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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.

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.

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.

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.

Context: Seizures are a recognized complication of acute overdose with the racemic (1:1 ratio of R- and S-enantiomers) selective serotonin reuptake inhibitor antidepressant citalopram., Objective: We tested the hypothesis that escitalopram (the therapeutically active S-enantiomer of citalopram) causes fewer seizures in overdose than citalopram at comparable doses of the S-enantiomer., Methods: Multicenter retrospective review of cases with citalopram and escitalopram overdose reported to German, Austrian, and Swiss Poisons Centers between 1997 and 2006., Results: 316 citalopram and 63 escitalopram cases were analyzed. Somnolence, nausea, vomiting, tachycardia, QT prolongation, and tremor occurred with similar frequency in both groups. There was a striking difference in the frequency of single and multiple seizures: 43 cases (13.5%) in the citalopram group and 1 case (1.6%) with a single seizure in the escitalopram group (p=0.0065)., Discussion and Conclusions: At comparable ingested doses of the S-enantiomer, the symptom profile for citalopram and escitalopram intoxications is similar except for seizures that occur more frequently in citalopram than in escitalopram poisoning.

Introduction: Altered mental status, autonomic dysfunction, and neuromuscular abnormalities are a characteristic triad of serotonin syndrome. No laboratory tests confirm the diagnosis of serotonin syndrome., Case Report: A 35-year-old woman took moclobemide, sertraline, and citalopram in a suicide attempt. She was conscious with mild tachycardia, hypertension, and tachypnea one hour after ingestion. In the second hour after ingestion diaphoresis, mydriasis, horizontal nystagmus, trismus, hyperreflexia, clonus, and tremor appeared. She became agitated and unresponsive. In the third hour after ingestion she became comatose and hyperthermic. She was anesthetized, paralyzed, intubated, and ventilated for 24 hours. Serum moclobemide, sertraline, and citalopram levels were above therapeutic levels. The serum serotonin level was within normal limits and the urinary 5-hydroxyindoleacetic acid:creatinine ratio was below the average daily value. The urinary serotonin:creatinine ratio was increased on arrival (1 mg/g)., Discussion and Conclusion: The urinary serotonin level is increased in serotonin syndrome due to a monoamine oxidase inhibitor and selective serotonin-reuptake inhibitors overdose. It is possible that urinary serotonin concentration could be used as a biochemical marker of serotonin syndrome.

A review of US poison center data for 2004 showed over 48,000 exposures to selective serotonin reuptake inhibitors (SSRIs). A guideline that determines the conditions for emergency department referral and prehospital care could potentially optimize patient outcome, avoid unnecessary emergency department visits, reduce health care costs, and reduce life disruption for patients and caregivers. An evidence-based expert consensus process was used to create the guideline. Relevant articles were abstracted by a trained physician researcher. The first draft of the guideline was created by the lead author. The entire panel discussed and refined the guideline before distribution to secondary reviewers for comment. The panel then made changes based on the secondary review comments. The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial management of patients with a suspected ingestion of an SSRI by 1) describing the process by which an ingestion of an SSRI might be managed, 2) identifying the key decision elements in managing cases of SSRI ingestion, 3) providing clear and practical recommendations that reflect the current state of knowledge, and 4) identifying needs for research. This guideline applies to ingestion of immediate-release forms of SSRIs alone. Co-ingestion of additional substances might require different referral and management recommendations depending on their combined toxicities. This guideline is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions may be at variance with this guideline and are the prerogative of the patient and the health professionals providing care, considering all of the circumstances involved. This guideline does not substitute for clinical judgment. Recommendations are in chronological order of likely clinical use. The grade of recommendation is in parentheses. 1) All patients with suicidal intent, intentional abuse, or in cases in which a malicious intent is suspected (e.g., child abuse or neglect) should be referred to an emergency department. This activity should be guided by local poison center procedures. In general, this should occur regardless of the dose reported (Grade D). 2) Any patient already experiencing any symptoms other than mild effects (mild effects include vomiting, somnolence [lightly sedated and arousable with speaking voice or light touch], mydriasis, or diaphoresis) should be transported to an emergency department. Transportation via ambulance should be considered based on the condition of the patient and the length of time it will take the patient to arrive at the emergency department (Grade D). 3) Asymptomatic patients or those with mild effects (defined above) following isolated unintentional acute SSRI ingestions of up to five times an initial adult therapeutic dose (i.e., citalopram 100 mg, escitalopram 50 mg, fluoxetine 100 mg, fluvoxamine 250 mg, paroxetine 100 mg, sertraline 250 mg) can be observed at home with instructions to call the poison center back if symptoms develop. For patients already on an SSRI, those with ingestion of up to five times their own single therapeutic dose can be observed at home with instructions to call the poison center back if symptoms develop (Grade D). 4) The poison center should consider making follow-up calls during the first 8 hours after ingestion, following its normal procedure. Consideration should be given to the time of day when home observation will take place. Observation during normal sleep hours might not reliably identify the onset of toxicity. Depending on local poison center policy, patients could be referred to an emergency department if the observation would take place during normal sleeping hours of the patient or caretaker (Grade D). 5) Do not induce emesis (Grade C). 6) The use of oral activated charcoal can be considered since the likelihood of SSRI-induced loss of consciousness or seizures is small. However, there are no data to suggest a specific clinical benefit. The routine use of out-of-hospital oral activated charcoal in patients with unintentional SSRI overdose cannot be advocated at this time (Grade C). 7) Use intravenous benzodiazepines for seizures and benzodiazepines and external cooling measures for hyperthermia (>104 degrees F [>40 degrees C]) for SSRI-induced serotonin syndrome. This should be done in consultation with and authorized by EMS medical direction, by a written treatment protocol or policy, or with direct medical oversight (Grade C).

Objective: Despite the frequency of use of citalopram, its clinical effects and pharmacokinetics in overdose in the pediatric patient are not well described. We describe the clinical course and drug levels following the ingestion of citalopram by a 10-month-old female., Case Report: A 10 month-old female ingested an unknown amount of citalopram. Approximately 40 min after ingestion, the child developed horizontal nystagmus, followed by a generalized, tonic-clonic seizure that lasted 2 to 3 min very shortly thereafter. The child received 1 mg of midazolam intramuscularly (IM), followed by 1 mg of midazolam intravenously (IV) for termination of this seizure, and was given a loading dose of 20 mg/kg of fosphenytoin IV. Elective orotracheal intubation was done to protect the airway. Despite the use of midazolam and fosphenytoin, the child had another seizure approximately 85 min following the ingestion. A third seizure was noted at approximately 100 min post-ingestion. In the course of treatment, activated charcoal was administered via nasogastric tube, and IV midazolam and phenobarbital were given. The child was transferred to a nearby facility with pediatric intensive care capabilities in stable condition. The child did not experience any hypotension or dysrhythmia, and the electrocardiographic QTc and QRS complex were normal throughout the clinical course. During the subsequent 48 h, the child awoke and regained normal function. This child's recovery was uneventful, and the child was discharged home without sequelae. Plasma levels of citalopram were 1400 ng/ml, 583 ng/ml, 416 ng/ml, and 296 ng/ml, at one, six, 13, and 23 h post-ingestion, respectively. The first level likely represents a predistributional level with subsequent levels giving an elimination t1/2 of 17.38 h., Conclusion: We report a case of citalopram poisoning in a 10-month-old infant with refractory seizures, and an absence of cardiovascular events with subsequent excellent outcome. The elimination of the parent drug corresponds to an approximate t1/2 of 15-20 h in this single case.