Pediatric ingestion of vilazodone compared to other selective serotonin reuptake inhibitor medications.

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.

Double, suicidal intoxication with hydroxycarbamide--a case report.

Hydroxycarbamide (HCB), also known as hydroxyurea, is an urea derivative used mainly as antineoplastic and antisickling agent. We described a 31 yrs. female, with essential thrombocythemia, who was admitted to our clinic because of double suicidal ingestion of hydroxycarbamide. First time it was 7.5 g of HCB with coingestion of 50 mg of diazepam, and several glasses of wine, second time it was 10 g of HCB, with coingestion of 100 mg paroxetine and few glasses of vodka. Both suicidal attempts were triggered by multiple reactive factors. At the time of admissions the patient was conscious, restless, with decreased mood. Transient decrease of total leukocyte count was noted on fourth day of first overdose. The second overdose led to no significant changes in blood count. There were no other abnormalities in biochemical results. According to the best of our knowledge this is the first report of acute suicidal intoxication with hydroxy-carbamide in an adult.

An autopsy case of poisoning with selective serotonin reuptake inhibitor, paroxetine.

A female in her twenties was found dead in her room. She had received medications for depression and panic disorder, and had attemped suicide several times. Many packets of prescribed drugs, including paroxetine, were found near the corpse. At autopsy, the lungs were edematous. The organs were slightly congested with putrefactive change. Autolytic rupture, considered as gastromalasia, was observed in the anterior cardiac portion of stomach wall. Toxicological examination revealed 0.78, 3.20 and 17.63 microg/ml of paroxetine in the heart blood, femoral blood and urine, respectively. Acetaminophen and phenobarbital were also identified within therapeutic or sub-lethal levels. Taking into consideration postmortem diffusion of drugs, we evaluated postmortem data and concluded that the death was mainly due to toxicity of paroxetine with serotonin syndrome.

Serotonin syndrome.

Serotonin syndrome is an under-reported and under-recognised condition that occurs on administration of selective serotonin re-uptake inhibitors alone, or in combination with other medication known to increase levels of 5-hydroxytryptamine. This case report demonstrates signs and symptoms associated with their overdose and illustrates the importance of recognition of this syndrome to instigate appropriate treatment for the patient.

Use of single-dose activated charcoal among Canadian pediatric emergency physicians.

OBJECTIVE: Gastric decontamination with single-dose activated charcoal (SDAC) is a mainstay in emergency department (ED) treatment of ingestions. Guidelines updated in 2005 encourage practitioners to use SDAC only in toxic ingestions presenting within 1 hour. Despite these guidelines, adult studies demonstrate a significant lack of consensus. This study examined the proposed use of SDAC for gastric decontamination in common pediatric ingestion scenarios by emergency physicians working in Canadian pediatric EDs. METHODS: A standardized survey consisting of 5 clinical scenarios was mailed to all physicians with a primary clinical appointment to the ED at 9 Canadian children's hospitals. RESULTS: One hundred thirty-one physicians were surveyed, and 95 (72%) responded. The majority of respondents were pediatricians (68.1%) with a mean of 15.0 years of experience (SD, 6.8 years). Of those surveyed; 91 (97.8%) would use SDAC for a toxic ingestion presenting in less than 1 hour; 35 (36.8%) would use SDAC for a toxic ingestion presenting after 3 hours; 61 (64.9%) would use SDAC for a nontoxic exploratory ingestion presenting in less than 1 hour; and 29 (30.5%) would use SDAC for a mildly symptomatic intentional ingestion presenting at an unknown time. Eleven (11.7%) would use SDAC for an ingestion of a substance that does not adsorb to SDAC. CONCLUSIONS: There is variation in the use of SDAC among emergency physicians working in Canadian pediatric EDs. This variation suggests that optimal management is not clear and that continued education and research are required.

Pharmaceutical drug overdose case reports. From the World Literature.

All pharmaceutical drugs have the potential to be misused or wrongly administered, which can result in toxic amounts of drug being ingested. To help you keep up-to-date with the latest data on outcomes and management of overdoses, both accidental and intentional, we have selected the following case reports recently published in the international medical literature and summarised in Reactions Weekly. Any claim of first report has been verified by a search of the Adisbase (a proprietary database of Adis International) and Medline. In addition, the World Health Organization (WHO) Adverse Drug Reaction database is also searched. This database, maintained by the Uppsala Monitoring Centre in Sweden, is the largest and most comprehensive adverse drug reaction source in the world, with information obtained from the National Centres of over 70 affiliate countries.

Very long half-life of paroxetine following intoxication in an extensive cytochrome P4502D6 metabolizer.

A very long half-life of paroxetine (195 h instead of the usual value of around 16 h) was measured after an overdose with 2 g paroxetine and 1 g clorazepate in a patient who was an extensive cytochrome P4502D6 metabolizer. The patient recovered well without any clinically significant complications. A consequence of the close monitoring of paroxetine levels in this patient was that it was decided not to reintroduce any other antidepressant despite her suicide attempt, until normal levels of paroxetine had been reached, which took over 1 month.

A depressed myocardium.

BACKGROUND: Venlafaxine is a potent neuronal serotonin and noradrenaline re-uptake inhibitor, and to a lesser extent an inhibitor of dopamine reuptake. Paroxetine is a potent selective inhibitor of serotonin reuptake. CASE REPORT: A 27-year-old man ingested 1987.5 mg of venlafaxine and 360 mg of paroxetine. He subsequently developed systolic and diastolic hypertension, transient electrocardiographic abnormalities, and an area of persistent myocardial damage. He recovered from his overdose with his blood pressure and electrocardiogram returning to normal. The area of myocardial damage was documented on echocardiogram as an area of marked hypokinesia at the basal anterior septum. Despite the absence of confirming blood levels or the absolute exclusion of cocaine, this case indicates that venlafaxine and paroxetine have the potential for serious cardiotoxicity when taken in overdose.

[Toxicologic findings in suicide with doxepin and paroxetine]. / Toxikologische Befunde bei einem Suicid mit Doxepin und Paroxetin.

A young nurse was found dead in her flat. In chemical-toxicological analysis the following femoral blood drug concentrations were determined: paroxetine 0.176 mg/l, doxepine 82.12 mg/l, desmethyldoxepine 0.34 mg/l. Additionally the drug concentrations were determined in various body fluids and organs. The results of the described fatality are discussed. For interpretation of toxicologic results in antidepressant fatalities ratios of parent drug to metabolite and postmortem drug redistribution should be taken into account.

Serotonin syndrome caused by overdose with paroxetine and moclobemide.

Well known clinical syndromes can be produced by overdose with more commonly ingested substances such as opiates or tricyclic antidepressants. A case of a much more unusual syndrome presenting to the accident and emergency department resulting from overdose with a combination of tablets is reported. The clinical presentation of serotonin syndrome and its management are described. This resulted from acute ingestion of paroxetine, a selective serotonin reuptake inhibitor, and moclobemide, a monoamine oxidase inhibitor.

Neurological recovery after prolonged verapamil-induced cardiac arrest.

A 15-year-old female survived a total of 65 minutes cardiac arrest following ingestion of verapamil and selective serotonin re-uptake inhibitors. We consider that the lack of neurological damage, despite evidence of significant renal and myocardial injury, may be related to the possible neuroprotective effect of a large dose of verapamil.

SSRI safety in overdose.

BACKGROUND: The morbidity and mortality caused by tricyclic antidepressant (TCA) overdose are well recognized. Among newer antidepressants, the selective serotonin reuptake inhibitors (SSRIs) are thought to be safer in overdose. This study was designed to describe the signs, symptoms, and mortality associated with SSRI overdose. METHOD: English-language articles identified through MEDLINE (1985 through 1997), and case reports from the American Association of Poison Control Centers (AAPCC) (1987 through 1996) and United States Food and Drug Administration (FDA) adverse event database (through 1997) that describe findings of fatal and nonfatal overdoses involving SSRIs alone or in combination with other ingestants were reviewed. RESULTS: SSRI antidepressants are rarely fatal in overdose when taken alone. During the 10 years that SSRI antidepressants have been marketed, there have been remarkably few fatal overdoses reported in the literature or to the AAPCC or FDA involving ingestion only of an SSRI. Moderate overdoses (up to 30 times the common daily dose) are associated with minor or no symptoms, while ingestions of greater amounts typically result in drowsiness, tremor, nausea, and vomiting. At very high doses (> 75 times the common daily dose), more serious adverse events, including seizures, electrocardiogram (ECG) changes, and decreased consciousness may occur. SSRI overdoses in combination with alcohol or other drugs are associated with increased toxicity, and almost all fatalities involving SSRIs have involved coingestion of other substances. CONCLUSION: The SSRI antidepressants are far safer than the TCAs in overdose. There is no apparent difference among SSRIs with respect to overdose safety.