Serotonin Syndrome (Syndrome, Serotonin)

An adverse drug interaction characterized by altered mental status, autonomic dysfunction, and neuromuscular abnormalities. It is most frequently caused by use of both serotonin reuptake inhibitors and monoamine oxidase inhibitors, leading to excess serotonin availability in the CNS at the serotonin 1A receptor.

Also Known As:

Networked: 1098 relevant articles (20 outcomes, 34 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Seizures (Absence Seizure)
2.	Hyperthermia
3.	Hypertension (High Blood Pressure)
4.	Hepatitis
5.	Neuroleptic Malignant Syndrome

Experts

1.	Prakash, Sanjay: 15 articles (10/2021 - 02/2014)
2.	Rathore, Chaturbhuj: 9 articles (10/2021 - 02/2016)
3.	Tao, Rui: 9 articles (01/2019 - 10/2010)
4.	Nisijima, Koichi: 7 articles (12/2015 - 07/2003)
5.	Callanan, John J: 6 articles (01/2019 - 04/2015)
6.	Ma, Zhiyuan: 6 articles (01/2019 - 10/2010)
7.	Shokry, Ibrahim M: 6 articles (01/2019 - 04/2015)
8.	Shioda, Katsutoshi: 6 articles (10/2012 - 07/2003)
9.	Mégarbane, Bruno: 5 articles (05/2021 - 12/2012)
10.	Kato, Satoshi: 5 articles (10/2012 - 07/2003)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Serotonin Syndrome:

1.	Cyproheptadine (Periactin)FDA Link 07/01/2023 - "Cyproheptadine and supportive care were used successfully to treat serotonin syndrome, and the patient was discharged home 14 days postoperatively. " 01/01/2004 - "Cyproheptadine is reported to be effective in treating serotonin syndrome. " 04/01/2021 - "He was administered cyproheptadine for presumed serotonin syndrome with temporal improvement in his symptoms. " 05/25/2018 - "He was diagnosed with delayed-onset serotonin syndrome, which responded well to re-administration of cyproheptadine, leading to resolution of symptoms by day 5 of his stay. " 07/01/2023 - "Based on the literature, there is no standardized method of weaning cyproheptadine when used for serotonin syndrome. "
2.	Serotonin (5 Hydroxytryptamine)IBA 01/01/2019 - "An excess of serotonin can be caused by the use of one or more serotinergic substances on the one hand, or by decreased clearance of these substances on the other hand We carried out a systematic literature search to make an estimation of substances and patient-related factors that might be associated with an increased risk of serotonin syndrome. " 01/01/2018 - "The primary study aim was to create a Serotonergic Expanded Bioactivity Matrix (SEBM) by using a molecular bioinformatics, polypharmacologic approach for assessment of the participation of individual 5-HT drugs in serotonin syndrome (SS) reports. " 10/01/2010 - "In this study, we tested the hypothesis that external cooling measures reduce the responsivity of 5-HT(2A) receptors to excessive 5-HT efflux, which may be a possible mechanism underlying the treatment of serotonin syndrome. " 11/30/2023 - "Serotonin syndrome: A pharmacovigilance comparative study of drugs affecting serotonin levels." 10/01/2023 - "Serotonin syndrome occurs when serotonin (5-hydroxytryptamine, 5-HT) levels increase and is accompanied by symptoms of mental status changes, neuromuscular abnormalities, and autonomic hyperactivity. "
3.	BenzodiazepinesIBA 01/01/2020 - "This patient progressively developed worsening serotonin syndrome, which was resistant to aggressive benzodiazepine administration. " 12/01/2014 - "Management of serotonin syndrome can be complex and may be refractory to treatment with benzodiazepines alone. " 11/01/2005 - "In patients in whom serotonin syndrome and NMS cannot be differentiated, benzodiazepines represent the safest therapeutic option. " 06/01/1987 - "These data describe a complex convulsive myoclonic syndrome that is behaviorally related to but pharmacologically distinct from the serotonin syndrome, which may be useful in studying serotonergic-benzodiazepine interactions in the pathophysiology of myoclonus." 09/01/2007 - "10) Use intravenous benzodiazepines for seizures and benzodiazepines and external cooling measures for hyperthermia (>104 degrees F, >40 degrees C) for serotonin syndrome. "
4.	DexmedetomidineFDA Link 12/01/2014 - "The objective of this series is to present 3 cases of serotonin syndrome that demonstrated clinical improvement with initiation of dexmedetomidine. " 12/01/2022 - "Twenty-six patients with serotonin syndrome were treated with dexmedetomidine. " 02/01/2021 - "On decompensation with suspected serotonin syndrome, the patient was treated with dexmedetomidine. " 02/01/2021 - "Dexmedetomidine has also been used in case reports to treat serotonin syndrome. " 08/01/2015 - "We recently encountered a case of serotonin syndrome that developed in the early postoperative period that was successfully treated with intravenous dexmedetomidine. "
5.	Selective Serotonin Reuptake Inhibitors (Serotonin Reuptake Inhibitors)IBA 06/01/1995 - "The combination of monoaminoxidase inhibitors (MAOI) with SSRIs--in the literature often described as effective in treatment resistant OCD--is inadvisable and strictly contra-indicated (cave: Serotonin-Syndrome). " 01/01/2004 - "This study shows SSRIs are relatively safe in overdose despite serotonin syndrome being common. " 08/01/2021 - "While SSRIs are known for their generally well tolerated side effect profile, serotonin syndrome can arise as a severe complication. " 08/01/2021 - "Serotonin Syndrome in Children and Adolescents Exposed to Selective Serotonin Reuptake Inhibitors - A Review of Literature." 03/01/2021 - "The selective serotonin reuptake inhibitors are perhaps the most commonly implicated group of medications associated with serotonin syndrome. "
6.	Antidepressive Agents (Antidepressants)IBA 11/07/2023 - "The most serious drug-drug interactions (serotonin syndrome and QTc prolongation) require close monitoring; however, DDI toward reducing the efficacy of antidepressants may be difficult to recognize. " 11/01/2023 - "Some patients taking serotonergic antidepressants have been noted to have unexplained mental status changes and/or neuromuscular changes without autonomic instability raising the possibility of a more chronic or attenuated form of serotonin syndrome. " 07/27/2023 - "A clinical review of antidepressants, their sexual side-effects, post-SSRI sexual dysfunction, and serotonin syndrome." 01/01/2023 - "Data on this is extremely scarce, and to the best of our knowledge, serotonin syndrome caused by low-dose antidepressants has not yet been discussed to any great extent in the literature. " 01/01/2023 - "Therefore, serotonin syndrome induced by low-dose antidepressants rarely occurs, and clinicians are more likely to misdiagnose patients who take low-dose antidepressants with similar symptoms. "
7.	Tramadol (K315)FDA LinkGeneric 05/01/2010 - "This study describes clinical manifestations, electrophysiological and hemodynamic findings, and the frequency of potential serotonin syndrome in tramadol overdose in a case series. " 11/25/2023 - "High tramadol concentrations in plasma seem to play a key role in prevalence of seizure and serotonin syndrome in tramadol-intoxicated adult Egyptians." 11/01/2021 - "The case presented here is based on a serotonin syndrome (SS) diagnosis, precipitated by newly prescribed tramadol in conjunction with previously prescribed serotonergic medications. " 12/01/2017 - "Tramadol alone can induce serotonin syndrome in overdose situations." 04/01/2017 - "Next, serotonin syndrome caused by tramadol combined with anti-depressants is remarked as assignable syndrome. "
8.	Monoamine Oxidase Inhibitors (Monoamine Oxidase Inhibitor)IBA 12/30/2020 - "We found that (i) despite being rare, serotonin syndrome was clinically relevant, (ii) the Hunter criteria could not be regarded as the gold standard for the diagnosis of serotonin syndrome since they missed more cases than the other two diagnostic criteria systems (Sternbach and Radomski criteria), (iii) Serotonin syndrome could occur in the absence of an elevated temperature, (iv) fast onset could not be regarded as a reliable clinical sign of serotonin syndrome, and (v) absence of monoamine oxidase inhibitors treatment did not exclude a diagnosis of serotonin syndrome. " 06/01/2009 - "monoamine oxidase inhibitors (MAOIs), with regard to the induction of the serotonin syndrome, has contributed to a gradual decline in their use in clinical practise. " 06/01/2005 - "In addition, this drug has some dopaminergic properties that can induce the serotonin syndrome if a monoamine oxidase inhibitor is used simultaneously. " 01/01/1982 - "Repeated monoamine oxidase inhibitor treatments may prevent the serotonin syndrome by causing a reduction of 3H-serotonin receptor binding sites in the brain stem and/or spinal cord." 12/30/2020 - "Specifically, we tested the following assumptions: (i) Despite being rare, serotonin syndrome is still clinically relevant; (ii) The Hunter criteria are the gold standard for diagnosing serotonin syndrome; (iii) Hyperthermia is common in cases of serotonin syndrome; (iv) Serotonin syndrome usually develops fast; (v) Severe serotonin syndrome usually or almost exclusively involves monoamine oxidase inhibitors. "
9.	Methylene Blue (Methylthioninium Chloride)FDA Link 11/01/2018 - "The review consisted of searches in MEDLINE databases using the key terms "methylene blue" and "serotonin syndrome". " 12/01/2017 - "Reply to Wolvetang et al: "Serotonin Syndrome After Methylene Blue Administration During Cardiac Surgery: A Case Report and Review"." 11/01/2016 - "However, there is no mention of serotonin syndrome caused by methylene blue in urological literature or for urological surgery. " 11/01/2016 - "Methylene blue is an intravenously administered agent that may potentiate serotonin syndrome. " 08/01/2016 - "Serotonin Syndrome After Methylene Blue Administration During Cardiac Surgery: A Case Report and Review."
10.	N-Methyl-3,4-methylenedioxyamphetamine (MDMA)IBA 01/01/2021 - "Reported Cases of Serotonin Syndrome in MDMA Users in FAERS Database." 03/01/2020 - ": The occasional ingestion of 3,4-methylenedioxy-N-methylamphetamine (MDMA) presents serious risks of side effects including death through multivisceral failure in a context of serotonin syndrome. " 03/01/2020 - "Multivisceral Failure in a Context of Serotonin Syndrome Induced by MDMA: The Investigation of a Unique and Nationwide Network." 01/01/2017 - "The purpose of the current article was to review available evidence regarding the effect of non-drug factors on serotonergic extrasynaptic receptor responsivity and the severity of MDMA-induced serotonin syndrome." 01/01/2017 - "Recent research has demonstrated that environmental conditions (i.e., non-drug factors) are more critical in determining the severity of MDMA-induced serotonin syndrome than the drug dose. "

Therapies and Procedures

1.	Therapeutics 08/01/2001 - "This preliminary study suggested that milder forms of the serotonin syndrome may exist for a group of patients in a clinical setting during FLU therapy." 06/01/2022 - "The central triad of features in serotonin syndrome are altered mental state, autonomic hyperactivity, and neuromuscular abnormalities in the context of a patient with new/altered serotonergic therapy, although not all these features are consistently present in all patients. " 10/01/2018 - "Family physicians play a key role in identifying and preventing serotonin syndrome by teaching patients to recognize symptoms and monitoring patients throughout therapy." 01/01/2013 - "Although food-related interactions with transdermal delivery of MAOI therapy can be lessened, clinicians still need to be vigilant for drug-drug interactions and serotonin syndrome. " 11/01/2006 - "Within a few hours the patient developed a lethal serotonin syndrome although ICU therapy was initiated immediately."
2.	Drug Therapy (Chemotherapy) 04/01/2015 - "Serotonin syndrome is a dangerous and rare complication of a pharmacotherapy and can lead to death. " 01/30/2009 - "The fact is a matter of considerable interest in view of the employed pharmacotherapy, giving rise to suspicion that the woman had not developed the serotonin syndrome during the almost 2-year antemortem period until she took toxic doses of both medications." 12/01/2006 - "Clinicians should obtain complete drug histories to identify patients at risk, strictly monitor drug therapy including concomitant drugs, and receive education about this potential drug interaction and the symptoms of serotonin syndrome." 07/01/2000 - "Serotonin syndrome is an underreported complication of pharmacotherapy that has been relatively ignored in the medical literature. " 07/01/1997 - "Serotonin syndrome is a potentially fatal complication of serotonergic drug therapy. "
3.	Polypharmacy 01/26/2021 - "Delayed onset serotonin syndrome in the setting of polypharmacy." 11/01/2020 - "The significance of serotonin syndrome due to drug-drug interactions has emerged as a prominent consideration when the effects of polypharmacy are reviewed. " 01/01/2020 - "Adolescent Polypharmacy and Serotonin Syndrome." 11/19/2018 - "This unique case illustrates that despite having specific criteria for diagnosis, serotonin syndrome can be a complicated diagnosis to make, particularly in the setting of multiple co-morbidities and polypharmacy. " 05/01/2011 - "Serotonin syndrome associated with polypharmacy in the elderly."
4.	Critical Care (Surgical Intensive Care) 01/01/2011 - "One of the patients developed almost fatal serotonin syndrome and required intensive care with ventilatory support. " 10/01/1997 - "Although they have fewer side-effects, they can cause significant physiological changes and drug interactions which have implications for the anaesthetist and the critical care physician, especially the potential to induce the serotonin syndrome." 10/01/2019 - "Protracted symptoms required critical care services throughout a 14 day hospital stay despite traditional treatment of serotonin syndrome. " 01/01/2009 - "MB-associated serotonin syndrome is an increasing and under recognized ('green') post-operative encephalopathy that warrants education to critical care neurologists and other physicians." 07/01/2006 - "Neuroleptic malignant syndrome and serotonin syndrome in the critical care setting: case analysis."
5.	Aftercare (After-Treatment) 10/01/2019 - "In the majority of serotonin syndrome cases, symptoms resolve rapidly after treatment initiation and discontinuation of the offending agents. " 07/01/1997 - "Serotonin syndrome usually occurs after treatment with monoamine oxydase inhibitors and drugs that enhance serotoninergic transmission. " 10/01/2022 - "Serotonin Syndrome After Treatment of Nausea and Vomiting in Pregnancy." 10/01/2017 - "After treatment with methylene blue, the patient experienced clinical decompensation and was diagnosed with serotonin syndrome based on a constellation of clinical findings. " 09/01/2004 - "We describe here the occurrence of a serotonin syndrome (SS) in a 64-year-old depressed female patient with alcoholic hepatic cirrhosis after treatment with SSRIs. "