Controversies in Serotonin Syndrome Diagnosis and Management: A Review

Uddin, Mohd Faisal; Alweis, Richard; Shah, Syed Raza; Lateef, Noman; Shahnawaz, Waqas; Ochani, Rohan Kumar; Dharani, Amin Muhammad; Shah, Syed Muhammad Ismail

doi:10.7860/jcdr/2017/29473.10696

Cited by 13 publications

(20 citation statements)

References 12 publications

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“…Recent reviews of SS have provided a comprehensive discussion of its clinical manifestations and diagnosis . Although a potentially life‐threatening condition, severe cases of SS are generally easily recognized and involve a constellation of symptoms that include some combination of autonomic dysfunction, mental status changes, and/or neuromuscular hypertonicity.…”

Section: Discussionmentioning

confidence: 99%

Implications of Off‐Target Serotoninergic Drug Activity: An Analysis of Serotonin Syndrome Reports Using a Systematic Bioinformatics Approach

et al. 2018

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Study Objective Serotonergic adverse drug events (ADEs) are caused by enhanced intra-synaptic concentrations of 5-hydroxytryptamine (5-HT). No systematic process currently exists for evaluating cumulative 5-HT and off-target toxicity of serotonergic drugs. The primary study aim was to create a Serotonergic Expanded Bioactivity Matrix (SEBM) employing a molecular bioinformatics, poly-pharmacologic approach for assessing the participation of individual 5-HT drugs in serotonin syndrome (SS) reports. Data Sources Publicly available databases including the Food and Drug Association (FDA) Adverse Event Reporting System (FAERS), ChEMBL, DrugBank, PubChem, and Kyoto Encyclopedia of Genes and Genomes (KEGG) were queried for computational and pharmacologic data. Design An in-house bioinformatics TargetSearch program was used to characterize 71 serotonergic drugs interacting at 13 serotonin receptor subtypes, and serotonin re-uptake transporter protein (SERT). Additionally, off-target interactions at norepinephrine transporter (NET), monoamine oxidase (MAO), and muscarinic receptors were included to define 7 poly-pharmacologic drug cohorts. Serotonin syndrome reports for each serotonergic drug were extracted from FAERS using Sternbach’s and Hunter’s criteria. Measurements and Main Results A proportional reporting adverse drug reaction (ADR) ratio (PRR) was calculated from each drug’s total ADEs and SS case reports and aggregated by drug bioactivity cohorts. Triple receptor interactions had a disproportionately higher number of SS cases using both Hunter’s criteria (mean PRR 1.72; 95% C.I. 1.05 to 2.39) and Sternbach’s (mean PRR 1.54, 95% C.I. 1.29 to 1.79). 5-Hydroxtryptamine agonists were associated with a significantly lower proportion of SS cases using Hunter’s and Sternbach’s criteria, respectively (mean PRR 0.49, 95% C.I. 0.17 to 0.81 and mean PRR 0.49, 95% C.I. 0.15 to 0.83). Drugs with disproportionately higher participation in SS vary considerably between the 2 diagnostic criteria. Conclusion The SEBM model suggests a possible poly-pharmacologic role in SS. Although further research is needed, off-target receptor activity may help explain differences in severity of toxicity and clinical presentation.

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Section: Discussionmentioning

confidence: 99%

Implications of Off‐Target Serotoninergic Drug Activity: An Analysis of Serotonin Syndrome Reports Using a Systematic Bioinformatics Approach

et al. 2018

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“…The mainstays of treatment in SS are discontinuing causative agents and supportive care [ 9 ]. Actions are aimed at normalising the vital signs and correcting acute metabolic derangement.…”

Section: Discussionmentioning

confidence: 99%

Hyperthermia and Rigidity Following Overdose of an Unknown Drug; A Case Report and Literature Review

Dean-Paccagnella

Creed

Kakollu

et al. 2018

BEAT

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Drug induced hyperthermia is a rare presentation which can rapidly lead to gross metabolic abnormality and death. These presentations are further complicated by the wide range of potentially causative agents. We present a case of rigidity and hyperthermia, following overdose of an initially unknown substance leading to challenging management decisions in the Emergency Department. This case was later identified as Serotonin Syndrome. The patient presented with trismus which was managed with rapid sequence induction of anaesthesia to allow airway protection. On extubation a significant degree of laryngeal oedema complicated weaning, a possible complication of Serotonin Syndrome not previously described in the literature. We discuss the pathophysiology of Serotonin Syndrome, important differentials and practical considerations in managing hypertonicity of unknown origin in a young person.

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“…Symptoms such as anxiety and akathisia can be misattributed to the patient's mental state, while hypertension, diarrhoea, or tremor can easily be dismissed as part of a systemic or metabolic disorder unrelated to drug therapy. 101 There are 3 diagnostic classification systems available, the Sternbach (SC), Radomski (RC), and Hunter Serotonin Toxicity Criteria (HSTC), all of which try to reflect symptoms and symptom constellations that are felt to be characteristic of serotonin toxicity and therefore SS. The most recent and commonly used criteria are the HSTC, which are set of decision rules that focus on the classic features of generalised clonus (inducible, spontaneous, and ocular), agitation, diaphoresis, tremor, and hyperreflexia 41 (Figure 3).…”

Section: Diagnosismentioning

confidence: 99%

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

Scotton

Hill

Williams

et al. 2019

Int J�Tryptophan�Res

158

161

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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-HT1Aand 5-HT2Asubtypes), 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.

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Controversies in Serotonin Syndrome Diagnosis and Management: A Review

Cited by 13 publications

References 12 publications

Implications of Off‐Target Serotoninergic Drug Activity: An Analysis of Serotonin Syndrome Reports Using a Systematic Bioinformatics Approach

Implications of Off‐Target Serotoninergic Drug Activity: An Analysis of Serotonin Syndrome Reports Using a Systematic Bioinformatics Approach

Hyperthermia and Rigidity Following Overdose of an Unknown Drug; A Case Report and Literature Review

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

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