scholarly journals Serotonin Syndrome: Pathophysiology, Clinical Features, Management, and Potential Future Directions

2019 ◽  
Vol 12 ◽  
pp. 117864691987392 ◽  
Author(s):  
William J Scotton ◽  
Lisa J Hill ◽  
Adrian C Williams ◽  
Nicholas M Barnes

Serotonin syndrome (SS) (also referred to as serotonin toxicity) is a potentially life-threatening drug-induced toxidrome associated with increased serotonergic activity in both the peripheral (PNS) and central nervous systems (CNS). It is characterised by a dose-relevant spectrum of clinical findings related to the level of free serotonin (5-hydroxytryptamine [5-HT]), or 5-HT receptor activation (predominantly the 5-HT1A and 5-HT2A subtypes), which include neuromuscular abnormalities, autonomic hyperactivity, and mental state changes. Severe SS is only usually precipitated by the simultaneous initiation of 2 or more serotonergic drugs, but the syndrome can also occur after the initiation of a single serotonergic drug in a susceptible individual, the addition of a second or third agent to long-standing doses of a maintenance serotonergic drug, or after an overdose. The combination of a monoamine oxidase inhibitor (MAOI), in particular MAO-A inhibitors that preferentially inhibit the metabolism of 5-HT, with serotonergic drugs is especially dangerous, and may lead to the most severe form of the syndrome, and occasionally death. This review describes our current understanding of the pathophysiology, clinical presentation and management of SS, and summarises some of the drugs and interactions that may precipitate the condition. We also discuss the newer novel psychoactive substances (NPSs), a growing public health concern due to their increased availability and use, and their potential risk to evoke the syndrome. Finally, we discuss whether the inhibition of tryptophan hydroxylase (TPH), in particular the neuronal isoform (TPH2), may provide an opportunity to pharmacologically target central 5-HT synthesis, and so develop new treatments for severe, life-threatening SS.

2015 ◽  
Vol 105 (3) ◽  
pp. 244-248 ◽  
Author(s):  
Robert G. Frykberg ◽  
Scott Gordon ◽  
Edward Tierney ◽  
Jaminelli Banks

Linezolid, a mild monoamine oxidase inhibitor, is a commonly used antibiotic drug for the treatment of complicated skin and skin structure infections, including diabetic foot infections. Use of linezolid has been associated with serotonin syndrome, a potentially life-threatening condition typically caused by the combination of two or more medications with serotonergic properties, due to increased serotonin release. The goals of this article are to highlight the risk factors associated with the development of serotonin syndrome related to the use of linezolid and to aid in its prevention and early diagnosis. In this case series we report on two hospitalized patients who, while being treated with linezolid for pedal infections, developed serotonin syndrome. Both individuals were also undergoing treatment with at least one serotonergic agent for depression and had received this medication within 2 weeks of starting the antibiotic drug therapy. In these individuals, we noted agitation, confusion, tremors, and tachycardia within a few days of initiation of linezolid therapy. Owing to the risk of serotonin toxicity, care should be taken when prescribing linezolid in conjunction with any other serotonergic agent. Although serotonin syndrome is an infrequent complication, it can be potentially life threatening. Therefore, risks and benefits of therapy should be weighed before use.


1998 ◽  
Vol 32 (4) ◽  
pp. 432-436 ◽  
Author(s):  
Vinod S Bhatara ◽  
Ryan D Magnus ◽  
K Lynn Paul ◽  
Sheldon H Preskorn

OBJECTIVE: To document a case of serotonin syndrome associated with venlafaxine and fluoxetine that did not involve a monoamine oxidase inhibitor, and to examine the multiple factors, including pharmacodynamic and pharmacokinetic interactions, that likely caused this adverse drug reaction (ADR). CASE SUMMARY: A 39-year-old white woman with depression and panic attacks was being treated with fluoxetine, trazodone, clonazepam, and cimetidine. After fluoxetine and clonazepam were abruptly discontinued, venlafaxine and lorazepam were started. Within 24 hours, she developed diaphoresis, tremors, slurred speech, myoclonus, restlessness, impaired thinking, and diarrhea. This constellation meets Sternbach's criteria for serotonin syndrome. DISCUSSION: The possible contributors to this ADR are discussed, including a single drug effect (e.g., an idiosyncratic reaction to venlafaxine), a pharmacokinetic interaction, a pharmacodynamic interaction, a combined pharmacokinetic–pharmacodynamic interaction, and the patient's panic disorder. CONCLUSIONS: As more serotonergic drugs are developed and used for psychiatric disorders, frequently in combination or close temporal proximity, clinicians must be aware of and consider the factors that may increase the risk of patients experiencing serotonin syndrome. OBJETIVO: Documentar un caso de síndrome de serotonina asociado a venlafaxin que no involucra un inhibidor de monoaminaoxidasa y examinar los factores múltiples, incluyendo interacciones farmacodinámicas y farmacocinéticas que pudieron causar esta reacción adversa. RESUMEN: Una mujer deprimida de 39 años estaba recibiendo fluoxetin, trazodon, clonazepam, y cimetidina. Después que fluoxetin y clonazepam fueron descontinuados abruptamente, se le empezó a administrar venlafaxin y lorazepam. Dentro de las 24 horas, desarrolló diaforesis, temblores, problemas del habla, mioclono, inquietud, problemas en concentrarse, y diarrea. Esta presentación llena los criterios de Sternbach para síndrome de serotonina. DISCUSIÓN: Se discuten los posibles contribuyentes para esta reacción adversa incluyendo el efecto a un solo medicamento (e.g., reacción idiosincrática a venlafaxin), interacción farmacocinética, interacción farmacodinámica, una interacción farmacocinéticafarmacodinámica combinada, y el desorden de pánico que sufría la paciente. CONCLUSIONES: Según se desarrollen y se utilicen más fármacos serotonérgicos para varios desórdenes siquiátricos, frecuentemente en combinación o cerca uno del otro, los médicos deben estar atentos y considerar todos los factores potenciales que pueden aumentar el riesgo a pacientes de padecer un sídrome de serotonina. OBJECTIF: Présenter un cas de syndrome sérotoninergique associé à l'utilisation de venlafaxine seule, sans inhibiteur de la monoamine oxydase, et examiner les multiples facteurs, incluant les interactions pharmacodynamiques et pharmacocinétiques, qui ont possiblement contribué à l'apparition de cette réaction indésirable au médicament. RÉSUMÉ DU CAS: Une femme de 39 ans, atteinte de dépression, était traitée avec de la fluoxétine, de la trazodone, du clonazépam, et de la cimétidine. Après l'arrêt subit de la fluoxétine et de clonazépam, on a débuté un traitement avec la venlafaxine et du lorazépam. En 24 heures, la patiente a développé de la diaphorèse, des tremblements, des difficultés d'élocution, de la myoclonie, de l'agitation psychomotrice, une altération de la pensée, et de la diarhée. Cette présentation clinique rencontre les critères de Sternbach définissant le syndrome sérotoninergique. DISCUSSION: Les éléments ayant pu contribuer à cette réaction indésirable au médicament sont discutés dans cet article et ils comprennent l'effet d'un seul médicament (e.g., une réaction idiosyncrasique à la venlafaxine), une interaction pharmacocinétique et/ou pharmacodynamique, et un trouble de panique sous-jacent chez cette patiente. CONCLUSIONS: De plus en plus de médicaments sérotoninergiques sont développés et employés dans divers désordres psychiatriques, ceux-ci sont fréquemment utilisés en association ou de façon successive, un agent étant débuté peu après l'arrêt d'un autre. Ainsi, les cliniciens doivent connaître et considérer tous les facteurs potentiels pouvant accroître le risque que ces patients développent un syndrome sérotoninergique.


Cephalalgia ◽  
2013 ◽  
Vol 34 (2) ◽  
pp. 148-153 ◽  
Author(s):  
Sanjay Prakash ◽  
Pooja Belani ◽  
Aditi Trivedi

Introduction Serotonin syndrome (SS) is a drug-induced constellation of various clinical features that result from excess central serotonergic tone. The clinical features range from barely perceptible to life-threatening conditions. Cases We describe four patients with acute headache (four days to three weeks) who were receiving serotonergic drugs for other indications. There was a temporal relation between the administration of the serotonergic drugs and the development of the headaches. All four patients fulfilled the Hunter Serotonin Toxicity Criteria for SS. In parallel, two patients fulfilled the Sternbach’s criteria for SS. Discontinuation of the serotonergic drugs and the administration of cyprohepatadine led to complete improvement in three to seven days in all four patients. Discussion A review of the literature suggests that some overlaps exist in the pathophysiology between SS and headache disorders, including medication-overuse headache. The overlap is also in the management. The drugs found to be effective in SS (cyproheptadine, chlorpromazine, olanzapine, etc.) are also known to have positive effects on some headache disorders. Conclusion Physicians should consider the diagnosis of SS in patients with new onset or worsening headache after the addition of serotonergic drugs, especially in the presence of objective signs on examination suggestive of the disorder such as tremor, fever, hyperreflexia, diaphoresis or tachycardia.


Author(s):  
Emily Anne Smith Bergbower ◽  
◽  
Enoch Cheung ◽  
Caron Hong ◽  
◽  
...  

Serotonin Syndrome (SS) is a serious toxidrome associated with significant morbidity when undiagnosed or improperly managed. We report a perioperative case of serotonin syndrome in an adolescent male on fluoxetine (selective serotonin reuptake inhibitor-SSRI) therapy secondary to an intraoperative combined opioid analgesic regiment. He received low dose methadone and fentanyl for induction for a LeFort osteotomy, the presumed trigger for his perioperative SS. This study demonstrates the essential need for anesthesiologists’ vigilance regarding identifying SS, risk factors of SS and implementation of immediate and effective management. Abbreviations: GAD: Generalized Anxiety Disorder; GPCR: G-protein Coupled Receptor; IV: Intravenous; MAOI: Monoamine Oxidase Inhibitor; MDD: Major Depressive Disorder; OR: Operating Room; PACU: Post-Anesthesia Care Unit; RAE: Right Angle Endotracheal; SERT: Serotonin Transporter; SNRI: Serotonin-Norepinephrine Reuptake Inhibitor; SS: Serotonin Syndrome; SSRI: Selective Serotonin Reuptake Inhibitor.


CNS Spectrums ◽  
2016 ◽  
Vol 22 (5) ◽  
pp. 391-396 ◽  
Author(s):  
Jonathan M. Meyer ◽  
Michael A. Cummings ◽  
George Proctor

Irreversible monoamine oxidase inhibitor (MAOI) antidepressants have significant efficacy in treatment-resistant unipolar depression, but in some instances patients may not achieve remission. Among the adjunctive and augmentation strategies, certain second-generation antipsychotics (SGAs) have approval for inadequate responders to antidepressant therapy, including aripiprazole, brexpiprazole, and quetiapine, with lurasidone and the olanzapine/fluoxetine combination indicated for bipolar depression. Clinicians may eschew SGA options in part due to the limited literature on SGA–MAOI combinations, with only one published case involving aripiprazole, and none for olanzapine, lurasidone, or brexpiprazole. In addition to the limited publication history on SGA–MAOI treatment, clinicians may also be deterred by uncertainty regarding SGA mechanisms and the risk of serotonin syndrome or other adverse outcomes. This paper describes the case of a 54-year-old male with a history of psychotic unipolar depression treated with a combination of phenelzine, aripiprazole, and quetiapine, and reviews the 12 published cases of SGA–MAOI combination therapy with a focus on the pharmacological basis for serotonin syndrome, and the SGA mechanisms that should not be associated with a risk for this syndrome.


1988 ◽  
Vol 33 (7) ◽  
pp. 633-634 ◽  
Author(s):  
Nathan Herrmann ◽  
Susan J. Lieff

An 81 year old depressed female is described who developed catatonic-like behaviours while on the combination of the monoamine oxidase inhibitor phenelzine, and the neuroleptic haloperidol. Alternative etiologies, and the roles of the individual agents are discussed. It is suggested that whenever there is evidence of drug-induced catatonia, consideration should be given to stopping all medications.


2019 ◽  
Vol 39 (01) ◽  
pp. 125-136 ◽  
Author(s):  
Suraj Rajan ◽  
Bonnie Kaas ◽  
Emile Moukheiber

AbstractMany acute and potentially life-threatening medical conditions have hyperkinetic or hypokinetic movement disorders as their hallmark. Here we review the clinical phenomenology, and diagnostic principles of neuroleptic malignant syndrome, malignant catatonia, serotonin syndrome, Parkinsonism hyperpyrexia, acute parkinsonism, acute chorea-ballism, drug-induced dystonia, and status dystonicus. In the absence of definitive lab tests and imaging, only a high index of clinical suspicion, awareness of at-risk populations, and variations in clinical presentation can help with diagnosis. We also discuss the principles of management and rationale behind treatment modalities in the light of more recent evidence.


CJEM ◽  
2002 ◽  
Vol 4 (02) ◽  
pp. 98-101 ◽  
Author(s):  
Andrew Ip ◽  
Tia Renouf

ABSTRACTSerotonin syndrome, a triad of autonomic instability, altered mental status and neuromuscular abnormalities, is usually attributed to serotonergic overdoses. Moclobemide is a new selective monoamine oxidase inhibitor (MAOI) that generally causes mild, self-limited gastrointestinal and central nervous system effects after ingestion. We present a case of serotonin syndrome that occurred after moclobemide overdose, and discuss the recognition and treatment of this important condition. Serotonin syndrome may become increasingly common because of the liberal use of selective serotonin reuptake inhibitors, new MAOIs and other agents such as codeine and meperidine, which have the potential for harmful interaction.


2016 ◽  
Vol 13 (3) ◽  
Author(s):  
Auston Rotheram ◽  
Wayne Harris ◽  
Colin Curtain ◽  
David Nihill

Serotonin toxicity, or serotonin syndrome, is a potentially life threatening adverse reaction to the use of one or more serotonergic drugs. Patients presenting with low level obscure symptoms may have pathophysiology rooted in adverse dopamine and serotonergic poly-pharmacy reactions involving illegal, over-the-counter and/or prescription drugs. In this clinical information paper an overview of serotonin toxicity, diagnostic criteria, and management strategies will be offered. Cultivating a high index of suspicion for serotonin toxicity across a broad patient demographic is recommended


Author(s):  
Philip M. Hopkins

Adverse drug reactions are implicated in more than 40% of anaesthesia-related deaths. Undoubtedly, many more patients experience morbidity from adverse drug reactions. Widely cited definitions of adverse drug reactions encompass common side-effects but this chapter focuses on those that are unexpected reactions to drugs administered by anaesthetists and that occur at normal drug doses. The chapter includes a comprehensive account of malignant hyperthermia, which remains a major contributor to anaesthesia related to deaths. Malignant hyperthermia is a pharmacogenetic condition triggered by potent inhalational anaesthetics and possibly also suxamethonium. The genetic basis, pathophysiology, clinical presentations, and management of malignant hyperthermia are discussed. The chapter covers two other pharmacogenetic conditions: the acute porphyrias and butyrylcholinesterase (plasma cholinesterase) deficiency. Drug-induced anaphylaxis is another cause of perioperative morbidity and mortality. Recent data indicate that anaphylaxis during anaesthesia may be much more common than previously thought. The other type of adverse drug reaction covered in the chapter is serotonin syndrome. Perioperative serotonin syndrome is most likely to occur when patients who are already taking serotonergic drugs, such as selective serotonin reuptake inhibitor antidepressants or ‘triptan’ antimigraine treatments, are given a second drug with serotonergic properties, such as tramadol.


Sign in / Sign up

Export Citation Format

Share Document