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Background: Serotonin syndrome and Parkinson's disease (PD) are two diseases whose symptoms partially overlap; this poses challenges in distinguishing them in clinical practice. Early manifestations such as tremor, akathisia, diaphoresis, hypertonia and hyperreflexia are common in mild-to-moderate serotonin syndrome and can also occur in PD. Without prompt recognition and treatment, serotonin syndrome can rapidly progress, potentially leading to severe complications such as multiple organ failure within hours. Given their disparate treatment strategies, accurate clinical distinction is crucial for effective treatment. This case study explores a patient with serotonin syndrome triggered by escitalopram in the context of PD psychosis (PDP), providing insights into diagnosis and treatment planning., Case Presentation: A 75-year-old Asian woman with a one-year history of PD, a two-month history of PDP, and a six-year history of depression presented with symptoms including hyperreflexia, tremor, hypertonia, impaired level of consciousness, and inappropriate behavior following a recent one-month adjustment in medication. Initially suspected of being drug-induced parkinsonism or worsening PD, therapeutic drug monitoring revealed warning levels of escitalopram. Subsequent diagnoses confirmed serotonin syndrome. This syndrome may result from increased cortical serotonin activity at the serotonin2A receptor due to dopamine and serotonin imbalances in PDP, compounded by increased dopamine-mediated serotonin release. Additionally, being an intermediate metabolizer of cytochrome P450 enzyme 2C19, the patient experienced excessive escitalopram accumulation, exacerbating her condition., Conclusions: This case underscores the critical need to differentiate between symptoms of serotonin syndrome and PD, particularly in manifestations like tremor and hypertonia. Careful consideration of receptor profiles in patients with PDP is essential when selecting antidepressants to mitigate the risk of serotonin syndrome., (© 2024. The Author(s).)

This column is the third in a 3-part series describing cases in which general medical knowledge, including psychiatric and clinical pharmacology, was instrumental in determining whether dereliction was the direct cause of damages in a malpractice suit. This case illustrates how not taking into account the following variables can result in a false-positive diagnosis of a lethal serotonin syndrome: (a) the time course of treatment, (b) the time course of symptoms, (c) the difference between antemortem plasma and postmortem whole-blood levels of highly protein bound and highly lipophilic drugs. The case also illustrates how taking those 3 variables into account led to the conclusion that there was no dereliction in the care of the patient that was the direct cause of his death, and hence, there was no medical malpractice., Competing Interests: Over his 45-year career, S.H.P. has worked with over 145 pharmaceutical and biotech companies in the United States and throughout the world. Over the past year, he has received grants/research support from or has served as a consultant, on the advisory board, or on the speaker’s bureau for Alkermes, BioXcel, and Janssen. There were no clinical trial and study contracts during the 2 years preceding this paper, but any would have been with and payments made to the Kansas University Medical Center Research Institute, a research institute affiliated with the Kansas University School of Medicine-Wichita. The remaining author declares no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Serotonin syndrome is a rare, life-threatening toxidrome caused by serotonergic agents. This syndrome classically presents with a combination of mental status changes, autonomic hyperactivity, and neuromuscular abnormalities. However, diagnosing the condition is difficult because of its variable symptoms at presentation. As a result, serotonin syndrome often is underreported, making it harder to understand, recognize, and treat. Patients with this condition may present to primary or urgent care or an ED, and may become acutely symptomatic during an inpatient admission. Clinicians must be able to identify at-risk patients and intervene to prevent potentially lethal complications., (Copyright © 2024 American Academy of Physician Associates.)

Serotonin syndrome (SS) is a drug-induced clinical syndrome characterised by a combination of cognitive, neuromuscular and autonomic dysfunctions. The symptoms may include mild non-specific symptoms such as tremors and diarrhoea to coma and sudden death. Herein, we describe a case of SS in which acute dizziness was associated with supine hypertension and orthostatic hypotension. A man in his mid-30s had a 10-month history of anxiety, depression and chronic tension-type headache. He had been on amitriptyline (25 mg daily) and sertraline (50 mg daily). Increment of sertraline (75 mg daily) and amitriptyline (75 mg daily) and the addition of tramadol led to the development of acute severe dizziness. Physical examinations demonstrate supine hypertension and orthostatic hypotension. He also met the diagnostic criteria of SS. The administration of cyproheptadine provided a complete response to dizziness, supine hypertension, orthostatic hypotension and other clinical features of SS., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: Serotonin syndrome is a potentially life-threatening condition resulting from the use of antidepressants, their interactions with other serotonergic medications, or poisoning. It presents with a triad of psychiatric, dysautonomic, and neurological symptoms and is sometimes fatal. While cyproheptadine is a specific treatment option, the optimal duration of its administration remains unclear. The purpose of this report is to quantitatively assess the endpoints of serotonin syndrome treatment. Based on the hypothesis that neurological pupil index (NPi) on a digital pupil recorder would correlate with the severity of the serotonin syndrome, we administered cyproheptadine using NPi as an indicator., Patient Concerns: A patient with a history of depression was brought to our hospital after he overdosed on 251 tablets of serotonin and noradrenaline reuptake inhibitors., Diagnoses: On day 3, the patient was diagnosed with serotonin syndrome., Interventions: Cyproheptadine syrup was administered at 4 mg every 4 hours. The NPi of the automated pupillometer was simultaneously measured. On day 5, the NPi exceeded 3.0 cyproheptadine was discontinued., Outcomes: The patient was discharged on day 7., Lessons: The lack of considerable improvement during the treatment period suggests that the patient may have improved on his own. In this case, the relationship between NPi and the severity of serotonin syndrome could not be determined., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Serotonin syndrome (SS) is an iatrogenic, drug-induced clinical syndrome caused by an increase in the intrasynaptic concentration of serotonin. Serotonin plays a significant role in the pathophysiology of migraines. Upregulation of 5-HT2A receptors is found in medication-overuse headache (MOH). Several migraine medications, both preventative and abortive drugs, act on serotonin receptors. We report two patients with chronic migraine who developed MOH. Besides headache, patients had frequent attacks of dizziness, restlessness, irritability, insomnia, excessive sweating, abdominal discomforts and tremors. These symptoms were suggestive of withdrawal headache. However, on physical examinations, we elicited hyperreflexia, hypertonia, clonus, tachycardia, hypertension, mydriasis and hyperactive bowel sound. Both patients also met the criteria for SS. Cyproheptadine was started. All features, including headaches, got better after cyproheptadine administration within 24 hours. In 7 days, there was practically total improvement. Both patients continued to take cyproheptadine as a preventative medicine, and migraine frequency was under control., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Acute toxic leukoencephalopathy and serotonin syndrome are rare neurological complications associated with various drugs and toxins, some of which overlap. However, the co-occurrence of these conditions is poorly documented. We present the case of a 14-year-old boy who suddenly developed altered consciousness and autonomic dysfunction after consuming excessive quantities of cough remedies containing dextromethorphan, chlorphenamine, dichlorobenzyl alcohol, and amylmetacreson. Magnetic resonance imaging of the brain revealed distinct white matter lesions. With supportive care, the patient rapidly improved, and the magnetic resonance imaging abnormalities disappeared. The swift resolution, typical magnetic resonance imaging findings, and a history of exposure to drugs affecting the central nervous system's serotonergic system suggested concurrent acute toxic leukoencephalopathy and serotonin syndrome. The components of cough medications can be hazardous in overdose due to their potential to enhance serotonin toxicity and cause direct or indirect central nervous system white matter damage. Early recognition and appropriate treatment are essential for recovery., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Serotonin syndrome is an acute, life-threatening illness characterized by mental status changes, neuromuscular symptoms, and autonomic instability. 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., Objective: Assessment of antidepressant blood levels to support the diagnosis of a subacute serotonin syndrome., Methods: At a tertiary psychiatric outpatient clinic, patients with unexplained mental status and/or neuromuscular changes without autonomic instability had antidepressant blood levels assessed., Results: Eleven patients were identified with signs and symptoms partially consistent with serotonin syndrome. Nine patients had cognitive changes, while four patients had motor changes, and three patients had psychosis. All patients had elevated blood levels of a single serotonergic antidepressant. Limited follow-up suggests that symptoms improve with reduction of antidepressant medication., Conclusions: These cases suggest that a more chronic, attenuated form of serotonin syndrome exists. Diagnostic criteria are proposed for a distinct clinical entity: subacute serotonin syndrome (SSS). Further research is required to validate these criteria. Clinicians should consider drawing antidepressant levels for patients with symptoms and signs suggestive of SSS-especially those at increased vulnerability for excessive serotonergic agonism. Given the high prevalence of antidepressant medication use, the awareness of SSS could lead to improved patient outcomes and public health., (Copyright © 2023 Academy of Consultation-Liaison Psychiatry. Published by Elsevier Inc. All rights reserved.)

Background: Serotonin syndrome (SS) is a potentially life-threatening adverse drug reaction due to an increased central and peripheral serotonin activity, which usually presents as a triad of behavioral changes, neuromuscular excitability, and autonomic instability. Probably SS is often misdiagnosed, and its symptoms are mistaken for psychiatric symptoms or general medical issues: the true incidence of SS is not clear, and literature concerning potential risk factors is scarce. Our aims were to examine the prevalence of SS in a naturalistic sample of hospitalized patients and to evaluate potential factors related to the risk of developing the condition., Methods: The sample included 133 patients being treated with serotonergic medications admitted to the psychiatric inpatient unit of the San Luigi Gonzaga Hospital. All patients received a medical examination (including a neurological examination) within 24 hours of admission. Serotonin syndrome was diagnosed according to Hunter Criteria., Results: Sixteen patients (12%) were diagnosed with SS. In the subgroup of subjects with SS, we found a higher rate of male patients when compared with subjects with no SS (62.5% vs 33.3%, P = 0.023)., Conclusions: SS probably is an underestimated condition, which should be carefully assessed in patients on serotonergic medications. Male gender was the only factor found to be significantly related to a higher risk of developing SS. Further studies on larger samples are needed, to gain more information on possible risk factors and to identify subjects more prone to developing SS, given the potential risk for patients' health., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Serotonin syndrome is a potentially life-threatening syndrome with manifestations spanning from mild adverse effects to life-threatening toxicity. The syndrome is caused by overstimulation of serotonin receptors by serotonergic drugs. Since the use of serotonergic drugs is increasing, primarily due to the widespread use of selective serotonin reuptake inhibitors, cases of serotonin syndrome have likely seen a parallel increase. The true incidence of serotonin syndrome remains unknown due to its diffuse clinical presentation., Objectives: This review aims to provide a clinically focused overview of serotonin syndrome, covering its pathophysiology, epidemiology, clinical manifestations, diagnostic criteria, differential diagnosis and treatment, as well as classifying serotonergic drugs and their mechanism of action. The pharmacological context is emphasized, as it is crucial for the detection and management of serotonin syndrome., Methods: Focused review based on a literature search using the PubMed database., Findings and Conclusion: Serotonin syndrome can occur through therapeutic use or overdose of a single serotonergic drug or as a drug interaction between two or more serotonergic drugs. Central clinical features consist of neuromuscular excitation, autonomic dysfunction and altered mental status, occurring in a patient undergoing new or altered serotonergic therapy. Early clinical recognition and treatment are crucial to prevent significant morbidity., (© 2023 The Authors. Basic & Clinical Pharmacology & Toxicology published by John Wiley & Sons Ltd on behalf of Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Purpose: This systematic review aims to evaluate the existing evidence associating linezolid to serotonin toxicity when used as monotherapy or when co-administered with other serotonergic agents., Methods: A systematic literature search using PubMed (till March 2023), IDWeek meetings (2003-2023), the European Congress of Clinical Microbiology and Infectious Disease Annual Meetings (2001-2023), and the American College of Clinical Pharmacy (1999-2023) identified studies and abstracts related to linezolid and serotonin toxicity., Results: A total of 84 studies were included. The data collected in retrospective/observational studies compared the incidence of serotonin toxicity with linezolid monotherapy at 0.0050% and linezolid combination therapy at 0.0134%. All cases which discontinued linezolid and serotonergic agent/s at signs and symptoms of toxicity found symptom resolution; 75% of cases reported serotonin toxicity resolution within 24-48 h after discontinuation., Conclusion: Linezolid therapy when optimal should not be deferred due to the risk of serotonin syndrome. The data collected reveals a low prevalence of serotonin toxicity in both linezolid monotherapy and linezolid concurrent with other serotonergic agents., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Migraine and depression have a bi-directional, positive association. The likelihood of these conditions being comorbidities is high, thus, the possibility of concomitant use of an antidepressant and a triptan is also increased. Case Presentation: We present a case of a 39-year-old female with a history of migraine with aura and depression who had brief episodes of exacerbated depressive symptoms following oral administration of sumatriptan 100 mg daily as needed while taking various selective serotonin reuptake inhibitor (SSRI) and serotonin and norepinephrine reuptake inhibitor (SNRI) medications on different occasions. The patient experienced 30-minute episodes of sweating and subjective increase in temperature approximately 2-3 hours after administration of sumatriptan 100 mg. This was followed by a transient exacerbation of sadness described by the patient as unhappiness, hopelessness, and tearfulness, which lasted 1 to 2 hours. To date, there are no other published case reports that have described this particular presentation. Several studies have reported possible serotonin syndrome as a result of the combination. Current evidence and known pharmacological actions of SSRIs/SNRIs and triptans are not well-defined enough to explain how one can experience episodic worsening depression. Conclusion: This case illustrates that clinicians should consider other potential adverse effects of the combined use of triptans and SSRIs/SNRIs beyond serotonin syndrome.

Background There are three commonly used sets of criteria to diagnose serotonin syndrome and all three diagnostic tools have all been shown to have shortcomings that do not fully encompass the possible symptoms of serotonin toxicity. Objective To describe a case of an atypical presentation of possible drug-induced serotonin syndrome, characterized by hypothermia, night sweats, muscle tremors, and confusion. Setting A rural and medically underserved area in eastern Washington State. Practice Description This patient case was identified as a part of a project to identify and intervene with complex and high-risk patients from local rural and underserved populations. The pharmacist identified the symptoms of possible drug-induced serotonin syndrome during a comprehensive medication review with the patient. Results The pharmacist identified a possible case of drug-induced serotonin syndrome and made a recommendation to the patient's physician that led to discontinuation of both fluoxetine and trazodone. At the follow-up visit, the patient reported that his symptoms had resolved completely. Discussion The three sets of diagnostic criteria for serotonin syndrome all include fever as a symptom, but do not list hypothermia. Effects at various 5-HT receptors and receptor subtypes have been linked to symptoms often seen in serotonin syndrome, but there are gaps in the currently used diagnostic criteria. Conclusion Pharmacists' comprehensive review of medications can allow identification of symptoms, such as hypothermia to identify possible serotonin syndrome.

Serotonin syndrome (SS) is a potentially fatal adverse drug reaction characterized by an exaggerated increase in serotonergic activity in the central and peripheral nervous systems. It presents a constellation of signs and symptoms related to behavioral changes, neuromuscular excitability, and autonomic instability. These symptoms can occur in both mild and severe forms. SS can be triggered by the therapeutic use of a drug that increases serotonin (5-HT) availability in the synaptic cleft or by the co-administration of two or more drugs that provide this increase. With the escalating use of antidepressants by the world's population, this adverse reaction may be more recurrent. However, SS is often overlooked by patients or not diagnosed by doctors. This review aims to improve awareness about SS and provide a pharmacological perspective to explain its occurrence. Evidence shows that other neurotransmitters may also be involved with the pathology of SS. Furthermore, SS and neuroleptic malignant syndrome (NMS) seem to be part of the same pathological spectrum, especially in atypical NMS cases. The emergence of the syndrome's symptoms may be closely related to pharmacokinetic and/or pharmacodynamic polymorphisms that lead to an increase in the 5-HT available to or 5-HT signaling by specific receptors, thus constituting an important area for future investigations., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Poian et al.)

BACKGROUND Serotonin toxicity, often referred to as 'serotonin syndrome,' is a drug-induced condition due to excess serotonin released from brain synapses, resulting in symptoms that may be autonomic, neuromuscular, and/or cognitive in nature. Most cases involve more than 1 of the following drug regimens: monoamine oxidase inhibitors (MAOIs), serotonin releasers, selective serotonin reuptake inhibitors (SSRIs), or serotonin-norepinephrine reuptake inhibitors (SNRIs). This report is of a 70-year-old woman who presented with confusion and muscle spasms due to serotonin toxicity associated with paroxetine and quetiapine treatment. CASE REPORT An elderly woman with dementia presented to the Emergency Department with fever, altered mental status, labile blood pressures, and inducible clonus. No known medication dosage increases had been made, nor had any new serotonergic agents been added to the patient's drug regimen. She underwent a thorough workup in the Emergency Department and later during her hospitalization. A presumptive diagnosis of serotonin toxicity was made early on during her stay, with the etiology attributed to use of paroxetine and quetiapine. Clinical improvement was observed after benzodiazepine administration, discontinuation of offending agents, and a brief cyproheptadine course. The patient survived her hospital stay and was ultimately discharged to hospice care with a return to her baseline level of functioning. CONCLUSIONS Diagnosing serotonin toxicity requires a high degree of clinical suspicion and can occur in the absence of increased dosage of existing, or initiation of new, serotonergic agents.

Introduction: Serotonin syndrome is a rare, frequently misdiagnosed, serious condition with high morbidity., Objective: This review highlights the pearls and pitfalls of serotonin syndrome, including diagnosis, initial resuscitation, and management in the emergency department (ED) based on current evidence., Discussion: Serotonin syndrome is a potentially deadly toxidrome marked by excess serotonin receptor activity or neurotransmission. Features of serotonin syndrome include 1) neuromuscular excitation such as tremor, hyperreflexia, and clonus; 2) autonomic dysfunction such as tachycardia, hypertension/hypotension, and hyperthermia; and 3) altered mental status such as agitation, delirium, and coma. Although serotonin syndrome may be more obvious in patients who have overdosed on serotonergic agents such as serotonin reuptake inhibitors (SSRIs), multiple other medications may also cause serotonin syndrome. Alternative diagnoses such as sepsis, neuroleptic malignant syndrome, and decompensated hyperthyroidism should be considered. The primary components of therapy include stopping the offending agent and supportive care, which focuses on agitation control, monitoring for and treating hyperthermia, and managing autonomic instability., Conclusions: An understanding of serotonin syndrome can assist emergency clinicians in diagnosing and managing this disease., Competing Interests: Declaration of Competing Interest None., (Published by Elsevier Inc.)

Background: Widespread prescription of antidepressants and their resulting role in serotonin syndrome (SS) are of great importance for clinical practice in the elderly. This study aims to investigate possible associations of antidepressant drug-induced SS with related variables in these patients., Methods: A total of 238 older adults using antidepressants were included. Patients who fulfilled the Hunter Serotonin Toxicity Criteria (HSTC) for SS were considered as the clinical groups (mild, moderate, or severe), and those who did not as the control group. We recorded all patients' demographic and clinical characteristics, including age, gender, comorbidity index, number of medications, daily equivalent dose of the relevant antidepressant according to fluoxetine per day, electrocardiogram test results, laboratory results, and management., Results: The mean age of all patients was 75.4 ± 7.6 years and 63.4% were female. Sixty patients had SS, while 178 patients did not. There was a significant difference between those with and without SS in terms of gender, frequency of combination antidepressant therapy, and daily equivalent antidepressant dose (P < 0.05). The most common diagnostic findings in SS patients were tremor and hyperreflexia and 31.7% was mild, and moderate in 68.3% with higher median age and number of medications (P < 0.041). Antidepressants were discontinued in all patients regardless of severity, of whom 71.7% were treated with benzodiazepines and 36.7% with cyproheptadine. After adjusting for age and sex, association with use of SSRI + SNRI, use of any combination therapy, and daily equivalent dose remained significant., Conclusions: The widespread single or combined use of antidepressants in older adults represents an increased clinical concern for SS and physicians should be aware of this drug-related complication in older patients., (© 2022 Japanese Psychogeriatric Society.)

The serotonin syndrome is a life-threatening adverse drug reaction resulting from excess serotonergic agonism due to interactions between multiple drugs, poisoning, or less commonly due to therapeutic action of a single drug. 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. The severity of serotonin syndrome can be assessed clinically based on the number and severity of features. Severe serotonin syndrome warrants more careful management on a high-dependency unit. In case of temperature exceeding 38.5°C, urgent cooling measures and sedation should be employed, progressing to rapid sequence intubation and paralysis if cooling measures are ineffective., Competing Interests: Competing interests: None declared. Refer to the online supplementary files to view the ICMJE form(s)., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Serotonin syndrome is a rare but potentially life-threatening condition caused by excess serotonin in the central and peripheral nervous systems. Patients with serotonin syndrome present with a range of mild to severe autonomic, neuromuscular and mental state signs and symptoms. A variety of drugs affect the serotonin pathways by modifying serotonin release and reuptake mechanisms, or reducing metabolism. There are also several genetic polymorphisms and clinical risk factors that affect the development and course of serotonin syndrome. This article describes the pathophysiology of serotonin syndrome and discusses diagnosis and treatment with reference to a case study of a patient who attended an emergency department (ED) with signs and symptoms of the condition following an increase in antidepressant medicines. The article aims to increase clinicians' awareness of serotonin syndrome to improve identification and treatment of patients who present to EDs with the condition., Competing Interests: None declared, (© 2021 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.)

Introduction: Serotonin syndrome (toxicity) describes adverse drug effects from toxic amounts of intra-synaptic central nervous system serotonin. A wide range of drugs have been implicated to cause serotonin toxicity, not all justifiably. The plausible agents all have a final common pathway resulting in a substantial increase in central nervous system serotonergic neurotransmission. Serotonin toxicity is characterized by neuromuscular excitation, mental status changes, and autonomic dysregulation. Signs and symptoms represent a spectrum of toxicity (mild to life-threatening) related to increasing serotonin concentrations. As there is no consensus on the threshold for "toxicity" or diagnostic criteria, the true incidence of serotonin toxicity is unknown. The incidence in overdose is easier to quantify and is reasonably common in serotonergic antidepressant overdoses. In a large case series of overdoses, moderate serotonin toxicity occurred in 14% of poisonings with a selective serotonin reuptake inhibitor. While half those ingesting a monoamine oxidase inhibitor in combination with a serotonergic agent in overdose exhibit at least moderately severe serotonin toxicity. In contrast, the incidence of serotonin toxicity in those on therapeutic serotonergic agents appears to be very low., Objectives: To provide a narrative review of the current diagnostic criteria, utilizing case reports of fatalities to evaluate how many meet the various diagnostic criteria and propose practical solutions to resolve controversies in diagnosis., Methods: A review of serotonin toxicity diagnostic criteria in the English literature was completed by searching Embase and PubMed from January 1990 to July 2021 for the keywords "serotonin syndrome/toxicity" paired with "diagnostic criteria" or "diagnosis." Also, fatal cases of serotonin toxicity identified from a recent systematic review were independently examined to determine what diagnostic criteria were met and whether serotonin toxicity or another cause was most likely., Review of Diagnosis Criteria: Serotonin toxicity is a clinical diagnosis, four diagnostic criteria (Sternbach, Serotonin Syndrome Scale, Radomski, and Hunter) have been proposed. However, the Serotonin Syndrome Scale has not been validated in patients with serotonin toxicity and only utilized in those on a serotonergic agent. The remaining three criteria are utilized more widely but have undergone little refinement or validation., Review of Fatal Cases: Shortfalls with diagnostic criteria can be illustrated by examining case fatalities. Of 55 fatal cases reviewed, 12 (22%) were unlikely to be serotonin toxicity. Sternbach and Radomski criteria were met by 25 (45%), 20 (36%) had insufficient data reported and 10 (18%) met an exclusion criterion. Few had sufficient information reported to determine whether Hunter Criteria were met, with only 13 (24%) documented as meeting the criteria, the remaining 42 (76%) had insufficient data., Resolving Shortfalls in Current Diagnostic Criteria: As serotonin toxicity is a clinical diagnosis, issues arise when basing the diagnosis on symptom criteria alone, without considering whether the drug/s ingested increase central nervous system serotonin or whether there is an alternative diagnosis. This has resulted in case reports and government warnings for drugs that cannot plausibly cause significant serotonin toxicity (e.g., ondansetron and antipsychotics). We propose when assessing for a serotonin toxidrome, both the causative agent(s) and clinical scenario is considered to determine the likelihood of serotonin toxicity. Then the clinical features assessed, those with a moderate to high prior probability (e.g., serotonergic drug-drug interaction, overdose, recent initiation or increase in dose of serotonergic agent/s) could be diagnosed based on the Hunter criteria. However, those with a low probability (e.g., stable therapeutic doses of a serotonergic agent) require more specific and stringent criteria. Finally, we propose a minimum dataset for case reports/series of serotonin toxicity., Conclusions: More complete and accurate reporting of serotonin toxicity cases is required in the future, to avoid further misleading associations that are physiologically implausible.

Background: Over-the-counter medication overdose is a difficult diagnostic challenge for many physicians as common drug screening assays cannot detect these substances. We present a case of acute psychosis, serotonin syndrome, and anticholinergic overdose-like properties in the setting of Coricidin HBP Cough & Cold tablets, known by their street name Triple-C. This is the first case report we are aware of involving a patient presenting with these symptoms and requiring critical-care-level support., Case Presentation: A 31-year-old African American female with a past medical history of anxiety, childhood asthma, previous methamphetamine abuse, and coronavirus disease 2019 infection in August 2020 was brought to the emergency department by the local police department with altered mental status. Initial blood work, including extended drug screens, were unremarkable for a definitive diagnosis. This patient required critical-care-level support and high sedation because of her symptoms. Collateral history revealed the patient regularly consumed Triple-C daily for the 6 weeks prior to admission. A trial off sedation was attempted after 24 hours with no complications. The patient admitted to regular Triple-C consumption and auditory hallucinations since adolescence. She was discharged safely after 48 hours back into the community. She was lost to follow-up with psychiatry and internal medicine; however, she was evaluated in the emergency room 1 month later with a similar psychiatric presentation., Conclusion: Overdose of Triple-C should be kept in the differential diagnosis of patients presenting with a triad of psychosis, serotonin syndrome, and anticholinergic overdose, in the setting of unknown substance ingestion., (© 2021. The Author(s).)