists (e.g., tryptophan), (iv) increased 5-HT release (e.g., amphetamines), and (v) CYP2D6 and CYP3A4 inhibitors (e.g., erythromycin). […] A number of drugs are associated with serotonin syndrome, which usually involves combination with an SSRI. These include SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline); MAOIs; SNRIs (duloxetine, venlafaxine, desvenlafaxine); tricyclic antidepressants (e.g., amitriptyline, clomipramine); other antidepressants (nefazodone, trazodone, mirtazapine); anxiolytic (buspirone); lithium; triptans; anticonvulsants (divalproex [Depakote]); analgesics (fentanyl, meperidine, pentazocine, tramadol); antibiotics/antivirals (linezolid, tedizolid [weak MAOI], ritonavir); over-the-counter (OTC) cough medications (dextromethorphan); some antipsychotics (risperidone, olanzapine); antiemetics (ondansetron, granisetron); other medications, such as metoclopramide, cyclobenzaprine, L-dopa; dietary supplements (tryptophan); herbal supplements (St. John wort, nutmeg); methylene blue; and drugs of abuse (e.g., methylenedioxymethamphetamine [MDMA], cocaine, D-lysergic acid diethylamide [LSD], amphetamine). […] The greatest number of adverse events are associated with SSRIs in combination with other substances, and the combination of SSRIs and MAOIs carries the greatest risk of developing serotonin toxicity.

• #44 Serotonin Syndrome | 5-Minute Clinical Consult

  https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116962/all/Serotonin_Syndrome

  A potentially life-threatening drug-induced syndrome that results from synaptic increase in serotonin (5-hydroxytryptamine [5-HT]) concentrations and stimulation of peripheral and CNS serotonergic receptors. […] Increased synaptic 5-HT or agonist concentration as a result of one or more of the following mechanisms: (i) decreased 5-HT breakdown (e.g., MAOI), (ii) decreased 5-HT reuptake (e.g., SSRI), (iii) increased 5-HT agonists (e.g., tryptophan), (iv) increased 5-HT release (e.g., amphetamines), and (v) CYP2D6 and CYP3A4 inhibitors (e.g., erythromycin). […] A number of drugs are associated with serotonin syndrome, which usually involves combination with an SSRI. These include SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline); MAOIs; SNRIs (duloxetine, venlafaxine, desvenlafaxine); tricyclic antidepressants (e.g., amitriptyline, clomipramine); other antidepressants (nefazodone, trazodone, mirtazapine); anxiolytic (buspirone); lithium; triptans; anticonvulsants (divalproex [Depakote]); analgesics (fentanyl, meperidine, pentazocine, tramadol); antibiotics/antivirals (linezolid, tedizolid [weak MAOI], ritonavir); over-the-counter (OTC) cough medications (dextromethorphan); some antipsychotics (risperidone, olanzapine); antiemetics (ondansetron, granisetron); other medications, such as metoclopramide, cyclobenzaprine, L-dopa; dietary supplements (tryptophan); herbal supplements (St. John wort, nutmeg); methylene blue; and drugs of abuse (e.g., methylenedioxymethamphetamine [MDMA], cocaine, D-lysergic acid diethylamide [LSD], amphetamine). […] The greatest number of adverse events are associated with SSRIs in combination with other substances, and the combination of SSRIs and MAOIs carries the greatest risk of developing serotonin toxicity.

• #45 Serotonin Syndrome: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17687-serotonin-syndrome

  Use certain illegal drugs or herbal products or over-the-counter drugs that affect serotonin levels. […] Antidepressants are the most commonly used medications that affect serotonin levels. […] Antidepressant drug classes and medication examples that can increase serotonin levels include: […] Selective serotonin reuptake inhibitors (SSRIs): […] This drug class is the most common antidepressant class involved in serotonin syndrome due to its widespread use. […] Other medications can also affect your bodys serotonin level, especially when combined with other drugs that affect serotonin. […] Other herbal and dietary supplements and illegal substances that affect serotonin levels and could cause serotonin syndrome include: […] Medical experts still have much to learn about serotonin syndrome.

• #46 Drug-Induced Serotonin Syndrome

  https://www.uspharmacist.com/article/drug-induced-serotonin-syndrome

  A potentially lethal condition, serotonin syndrome (SS) is caused most often when certain antidepressant agents are taken concurrently with other drugs that modulate synaptic serotonin levels. […] SS may occur when central and peripheral serotonin receptors are overstimulated through the action of antidepressant medications or drugs of abuse. […] Drug classes implicated include antimigraine agents; triptans (e.g., sumatriptan); antidepressants (e.g., SSRIs, serotonin norepinephrine reuptake inhibitors [SNRIs], buspirone, tricyclic antidepressants, monoamine oxidase inhibitors [MAOIs]); antipsychotics; anticonvulsants; antiparkinsonian agents; analgesics (e.g., meperidine, tramadol); OTC products (e.g., cough and cold medication containing dextromethorphan); herbal products (e.g., St. John’s wort [Hypericum perforatum]; and the antibiotic linezolid.

• #47 Serotonin Syndrome | 5-Minute Clinical Consult

  https://www.unboundmedicine.com/5minute/view/5-Minute-Clinical-Consult/116962/all/Serotonin_Syndrome

  A potentially life-threatening drug-induced syndrome that results from synaptic increase in serotonin (5-hydroxytryptamine [5-HT]) concentrations and stimulation of peripheral and CNS serotonergic receptors. […] Increased synaptic 5-HT or agonist concentration as a result of one or more of the following mechanisms: (i) decreased 5-HT breakdown (e.g., MAOI), (ii) decreased 5-HT reuptake (e.g., SSRI), (iii) increased 5-HT agonists (e.g., tryptophan), (iv) increased 5-HT release (e.g., amphetamines), and (v) CYP2D6 and CYP3A4 inhibitors (e.g., erythromycin). […] A number of drugs are associated with serotonin syndrome, which usually involves combination with an SSRI. These include SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline); MAOIs; SNRIs (duloxetine, venlafaxine, desvenlafaxine); tricyclic antidepressants (e.g., amitriptyline, clomipramine); other antidepressants (nefazodone, trazodone, mirtazapine); anxiolytic (buspirone); lithium; triptans; anticonvulsants (divalproex [Depakote]); analgesics (fentanyl, meperidine, pentazocine, tramadol); antibiotics/antivirals (linezolid, tedizolid [weak MAOI], ritonavir); over-the-counter (OTC) cough medications (dextromethorphan); some antipsychotics (risperidone, olanzapine); antiemetics (ondansetron, granisetron); other medications, such as metoclopramide, cyclobenzaprine, L-dopa; dietary supplements (tryptophan); herbal supplements (St. John wort, nutmeg); methylene blue; and drugs of abuse (e.g., methylenedioxymethamphetamine [MDMA], cocaine, D-lysergic acid diethylamide [LSD], amphetamine). […] The greatest number of adverse events are associated with SSRIs in combination with other substances, and the combination of SSRIs and MAOIs carries the greatest risk of developing serotonin toxicity.

• #48 Drug-Induced Serotonin Syndrome

  https://www.uspharmacist.com/article/drug-induced-serotonin-syndrome

  A potentially lethal condition, serotonin syndrome (SS) is caused most often when certain antidepressant agents are taken concurrently with other drugs that modulate synaptic serotonin levels. […] SS may occur when central and peripheral serotonin receptors are overstimulated through the action of antidepressant medications or drugs of abuse. […] Drug classes implicated include antimigraine agents; triptans (e.g., sumatriptan); antidepressants (e.g., SSRIs, serotonin norepinephrine reuptake inhibitors [SNRIs], buspirone, tricyclic antidepressants, monoamine oxidase inhibitors [MAOIs]); antipsychotics; anticonvulsants; antiparkinsonian agents; analgesics (e.g., meperidine, tramadol); OTC products (e.g., cough and cold medication containing dextromethorphan); herbal products (e.g., St. John’s wort [Hypericum perforatum]; and the antibiotic linezolid.

• #49 Surprising Drugs That Can Cause Serotonin Syndrome

  https://www.pharmacytimes.com/view/surprising-drugs-that-can-cause-serotonin-syndrome

  Other unexpected causes of serotonin syndrome are recreational drugs. […] Cocaine has been used medicinally and illicitly for centuries, but its propensity to cause serotonin syndrome is widely known. […] The compound 3,4-methylenedioxymethamphetamine (MDMA) can cause serotonin syndrome by impairing serotonin reuptake from the synaptic cleft into the presynaptic neuron. […] Ayahuasca has monoamine oxidase-inhibiting harmala alkaloids in most of its formulations. […] Serotonin syndrome caused by food alone is highly unlikely because the active compounds would have to be ingested in high quantities to potentiate toxic serotonin activity. […] Nutmeg might be the most studied and well-known food to cause serotonin syndrome. […] Curcumin is another offending agent. […] Tryptophan directly increases serotonin production.

• #50 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  Serotonin syndrome is typically caused by the use of two or more serotonergic medications or drugs. […] This may include selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), amphetamines, pethidine (meperidine), tramadol, dextromethorphan, buspirone, L-tryptophan, 5-hydroxytryptophan, St. John’s wort, triptans, MDMA, ondansetron, metoclopramide, or cocaine. […] It occurs in about 15% of SSRI overdoses. […] It is a predictable consequence of excess serotonin on the central nervous system. […] Many cases of serotonin toxicity occur in people who have ingested drug combinations that synergistically increase synaptic serotonin. […] It may also occur due to an overdose of a single serotonergic agent.

• #51 Serotonin Syndrome: Symptoms, Causes & Treatment – SelfHacked

  https://selfhacked.com/blog/serotonin-syndrome/

  Any nausea medication that interacts with serotonin receptors can increase the risk of serotonin syndrome. […] St. Johns Wort can interact negatively with many medications, including SSRIs, and these combinations may cause serotonin syndrome. […] SAM-e can significantly raise serotonin production, so it may, in theory, pose a risk for serotonin syndrome if taken at a high dose or in combination with other drugs. […] Ginseng increases serotonin in the brain (especially in the hippocampus), posing a risk for serotonin syndrome when taken in high quantities or in combination with other drugs that affect serotonin levels. […] L-tryptophan directly increases the production of serotonin. If taken at too high a dose, or in combination with another drug that increases serotonin levels, there is a potential risk of serotonin syndrome.

• #52 Surprising Drugs That Can Cause Serotonin Syndrome

  https://www.pharmacytimes.com/view/surprising-drugs-that-can-cause-serotonin-syndrome

  Other unexpected causes of serotonin syndrome are recreational drugs. […] Cocaine has been used medicinally and illicitly for centuries, but its propensity to cause serotonin syndrome is widely known. […] The compound 3,4-methylenedioxymethamphetamine (MDMA) can cause serotonin syndrome by impairing serotonin reuptake from the synaptic cleft into the presynaptic neuron. […] Ayahuasca has monoamine oxidase-inhibiting harmala alkaloids in most of its formulations. […] Serotonin syndrome caused by food alone is highly unlikely because the active compounds would have to be ingested in high quantities to potentiate toxic serotonin activity. […] Nutmeg might be the most studied and well-known food to cause serotonin syndrome. […] Curcumin is another offending agent. […] Tryptophan directly increases serotonin production.

• #53 Serotonin Syndrome: Causes, Symptoms, and Treatment

  https://www.webmd.com/brain/serotonin-syndrome-causes-symptoms-treatments

  Some other prescription and over-the-counter drugs that can raise your serotonin levels, either alone or when you take them together, include buspirone, trazodone, and certain migraine treatments. […] Dietary supplements such as St. John’s wort, ginseng, and tryptophan can cause serotonin syndrome when you take them with antidepressants. […] Some recreational drugs, such as LSD, cocaine, ecstasy, and amphetamines can also cause serotonin syndrome if you take them with antidepressants.

• #54 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  Serotonin syndrome is typically caused by the use of two or more serotonergic medications or drugs. […] This may include selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), amphetamines, pethidine (meperidine), tramadol, dextromethorphan, buspirone, L-tryptophan, 5-hydroxytryptophan, St. John’s wort, triptans, MDMA, ondansetron, metoclopramide, or cocaine. […] It occurs in about 15% of SSRI overdoses. […] It is a predictable consequence of excess serotonin on the central nervous system. […] Many cases of serotonin toxicity occur in people who have ingested drug combinations that synergistically increase synaptic serotonin. […] It may also occur due to an overdose of a single serotonergic agent.

• #55 Serotonin syndrome Information | Mount Sinai – New York

  https://www.mountsinai.org/health-library/diseases-conditions/serotonin-syndrome

  Serotonin syndrome (SS) is a potentially life-threatening drug reaction. It causes the body to have too much serotonin, a chemical produced by some nerve cells. […] SS most often occurs when two or more medicines or drugs that affect the body’s level of serotonin are taken together at the same time. The medicines cause too much serotonin to be released or to remain in the brain area. […] Older antidepressants called monoamine oxidase inhibitors (MAOIs) can also cause SS when combined with the medicines described above, as well as meperidine (Demerol, a painkiller), fentanyl, dextromethorphan (cough medicine), and others. […] Street drugs, such as methamphetamine or other amphetamines, cocaine, opiates, ecstasy, LSD, and others have also been associated with SS.

• #56 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  Various drugs, other than SSRIs, also have clinically significant potency as serotonin reuptake inhibitors, (such as tramadol, amphetamine, and MDMA) and are associated with severe cases of the syndrome. […] Cases where opioids alone are the cause of SS are typically seen with tramadol, because of its dual mechanism as a serotonin-norepinephrine reuptake inhibitor. […] SS caused by tramadol can be particularly problematic if an individual taking the drug is unaware of the risks associated with it and attempts to self-medicate symptoms such as headache, agitation, and tremors with more opioids, further exacerbating the condition.

• #57 Serotonin Syndrome

  https://emed.ie/Toxicology/Serotonin_Syndrome.php

  A toxic drug effect characterised by mental state changes and a variety of autonomic and neuromuscular manifestations. […] Causes are usually intentional self-poisoning with serotonergic agents or when drugs that inhibit the cytochrome P450 are added to therapeutic regimens of SSRIs. […] Specific agents that may be implicated in serotonin syndrome include: amphetamines and their derivatives (ecstasy, dextroamphetamine, methamphetamine, and sibutramine), analgesics (cyclobenzaprine, fentanyl, meperidine, tramadol), antidepressants/mood stabilizers (buspirone, lithium), MAOIs (such as phenelzine), SSRIs (such as fluoxetine) serotonin-norepinephrine reuptake inhibitors (e.g. venlafaxine), St. John’s wort, TCADs, antiemetics (metoclopramide, ondansetron), antimigraine drugs (carbamazepine, ergot alkaloids, triptans, valproic acid).

• #58 Serotonin Syndrome

  https://emed.ie/Toxicology/Serotonin_Syndrome.php

  A toxic drug effect characterised by mental state changes and a variety of autonomic and neuromuscular manifestations. […] Causes are usually intentional self-poisoning with serotonergic agents or when drugs that inhibit the cytochrome P450 are added to therapeutic regimens of SSRIs. […] Specific agents that may be implicated in serotonin syndrome include: amphetamines and their derivatives (ecstasy, dextroamphetamine, methamphetamine, and sibutramine), analgesics (cyclobenzaprine, fentanyl, meperidine, tramadol), antidepressants/mood stabilizers (buspirone, lithium), MAOIs (such as phenelzine), SSRIs (such as fluoxetine) serotonin-norepinephrine reuptake inhibitors (e.g. venlafaxine), St. John’s wort, TCADs, antiemetics (metoclopramide, ondansetron), antimigraine drugs (carbamazepine, ergot alkaloids, triptans, valproic acid).

• #59 Conundrums in neurology: diagnosing serotonin syndrome – a meta-analysis of cases | BMC Neurology | Full Text

  https://bmcneurol.biomedcentral.com/articles/10.1186/s12883-016-0616-1

  Serotonin syndrome is a toxic state, caused by serotonin (5HT) excess in the central nervous system. […] The syndrome is thought to arise from 5HT1A and 5HT2 receptor stimulation and has been linked to variety of drugs with direct or indirect serotonergic actions. […] The risk of SS is higher when two or more serotonergic drugs are used in conjunction but cases caused by a single serotonergic agent have also been reported. […] The list of drugs associated with serotonergic toxicity is long, although experts do not always agree. […] Non-antidepressant agent with monoamine oxidase (MAO) inhibiting properties such as MAO-B inhibitors for the treatment of Parkinsons disease, the antibiotic linezolid or the contrast dye and methylene blue can also provoke serotonin excess and SS. […] Herbal medicines such as St Johns wort (hypericum perforatum) and illicit substances such as lysergic acid diethylamide (LSD) and 3,4-methylendioxy-methamphetamine (MDMA) are further examples.

• #60 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  The combination of monoamine oxidase inhibitors (MAOIs) with precursors such as L-tryptophan or 5-hydroxytryptophan pose a particularly acute risk of life-threatening serotonin syndrome. […] The case of combination of MAOIs with tryptamine agonists (commonly known as ayahuasca) can present similar dangers as their combination with precursors, but this phenomenon has been described in general terms as the cheese effect. […] Many MAOIs irreversibly inhibit monoamine oxidase. […] With respect to tricyclic antidepressants, only clomipramine and imipramine have a risk of causing SS. […] The relative risk and severity of serotonergic side effects and serotonin toxicity, with individual drugs and combinations, is complex. […] SS has been reported in patients of all ages, including the elderly, children, and even newborn infants due to in utero exposure.

• #61 Surprising Drugs That Can Cause Serotonin Syndrome

  https://www.pharmacytimes.com/view/surprising-drugs-that-can-cause-serotonin-syndrome

  Other unexpected causes of serotonin syndrome are recreational drugs. […] Cocaine has been used medicinally and illicitly for centuries, but its propensity to cause serotonin syndrome is widely known. […] The compound 3,4-methylenedioxymethamphetamine (MDMA) can cause serotonin syndrome by impairing serotonin reuptake from the synaptic cleft into the presynaptic neuron. […] Ayahuasca has monoamine oxidase-inhibiting harmala alkaloids in most of its formulations. […] Serotonin syndrome caused by food alone is highly unlikely because the active compounds would have to be ingested in high quantities to potentiate toxic serotonin activity. […] Nutmeg might be the most studied and well-known food to cause serotonin syndrome. […] Curcumin is another offending agent. […] Tryptophan directly increases serotonin production.

• #62 Orphanet: Serotonin syndrome

  https://www.orpha.net/en/disease/detail/43116

  A rare neurologic disease characterized by an excess of serotonin in the central nervous system, associated with the use of various agents, including selective serotonin reuptake inhibitors (SSRIs) and recreational stimulants. […] SSRIs and monoamine oxidase inhibitors (MAOIs) may be responsible for this syndrome at toxic but also at therapeutic concentrations. The syndrome may appear: a few hours to a few days after the initiation of the treatment; following simultaneous combination (counter-indication) of MAOIs-A (toloxatone, moclobemide) and SSRIs or successive combination with an excessively short pill-free interval; as the result of drug-drug interactions; or in some cases of acute poisoning. Individual susceptibility and severity of clinical effects may be explained by interindividual pharmacokinetic and pharmacodynamic differences. Various recreational stimulants including amphetamines (especially MDMA), synthetic cathinones, and cannabinoids are also increasingly involved.

• #63 Serotonin Syndrome: Symptoms, Causes, Diagnosis, Treatment

  https://www.healthline.com/health/serotonin-syndrome

  Serotonin syndrome, also called serotonin toxicity, is a potentially serious reaction usually caused by medications that increase serotonin. […] Serotonin syndrome results from the use of drugs, supplements, and other substances. […] It can happen if you: accidentally use medications that are not suitable or at a dosage that is too high, combine two drugs that boost serotonin, intentionally take too much of a drug. […] Typically, the condition occurs when you combine two or more medications, illegal drugs, or nutritional supplements that increase serotonin levels. […] Taking too much of a drug or combining two drugs that boost serotonin can sometimes trigger serotonin syndrome.

• #64 Recognize the Signs and Symptoms of Serotonin Syndrome

  https://www.verywellmind.com/what-is-serotonin-syndrome-379651

  Serotonin syndrome is a potentially life-threatening condition caused by elevated serotonin concentrations in your body from certain medications. […] Serotonin syndrome, also known as serotonin toxicity, happens as the result of taking serotonergic drugs, which are medications that affect the level of serotonin in your body. It may be brought on by several different circumstances, including: […] Taking one serotonergic medication: It’s unlikely that using one serotonergic medication by itself will cause serotonin syndrome, but it can happen in certain people who are sensitive to serotonin, especially when the dose is increased. […] Overdosing: You can end up with serotonin syndrome if you ingest too much of your serotonergic medication(s), whether an overdose is accidental or purposeful. […] Taking two serotonergic medications together: The most common cause of serotonin syndrome involves a person taking two (or more) serotonergic drugs at the same time, often without realizing it.

• #65 Serotonin Syndrome: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17687-serotonin-syndrome

  Serotonin syndrome happens when you have too much serotonin (a normal chemical) in your body. Its usually caused by taking drugs or medications that affect serotonin levels. […] Serotonin syndrome is a potentially life-threatening drug reaction that results from having too much serotonin in your body. […] Serotonin syndrome happens most often when you either take a new drug or take an increased dose of a drug that increases the level of serotonin in your body. […] A rise in serotonin levels in your body causes serotonin syndrome. This increase in serotonin can happen if you: […] Take more than one medication that affects serotonin levels. […] Recently started on a medication or increased the dose of a medication known to increase serotonin levels. […] Take too much of one serotonin-related medication, accidentally or on purpose.

• #66 Demystifying serotonin syndrome (or serotonin toxicity)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6184959/

  Serotonin toxicity is a drug-induced condition caused by too much serotonin in synapses in the brain. […] Serotonin toxicity most often happens when 2 serotonin-elevating drugs are used together. […] The use of an MAOI with an SSRI, an SNRI, or another MAOI is the most concerning drug combination. […] Serotonin toxicity is an important topic for primary care providers. […] Education of both practitioners and patients is the only way to prevent serotonin toxicity.

• #67 The Serotonin Syndrome: From Molecular Mechanisms to Clinical Practice

  https://www.mdpi.com/1422-0067/20/9/2288

  The combination of an MAOI with an SSRI, and SNRI or another MAOI is the most dangerous combination and the most likely to result in SS. […] Increased production of serotonin (through an overabundance of the precursor molecule L-tryptophan) as well as decreased metabolism of serotonin (by the administration of MAOI), may each cause receptor overstimulation and SS. […] Several discrete mechanisms have been hypothesized to explain how drugs cause SS, although it is likely that more than one of these mechanisms may need to be simultaneously triggered in order to result in clinically significant SS. […] It appears that certain individuals with known polymorphisms at the T102C site of the 5-HT2A receptor gene may be predisposed to developing SS. […] Individual variations in serotonin metabolism by CYPs have also been proposed to contribute to SS susceptibility. […] SERT proteins are critical to the termination of synaptic serotonergic activity.

• #68 Drug-Induced Serotonin Syndrome

  https://www.uspharmacist.com/article/drug-induced-serotonin-syndrome

  A potentially lethal condition, serotonin syndrome (SS) is caused most often when certain antidepressant agents are taken concurrently with other drugs that modulate synaptic serotonin levels. […] SS may occur when central and peripheral serotonin receptors are overstimulated through the action of antidepressant medications or drugs of abuse. […] Drug classes implicated include antimigraine agents; triptans (e.g., sumatriptan); antidepressants (e.g., SSRIs, serotonin norepinephrine reuptake inhibitors [SNRIs], buspirone, tricyclic antidepressants, monoamine oxidase inhibitors [MAOIs]); antipsychotics; anticonvulsants; antiparkinsonian agents; analgesics (e.g., meperidine, tramadol); OTC products (e.g., cough and cold medication containing dextromethorphan); herbal products (e.g., St. John’s wort [Hypericum perforatum]; and the antibiotic linezolid.

• #69 Serotonin syndrome: a spectrum of toxicity | BJPsych Advances | Cambridge Core

  https://www.cambridge.org/core/journals/bjpsych-advances/article/serotonin-syndrome-a-spectrum-of-toxicity/BB07FCAF5DC69DF5FFC0AEB113147A9E

  Higher risk of serotonin syndrome is associated with increasing age, increasing dose of serotonergic agents and serotonergic agents in combination with medications that have high CYP2D6 inhibitory function. […] Commonly prescribed medications, such as antidepressants with tramadol, may interact, and at higher doses, tramadol is reported as being able to both block reuptake and induce release of serotonin. […] A higher incidence of serotonin syndrome has been reported in patients who are undergoing haemodialysis for end-stage renal disease and who are taking SSRIs; this may be due to decreased renal function. […] The prognosis is good, especially where there has been early recognition, immediate discontinuation of the causal medication and rapid establishment of appropriate supportive measures.

• #70 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  The combination of monoamine oxidase inhibitors (MAOIs) with precursors such as L-tryptophan or 5-hydroxytryptophan pose a particularly acute risk of life-threatening serotonin syndrome. […] The case of combination of MAOIs with tryptamine agonists (commonly known as ayahuasca) can present similar dangers as their combination with precursors, but this phenomenon has been described in general terms as the cheese effect. […] Many MAOIs irreversibly inhibit monoamine oxidase. […] With respect to tricyclic antidepressants, only clomipramine and imipramine have a risk of causing SS. […] The relative risk and severity of serotonergic side effects and serotonin toxicity, with individual drugs and combinations, is complex. […] SS has been reported in patients of all ages, including the elderly, children, and even newborn infants due to in utero exposure.

• #71 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  Serotonin syndrome is typically caused by the use of two or more serotonergic medications or drugs. […] This may include selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), amphetamines, pethidine (meperidine), tramadol, dextromethorphan, buspirone, L-tryptophan, 5-hydroxytryptophan, St. John’s wort, triptans, MDMA, ondansetron, metoclopramide, or cocaine. […] It occurs in about 15% of SSRI overdoses. […] It is a predictable consequence of excess serotonin on the central nervous system. […] Many cases of serotonin toxicity occur in people who have ingested drug combinations that synergistically increase synaptic serotonin. […] It may also occur due to an overdose of a single serotonergic agent.

• #72 Serotonin Syndrome: Symptoms, Treatment, and More

  https://www.verywellhealth.com/serotonin-syndrome-1719929

  The buildup of the chemical serotonin in the body can cause a potentially fatal (albeit rare) disease known as serotonin syndrome. This syndrome mostly occurs when you take a cocktail of medications that increase serotonin, such as a triptan for your migraines and an antidepressant for your depression, both of which act to increase levels of serotonin in the brain. […] There are three ways in which serotonin syndrome may occur. […] Use of two or more serotonergic medications (meaning medications that increase serotonin levels) […] An overdose of a single serotonergic medication […] Increasing the dose of a single serotonergic medication. […] There are also a number of migraine-related medications that have the potential to cause serotonin syndrome. […] Other non-migraine-related medications that may contribute to the development of serotonin syndrome include Tramadol (Ultram), which is a pain medication, certain illegal drugs such as cocaine and MDMA (ecstasy), St. John’s Wort, Robitussin (dextromethorphan), monoamine-oxidase inhibitors (MAOIs), and lithium. […] Serotonin syndrome usually occurs within one day of increasing a medication dose or adding on a serotonin-increasing medication.

• #73 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  Serotonin syndrome is typically caused by the use of two or more serotonergic medications or drugs. […] This may include selective serotonin reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI), monoamine oxidase inhibitor (MAOI), tricyclic antidepressants (TCAs), amphetamines, pethidine (meperidine), tramadol, dextromethorphan, buspirone, L-tryptophan, 5-hydroxytryptophan, St. John’s wort, triptans, MDMA, ondansetron, metoclopramide, or cocaine. […] It occurs in about 15% of SSRI overdoses. […] It is a predictable consequence of excess serotonin on the central nervous system. […] Many cases of serotonin toxicity occur in people who have ingested drug combinations that synergistically increase synaptic serotonin. […] It may also occur due to an overdose of a single serotonergic agent.

• #74 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  Various drugs, other than SSRIs, also have clinically significant potency as serotonin reuptake inhibitors, (such as tramadol, amphetamine, and MDMA) and are associated with severe cases of the syndrome. […] Cases where opioids alone are the cause of SS are typically seen with tramadol, because of its dual mechanism as a serotonin-norepinephrine reuptake inhibitor. […] SS caused by tramadol can be particularly problematic if an individual taking the drug is unaware of the risks associated with it and attempts to self-medicate symptoms such as headache, agitation, and tremors with more opioids, further exacerbating the condition.

• #75 Serotonin Syndrome: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17687-serotonin-syndrome

  Serotonin syndrome happens when you have too much serotonin (a normal chemical) in your body. Its usually caused by taking drugs or medications that affect serotonin levels. […] Serotonin syndrome is a potentially life-threatening drug reaction that results from having too much serotonin in your body. […] Serotonin syndrome happens most often when you either take a new drug or take an increased dose of a drug that increases the level of serotonin in your body. […] A rise in serotonin levels in your body causes serotonin syndrome. This increase in serotonin can happen if you: […] Take more than one medication that affects serotonin levels. […] Recently started on a medication or increased the dose of a medication known to increase serotonin levels. […] Take too much of one serotonin-related medication, accidentally or on purpose.

• #76 Serotonin Syndrome: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17687-serotonin-syndrome

  Serotonin syndrome happens when you have too much serotonin (a normal chemical) in your body. Its usually caused by taking drugs or medications that affect serotonin levels. […] Serotonin syndrome is a potentially life-threatening drug reaction that results from having too much serotonin in your body. […] Serotonin syndrome happens most often when you either take a new drug or take an increased dose of a drug that increases the level of serotonin in your body. […] A rise in serotonin levels in your body causes serotonin syndrome. This increase in serotonin can happen if you: […] Take more than one medication that affects serotonin levels. […] Recently started on a medication or increased the dose of a medication known to increase serotonin levels. […] Take too much of one serotonin-related medication, accidentally or on purpose.

• #77 UMEM Educational Pearls – University of Maryland School of Medicine, Department of Emergency Medicine

  https://umem.org/educational_pearls/2890/

  Serotonin syndrome is not an idiopathic drug reaction, but the result of excess serotonin in the nervous system. […] It is classically associated with administration of two serotonergic agents, but it can occur after initiation of a single agent or increasing the dose of a serotonergic agent in individuals who are particularly sensitive to serotonin. […] Although selective serotonin reuptake inhibitors (SSRIs) are most commonly implicated, there are other medications encountered in the Emergency Department that can also play a role in serotonin syndrome. […] There are also reports of serotonin syndrome occurring with methadone, trazodone, and metaxalone (Skelaxin).

• #78 Prevention, Diagnosis, and Management of Serotonin Syndrome | AAFP

  https://www.aafp.org/pubs/afp/issues/2010/0501/p1139.html

  Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonergic activity in the nervous system. […] Most reported cases of serotonin syndrome are in patients using multiple serotonergic drugs or who have had considerable exposure to a single serotonin-augmenting drug. […] Serotonin syndrome can occur with any increase in serotonergic neurotransmission. The majority of cases are iatrogenic from synergistic medication use, although cases of intentional self-poisoning with serotonergic agents also occur. […] Another mechanism for development of serotonin syndrome is the addition of drugs that inhibit the cytochrome P450 2D6 and/or 3A4 (CYP3A4) isoenzymes to therapeutic regimens of selective serotonin reuptake inhibitors (SSRIs). […] A remarkable number of drugs from different classes have been implicated as causing serotonin syndrome. […] Most reported cases are in patients taking multiple serotonergic agents or who have had considerable exposure to a single serotonin-augmenting drug.

• #79 Serotonin syndrome – EMCrit Project

  https://emcrit.org/ibcc/serotonin/

  Serotonin syndrome can occur for a variety of reasons: (1) Overdose of a serotonergic medication (e.g., SSRI or illicits). Serotonin syndrome occurs in ~15% of SSRI overdoses. […] (2) Inadvertent interaction between several serotonergic medications: 2a) Addition of drugs which are directly serotonergic. 2b) Addition of drugs which cause drug-drug interactions, increasing the levels of other serotonergic medications (i.e. the new medication doesn’t necessarily need to directly affect serotonin signaling). […] (3) Renal dysfunction may cause accumulation of serotonergic medications (e.g., sertraline). […] In practice, most episodes of serotonin syndrome result from multiple drugs interacting together. When in doubt, enter the whole medication list into a program such as the Medscape drug interaction program; this may reveal unexpected interactions.

• #80 Prevention, Diagnosis, and Management of Serotonin Syndrome | AAFP

  https://www.aafp.org/pubs/afp/issues/2010/0501/p1139.html

  Serotonin syndrome is a potentially life-threatening condition caused by excessive serotonergic activity in the nervous system. […] Most reported cases of serotonin syndrome are in patients using multiple serotonergic drugs or who have had considerable exposure to a single serotonin-augmenting drug. […] Serotonin syndrome can occur with any increase in serotonergic neurotransmission. The majority of cases are iatrogenic from synergistic medication use, although cases of intentional self-poisoning with serotonergic agents also occur. […] Another mechanism for development of serotonin syndrome is the addition of drugs that inhibit the cytochrome P450 2D6 and/or 3A4 (CYP3A4) isoenzymes to therapeutic regimens of selective serotonin reuptake inhibitors (SSRIs). […] A remarkable number of drugs from different classes have been implicated as causing serotonin syndrome. […] Most reported cases are in patients taking multiple serotonergic agents or who have had considerable exposure to a single serotonin-augmenting drug.

• #81 Serotonin syndrome – EMCrit Project

  https://emcrit.org/ibcc/serotonin/

  Some examples of combinations reported to cause serotonin syndrome are listed below. […] In some cases, serotonin syndrome can be precipitated by non-serotonergic drugs that inhibit the metabolism of other serotonergic medications. […] CYP3A4 is responsible for metabolizing the most serotonergic medications.

• #82 Serotonin syndrome (serotonin toxicity) – UpToDate

  https://www.uptodate.com/contents/serotonin-syndrome-serotonin-toxicity

  Serotonin syndrome may result from any combination of drugs that has the net effect of increasing serotonergic neurotransmission. […] Episodes of serotonin syndrome involving a monoamine oxidase inhibitor (MAOI) may be more severe and more often lead to adverse outcomes, including death. […] The diagnosis of serotonin syndrome is made solely on clinical grounds. […] The majority of cases of serotonin syndrome present within 24 hours, and most within six hours, of a change in dose or initiation of a drug. […] The differential diagnosis of serotonin syndrome includes neuroleptic malignant syndrome (NMS), anticholinergic toxicity, acute extrapyramidal syndromes, malignant hyperthermia, sympathomimetic intoxication, sedative-hypnotic withdrawal, and thyroid storm. […] Serotonin syndrome can be avoided by applying pharmacologic principles, educating clinicians, and modifying prescription practices.

• #83 Detecting and Managing Serotonin Syndrome – Psychiatry Advisor

  https://www.psychiatryadvisor.com/features/detecting-and-managing-serotonin-syndrome/

  Serotonin syndrome tends to be underrecognized by physicians because you have to be careful and on the lookout, since its presentation can be subtle. […] The onset of serotonin syndrome can occur within hours of an exposure to a serotonergic agent, but can be delayed for as much as 24 hours. […] It is important to note that serotonin syndrome can progress from mild to florid and serious very quickly, especially in the setting of the combination of an SSRI or serotonin-norepinephrine reuptake inhibitor and a drug of abuse, such as cocaine. […] Classical symptoms of serotonin syndrome are listed in the Hunter Serotonin Toxicity Criteria for diagnosing serotonin syndrome. […] There is no laboratory test that confirms serotonin syndrome and serum serotonin levels do not necessarily correlate with clinical findings. […] It is essential to take a careful patient history, finding out what medications (prescription and over-the-counter) and dietary supplements the patient might have been using, for how long, and whether the dose was recently increased.

• #84 Drug-Induced Serotonin Syndrome

  https://www.uspharmacist.com/article/drug-induced-serotonin-syndrome

  SS typically occurs when a patient takes two or more drugs that elevate serotonin levels through different mechanisms, but the syndrome can occur with the use of individual agents. […] Mechanisms that cause SS include increased serotonin production, inhibition of serotonin reuptake, inhibition of serotonin metabolism, increased serotonin release, and stimulation of serotonin receptors. […] Two serotonergic drugs do not need to be administered concurrently to cause SS; the syndrome can occur up to 6 weeks after discontinuation of just one such drug with a long-acting dosage form, like fluoxetine (Prozac, Sarafem) or an MAOI (e.g., isocarboxazid, phenelzine). […] Concurrent use of medications that interact with serotonergic drugs, thereby resulting in inhibition of the CYP450 metabolic pathway, can also contribute to SS.

• #85 Serotonin syndrome: Preventing, recognizing, and treating it | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/83/11/810

  Serotonin syndrome is caused by elevated serotonin levels in the central and peripheral nervous systems. […] Conditions that can alter the regulation of serotonin include therapeutic doses, drug interactions, intentional or unintentional overdoses, and overlapping transitions between medications. […] The only drugs that have been reliably confirmed to precipitate serotonin syndrome are MAOIs, SSRIs, SNRIs, and serotonin releasers. […] An estimated 15% of SSRI overdoses lead to mild or moderate serotonin toxicity. […] The combination of age and comorbidities may increase the risk for this condition. […] Serotonin syndrome characteristically presents as the triad of autonomic dysfunction, neuromuscular excitation, and altered mental status. […] Symptoms of serotonin toxicity arise within an hour of a precipitating event (eg, ingestion) in approximately 28% of patients, and within 6 hours in 61%.

• #86 Serotonin syndrome: Preventing, recognizing, and treating it | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/83/11/810

  Serotonin syndrome is caused by elevated serotonin levels in the central and peripheral nervous systems. […] Conditions that can alter the regulation of serotonin include therapeutic doses, drug interactions, intentional or unintentional overdoses, and overlapping transitions between medications. […] The only drugs that have been reliably confirmed to precipitate serotonin syndrome are MAOIs, SSRIs, SNRIs, and serotonin releasers. […] An estimated 15% of SSRI overdoses lead to mild or moderate serotonin toxicity. […] The combination of age and comorbidities may increase the risk for this condition. […] Serotonin syndrome characteristically presents as the triad of autonomic dysfunction, neuromuscular excitation, and altered mental status. […] Symptoms of serotonin toxicity arise within an hour of a precipitating event (eg, ingestion) in approximately 28% of patients, and within 6 hours in 61%.

• #87 Serotonin Syndrome | Doctor

  https://patient.info/doctor/serotonin-syndrome

  Drugs implicated in SS include: Antidepressants: SSRI, SNRI, TCA, MAOI, St John’s wort, lithium. […] It is worth checking with a reputable formulary or toxicologist whether there are any known drug interactions causing the syndrome, where it is suspected in an individual taking serotonergic agents. […] Although the epidemiology of SS has yet to be extensively studied, the combination of age and comorbidities may increase the risk.

• #88 Serotonin syndrome: a spectrum of toxicity | BJPsych Advances | Cambridge Core

  https://www.cambridge.org/core/journals/bjpsych-advances/article/serotonin-syndrome-a-spectrum-of-toxicity/BB07FCAF5DC69DF5FFC0AEB113147A9E

  Higher risk of serotonin syndrome is associated with increasing age, increasing dose of serotonergic agents and serotonergic agents in combination with medications that have high CYP2D6 inhibitory function. […] Commonly prescribed medications, such as antidepressants with tramadol, may interact, and at higher doses, tramadol is reported as being able to both block reuptake and induce release of serotonin. […] A higher incidence of serotonin syndrome has been reported in patients who are undergoing haemodialysis for end-stage renal disease and who are taking SSRIs; this may be due to decreased renal function. […] The prognosis is good, especially where there has been early recognition, immediate discontinuation of the causal medication and rapid establishment of appropriate supportive measures.

• #89 Serotonin syndrome (serotonin toxicity) – UpToDate

  https://www.uptodate.com/contents/serotonin-syndrome-serotonin-toxicity

  Serotonin syndrome, also referred to as serotonin toxicity, is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. It is seen with therapeutic medication use, inadvertent interactions between drugs, and intentional self-poisoning. […] Serotonin syndrome may involve a spectrum of clinical findings, which often include mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. […] The selective serotonin reuptake inhibitors (SSRIs) are perhaps the most commonly implicated group of medications associated with serotonin syndrome. […] The syndrome has been described following intentional overdose, and even in post-cardiac arrest patients treated with therapeutic hypothermia. […] However, the true incidence of serotonin syndrome may be under-represented in data such as the NPDS for a number of reasons.

• #90 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  The combination of monoamine oxidase inhibitors (MAOIs) with precursors such as L-tryptophan or 5-hydroxytryptophan pose a particularly acute risk of life-threatening serotonin syndrome. […] The case of combination of MAOIs with tryptamine agonists (commonly known as ayahuasca) can present similar dangers as their combination with precursors, but this phenomenon has been described in general terms as the cheese effect. […] Many MAOIs irreversibly inhibit monoamine oxidase. […] With respect to tricyclic antidepressants, only clomipramine and imipramine have a risk of causing SS. […] The relative risk and severity of serotonergic side effects and serotonin toxicity, with individual drugs and combinations, is complex. […] SS has been reported in patients of all ages, including the elderly, children, and even newborn infants due to in utero exposure.

• #91 Serotonin Syndrome: Symptoms, Causes & Treatment – SelfHacked

  https://selfhacked.com/blog/serotonin-syndrome/

  Susceptibility to serotonin syndrome can depend largely and how your body processes drugs that increase serotonin. […] Over 80 variants of the CYP2D6 gene exist, and 7-10% of the European population has a version that results in a slow metabolism and more of the drug building up. People who carry slow versions of this gene may be more prone to developing serotonin syndrome.

• #92 The Serotonin Syndrome: From Molecular Mechanisms to Clinical Practice

  https://www.mdpi.com/1422-0067/20/9/2288

  The combination of an MAOI with an SSRI, and SNRI or another MAOI is the most dangerous combination and the most likely to result in SS. […] Increased production of serotonin (through an overabundance of the precursor molecule L-tryptophan) as well as decreased metabolism of serotonin (by the administration of MAOI), may each cause receptor overstimulation and SS. […] Several discrete mechanisms have been hypothesized to explain how drugs cause SS, although it is likely that more than one of these mechanisms may need to be simultaneously triggered in order to result in clinically significant SS. […] It appears that certain individuals with known polymorphisms at the T102C site of the 5-HT2A receptor gene may be predisposed to developing SS. […] Individual variations in serotonin metabolism by CYPs have also been proposed to contribute to SS susceptibility. […] SERT proteins are critical to the termination of synaptic serotonergic activity.

• #93 The Serotonin Syndrome: From Molecular Mechanisms to Clinical Practice

  https://www.mdpi.com/1422-0067/20/9/2288

  The combination of an MAOI with an SSRI, and SNRI or another MAOI is the most dangerous combination and the most likely to result in SS. […] Increased production of serotonin (through an overabundance of the precursor molecule L-tryptophan) as well as decreased metabolism of serotonin (by the administration of MAOI), may each cause receptor overstimulation and SS. […] Several discrete mechanisms have been hypothesized to explain how drugs cause SS, although it is likely that more than one of these mechanisms may need to be simultaneously triggered in order to result in clinically significant SS. […] It appears that certain individuals with known polymorphisms at the T102C site of the 5-HT2A receptor gene may be predisposed to developing SS. […] Individual variations in serotonin metabolism by CYPs have also been proposed to contribute to SS susceptibility. […] SERT proteins are critical to the termination of synaptic serotonergic activity.

• #94 Serotonin Syndrome: Symptoms, Causes & Treatment – SelfHacked

  https://selfhacked.com/blog/serotonin-syndrome/

  Susceptibility to serotonin syndrome can depend largely and how your body processes drugs that increase serotonin. […] Over 80 variants of the CYP2D6 gene exist, and 7-10% of the European population has a version that results in a slow metabolism and more of the drug building up. People who carry slow versions of this gene may be more prone to developing serotonin syndrome.

• #95 The Serotonin Syndrome: From Molecular Mechanisms to Clinical Practice

  https://www.mdpi.com/1422-0067/20/9/2288

  The combination of an MAOI with an SSRI, and SNRI or another MAOI is the most dangerous combination and the most likely to result in SS. […] Increased production of serotonin (through an overabundance of the precursor molecule L-tryptophan) as well as decreased metabolism of serotonin (by the administration of MAOI), may each cause receptor overstimulation and SS. […] Several discrete mechanisms have been hypothesized to explain how drugs cause SS, although it is likely that more than one of these mechanisms may need to be simultaneously triggered in order to result in clinically significant SS. […] It appears that certain individuals with known polymorphisms at the T102C site of the 5-HT2A receptor gene may be predisposed to developing SS. […] Individual variations in serotonin metabolism by CYPs have also been proposed to contribute to SS susceptibility. […] SERT proteins are critical to the termination of synaptic serotonergic activity.

• #96 Serotonin syndrome: Preventing, recognizing, and treating it | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/83/11/810

  Serotonin crisis is usually caused by the co-ingestion of multiple serotonergic agents, such as an antidepressant with an aforementioned opioid and antiemetic; combining an SSRI and an MAOI poses the greatest risk. […] The two mainstays of serotonin syndrome management are to discontinue the serotonergic agent and to give supportive care. […] Prevention of serotonin syndrome begins with improving education and awareness in patients and healthcare providers.

• #97 Serotonin syndrome (serotonin toxicity) – UpToDate

  https://www.uptodate.com/contents/serotonin-syndrome-serotonin-toxicity

  Serotonin syndrome may result from any combination of drugs that has the net effect of increasing serotonergic neurotransmission. […] Episodes of serotonin syndrome involving a monoamine oxidase inhibitor (MAOI) may be more severe and more often lead to adverse outcomes, including death. […] The diagnosis of serotonin syndrome is made solely on clinical grounds. […] The majority of cases of serotonin syndrome present within 24 hours, and most within six hours, of a change in dose or initiation of a drug. […] The differential diagnosis of serotonin syndrome includes neuroleptic malignant syndrome (NMS), anticholinergic toxicity, acute extrapyramidal syndromes, malignant hyperthermia, sympathomimetic intoxication, sedative-hypnotic withdrawal, and thyroid storm. […] Serotonin syndrome can be avoided by applying pharmacologic principles, educating clinicians, and modifying prescription practices.

• #98 Serotonin syndrome (serotonin toxicity) – UpToDate

  https://www.uptodate.com/contents/serotonin-syndrome-serotonin-toxicity/print

  Serotonin syndrome, also referred to as serotonin toxicity, is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. It is seen with therapeutic medication use, inadvertent interactions between drugs, and intentional self-poisoning. […] The selective serotonin reuptake inhibitors (SSRIs) are perhaps the most commonly implicated group of medications associated with serotonin syndrome. The United States’ National Poison Data System (NPDS) consistently reports tens of thousands of exposures to SSRIs, many of which involve serotonin syndrome. Notably, SSRIs are less commonly associated with causing severe serotonin syndrome compared with medications that inhibit monoamine oxidase (MAO). […] Serotonin syndrome may result from any combination of drugs that has the net effect of increasing serotonergic neurotransmission. The syndrome is classically associated with the simultaneous administration of two serotonergic agents, but it can occur after initiation of a single serotonergic drug or increasing the dose of a serotonergic drug in individuals who are particularly sensitive to serotonin. […] Episodes of serotonin syndrome involving a monoamine oxidase inhibitor (MAOI) may be more severe and more often lead to adverse outcomes, including death.

• #99 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  Various drugs, other than SSRIs, also have clinically significant potency as serotonin reuptake inhibitors, (such as tramadol, amphetamine, and MDMA) and are associated with severe cases of the syndrome. […] Cases where opioids alone are the cause of SS are typically seen with tramadol, because of its dual mechanism as a serotonin-norepinephrine reuptake inhibitor. […] SS caused by tramadol can be particularly problematic if an individual taking the drug is unaware of the risks associated with it and attempts to self-medicate symptoms such as headache, agitation, and tremors with more opioids, further exacerbating the condition.

• #100 Pulsenotes | Serotonin syndrome

  https://app.pulsenotes.com/specialities/psychiatry/notes/serotonin-syndrome

  A range of agents can induce SS by a variety of mechanisms that ultimately increase serotonergic transmission in the CNS: Increased release of serotonin: Amphetamines, MDMA (ecstasy), cocaine; Impaired serotonin reuptake: SSRIs, SNRIs, MDMA, tricycle antidepressants, serotonin modulators; Inhibit serotonin metabolism: Monoamine oxidase inhibitors; Serotonin receptor agonists: Buspirone, Triptans; Increased sensitivity of serotonin receptor: Lithium. […] SS may occur due to exposure to a single agent that affects serotonergic transmission or a combination of drugs that collectively cause a net increase in serotonergic transmission.

• #101 Serotonin syndrome – EMCrit Project

  https://emcrit.org/ibcc/serotonin/

  Most cases are mild-moderate, and will improve in about a day following cessation of medications. However, serotonin syndrome can be severe and may require ICU admission. […] The main challenge is recognition: If serotonin syndrome is recognized early and causative drugs are stopped immediately, then patients will generally do very well. […] Roughly two forms of serotonin syndrome will be seen in the ICU: (1) Patients presenting to the hospital with serotonin syndrome (e.g., due to illicit intoxication or outpatient polypharmacy). (2) Nosocomial serotonin syndrome. ICU patients who are continued on their outpatient psychiatric medications may easily be exposed to one or more serotonergic medications, creating a risk of serotonin syndrome. Many housekeeping medications that we don’t think about much can promote serotonin syndrome (e.g., ondansetron, fentanyl, metoclopramide).

• #102 Serotonin syndrome – EMCrit Project

  https://emcrit.org/ibcc/serotonin/

  Most cases are mild-moderate, and will improve in about a day following cessation of medications. However, serotonin syndrome can be severe and may require ICU admission. […] The main challenge is recognition: If serotonin syndrome is recognized early and causative drugs are stopped immediately, then patients will generally do very well. […] Roughly two forms of serotonin syndrome will be seen in the ICU: (1) Patients presenting to the hospital with serotonin syndrome (e.g., due to illicit intoxication or outpatient polypharmacy). (2) Nosocomial serotonin syndrome. ICU patients who are continued on their outpatient psychiatric medications may easily be exposed to one or more serotonergic medications, creating a risk of serotonin syndrome. Many housekeeping medications that we don’t think about much can promote serotonin syndrome (e.g., ondansetron, fentanyl, metoclopramide).

• #103 Serotonin syndrome – EMCrit Project

  https://emcrit.org/ibcc/serotonin/

  Most cases are mild-moderate, and will improve in about a day following cessation of medications. However, serotonin syndrome can be severe and may require ICU admission. […] The main challenge is recognition: If serotonin syndrome is recognized early and causative drugs are stopped immediately, then patients will generally do very well. […] Roughly two forms of serotonin syndrome will be seen in the ICU: (1) Patients presenting to the hospital with serotonin syndrome (e.g., due to illicit intoxication or outpatient polypharmacy). (2) Nosocomial serotonin syndrome. ICU patients who are continued on their outpatient psychiatric medications may easily be exposed to one or more serotonergic medications, creating a risk of serotonin syndrome. Many housekeeping medications that we don’t think about much can promote serotonin syndrome (e.g., ondansetron, fentanyl, metoclopramide).

• #104 Serotonin syndrome (serotonin toxicity) – UpToDate

  https://www.uptodate.com/contents/serotonin-syndrome-serotonin-toxicity

  Serotonin syndrome may result from any combination of drugs that has the net effect of increasing serotonergic neurotransmission. […] Episodes of serotonin syndrome involving a monoamine oxidase inhibitor (MAOI) may be more severe and more often lead to adverse outcomes, including death. […] The diagnosis of serotonin syndrome is made solely on clinical grounds. […] The majority of cases of serotonin syndrome present within 24 hours, and most within six hours, of a change in dose or initiation of a drug. […] The differential diagnosis of serotonin syndrome includes neuroleptic malignant syndrome (NMS), anticholinergic toxicity, acute extrapyramidal syndromes, malignant hyperthermia, sympathomimetic intoxication, sedative-hypnotic withdrawal, and thyroid storm. […] Serotonin syndrome can be avoided by applying pharmacologic principles, educating clinicians, and modifying prescription practices.

• #105 Detecting and Managing Serotonin Syndrome – Psychiatry Advisor

  https://www.psychiatryadvisor.com/features/detecting-and-managing-serotonin-syndrome/

  Serotonin syndrome tends to be underrecognized by physicians because you have to be careful and on the lookout, since its presentation can be subtle. […] The onset of serotonin syndrome can occur within hours of an exposure to a serotonergic agent, but can be delayed for as much as 24 hours. […] It is important to note that serotonin syndrome can progress from mild to florid and serious very quickly, especially in the setting of the combination of an SSRI or serotonin-norepinephrine reuptake inhibitor and a drug of abuse, such as cocaine. […] Classical symptoms of serotonin syndrome are listed in the Hunter Serotonin Toxicity Criteria for diagnosing serotonin syndrome. […] There is no laboratory test that confirms serotonin syndrome and serum serotonin levels do not necessarily correlate with clinical findings. […] It is essential to take a careful patient history, finding out what medications (prescription and over-the-counter) and dietary supplements the patient might have been using, for how long, and whether the dose was recently increased.

• #106 Detecting and Managing Serotonin Syndrome – Psychiatry Advisor

  https://www.psychiatryadvisor.com/features/detecting-and-managing-serotonin-syndrome/

  Serotonin syndrome tends to be underrecognized by physicians because you have to be careful and on the lookout, since its presentation can be subtle. […] The onset of serotonin syndrome can occur within hours of an exposure to a serotonergic agent, but can be delayed for as much as 24 hours. […] It is important to note that serotonin syndrome can progress from mild to florid and serious very quickly, especially in the setting of the combination of an SSRI or serotonin-norepinephrine reuptake inhibitor and a drug of abuse, such as cocaine. […] Classical symptoms of serotonin syndrome are listed in the Hunter Serotonin Toxicity Criteria for diagnosing serotonin syndrome. […] There is no laboratory test that confirms serotonin syndrome and serum serotonin levels do not necessarily correlate with clinical findings. […] It is essential to take a careful patient history, finding out what medications (prescription and over-the-counter) and dietary supplements the patient might have been using, for how long, and whether the dose was recently increased.

• #107 Detecting and Managing Serotonin Syndrome – Psychiatry Advisor

  https://www.psychiatryadvisor.com/features/detecting-and-managing-serotonin-syndrome/

  Serotonin syndrome is caused by drugs that either affect serotonin metabolism or act as direct serotonin receptor agonists, or both, and takes place in the setting of excess stimulation of central and peripheral serotonin receptors. […] Drugs that can cause serotonin syndrome do so by inhibiting serotonin reuptake, increasing serotonin synthesis, decreasing serotonin metabolism, increasing serotonin release, or activating serotonergic receptors. […] The actual incidence of serotonin syndrome and associated morbidity is likely underestimated, as serotonin syndrome is frequently underdiagnosed and underreported and can easily be overlooked, especially when mild. […] It has been suggested that more than 85% of physicians are not familiar with the existence of serotonin syndrome or which drugs or drug combinations may cause it.

• #108 Serotonin syndrome: a spectrum of toxicity | BJPsych Advances | Cambridge Core

  https://www.cambridge.org/core/journals/bjpsych-advances/article/serotonin-syndrome-a-spectrum-of-toxicity/BB07FCAF5DC69DF5FFC0AEB113147A9E

  Serotonin syndrome can present as a spectrum of different symptoms and signs and in varying degrees of severity. […] In practice, serotonin syndrome usually results from drug interactions, classically secondary to the combined overdose of an SSRI with an (irreversible) monoamine oxidase inhibitor (MAOI), which in around 50% of cases is believed to result in severe serotonin syndrome. […] Severe serotonin toxicity can have a rapid onset and deterioration; death can ensue within 24 h. […] In some cases symptoms may be misattributed to deterioration in mental state, with the risk of increasing or additional medication. […] There appears to be a sequential stimulatory effect in the presence of excess serotonin, which corresponds roughly to the spectrum of increasing toxicity. […] There is support for the theory that a particular concentration of serotonin is a prerequisite for the development of serotonin syndrome. However, there is considerable inter-individual variation and this variability has its basis in genetic factors, which include polymorphisms of CYP2D6, SERT or the serotonin receptors themselves.

• #109 Serotonin Syndrome: Practice Essentials, Problem, Management

  https://emedicine.medscape.com/article/2500075-overview

  Serotonin syndrome can be precipitated by pharmaceuticals, botanicals, and recreational drugs. […] Drugs with serotoninergic properties have the ability to increase the level of serotonin or to act as direct agonists of postsynaptic serotonin receptors in the central nervous system (CNS). […] The majority of concerning combinations involve the use of a monoamine oxidase inhibitor (MAOI), a selective serotonin reuptake inhibitor (SSRI), or a serotonin-norepinephrine reuptake inhibitor (SNRI). […] Serotonin syndrome is diagnosed on the basis of clinical manifestations, as well as a comprehensive medication review. […] According to the Hunter criteria, the patient must have taken a serotoninergic agent within the preceding 5 weeks and must also have one of the following: Muscle rigidity plus temperature higher than 38C plus ocular clonus/inducible clonus; Ocular clonus plus agitation/diaphoresis; Inducible clonus plus agitation/diaphoresis; Spontaneous clonus; Tremor plus hyperreflexia; Hypertonia.

• #110 Serotonin Syndrome: Practice Essentials, Problem, Management

  https://emedicine.medscape.com/article/2500075-overview

  Serotonin syndrome can be precipitated by pharmaceuticals, botanicals, and recreational drugs. […] Drugs with serotoninergic properties have the ability to increase the level of serotonin or to act as direct agonists of postsynaptic serotonin receptors in the central nervous system (CNS). […] The majority of concerning combinations involve the use of a monoamine oxidase inhibitor (MAOI), a selective serotonin reuptake inhibitor (SSRI), or a serotonin-norepinephrine reuptake inhibitor (SNRI). […] Serotonin syndrome is diagnosed on the basis of clinical manifestations, as well as a comprehensive medication review. […] According to the Hunter criteria, the patient must have taken a serotoninergic agent within the preceding 5 weeks and must also have one of the following: Muscle rigidity plus temperature higher than 38C plus ocular clonus/inducible clonus; Ocular clonus plus agitation/diaphoresis; Inducible clonus plus agitation/diaphoresis; Spontaneous clonus; Tremor plus hyperreflexia; Hypertonia.

• #111 Serotonin Syndrome: Practice Essentials, Problem, Management

  https://emedicine.medscape.com/article/2500075-overview

  Serotonin syndrome can be precipitated by pharmaceuticals, botanicals, and recreational drugs. […] Drugs with serotoninergic properties have the ability to increase the level of serotonin or to act as direct agonists of postsynaptic serotonin receptors in the central nervous system (CNS). […] The majority of concerning combinations involve the use of a monoamine oxidase inhibitor (MAOI), a selective serotonin reuptake inhibitor (SSRI), or a serotonin-norepinephrine reuptake inhibitor (SNRI). […] Serotonin syndrome is diagnosed on the basis of clinical manifestations, as well as a comprehensive medication review. […] According to the Hunter criteria, the patient must have taken a serotoninergic agent within the preceding 5 weeks and must also have one of the following: Muscle rigidity plus temperature higher than 38C plus ocular clonus/inducible clonus; Ocular clonus plus agitation/diaphoresis; Inducible clonus plus agitation/diaphoresis; Spontaneous clonus; Tremor plus hyperreflexia; Hypertonia.

• #112 Serotonin Syndrome: Practice Essentials, Problem, Management

  https://emedicine.medscape.com/article/2500075-overview

  Serotonin syndrome can be precipitated by pharmaceuticals, botanicals, and recreational drugs. […] Drugs with serotoninergic properties have the ability to increase the level of serotonin or to act as direct agonists of postsynaptic serotonin receptors in the central nervous system (CNS). […] The majority of concerning combinations involve the use of a monoamine oxidase inhibitor (MAOI), a selective serotonin reuptake inhibitor (SSRI), or a serotonin-norepinephrine reuptake inhibitor (SNRI). […] Serotonin syndrome is diagnosed on the basis of clinical manifestations, as well as a comprehensive medication review. […] According to the Hunter criteria, the patient must have taken a serotoninergic agent within the preceding 5 weeks and must also have one of the following: Muscle rigidity plus temperature higher than 38C plus ocular clonus/inducible clonus; Ocular clonus plus agitation/diaphoresis; Inducible clonus plus agitation/diaphoresis; Spontaneous clonus; Tremor plus hyperreflexia; Hypertonia.

• #113 Serotonin Syndrome: Practice Essentials, Problem, Management

  https://emedicine.medscape.com/article/2500075-overview

  Serotonin syndrome can be precipitated by pharmaceuticals, botanicals, and recreational drugs. […] Drugs with serotoninergic properties have the ability to increase the level of serotonin or to act as direct agonists of postsynaptic serotonin receptors in the central nervous system (CNS). […] The majority of concerning combinations involve the use of a monoamine oxidase inhibitor (MAOI), a selective serotonin reuptake inhibitor (SSRI), or a serotonin-norepinephrine reuptake inhibitor (SNRI). […] Serotonin syndrome is diagnosed on the basis of clinical manifestations, as well as a comprehensive medication review. […] According to the Hunter criteria, the patient must have taken a serotoninergic agent within the preceding 5 weeks and must also have one of the following: Muscle rigidity plus temperature higher than 38C plus ocular clonus/inducible clonus; Ocular clonus plus agitation/diaphoresis; Inducible clonus plus agitation/diaphoresis; Spontaneous clonus; Tremor plus hyperreflexia; Hypertonia.

• #114 Serotonin Syndrome: Practice Essentials, Problem, Management

  https://emedicine.medscape.com/article/2500075-overview

  Serotonin syndrome can be precipitated by pharmaceuticals, botanicals, and recreational drugs. […] Drugs with serotoninergic properties have the ability to increase the level of serotonin or to act as direct agonists of postsynaptic serotonin receptors in the central nervous system (CNS). […] The majority of concerning combinations involve the use of a monoamine oxidase inhibitor (MAOI), a selective serotonin reuptake inhibitor (SSRI), or a serotonin-norepinephrine reuptake inhibitor (SNRI). […] Serotonin syndrome is diagnosed on the basis of clinical manifestations, as well as a comprehensive medication review. […] According to the Hunter criteria, the patient must have taken a serotoninergic agent within the preceding 5 weeks and must also have one of the following: Muscle rigidity plus temperature higher than 38C plus ocular clonus/inducible clonus; Ocular clonus plus agitation/diaphoresis; Inducible clonus plus agitation/diaphoresis; Spontaneous clonus; Tremor plus hyperreflexia; Hypertonia.

• #115 Serotonin Syndrome: Practice Essentials, Problem, Management

  https://emedicine.medscape.com/article/2500075-overview

  Serotonin syndrome can be precipitated by pharmaceuticals, botanicals, and recreational drugs. […] Drugs with serotoninergic properties have the ability to increase the level of serotonin or to act as direct agonists of postsynaptic serotonin receptors in the central nervous system (CNS). […] The majority of concerning combinations involve the use of a monoamine oxidase inhibitor (MAOI), a selective serotonin reuptake inhibitor (SSRI), or a serotonin-norepinephrine reuptake inhibitor (SNRI). […] Serotonin syndrome is diagnosed on the basis of clinical manifestations, as well as a comprehensive medication review. […] According to the Hunter criteria, the patient must have taken a serotoninergic agent within the preceding 5 weeks and must also have one of the following: Muscle rigidity plus temperature higher than 38C plus ocular clonus/inducible clonus; Ocular clonus plus agitation/diaphoresis; Inducible clonus plus agitation/diaphoresis; Spontaneous clonus; Tremor plus hyperreflexia; Hypertonia.

• #116 Serotonin syndrome: Preventing, recognizing, and treating it | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/83/11/810

  Serotonin crisis is usually caused by the co-ingestion of multiple serotonergic agents, such as an antidepressant with an aforementioned opioid and antiemetic; combining an SSRI and an MAOI poses the greatest risk. […] The two mainstays of serotonin syndrome management are to discontinue the serotonergic agent and to give supportive care. […] Prevention of serotonin syndrome begins with improving education and awareness in patients and healthcare providers.

• #117 Demystifying serotonin syndrome (or serotonin toxicity)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6184959/

  Serotonin toxicity is a drug-induced condition caused by too much serotonin in synapses in the brain. […] Serotonin toxicity most often happens when 2 serotonin-elevating drugs are used together. […] The use of an MAOI with an SSRI, an SNRI, or another MAOI is the most concerning drug combination. […] Serotonin toxicity is an important topic for primary care providers. […] Education of both practitioners and patients is the only way to prevent serotonin toxicity.

• #118 Serotonin syndrome (serotonin toxicity) – UpToDate

  https://www.uptodate.com/contents/serotonin-syndrome-serotonin-toxicity

  Serotonin syndrome may result from any combination of drugs that has the net effect of increasing serotonergic neurotransmission. […] Episodes of serotonin syndrome involving a monoamine oxidase inhibitor (MAOI) may be more severe and more often lead to adverse outcomes, including death. […] The diagnosis of serotonin syndrome is made solely on clinical grounds. […] The majority of cases of serotonin syndrome present within 24 hours, and most within six hours, of a change in dose or initiation of a drug. […] The differential diagnosis of serotonin syndrome includes neuroleptic malignant syndrome (NMS), anticholinergic toxicity, acute extrapyramidal syndromes, malignant hyperthermia, sympathomimetic intoxication, sedative-hypnotic withdrawal, and thyroid storm. […] Serotonin syndrome can be avoided by applying pharmacologic principles, educating clinicians, and modifying prescription practices.

• #119 Detecting and Managing Serotonin Syndrome – Psychiatry Advisor

  https://www.psychiatryadvisor.com/features/detecting-and-managing-serotonin-syndrome/

  Serotonin syndrome tends to be underrecognized by physicians because you have to be careful and on the lookout, since its presentation can be subtle. […] The onset of serotonin syndrome can occur within hours of an exposure to a serotonergic agent, but can be delayed for as much as 24 hours. […] It is important to note that serotonin syndrome can progress from mild to florid and serious very quickly, especially in the setting of the combination of an SSRI or serotonin-norepinephrine reuptake inhibitor and a drug of abuse, such as cocaine. […] Classical symptoms of serotonin syndrome are listed in the Hunter Serotonin Toxicity Criteria for diagnosing serotonin syndrome. […] There is no laboratory test that confirms serotonin syndrome and serum serotonin levels do not necessarily correlate with clinical findings. […] It is essential to take a careful patient history, finding out what medications (prescription and over-the-counter) and dietary supplements the patient might have been using, for how long, and whether the dose was recently increased.

• #120 Serotonin Syndrome

  https://www.uspharmacist.com/article/serotonin-syndrome

  Serotonin syndrome, also referred to as serotonin toxicity, is one such condition that, in some cases, may be fatal. Medications with serotonergic activity, some even available OTC, are the culprits of this potentially preventable complex of symptoms. The incidence of serotonin syndrome is increasing with the expanded use of serotonergic agents and, specifically, with polypharmacy. The most common drug combinations associated with serotonin syndrome involve the monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), and the tricyclic antidepressants (TCAs). While there are several mechanisms that result in excess serotonin, severe, life-threatening serotonin toxicity occurs only with combinations of medications acting at different sites, most frequently including an MAOI and an SSRI. This condition is more likely to occur when a medication is initially introduced into the regimen or when the dosage is increased. Serotonin syndrome is a potentially preventable, drug-related complication that occurs from increased serotonin activity in the central nervous system through a variety of mechanisms including an increase in serotonin synthesis, a decrease in serotonin metabolism, an increase in serotonin release, inhibition of serotonin uptake, direct serotonin receptor stimulation, and a nonspecific increase in serotonin activity. The toxicity is characterized by an altered mental status, neuromuscular excitation, and autonomic stimulation. The patient’s medication history is positive for serotonergic drugs. Serotonin syndrome is diagnosed only after all other potential causes of symptoms have been ruled out. Published case reports warn that clinicians treating patients with a combination of serotonergic antidepressants and atypical antipsychotics for psychotic depression should be aware of the potential for serotonin syndrome. It is the combination of serotonergic drugs, acting by different mechanisms, that is capable of raising intrasynaptic serotonin to a level that is life threatening. Complications can occur, such as uncontrolled muscle spasms causing severe muscle breakdown and resulting in renal damage, if not recognized and treated appropriately. The combination that most commonly does this is an MAOI drug combined with any serotonin reuptake inhibitor (SRI). Treatment involves removal of the causative agents and may also include the use of serotonin antagonists. Symptoms typically resolve within 24 hours after withdrawal of the serotonergic medication. Clinicians should obtain complete medication histories to identify patients at risk, strictly monitor medication therapy including concomitant agents, and receive education about serotonin syndrome.

• #121 Drug-Induced Serotonin Syndrome

  https://www.uspharmacist.com/article/drug-induced-serotonin-syndrome

  SS typically occurs when a patient takes two or more drugs that elevate serotonin levels through different mechanisms, but the syndrome can occur with the use of individual agents. […] Mechanisms that cause SS include increased serotonin production, inhibition of serotonin reuptake, inhibition of serotonin metabolism, increased serotonin release, and stimulation of serotonin receptors. […] Two serotonergic drugs do not need to be administered concurrently to cause SS; the syndrome can occur up to 6 weeks after discontinuation of just one such drug with a long-acting dosage form, like fluoxetine (Prozac, Sarafem) or an MAOI (e.g., isocarboxazid, phenelzine). […] Concurrent use of medications that interact with serotonergic drugs, thereby resulting in inhibition of the CYP450 metabolic pathway, can also contribute to SS.

• #122 Demystifying serotonin syndrome (or serotonin toxicity)

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6184959/

  Serotonin toxicity is a drug-induced condition caused by too much serotonin in synapses in the brain. […] Serotonin toxicity most often happens when 2 serotonin-elevating drugs are used together. […] The use of an MAOI with an SSRI, an SNRI, or another MAOI is the most concerning drug combination. […] Serotonin toxicity is an important topic for primary care providers. […] Education of both practitioners and patients is the only way to prevent serotonin toxicity.

• #123 Serotonin Syndrome: What It Is, Causes, Symptoms & Treatment

  https://my.clevelandclinic.org/health/diseases/17687-serotonin-syndrome

  Serotonin syndrome happens when you have too much serotonin (a normal chemical) in your body. Its usually caused by taking drugs or medications that affect serotonin levels. […] Serotonin syndrome is a potentially life-threatening drug reaction that results from having too much serotonin in your body. […] Serotonin syndrome happens most often when you either take a new drug or take an increased dose of a drug that increases the level of serotonin in your body. […] A rise in serotonin levels in your body causes serotonin syndrome. This increase in serotonin can happen if you: […] Take more than one medication that affects serotonin levels. […] Recently started on a medication or increased the dose of a medication known to increase serotonin levels. […] Take too much of one serotonin-related medication, accidentally or on purpose.

• #124 Serotonin syndrome (serotonin toxicity) – UpToDate

  https://www.uptodate.com/contents/serotonin-syndrome-serotonin-toxicity

  Serotonin syndrome, also referred to as serotonin toxicity, is a potentially life-threatening condition associated with increased serotonergic activity in the central nervous system. It is seen with therapeutic medication use, inadvertent interactions between drugs, and intentional self-poisoning. […] Serotonin syndrome may involve a spectrum of clinical findings, which often include mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. […] The selective serotonin reuptake inhibitors (SSRIs) are perhaps the most commonly implicated group of medications associated with serotonin syndrome. […] The syndrome has been described following intentional overdose, and even in post-cardiac arrest patients treated with therapeutic hypothermia. […] However, the true incidence of serotonin syndrome may be under-represented in data such as the NPDS for a number of reasons.

• #125 The Serotonin Syndrome: From Molecular Mechanisms to Clinical Practice

  https://www.mdpi.com/1422-0067/20/9/2288

  The combination of an MAOI with an SSRI, and SNRI or another MAOI is the most dangerous combination and the most likely to result in SS. […] Increased production of serotonin (through an overabundance of the precursor molecule L-tryptophan) as well as decreased metabolism of serotonin (by the administration of MAOI), may each cause receptor overstimulation and SS. […] Several discrete mechanisms have been hypothesized to explain how drugs cause SS, although it is likely that more than one of these mechanisms may need to be simultaneously triggered in order to result in clinically significant SS. […] It appears that certain individuals with known polymorphisms at the T102C site of the 5-HT2A receptor gene may be predisposed to developing SS. […] Individual variations in serotonin metabolism by CYPs have also been proposed to contribute to SS susceptibility. […] SERT proteins are critical to the termination of synaptic serotonergic activity.

• #126 Serotonin syndrome – Wikipedia

  https://en.wikipedia.org/wiki/Serotonin_syndrome

  The combination of monoamine oxidase inhibitors (MAOIs) with precursors such as L-tryptophan or 5-hydroxytryptophan pose a particularly acute risk of life-threatening serotonin syndrome. […] The case of combination of MAOIs with tryptamine agonists (commonly known as ayahuasca) can present similar dangers as their combination with precursors, but this phenomenon has been described in general terms as the cheese effect. […] Many MAOIs irreversibly inhibit monoamine oxidase. […] With respect to tricyclic antidepressants, only clomipramine and imipramine have a risk of causing SS. […] The relative risk and severity of serotonergic side effects and serotonin toxicity, with individual drugs and combinations, is complex. […] SS has been reported in patients of all ages, including the elderly, children, and even newborn infants due to in utero exposure.

• #127 The Serotonin Syndrome: From Molecular Mechanisms to Clinical Practice

  https://www.mdpi.com/1422-0067/20/9/2288

  The combination of an MAOI with an SSRI, and SNRI or another MAOI is the most dangerous combination and the most likely to result in SS. […] Increased production of serotonin (through an overabundance of the precursor molecule L-tryptophan) as well as decreased metabolism of serotonin (by the administration of MAOI), may each cause receptor overstimulation and SS. […] Several discrete mechanisms have been hypothesized to explain how drugs cause SS, although it is likely that more than one of these mechanisms may need to be simultaneously triggered in order to result in clinically significant SS. […] It appears that certain individuals with known polymorphisms at the T102C site of the 5-HT2A receptor gene may be predisposed to developing SS. […] Individual variations in serotonin metabolism by CYPs have also been proposed to contribute to SS susceptibility. […] SERT proteins are critical to the termination of synaptic serotonergic activity.

• #128 Serotonin syndrome (serotonin toxicity) – UpToDate

  https://www.uptodate.com/contents/serotonin-syndrome-serotonin-toxicity

  Serotonin syndrome may result from any combination of drugs that has the net effect of increasing serotonergic neurotransmission. […] Episodes of serotonin syndrome involving a monoamine oxidase inhibitor (MAOI) may be more severe and more often lead to adverse outcomes, including death. […] The diagnosis of serotonin syndrome is made solely on clinical grounds. […] The majority of cases of serotonin syndrome present within 24 hours, and most within six hours, of a change in dose or initiation of a drug. […] The differential diagnosis of serotonin syndrome includes neuroleptic malignant syndrome (NMS), anticholinergic toxicity, acute extrapyramidal syndromes, malignant hyperthermia, sympathomimetic intoxication, sedative-hypnotic withdrawal, and thyroid storm. […] Serotonin syndrome can be avoided by applying pharmacologic principles, educating clinicians, and modifying prescription practices.

• #129 Serotonin syndrome: Preventing, recognizing, and treating it | Cleveland Clinic Journal of Medicine

  https://www.ccjm.org/content/83/11/810

  Serotonin crisis is usually caused by the co-ingestion of multiple serotonergic agents, such as an antidepressant with an aforementioned opioid and antiemetic; combining an SSRI and an MAOI poses the greatest risk. […] The two mainstays of serotonin syndrome management are to discontinue the serotonergic agent and to give supportive care. […] Prevention of serotonin syndrome begins with improving education and awareness in patients and healthcare providers.

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