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: 714 relevant articles (9 outcomes, 22 trials/studies)

Relationship Network

Disease Context: Research Results

Related Diseases

1.	Hepatitis
2.	Tremor (Tremors)
3.	Seizures (Seizure)
4.	Parkinson Disease (Parkinson's Disease)
5.	Lethargy

Experts

1.	Nisijima, Koichi: 7 articles (12/2015 - 07/2003)
2.	Shioda, Katsutoshi: 6 articles (10/2012 - 07/2003)
3.	Tao, Rui: 5 articles (04/2015 - 10/2010)
4.	Kato, Satoshi: 5 articles (10/2012 - 07/2003)
5.	Ma, Zhiyuan: 4 articles (04/2015 - 10/2010)
6.	Fox, Meredith A: 4 articles (11/2013 - 10/2007)
7.	Tepper, Stewart J: 4 articles (02/2012 - 02/2007)
8.	Murphy, Dennis L: 4 articles (09/2009 - 10/2007)
9.	Isbister, Geoffrey K: 4 articles (09/2007 - 10/2003)
10.	Fink, Heidrun: 3 articles (01/2015 - 02/2006)

Drugs and Biologics

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

1.	Cyproheptadine (Periactin)FDA Link 01/01/2004 - "Cyproheptadine is reported to be effective in treating serotonin syndrome. " 01/01/2015 - "A Case of Serotonin Syndrome Following Cyproheptadine Withdrawal." 01/01/2013 - "Serotonin syndrome was suspected and the patient was started on cyproheptadine. " 07/01/2003 - "Cyproheptadine and the treatment of an unconscious patient with the serotonin syndrome." 07/01/2001 - "In the index patient as well as in three subsequent cases of serotonin syndrome, pupil diameter, muscle tone, mental status, and vital signs were monitored before and after a test dose of cyproheptadine as medications were discontinued and antiserotonergic therapy begun. "
2.	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. " 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. " 12/01/2014 - "Accordingly, health care providers may consider using dexmedetomidine as adjunctive therapy for cases of severe serotonin syndrome that are refractory to standard treatment." 12/01/2014 - "Dexmedetomidine in the treatment of serotonin syndrome." 08/01/2015 - "The present case and related reverse translational experiment demonstrate that dexmedetomidine may be more beneficial for the treatment of serotonin syndrome compared to the current recommended treatment with benzodiazepines. "
3.	Antidepressive Agents (Antidepressants)IBA 01/01/2011 - "Interactions resulting in excessive transmitter release could cause adverse events such as serotonin syndrome, while attenuation of monoamine release could impact the clinical efficacy of antidepressants. " 05/01/2015 - "Several common botanicals and supplements can potentiate serotonin syndrome when used in combination with antidepressants. " 04/01/2015 - "antidepressants, they can provoke serotonin syndrome. " 01/01/2015 - "Serotonin syndrome is a rare but potentially fatal side effect of antidepressants that results from the effects of drug activity on both central and peripheral serotonergic receptors. " 02/01/2013 - "The relative safety of the SSRIs in overdose despite the occurrence of serotonin syndrome makes them more desirable than other antidepressants. "
4.	N-Methyl-3,4-methylenedioxyamphetamine (MDMA)IBA 04/01/2015 - "Our results showed that MDMA at 3 mg/kg, but not 0.3 or 1 mg/kg, caused a mild serotonin syndrome in rats. " 04/01/2015 - "Illicit use of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) may cause a mild or severe form of the serotonin syndrome. " 04/01/2015 - "Mechanisms and environmental factors that underlying the intensification of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy)-induced serotonin syndrome in rats." 01/01/2013 - "Search terms included "serotonin syndrome", "ecstasy", "MDMA", "pediatric", and "SSRI". " 01/01/2013 - "An electronic search of the major behavioral science bibliographic databases (Pubmed, PsycINFO, Medline) was conducted to retrieve peer-reviewed articles, which detail the clinical characteristics, biological mechanisms and social implications of SSRIs, MDMA, and their potential synergism in causing serotonin syndrome in the pediatric and young adult population. "
5.	BenzodiazepinesIBA 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. " 05/01/2007 - "7) Use intravenous benzodiazepines for seizures and benzodiazepines and external cooling measures for hyperthermia (>104 degrees F [>40 degrees C]) for SSRI-induced serotonin syndrome. "
6.	Chlorpromazine (Thorazine)FDA Link 02/03/1997 - "Successful treatment of the toxic serotonin syndrome with chlorpromazine." 09/16/1996 - "Successful treatment of serotonin syndrome with chlorpromazine." 01/01/1999 - "There is some evidence suggesting the efficacy of chlorpromazine and cyproheptadine in the treatment of serotonin syndrome. " 04/01/2015 - "Patients with a severe serotonin syndrome require symptomatic intensive care and specifically a pharmacological antagonism with cyproheptadine or chlorpromazine. "
7.	5-HT2C Serotonin ReceptorIBA 03/15/2008 - "Among these compounds, 6,7-dichloro-2,3,4,5-tetrahydro-1H-3-benzazepine (6) was effective in a rat penile erection model when administered po, which is a symptom of the serotonin syndrome reflecting 5-HT(2C) receptor activation. " 02/01/2005 - "We extend these findings to show that a partial 5-HT(1A) agonist activity is revealed by the 5-HT(2C) receptor antagonist (SB 206,553) in this animal model, as measured by evaluation of serotonin syndrome behavior. "
8.	BPC 157IBA 04/11/2005 - "Gastric pentadecapeptide BPC 157 effective against serotonin syndrome in rats." 04/11/2005 - "Thereby, in severe serotonin syndrome, gastric pentadecapeptide BPC 157 (alone, no behavioral or temperature effect) has a beneficial activity, which is likely, particular, and mostly related to a rather specific counteraction of 5-HT2A receptors phenomena." 04/11/2005 - "Indicatively, severe serotonin syndrome in pargyline + L-tryptophan rats is considerably inhibited even by lower pentadecapeptide BPC 157 doses regimens (particularly disturbances such as hyperthermia and wet dog shake thought to be related to stimulation of 5-HT2A receptors), while the highest pentadecapeptide dose counteracts mild disturbances present in pargyline rats (mild hypothermia, feeble hind limbs abduction). " 04/11/2005 - "In all experiments, gastric pentadecapeptide BPC 157 contrasts with serotonin-syndrome either (i) presentation (i.e., particularly counteracted) or (ii) initiation (i.e., neither a serotonin substrate (counteraction of pargyline), nor an inductor for serotonin syndrome (no influence on L-tryptophan challenge)). " 04/11/2005 - "Thereby, we investigate this peptide (10 microg, 10 ng, 10 pg/kg i.p.) in (i) full serotonin syndrome in rat combining pargyline (irreversible MAO-inhibition; 75 mg/kg i.p.) and subsequent L-tryptophan (5-HT precursor; 100 mg/kg i.p.; BPC 157 as a co-treatment), or (ii, iii) using pargyline or L-tryptophan given separately, as a serotonin-substrate with (ii) pargyline (BPC 157 as a 15-min posttreatment) or as a potential serotonin syndrome inductor with (iii) L-tryptophan (BPC 157 as a 15 min-pretreatment). "
9.	EVAC protocol (CAVE)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). "
10.	Serotonin (5 Hydroxytryptamine)IBA 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. " 08/01/2015 - "Serotonin syndrome is a drug-related toxicity caused by excess serotonin within the central nervous system. " 06/01/2015 - "Serotonin syndrome is a potentially life-threatening condition caused by excessive central and peripheral stimulation of serotonin brainstem receptors, usually triggered by inadvertent interactions between agents with serotonergic activity. " 04/01/2015 - "Features of serotonin syndrome according to Sternbach's criteria and Hunter's serotonin toxicity criteria were evaluated from records. " 01/15/2015 - "In humans, the ingestion of the combination of two or more serotonin (5-HT)-enhancing drugs but also of a single drug in overdose can induce serious adverse effects, which are characteristics of the serotonin syndrome (SS). "

Therapies and Procedures

1.	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. "
2.	Polypharmacy 05/01/2011 - "Serotonin syndrome associated with polypharmacy in the elderly." 12/01/2006 - "Serotonin syndrome is becoming more common, and with the utilization of polypharmacy on many palliative care services should be considered as unifying differential diagnosis in the appropriate setting." 08/01/2014 - "Serotonin syndrome in a patient with chronic pain polypharmacy." 05/01/2005 - "More commonly an adverse drug reaction may be seen among the older patients who are particularly vulnerable to the serotonin syndrome due to multiple co-morbidity and polypharmacy. " 04/01/1998 - "Serotonin syndrome induced by venlafaxine and fluoxetine: a case study in polypharmacy and potential pharmacodynamic and pharmacokinetic mechanisms."
3.	Critical Care 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." 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." 07/01/2006 - "Neuroleptic malignant syndrome and serotonin syndrome in the critical care setting: case analysis." 10/01/2009 - "[Serotonin syndrome after administration of mirtazapine in a critical care unit]." 10/01/2014 - "Although this article focuses on serotonin syndrome as a result of an adverse interaction of selective serotonin reuptake inhibitors (SSRI) and fentanyl, it is important for not only anesthesia professionals, but all clinicians--such as those in emergency medicine and critical care--to be aware of this syndrome and its management. "
4.	Intensive Care (Surgical Intensive Care) 01/01/2011 - "One of the patients developed almost fatal serotonin syndrome and required intensive care with ventilatory support. " 01/01/2004 - "Outcomes examined were length of stay [LOS], intensive care [ICU] admission rate, coma, seizures, electrocardiographic [ECG] abnormalities, and presence of serotonin syndrome [SS]. " 04/01/2015 - "Patients with a severe serotonin syndrome require symptomatic intensive care and specifically a pharmacological antagonism with cyproheptadine or chlorpromazine. "
5.	Parathyroidectomy 04/01/2015 - "Despite its favorable safety profile, there have been reports of methylene blue-induced encephalopathy and serotonin syndrome in patients undergoing parathyroidectomy. " 01/01/2009 - "Methylene blue-associated serotonin syndrome: a 'green' encephalopathy after parathyroidectomy." 01/01/2008 - "To report a case of autonomic, neurological and neuromuscular instability following methylene blue infusion for parathyroidectomy; to advance the argument for a diagnosis of serotonin syndrome; and to consider this diagnosis in previous, unexplained reports of adverse reactions amongst patients undergoing parathyroidectomy using methylene blue. " 01/01/2008 - "[Serotonin syndrome following methylene blue infusion during parathyroidectomy: a case report and literature review]."