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Desvenlafaxine (O-desmethylvenlafaxine) and paroxetine are antidepressants that inhibit serotonin reuptake. Despite their relatively safe profiles, several serious side effects, including serotonin syndrome, bleeding, mania, and high blood pressure, are observed. We report the confirmation of the death of a 41-year-old female, with an overdose of desvenlafaxine and paroxetine suspected as the main cause of death. To quantify the level of desvenlafaxine and paroxetine in whole blood and urine, solid phase extraction combined with liquid chromatography-tandem mass spectrometry was developed and validated. Calibration curves were linear with coefficients of determination (r 2 ) >0.999 for desvenlafaxine and paroxetine. The limits of detection and the limits of quantification for both desvenlafaxine and paroxetine were 0.001 µg/mL and 0.02 µg/mL, respectively. Desvenlafaxine and paroxetine were detected in the postmortem samples, along with various psychiatric drugs, and the blood alcohol content level was below 0.010%. The concentrations of desvenlafaxine and paroxetine in the heart blood were 11.0 µg/mL and 2.1 µg/mL, respectively, indicating lethal concentrations. In the urine, the concentrations of desvenlafaxine and paroxetine were 87.7 µg/mL and 3.5 µg/mL, respectively. This is the first report to determine the blood concentration of desvenlafaxine in a fatal intoxication caused by an overdose of desvenlafaxine single formulation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Food aspiration is one of the major health risks for elderly people in nursing homes which could lead to death. Moreover, misconducts in pharmacotherapy may represent a potential risk of adverse drug reactions. It is reported here the toxicological evaluation of a combined death by food aspiration and acute escitalopram intoxication of a psychiatric subject, occurred in a nursing home. An 89-year-old man, suffering from dysphagia and Alzheimer's, was resident in a nursing home. He was fed with a liquid diet administered directly in mouth using a syringe. The man was also being treated with escitalopram 10 mg tablet. One evening, after receiving the meal in the usual way, the man complained of sudden illness. Carried to the emergency room, the man died about 3 h later with a diagnosis of cardiogenic shock subsequentially to ab ingestis. The histological findings revealed the presence of exogenous material, probably food, up to the finest bronchial branches. The toxicological examination revealed the presence of escitalopram and its main metabolite, desmethylcitalopram: in the blood 1972 ng/ml and 285 ng/ml, in the brain 4657 ng/g and 1025 ng/g, in the gastric content 2317 ng/g and 423 ng/g, in the lung 21,771 ng/g and 468 ng/g, respectively. The bad practice of the nurses to dissolve the escitalopram tablet in the liquefied food and to administer the therapy with a syringe directly into the mouth emerged thanks this investigation. Following food aspiration, escitalopram was absorbed by inhalation route, reaching high concentrations in blood and tissues. The death occurred due to a combined mechanism between food aspiration and the escitalopram toxic action., (© 2024. The Author(s).)

Introduction: Vilazodone is a novel antidepressant approved for the treatment of major depressive disorder. It acts as a serotonin reuptake inhibitor and 5-HT1A partial agonist. It may lead to a more rapid rise in serotonin concentration in the synaptic cleft than selective serotonin reuptake inhibitors (SSRIs), which could potentially cause more severe toxicity in overdose. Methods: We performed a systematic review of the medical literature to identify all available peer reviewed evidence regarding vilazodone poisoning. Results: We identified nine unique articles describing vilazodone poisoning. These included eleven unique case reports of vilazodone poisoning, three reviews of data from the National Poison Data System, and one review of data from the Toxicology Investigators Consortium. Children were frequently symptomatic, and many developed seizures and/or serotonin syndrome. Adults and adolescents also developed serotonin syndrome after single-substance ingestion of vilazodone. ICU admission, endotracheal intubation, and parenteral benodiazepines were frequently required. Discussion: Vilazodone, unlike SSRIs, may frequently cause serotonin syndrome in single-substance ingestions. Children ingesting as little as the minimum daily dose of vilazodone, 10 mg, suffered major clinical toxicity. Conclusion: Vilazodone poisoning may produce serious clinical effects, including serotonin syndrome and seizures. Young children are at particularly high risk and may become critically ill after ingestion of very small amounts of vilazodone. Admission of poisoned children to a monitored setting and prolonged clinical observation of poisoned adults may be reasonable.

The prevalence of serotonin syndrome increases over the past several years as more serotonergic medications are being used in clinical practice. It is a potentially lethal condition caused by excessive serotonergic activity. Common causes of serotonin syndrome are the use of prescription medications, illicit drugs, or a combination of substances, leading to an increase in the activity of serotonin in the central and peripheral nervous system. The clinical symptoms range from mild to severe. We report a case of a 25-year-old woman with polysubstance abuse, including cocaine, who presented with confusion, rigidity, high-grade fever, and reduced biventricular function on echocardiogram. Based on the combination of substance used history, clinical presentation, and echocardiogram findings, she was diagnosed with serotonin syndrome complicated by takotsubo cardiomyopathy. She improved after being treated in the intensive care unit and was discharged from the hospital. This patient demonstrates the importance of recognizing and promptly initiating management of serotonin syndrome in order to improve morbidity and mortality.

Introduction: Citalopram is a selective serotonin reuptake inhibitor used for treatment of depression. Metabolism is primarily through CYP3A4 and CYP2C19; activity of the latter can vary depending on genetics. Although rare after single agent exposure, large citalopram ingestions can lead to serotonin syndrome. We report a case of citalopram overdose in an intermediate CYP2C19 metabolizer complicated by severe serotonin syndrome., Case Details: A 25-year-old female presented after intentional citalopram overdose with seizures, tachycardia, persistent neuromuscular findings, and severe hyperthermia requiring aggressive sedation and cooling. Protracted symptoms required critical care services throughout a 14 day hospital stay despite traditional treatment of serotonin syndrome. Pharmacogenomic studies revealed intermediate CYP2C19 metabolism which reduces citalopram inactivation and may cause increased levels and toxicity., Discussion: In the majority of serotonin syndrome cases, symptoms resolve rapidly after treatment initiation and discontinuation of the offending agents. Severe cases are typically associated with ingestion of multiple serotonergic agents. Our patient had severe toxicity after single agent ingestion. Pharmacogenetic testing identified abnormal CYP2C19 activity and previous cases have associated enzyme dysfunction and citalopram toxicity., Conclusion: Citalopram overdose may be associated with severe serotonin syndrome and further investigation is warranted to understand the impact of enzyme genotype on toxicity., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Introduction: We described calls to U.S. poison centers (PCs) related to potential exposure to substances through breast milk. Materials and Methods: We analyzed National Poison Data System calls between 2001 and 2017 with "Exposure through breast milk" or "Drug use during breastfeeding" as the coded scenario. Data handling and descriptive statistics were carried out using SAS JMP 12.01. Results: U.S. PCs received 76,416 information calls and 2,319 exposure calls related to breast milk. Exposure calls were from a residence in 76% ( n  = 1,758), from health care facilities (HCFs) in 15.5% ( n  = 360), and from a workplace in 0.6% ( n  = 15). A total of 466 exposures (20.1%) were subsequently managed at a HCF: 269 were evaluated and released (58%), 38 were admitted to intensive care unit (8.2%), and 53 were admitted to hospital floor (11%). Medical outcomes included 1 death (0.04%), 8 major effect (0.3%), 43 moderate effect (1.9%), 170 minor effect (7.3%), and 390 no effect (16.8%). Exposure calls that reported major effects involved opioids, benzodiazepines, ethanol, cyclobenzaprine, insulin, and amphetamines. Exposure calls most commonly involved antibiotics, antifungals, benzodiazepines, opioids, and selective serotonin reuptake inhibitors (SSRIs). A total of 1,192 exposures (51.4%) had reported signs/symptoms including drowsiness, agitation, rash, and vomiting/diarrhea. Information calls most commonly involved systemic antibiotics, SSRIs, antihistamines, corticosteroids, and benzodiazepines. Conclusions: Substances common to both exposure and information calls included antibiotics, benzodiazepines, and SSRIs. Most cases of severe toxicity included potential exposures through breast milk to benzodiazepines and opioids. These data may help inform educational outreach, risk assessment, and bedside care for breastfeeding mothers.

Fluvoxamine is a selective serotonin reuptake inhibitor that has been considered relatively safe in overdose. At therapeutic and supratherapeutic concentrations, fluvoxamine affects cardiac conduction, prolongs QTc interval, causes hypotension, obtundation, and can increase propensity for seizures. A man in his 60s was found dead at his home with a postmortem fluvoxamine peripheral blood concentration of 4.9 mg/L, and a liver concentration of 440 mg/kg. His cause of death was determined to be acute fluvoxamine toxicity., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The use of selective serotonin reuptake inhibitors (SSRIs) like citalopram in the clinical treatment of depressive symptoms in children and adolescents has become increasingly common, although application is mostly off-label. The increasing number of prescriptions is not only due to their good efficacy, but also due to their good tolerability and the comparatively low risk in cases of intoxication. However, there is discussion about the cardiac safety of overdose ingestion of citalopram. Here, we report in detail on an adolescent with depressive symptoms who used 800 mg of citalopram in order to attempt suicide. In contrast to other case reports in adults, our patient showed only mild neurological symptoms and no cardiac toxicity or symptoms of a serotonin syndrome, despite a high citalopram blood concentration measured about two hours following ingestion of citalopram (633 ng/ml; therapeutic reference range for adults 50-110 ng/ml).

Depression is known to be a risk factor for suicide. Currently, the most used antidepressants are selective serotonin reuptake inhibitors (SSRIs). Not all users, however, benefit from them. In such cases, treatment failure can be explained in part by genetic differences. In this study, we investigated the role of pharmacogenetic factors in citalopram-positive completed suicides (n = 349). Since citalopram is metabolized by CYP2C19 and CYP2D6 enzymes, the study population was genotyped for clinically relevant CYP2C19 and CYP2D6 polymorphisms and CYP2D6 copy number variation. To assess genetic differences between suicide cases and Finns in general, Finnish population samples (n = 855) were used as controls. Also, the role of drug interactions among suicide cases was evaluated. We found enrichment of a combined group of genetically predicted poor and ultrarapid metabolizer phenotypes (gMPs) of CYP2C19 among suicide victims compared to controls 0.356 [0.31-0.41] vs. 0.265 [0.24-0.30] (p = 0.0065). In CYP2D6 gMPs, there was no difference between cases and controls when the study population was analyzed as a whole. However, there were significantly more poor metabolizers among females who committed suicide by poisoning compared to female controls. In 8% of all drug poisoning deaths, lifetime drug-drug interaction was evaluated having a contribution to the fatal outcome. From clinical perspective, pharmacogenetic testing prior to initiation of SSRI drug could be beneficial. It may also be useful in medico-legal settings as it may elucidate obscure poisoning cases. Also, the possibility of unintentional drug interactions should be taken into account in drug poisoning deaths.

Serotonin syndrome (SS) is a serious toxicity that manifests with symptoms such as tremor, hyperthermia, agitation, and altered mental status that may lead to seizures, coma, or death. Selective serotonin reuptake inhibitors may precipitate SS, particularly in combination with other drugs that possess serotonergic activity. We present a case of SS in a 14-month-old after an ingestion of the selective serotonin reuptake inhibitor vilazodone.

Serotonin-specific reuptake inhibitors (SSRIs) are generally considered safe drugs but fatal adverse effects do sometimes occur, often as a consequence of interactions with other serotonin active drugs. Polypharmacy is usually a problem that the elderly encounter, but it can also have dire consequences for young people, especially when an underlying heart condition is present. Thus, failure to diagnose heart disease and the use of contraindicated medications can be a lethal combination, irrespective of age. Here we present a case of a young adult suffering from bipolar disorder who used a combination of two SSRIs (citalopram and fluoxetine) and a monoamine oxidase inhibitor (MAO; moclobemide) with tragic consequences. The deceased also suffered from undiagnosed hypertrophic cardiomyopathy and was carrier of a genotype that may have predisposed him to increased sensitivity to SSRIs. The apparent difficulty in establishing the manner of death in this case is also discussed.

Vilazodone hydrochloride is the first member in a new class of antidepressants called indolealkylamines and was approved for use in the United States in 2011 for major depressive disorder. It has a combined mechanism of action of a selective serotonin reuptake inhibitor and a partial agonist of serotonin 5-HT1A receptors. It has not been approved for use in the pediatric population, and toxicity from exploratory vilazodone ingestion has been rarely described to date. We describe 2 children with laboratory-confirmed vilazodone ingestions that led to significant toxicity including refractory status epilepticus in 1 patient and likely transient seizure activity in the other. Both patients required multiple doses of benzodiazepines; in the more severe case, barbiturates were added to control seizure activity. These children returned to baseline and had no prolonged neurologic complications. Pediatric experience with vilazodone is limited; however, the literature demonstrates 3 additional case reports of children experiencing seizure after vilazodone ingestion. With the 2 new cases presented here, it seems prudent to educate prescribers and families of the potential dangers of ingestion of vilazodone tablets by young children.

Background: Selective serotonin reuptake inhibitor (SSRI) exposures among children younger than 6 years of age are generally well tolerated. Vilazodone is an SSRI with partial agonism at the 5-HT 1A receptor with demonstrated clinical efficacy for depression whose off-label usage is likely to increase. Recent evidence suggests that unintentional ingestion of vilazodone in children under 6 years old is associated with more severe clinical effects than other SSRIs. We chose to evaluate dose and outcomes for pediatric vilazodone ingestions., Methods: A retrospective analysis of single-substance exposures associated with vilazodone among children younger than 6 years of age from 2011 through 2016 was conducted using data from the National Poison Data System., Results: During 2011-2016, 753 vilazodone ingestions among children <6 years old were reported to US poison control centers. A near majority (49.0%, n = 369) experienced one or more clinical effects. The dose ingested was reported for 596 children (79%). The median dose associated with major effects was 50.0mg (Mean: 106.0) compared with 40.0mg (Mean 81.1) for moderate effects. Half (50.0%) of children with a major effect and 54.0% with a moderate effect ingested ≤40 mg of vilazodone. As the dose of vilazodone ingested increased, the proportions of exposures admitted to a healthcare facility (HCF) (p < .001) and with serious outcomes (p < .001) both increased. Children ≤2 years had higher proportions of HCF admission (33.8% vs 23.1%) and serious outcomes (27.0% vs 17.7%) than children 3-5 years of age. Clinical effects, such as coma, seizures, ataxia, and hallucinations/delusions, were observed among children ingesting doses of vilazodone as low as 10 mg., Conclusions: Exposure to vilazodone poses a unique and potentially serious threat to children <6 years of age. Children in this age group who are exposed to vilazodone should be evaluated promptly in a clinical setting. Off-label use of vilazodone in children under 6 years should be discouraged until further research is conducted regarding its safety in this population.

Background: Vilazodone is an antidepressant with selective serotonin reuptake inhibition and partial 5HT1A agonism. Serotonin syndrome is believed to be due to excessive stimulation of 5-HT2A and 5-HT1A receptors, resulting in the clinical triad of altered mentation, autonomic instability and neuromuscular abnormalities. The goal of this study is to define serotonergic effects after vilazodone exposure., Methods: A retrospective review of two databases: the American Association of Poison Controls Centers' National Poison Data System (NPDS) and the American College of Medical Toxicology's Toxicology Investigators Consortium (ToxIC Registry). A case series of four patients from one medical toxicology service is also presented., Results: During the 52-month study period, a total of 3192 vilazodone human exposures were reported to NPDS. Of these, 1734 (54%) were isolated vilazodone cases. The clinical effects of vilazodone toxicity included drowsiness (20%), vomiting (14%), tachycardia (11%) and agitation (10%). Most patients (71%) had symptoms for between 2 and 24 h, though some (14%) remained symptomatic for more than 24 h. The most common treatment was intravenous fluids (15%) and the most serious intubation (2%). From the ToxIC Registry, a total of 23 cases of vilazodone exposures were identified. Of these, 17 (74%) had vilazodone listed as the first (primary) agent and 10 (43%) involved vilazodone-only ingestions. Nine (39%) cases documented serotonin syndrome; and most (8/9; 89%) listed vilazodone as the primary agent. All (n = 4) subjects in the case series with acute vilazodone toxicity had serotonin syndrome., Conclusions: Vilazodone overdose, including vilazodone-only ingestions, are associated with serotonin syndrome. Serotonergic toxicity and appropriate treatments should be considered when caring for patients with vilazodone ingestions.

Background: Unintentional ingestion of selective serotonin reuptake inhibitor (SSRI) medications is common amongst children <6 years of age. Current evidence-based management guidelines are based on a low incidence of significant medical outcomes in these children., Objective: To describe and compare outcomes of pediatric exposures to vilazodone with other SSRIs., Methods: A retrospective observational case series analysis of both single and polysubstance SSRI exposures amongst children <6 years old reported to the National Poison Data System (NPDS)., Results: 11,384 SSRI exposures in children <6 years of age reported to NPDS between January 2012 and June 2016 were assessed. Vilazodone only accounted for 5.9% of all exposures, but resulted in the highest proportion of health care facility admission compared to other SSRIs, both in single substance (165 of 531 (31.1%); OR 9.0 [7.3-11.2]) and polysubstance (57 of 107 (53.3%); OR 4.1 [2.7-6.2]) exposures. Children exposed to vilazodone also have higher odds of experiencing a major or moderate outcome in single (134 of 531 (25.2%); OR 20.5 [15.5-27.1]) and polysubstance (37 of 107 (35.6%); OR 5.9 [3.7-9.0]) exposures compared to other SSRIs. Several severe clinical outcomes, such as seizure and coma, were more common among the vilazodone exposures., Conclusions: Exposure to vilazodone in this age group results in an increased rate of hospitalization as well as more severe clinical effects as compared to other SSRIs. Current evidence-based SSRI exposure management guidelines may not be appropriate for the management of vilazodone ingestion in this age group.

Duloxetine is a second-generation selective serotonin and norepinephrine reuptake inhibitor used primarily for the treatment of depression. Relatively few fatalities have been reported in association with its use. Similarly, there are no known reports that provide a comprehensive analysis of blood, fluid and tissue samples in an overdose setting. Herein we present a fatal case of duloxetine toxicity with both the highest reported post-mortem blood concentration and a comprehensive toxicological analysis of duloxetine in femoral blood, vitreous humor, liver tissue, urine and gastric contents. In doing so, we hope to provide data that can assist both toxicologists and forensic pathologists with assessing duloxetine toxicity in the future., (Published by Oxford University Press 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Vilazodone is a selective serotonin reuptake inhibitor and 5HT1A agonist recently approved to treat depression in adults. To date, there are minimal data available regarding the expected course and treatment of acute vilazodone ingestions., Case Report: We report a case of a previously healthy 19-month-old girl who presented after an acute ingestion of an estimated 37 mg/kg vilazodone. She was taken to an outside emergency department approximately 1 h after an unwitnessed ingestion. Initially, the patient was noted to have decreased responsiveness, sluggish but reactive pupils, altered mental status, and reported seizure activity. She was given intravenous lorazepam for seizure control, intubated, and transferred to a pediatric tertiary care facility, where she continued to show signs of serotonin toxicity and received treatment with benzodiazepines and cyproheptadine. Despite vilazodone's long half-life and the large amount ingested, the patient was extubated within 10 h of presentation, had returned to baseline mental status by 22 h, and was discharged home approximately 57 h after ingestion. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Accidental ingestions are common in the pediatric population. Emergency physicians need to be aware of the signs and symptoms of acute medication toxicities, the expected clinical course, and the necessary supportive measures used to treat these patients. Because vilazodone is a recently approved medication, there is little experience with acute vilazodone ingestions. This report considerably increases the understanding of vilazodone's effects in the setting of an acute ingestion., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Citalopram is a selective serotonin reuptake inhibitor (SSRI) with cardiac and neurologic toxicities as well as the potential for serotonin syndrome. In most instances, patients recover fully from toxic ingestions of SSRIs. We describe a fatal case of a citalopram overdose., Case Report: A 35-year-old woman presented to the emergency department after having witnessed seizures at home. An empty citalopram prescription bottle was located, and an intentional overdose was suspected. At the scene, she was found to be in cardiac arrest with pulseless electrical activity and underwent cardiopulmonary resuscitation, including intravenous epinephrine and bicarbonate. In the emergency department, her physical exam was notable for cough and gag reflexes and movement in all extremities with increased muscle tone and tachycardia. Her initial postresuscitation ECG showed sinus rhythm with QRS 92 ms and QTc 502 ms. Her temperature was initially normal, but she rapidly became febrile to 41.8 °C shortly after admission. She was treated symptomatically and with cyproheptadine for suspected serotonin syndrome (SS) but became increasingly hemodynamically unstable over the next 6 h and then developed torsades des pointes (TdP) progressing to pulseless, wide complex tachycardia. She underwent cardiopulmonary resuscitation (CPR) for approximately 50 min but ultimately expired. Postmortem serum analysis revealed a citalopram concentration of 7300 ng/mL (therapeutic range 9-200 ng/mL) and THC, but no other non-resuscitation drugs or substances., Case Discussion: Citalopram overdoses often have only mild to moderate symptoms, particularly with ingestions under 600 mg in adults. However, with higher doses, severe manifestations have been described, including QTc prolongation, TdP, and seizures. Serotonin syndrome has also been described in SSRI overdose, and our patient exhibited signs consistent with SS, including increased muscle tone and autonomic dysregulation. Our patient's serum concentration suggests a massive overdose, with major clinical effects, possible SS, and death., Conclusions: Although most patients recover from citalopram overdose, high-dose ingestions can produce severe effects and fatalities may occur. In this case, it is likely that the patient's delayed presentation also contributed significantly to her death. The clinician must be aware of the potential for large ingestions of citalopram to produce life-threatening effects and monitor closely for the neurologic, cardiovascular, and other manifestations that, in rare cases, can be fatal.

Incidence of poisonings with serotonin reuptake inhibitors (SRIs) is growing. SRI toxicity is considered low, but its actual impact in multi-drug poisonings remains unclear. Our objective was to evaluate the consequences of SRI exposure in patients referred to the emergency department (ED) for deliberate multi-drug exposure. Patients admitted for multi-drug exposure involving at least one SRI were matched with patients who did not ingest any SRI, according to age, gender, type of drug and ingested doses. Features of serotonin syndrome according to Sternbach's criteria and Hunter's serotonin toxicity criteria were evaluated from records. In 4 years, 148 SRI-exposed patients were included and compared to 296 matched controls. The SRIs mainly involved were escitalopram (22%), venlafaxine (20%), fluoxetine (19%), citalopram (15%) and paroxetine (11%). Serotonin syndrome was diagnosed in one patient, but actually occurred in five SRI-exposed patients based on the retrospective evaluation of records. Twenty patients (14%) exhibited one or more serotonin syndrome criteria. At least two of 11 of Sternbach's criteria and two of nine of Hunter's serotonin toxicity criteria were missing in each chart. Using a conditional logistic regression analysis, seizures (p = 0.04) and serotonin syndrome (p = 0.01 based on Sternbach's criteria and p = 0.004 based on Hunter's serotonin toxicity criteria) more frequently occurred in SRI-exposed patients. Requirement for mechanical ventilation was significantly increased (p = 0.03), although admission to the intensive care unit was not. In multi-drug-poisoned patients admitted to the ED, exposure to SRIs significantly increases the risk of seizures and requirement for mechanically ventilation. Diagnosis of serotonin syndrome remains insufficient justifying improved training., (© 2014 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Serotonin syndrome (SS) is a complication after overdosage with antidepressants. SS increases the level of circulating serotonin. Fatal outcome of SS is most often seen in cases where there has been an overdosage with selective serotonin reuptake inhibitors (SSRI)/selective noradrenaline reuptake inhibitors (SNRI) in combination with other serotonin increasing drugs. This case report describes the rapid development of symptoms in a 54-year-old man who ingested a total amount of 6.5 g of SSRI and SNRI drugs as the only drug types. It proves the importance of being aware of the symptoms of SS when the patient is first seen in the emergency department.

We describe a case of pendular nystagmus as a previously unreported side effect of venlafaxine, and speculate to its importance in the recognition of the serotonin syndrome. In particular, we discuss the importance of identifying incomplete forms of the syndrome, such as those presenting with predominantly ocular manifestations, as is in our case.

Background: This is a case of a citalopram and olanzapine overdose causing seizures and severe cardiotoxicity., Case Report: A 21-year-old man presented unresponsive, with seizures, to an Emergency Department. The patient's initial electrocardiogram demonstrated a widened QRS of 160 ms and a normal QT/QTc interval of 400/487 ms consistent with cardiac sodium channel blockade. Within 30 min of arrival, peak citalopram and olanzapine levels were measured to be 522 ng/mL and 505 ng/mL, respectively. Measured levels remained supratherapeutic until 13.6 h and 42.6 h after arrival for citalopram and olanzapine, respectively. The patient developed bradycardia and hypotension that required multimodal therapies including sodium bicarbonate boluses, vasopressors, and transvenous pacing. Seizures and cardiotoxicity continued while citalopram, but not olanzapine, was supratherapeutic., Conclusions: This case describes cardiotoxicity directly correlated with supratherapeutic citalopram levels in overdose., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Introduction: Lamotrigine is a phenyltriazine compound that inhibits voltage-gated sodium channels, decreasing release of glutamate and aspartate, and inhibits serotonin, norepinephrine and dopamine reuptake. Reports of toxicity in the literature are limited to case reports and primarily involve coingestants. This case series is intended to report the clinical manifestations of lamotrigine toxicity., Methods: This retrospective case series from 2003 to 2012 studies the effects of lamotrigine toxicity when not confounded by coingestants. Admission records at an inpatient toxicology center were reviewed for lamotrigine-only exposure based on history with supporting laboratory data when available. After identification, these charts were reviewed again to characterize vital signs, neurological examination findings, specific laboratory and electrocardiography parameters, and complications., Results: Fifty-seven patients were identified with possible lamotrigine toxicity. Nine patients, including three toddlers, had lamotrigine-only ingestions. Three of these patients had seizures, four were hypertensive, five were tachycardic, and four experienced tachypnea. Mental status was altered in all nine (depressed (n = 4), agitated (n = 5) or both (n = 3)). Five patients were hyperreflexic and experienced intermittent myoclonus, and two had inducible clonus. On electrocardiogram, two patients experienced QRS prolongation (114-116 ms), and four had QTc prolongation (463-586 ms). No patient had life-threatening symptoms or signs. Serum levels of lamotrigine were available in seven patients, and averaged 35.4 mg/L (17-90 mg/L). The therapeutic range for sLTG is 3-14 mg/L., Conclusions: Lamotrigine toxicity manifested with minor-moderate neurologic and/or electrocardiographic effects. Toxicity reflects the known pharmacologic actions of lamotrigine: serotonin, norepinephrine and dopamine reuptake inhibition, and sodium channel blockade.

This case demonstrates an acute presentation of unwitnessed seizure causing typical injuries. Progress in hospital was complicated by worsening autonomic disturbance and agitation, typical for serotonin syndrome, suspected in light of recent selective serotonin reuptake inhibitor antidepressant initiation. Supportive care required treatment in the intensive care unit setting but full recovery ensued. This case not only reminds clinicians of the potential pitfalls in assessing postictal injured patients, but also that serotonin syndrome requires a high-index of diagnostic suspicion given the range of presenting features. Management ranges from simple withdrawal of the offending agent to specific therapies such as a cyproheptadine.

Many antidepressants inhibit serotonin or norepinephrine reuptake or both to achieve their clinical effect. The selective serotonin reuptake inhibitor class of antidepressants (SSRIs) includes citalopram, escitalopram (active enantiomer of citalopram), fluoxetine, fluvoxamine, paroxetine, and sertraline. The SSRIs are as effective as tricyclic antidepressants in treatment of major depression with less significant side effects. As a result, they have become the largest class of medications prescribed to humans for depression. They are also used to treat obsessive-compulsive disorder, panic disorders, alcoholism, obesity, migraines, and chronic pain. An SSRI (fluoxetine) has been approved for veterinary use in treatment of canine separation anxiety. SSRIs act specifically on synaptic serotonin concentrations by blocking its reuptake in the presynapse and increasing levels in the presynaptic membrane. Clinical signs of SSRI overdose result from excessive amounts of serotonin in the central nervous system. These signs include nausea, vomiting, mydriasis, hypersalivation, and hyperthermia. Clinical signs are dose dependent and higher dosages may result in the serotonin syndrome that manifests itself as ataxia, tremors, muscle rigidity, hyperthermia, diarrhea, and seizures. Current studies reveal no increase in appearance of any specific clinical signs of serotonin toxicity with regard to any SSRI medication. In people, citalopram has been reported to have an increased risk of electrocardiographic abnormalities. Diagnosis of SSRI poisoning is based on history, clinical signs, and response to therapy. No single clinical test is currently available to confirm SSRI toxicosis. The goals of treatment in this intoxication are to support the animal, prevent further absorption of the drug, support the central nervous system, control hyperthermia, and halt any seizure activity. The relative safety of the SSRIs in overdose despite the occurrence of serotonin syndrome makes them more desirable than other antidepressants. The prognosis in animals that receive treatment is excellent. In one retrospective study, there were no deaths in 313 SSRI-poisoned dogs. No characteristic or classic histopathologic lesions result from SSRI toxicosis. Differential diagnoses for SSRI overdose must include ingestions of other serotonergic medications such as phenylpiperidine opioids (fentanyl and tramadol), mirtazapine, buspirone, amitraz, and chlorpheniramine., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Brain MRI and ¹⁸F-FDG PET/CT scans were performed in a patient who had survived a suicide attempt by fluoxetine overdose. The patient presented with the following clinical signs and symptoms, and neuroimaging findings: severe signs of serotonin toxicity, including comatose state, akinetic rigid syndrome and dysautonomia; bilateral globus pallidus changes consistent with extensive pallidal necrosis and subsequent reversible diffuse ischemic changes in white matter, with posterior predominance, involving the splenium of the corpus callosum on brain MRI; and marked hypometabolism in the frontal, parietal and temporal cortical regions as well as in both caudate nuclei on ¹⁸F-FDG PET/CT performed 37 days later. These findings suggest that acute severe serotonin toxicity can induce structural and long-standing functional changes in multiple cortical and subcortical brain regions that are associated with cognitive and extrapyramidal syndromes., (Copyright © 2011. Published by Elsevier Masson SAS.)

Context: In adults, citalopram is more likely to cause seizures and ECG changes than other selective serotonin reuptake inhibitors (SSRIs). Data in children are lacking, yet the 2007 American Association of Poison Control Centers out-of-hospital citalopram consensus guideline mirrors the guideline for other SSRIs., Objective: To compare the clinical effects and hazard index of citalopram with other SSRIs in pediatric ingestions., Methods: An 11-year retrospective analysis of national poison center data was conducted. Acute, known-type SSRI ingestions in children younger than 6 years with known outcome were included. Clinical effects and hazard index (number of major or fatal outcomes/1000 SSRI ingestions) were compared. Citalopram dose-response was evaluated., Results: The 35 296 included cases by SSRI type were citalopram (3747), escitalopram (4815), fluoxetine (5946), fluvoxamine (273), paroxetine (7157), and sertraline (13 358). The overall hazard index was 0.340. The hazard index for citalopram (0.801) was 2.8-fold higher than for non-citalopram SSRIs (0.285). Comparing seizures (single or multiple discrete) and cardiac effects (conduction disturbances, other ECG changes or other dysrhythmia) of citalopram with the other SSRIs, pediatric citalopram ingestions were more likely to develop seizures (5 of 3747 [0.13%] vs. 10 of 31 549 [0.03%], OR = 4.2; 1.4-12.3) and cardiac toxicity (9 of 3747 [0.24%] vs. 25 of 31 549 [0.08%], OR = 3.0; 1.4-6.5). Clinical effects occurring more frequently with other SSRIs included tachycardia (p = 0.0236), oral irritation (p = 0.0412), vomiting (p = 0.0036), agitation/irritability (p = 0.0104), and hyperthermia (p = 0.0314). There was a dose response only for single or multiple discrete seizures, mydriasis and clinically significant responses (a predetermined subset of CNS and cardiopulmonary clinical effects). Meaningful triage thresholds for citalopram could not be determined due to the low frequency of significant clinical effects., Conclusion: Children develop minimal toxicity with SSRI ingestions. Seizures and ECG changes, while uncommon, occur more frequently with citalopram. Doses associated with significant outcomes suggest that the triage guideline for citalopram does not need to be modified.

Introduction: We report a case of ethcathinone and methylone poisoning with severe clinical toxicity. This is to our knowledge the first case reported in the medical toxicology literature., Case Report: A 22-year-old woman was brought to the emergency department following several episodes of tonicoclonic seizures, a few hours after ingesting "legal ecstasy". The patient needed intubation for recurrent seizures, and she was found to have severe hyponatremia (120 mmol/L) that was corrected with hypertonic saline. The patient's mental status improved rapidly, and she was extubated the day following her admission. However, she developed prolonged rhabdomyolysis (CK 34.537 U/L) that required a 6-day hospitalisation., Discussion: The seizures and the hyponatremia may be explained by the MDMA-like characteristics of methylone that may induce inappropriate secretion of antidiuretic hormone mediated via the serotonin system. The combination of methylone and ethcatinone (both acting like serotonin reuptake inhibitors) might have contributed to neurologic manifestations compatible with serotonin toxicity, although our patient never had autonomic instability. Our patient had a prolonged period of rhabdomyolysis which may also be explained by excessive serotonin activity resulting in an increased motor hyperactivity. The public has to be aware of this growing health problem. Clinicians must report future cases of toxicity related to the use of cathinone synthetic derivatives in order to increase our knowledge of these substances.

Both moclobemide and fluoxetine are used in the treatment of depression, and have been shown to produce fewer side effects than conventional tricyclic antidepressants. A combination of moclobemide and fluoxetine has been used in refractory depression, however there is potential for severe serotonin toxicity. We describe a lethal case of serotonin toxicity in a 36 year-old woman after she ingested multiple drugs, including moclobemide 4500 mg, fluoxetine 200 mg, propranolol 300 mg and several benzodiazepines. The clinical features included coma, mydriasis, hyperthermia, tremor, hyperreflexia, rhabdomyolysis, renal failure and respiratory insufficiency. Eventually, the patient died of disseminated intravascular coagulation and circulatory collapse at 22.5 h postingestion. Toxicological analysis of the patient's blood confirmed high levels of moclobemide 150 μg/mL (therapeutic 1-3 μg/mL), fluoxetine 3750 ng/mL (therapeutic 47-469 ng/mL) and several benzodiazepines. In conclusion, a combination of moclobemide and fluoxetine should be avoided in depressed patients with high suicidal tendencies. Moreover, early recognition and aggressive intervention are the mainstays in the management of potentially life-threatening serotonin toxicity.

Aims: To investigate the relationship between decontamination procedures and seizure events caused by venlafaxine overdose and to estimate the time at which 90% of patients would have had their first seizure in the presence and absence of decontamination., Methods: Data were collected from 319 patients who took an overdose of venlafaxine on 436 occasions. Seizures occurred on 24 of 436 occasions (5%). Patients received one of single dose activated charcoal (SDAC), whole bowel irrigation (WBI), a combination of either (SDAC/WBI) or no decontamination. Logistic regression and time to event analysis were used to investigate the influence of dose and decontamination on the probability of seizures and time to 90% (t(90) ) of seizure, respectively., Results: A linear logistic regression model described the data. Simulation from the model showed that the probability of seizure was 0.05 (0.03-0.08), 0.19 (0.09-0.35) and 0.75 (0.30-0.96) at 1000, 5000 and 10 000 mg, respectively (median and 95% credible interval). At the mean dose of 2100 mg the odds ratios (OR) in the presence of SDAC, WBI and SDAC/WBI were 0.48 (0.25-0.89), 0.71 (0.35-1.22) and 0.25 (0.08-0.62), respectively. A modified Gompertz model described the time to seizure events. Simulations from the Gompertz model showed that the t(90) values for first seizure was 26 h and was not affected by dose or decontamination procedure., Conclusion: SDAC/WBI provided greater benefits than the sum of the independent effects of SDAC and WBI. Patients should be observed for at least 24 h for seizures based on the dose and risk of seizure occurring., (© 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.)

Venlafaxine (VEN) is an antidepressant found to possess a higher fatal toxicity index (FTI, i.e., deaths in proportion to consumption) than other newer antidepressants and selective serotonin reuptake inhibitors (SSRIs). The aim of this study was to elucidate using post-mortem cases whether the apparent high toxicity of VEN is associated with adverse drug interactions, pharmacogenetic factors and/or the manner of death. Within a 2-year period, a comprehensive post-mortem database and death certificates were searched for cases with laboratory findings of VEN, findings of other drugs, associated background information and the cause and manner of death. In 123 cases, the concentrations of VEN and its two metabolites, O-desmethylvenlafaxine (O-VEN) and N-desmethylvenlafaxine (N-VEN), and the CYP2D6 genotype were determined in post-mortem blood. The median concentrations of VEN, O-VEN and N-VEN were 560, 420 and 49 µg/l, respectively. A prominent feature of the VEN-positive cases was the high abundance of interacting drugs (46%), being more common with higher VEN concentrations. Compared to other common antidepressants, VEN-positive cases showed the highest suicide frequency, but also the proportion of suicidal VEN poisonings of all suicides was substantially higher than that of mirtazapine or SSRIs. Relative CYP2D6 activity did not predispose to high VEN concentrations, and the frequency of the extreme phenotypes followed the general population. In conclusion, the high suicide potential of VEN in combination with the high prevalence of drugs causing adverse interactions could be the reason for the observed high FTI.

Background: Venlafaxine is an antidepressant whose adverse event profile is similar to that of the SSRIs (selective serotonin reuptake inhibitors). Serious complications due to venlafaxine overdose have been described. These generally have been resolved with supportive measures alone. However, although patients usually recover even after massive intake of the drug, death may occur in rare cases., Objective: This article reports a case of dementia after an overdose of venlafaxine., Case Report: We present a case of severe cognitive deterioration in a 48-year-old woman after venlafaxine overdose in a suicide attempt. She became comatose after the overdose. On recovery from the coma, she suffered irreversible motor and cognitive alterations and seizures. Several factors could justify the possible association of these side effects with venlafaxine overdose: time relationship, severe focal deficit and other neurological signs, symptomatic fluctuation, relationship of serotonin networks with the cognitive functions and deficits related to the network damage, and the potential capacity of venlafaxine to damage the central nervous system. However, other alternatives, especially factors that could implicate a hypoxic encephalopathy as the origin of the dementia, cannot be entirely ruled out., Conclusion: Venlafaxine seems to have special toxicity vis-à-vis the SSRIs, and this case adds to the literature supporting this. Cognitive function should be monitored after an overdose with venlafaxine., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Unlabelled: Serotonin syndrome is caused by excess serotonin in the central nervous system. It usually occurs as adverse drug-therapy (neuroleptic agents, monoamine oxidase inhibitors, serotonin reuptake inhibitors and others)., Case Presentation: a 50-year-old woman with a history of depression, was admitted to our hospital, due to suicidal drug poisoning (moclobemide- 4500 mg, venlafaxine 1050 mg, mianserin 300 mg and cytisine 30mg). She was also drunk. The patient was unconscious and sweaty, on the ECG tachycardia (120/min) was observed. In addition, several hours after admission, the patient developed acute respiratory failure, we observed myoclonus, lockjaw, body temperature increased to 37.3 degrees Celsius, and blood pressure was 170/80 mmHg. During the neurological examination there was a tendency to bilaterall Babinski sign and the nystagmus was present. The patient was intubated, and we started an intravenous infusion of Relanium. In laboratory studies: ethanol: 2.52 g/l, tests for benzodiazepines and tricyclic antidepressants were negative, WBC 13.1 tys/microl, CPK was elevated to 372 U/L, other parameters (electrolytes, transaminases, serum total protein, glucose, CRP, creatinine) were normal. The patient required intensive care and treatment during the next two days. The diagnosis of serotonin syndrome was based on the Hunter's criteria, which are more sensitive and more specific than Sternbach's criteria. The patient was discharged from hospital in good condition.

A 22-year-old woman was found dead in her bed, and subsequent postmortem examination was performed using ordinary methods such as external examination, Triage®, and computed tomography (CT) scan which demonstrated a high-density content of the duodenum. Autopsy and quantitative analysis of drugs present in the GI tract showed that high amounts of radiopaque psychotic agents such as fluvoxamine maleate, carbamazepine, and zolpidem tartrate had been responsible for the high-density profile of the duodenum. Postmortem quantitative analysis of drugs in the blood suggested that death had been caused by fatal intoxication with fluvoxamine maleate. Thus, postmortem CT could offer an opportunity to suspect drug intoxication due to radiopaque psychotic agents such as chloral hydrate, phenothiazine, bromovaleryl urea, fluvoxamine maleate, and probably zolpidem tartrate, although it is neither a specific nor a quantitative test for drugs. Therefore, postmortem CT happened to provide clues to investigation of drug intoxication in the present case., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: To describe a case of a patient who became comatose after taking an overdose of duloxetine, a serotonin-norepinephrine reuptake inhibitor., Case Summary: A 49-year-old male ingested an overdose of duloxetine approximately 2 hours before presentation to the emergency department. On arrival he was drowsy, but easily awakened and oriented, with Glasgow Coma Score 14 (eyes 3, motor 6, verbal 5). Immediately after admission, charcoal and magnesium sulfate were given to prevent further systemic absorption of medication through the gastrointestinal tract. No gastric lavage was performed. Six hours after drug intake the patient became unconscious (Glasgow Coma Score 7, eyes 2, motor 4, verbal 1). Full toxicologic screening showed a toxic duloxetine plasma concentration of 0.86 mg/L. The patient was admitted to the intensive care unit (ICU) and, on arrival, urinary retention was noted. During ICU admission the patient remained hemodynamically stable; approximately 12 hours after ingestion of duloxetine, he regained consciousness. Over the next 3 days the urinary output decreased to 60 mL/day. After 4 days patient was discharged without any remaining symptoms. Based on repeated plasma duloxetine serum concentration determinations, a plasma half-life of duloxetine was calculated to be 18 hours (reference range 9-19)., Discussion: The Naranjo probability scale suggested that duloxetine was the probable cause for the symptoms described., Conclusion: Overdose with duloxetine can induce coma several hours after intake, with a fast reversal in our case.

Background: Drugs most commonly responsible for the acquired form of long QT syndrome are antibiotics and antidepressants. Escitalopram overdose leading to prolongation of the QTc interval has only twice been previously described in the literature., Methods: We report a 33-year-old Caucasian woman who attempted suicide by ingesting 15-20 pills of lithium (300 mg each), 15-20 pills of escitalopram (20 mg each), and alcohol. An electrocardiogram (ECG) on admission to the medicine telemetry unit showed a QTc prolongation of 491 ms and normal sinus rhythm. Repeat ECG 18 hours after admission showed a QTc of 502 ms and sinus bradycardia. Serial ECGs were continued with the following results of QTc/hours after admission: 499 ms/2, 485 ms/25 (> 1 day), 469 ms/41, 461 ms/71, 476 ms/97 (> 4 days). After the QTc interval had declined to 461 ms after more than 2 days (71 hours), the patient was transferred to the inpatient psychiatry ward service., Conclusions: Prescribers may wish to exercise caution when administering escitalopram to patients who have suicidal ideations and depression. In the event of an overdose, QT prolongation can occur and ECG monitoring should take place for at least 2 days after ingestion in order to prevent life-threatening arrhythmias such as torsades de pointes (tdp). Other factors and drugs that could contribute to prolongation of the QT interval should be taken into account when determining the time period needed for ECG monitoring in the individual patient.