quetiapine-fumarate and Drug-Overdose

Information regarding deaths caused by poisoning or adverse effects of medication in Danish persons not using illicit narcotic drugs (PNUIDs) is sparse. To characterize aetiology, demographics, and death scene, we reviewed all legal autopsies performed at Aarhus University from 2017 to 2019 and isolated 96 deaths caused by medications in PNUIDs. Suicides caused by medication overdose accounted for 38%. Opioids and psychotropic medications were the main cause of death in 48% and 35% of the 96 cases, respectively. Morphine, tramadol, and quetiapine were the most commonly involved individual medications. A single medication caused death in 50% of cases, and multiple substances were involved in 50%. The median total number [interquartile range] of detected medications was 5 [4-6], with a higher number in females (5 [4-7]) than males (4 [2-5]), p = 0.009. Median age was 51 [42.5-61.5] years, and 57% were female. Scene of death most frequently involved a body on a bed or couch in the decedent's own home (72%). In conclusion, opioids and psychotropic medications dominated by morphine, tramadol and quetiapine most frequently caused medication-related deaths in PNUIDs. Monitoring this type of death may yield important knowledge to direct prophylactic initiatives regarding medication use and prescription.

Topics: Analgesics, Opioid; Autopsy; Denmark; Drug Overdose; Female; Humans; Illicit Drugs; Male; Middle Aged; Morphine Derivatives; Narcotics; Psychotropic Drugs; Quetiapine Fumarate; Suicide; Tramadol

Opioid poisoning is a frequent cause of death in drug addicts and occurs with opioid treatment. Quetiapine is often found in forensic autopsies and may increase the risk of fatal opioid poisoning by enhancing sedation, respiratory depression, hypotension and QT prolongation. We systematically searched for studies of acute toxicity of quetiapine or other antipsychotics combined with morphine or methadone. Case reports describing toxicity of quetiapine combined with morphine or methadone were also included. We retrieved one human study that observed pharmacokinetic interaction between quetiapine and methadone, and 16 other human studies. Fourteen investigated the combination of droperidol and morphine in treatment doses, and some indicated an additive sedative effect. Five animal studies with acepromazine in combination with morphine or methadone were located and indicated an additive effect on sedation and hypotension. Six forensic case reports in which death could have been caused solely by quetiapine, the opioid, or other drugs were found. Thus, acute toxicity of quetiapine combined with morphine or methadone has not been studied. Because of quetiapine's effects on alpha-adrenoceptors, muscarinic and histamine receptors, human ether-a-go-go-channels and methadone kinetics, we suggest further research to clarify if the indicated additive effects of opioids and droperidol or acepromazine are also true for quetiapine.

Topics: Adolescent; Adult; Analgesics, Opioid; Animals; Antipsychotic Agents; Arrhythmias, Cardiac; Autopsy; Cause of Death; Consciousness; Drug Interactions; Drug Overdose; Female; Forensic Toxicology; Humans; Hypotension; Male; Methadone; Middle Aged; Morphine; Opioid-Related Disorders; Quetiapine Fumarate; Respiratory Insufficiency; Risk Assessment; Risk Factors

Quetiapine is a frequently prescribed antipsychotic and therefore often used in overdose. Delirium (with anticholinergic delirium as a specific condition) is described as a serious complication of quetiapine intoxication.
AIM: To assess the scientific literature on delirium as a side effect of quetiapine intoxication: incidence, symptoms and treatment.
METHOD: A systematic Medline literature search.
RESULTS: The systematic literature search resulted in 36 papers: 11 cohort studies, 24 case reports (22 papers) and 3 review papers. The reported incidence varied greatly, probably due to different quality of assessment. The clinical picture is characterized by a varying combination of peripheral and central symptoms, with agitation occurring frequently. Treatment is mainly supportive. Physostigmine is described as a specific treatment for anticholinergic delirium/toxidrome. Effectiveness of other pharmacological interventions remains unclear.
CONCLUSION: Delirium due to quetiapine intoxication is described repeatedly. Presumably there is an underreporting of this condition and associated symptoms. Better knowledge could lead to better detection and treatment.

Topics: Antipsychotic Agents; Delirium; Drug Overdose; Humans; Incidence; Quetiapine Fumarate

Overdoses with cardio-depressive medications can result in toxin-induced cardiogenic shock (TICS), a life-threatening condition characterized by severe hypotension and ineffective tissue perfusion. Vasopressors are often employed in the treatment of shock to increase heart rate and blood pressure. We sought to conduct a systematic review of the literature to evaluate the effectiveness of vasopressors in improving hemodynamic function and survival in the treatment of TICS.. We searched PubMed, EMBASE, TOXLINE, and International Pharmaceutical Abstracts.. We included studies evaluating the use of vasopressors in humans or animals with TICS. We limited human study types to randomized controlled trials, clinical trials, observational studies, and case reports.. Our search yielded 913 citations and 144 of these met our inclusion criteria. 130 were human case reports and 14 were animal studies.. Human case report data showed vasopressors were ineffective more often than they were partially or fully effective. In the majority of animal studies, vasopressor treatment failed to improve hemodynamic parameters and resulted in decreased survival.. Human case reports and controlled animal experiments lead to different conclusions about vasopressors in TICS. Most animal studies indicate that vasopressors impair hemodynamic function and increase mortality. In contrast, human case reports suggest that vasopressors are often ineffective but not necessarily harmful.

Topics: Animals; Antidepressive Agents, Tricyclic; Blood Pressure; Calcium Channel Blockers; Disease Models, Animal; Drug Overdose; Glucagon; Heart Rate; Hemodynamics; Humans; Observational Studies as Topic; Quetiapine Fumarate; Randomized Controlled Trials as Topic; Shock, Cardiogenic; Vasoconstrictor Agents

As the use of atypical antipsychotic medications (AAPMs) increases, the number of overdoses continues to grow. Cardiovascular toxicity was common with older psychiatric medications but seems uncommon with AAPM. We conducted a systematic literature review to describe the cardiovascular effects reported after overdose of 5 common AAPM: aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone. We included case reports and case series describing overdose of these 5 medications identified in a search of MEDLINE, EMBASE, and abstracts from major toxicology meetings. We found 13 pediatric cases (age, <7 years), 22 adolescent cases (age, 7-16 years), and 185 adult cases. No pediatric case described a ventricular dysrhythmia or a cardiovascular death. In the adolescent and adult cases, we found numerous reports of prolonged corrected QT interval and hypotension, but there were only 3 cases of ventricular dysrhythmia and 3 deaths that may have been due to direct cardiovascular toxicity. The results from case series reports were similar to the single case report data. Our review suggests that overdose of AAPM is unlikely to cause significant cardiovascular toxicity.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cardiovascular System; Dibenzothiazepines; Drug Overdose; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles

Atypical antipsychotic medications (second-generation antipsychotics) have been increasingly used in the treatment of a number of psychotic disorders since their introduction in 1988, with the newest medication introduced in 2002. Justification for their use includes claims of equal or improved antipsychotic activity over first-generation antipsychotics, increased tolerability, and decreased side effects. However, there are still significant adverse effects and toxicities with this class of medications. Toxicologic exposures and fatalities associated with atypical antipsychotics continue to increase in the United States, with 32,422 exposures and 72 deaths in 2003. There have also been Food and Drug Administration warnings in the past year about how some atypical antipsychotics have been marketed to minimize the potentially fatal risks and claiming superior safety to other atypical antipsychotics without adequate substantiation, indicating the toxicologic potential of these agents may be underestimated.. Continued research to evaluate adverse effects and tolerability of atypical antipsychotics compared with first-generation antipsychotics and each other is reviewed. This article also reviews the pharmacodynamics, pharmacokinetics, and drug interactions with these medications. New therapeutic monitoring recommendations for this class of medications have also been proposed. Finally, clinical toxicity in overdose and management are reviewed.. While new atypical antipsychotic medications may have a safer therapeutic and overdose profile than first-generation antipsychotic medications, many adverse and toxic effects still need to be considered in therapeutic monitoring and overdose management.

Topics: Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Cardiomyopathies; Child; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Drug Interactions; Drug Overdose; Dry Eye Syndromes; Humans; Hyperlipidemias; Hypotension; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Seizures; Thiazoles

Quetiapine, a dibenzothiazepine derivative, is a atypical antipsychotic which has greater in vitro binding affinity for serotonin 5-HT2 receptors than for dopamine D2 receptors. Quetiapine effectively treats both the positive and the negative symptoms of schizophrenia and is also associated with an incidence of extrapyramidal symptoms no greater than placebo across the entire dose range. In addition, it does not cause persistent hyperprolactinaemia. Quetiapine is associated with high levels of patient acceptability and satisfaction, which may result from its combination of efficacy and relatively benign adverse effect profile. The drug is well tolerated and has a low propensity to cause adverse events both during acute and long term treatment in the adult populations. The adverse effect profile of quetiapine makes the drug advantageous for patient populations who are susceptible to the adverse effects of drugs. Indeed, preliminary data show quetiapine to be very well tolerated in the elderly. Overdoses of quetiapine of up to 20g have been reported; however, with appropriate management in an intensive care setting there have been no reported fatalities. Quetiapine is metabolised by the cytochrome P450 3A4 isoenzyme, and the dose may need to be adjusted if quetiapine is co-administered with drugs which affect the activity of this isoenzyme. Overall, quetiapine has a favourable risk-benefit profile that should make it a valuable first-line agent in the treatment of schizophrenia.

Topics: Adolescent; Aged; Antipsychotic Agents; Dibenzothiazepines; Drug Interactions; Drug Overdose; Humans; Quetiapine Fumarate; Schizophrenia

Borderline personality disorder (BPD) is common and poses many clinical challenges. Despite limited evidence of effectiveness, psychotropic medications are often prescribed. We aimed to characterise overdose presentations in patients with BPD.. This is a retrospective observational series of patients with BPD presenting to a tertiary hospital following an overdose from January 2019 to December 2020. Medical records were reviewed to determine baseline characteristics, overdose details, clinical features, treatment, and disposition.. There were 608 presentations in 370 people (76% female), median age 28 years (range 16-75 years). The majority (331[89%]) of patients were prescribed at least one psychotropic medication, with 129 (35%) being prescribed three or more different psychotropic agents. Of the total prescribed psychotropics, 520/1459 (36%) were for off-label indications. The majority of agents (860/1487[58%]) taken in overdose were prescribed. The commonest drug classes taken in overdose were benzodiazepines (241[16%]) and antipsychotics (229[15%]). Severe toxicity occurred in 99 (16%) cases with either coma (GCS<9) or hypotension (systolic BP <90 mmHg). The commonest agent associated with severe toxicity was quetiapine 39/99 (39%).. Psychotropic polypharmacy is common in BPD, often with off-label indications. Prescribed medications are commonly taken in overdose. Quetiapine is over-represented both in off-label prescribing and associated harm.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Borderline Personality Disorder; Drug Overdose; Female; Humans; Male; Middle Aged; Off-Label Use; Psychotropic Drugs; Quetiapine Fumarate; Retrospective Studies; Young Adult

Much of the responsibility for the increasing drug overdoses in the US has been attributed to opioids but most opioid overdoses also involve another drug. The objective of this study was to identify the drugs involved in polysubstance arrests. The substances that were more likely to be found in conjunction with other substances, using the drug arrests reported to Maine's Diversion Alert Program (DAP) were examined.. Single and multiple drug arrests were quantified (N = 9,216). Multiple drug arrest percentages were compared to single drug arrest percentages to create a Multiple-to-Single Ratio (MSR) specific to each drug family and each drug to identify over (MSR > 1) and under-representation (MSR < 1).. Over three-fifths (63.8%) of all arrests involved a single drug. Opioids accounted for over-half (53.5%) of single arrests, followed by stimulants (27.7%) and hallucinogens (7.7%). Similarly, nearly two-fifths (39.6%) of multiple arrests were for opioids, followed by stimulants (30.8%) and miscellaneous (13.0%). Miscellaneous psychoactive prescription substances (e.g. clonidine, gabapentin, cyclobenzaprine, hydroxyzine) had the highest (1.51) MSR of any drug family. Conversely, stimulants (0.63), opioids (0.42), and hallucinogens (0.35) were significantly underrepresented in polysubstance arrests. Carisoprodol (8.80), amitriptyline (6.34), and quetiapine (4.69) had the highest MSR. Bath-salts (0.34), methamphetamine (0.44), and oxycodone (0.54) had the lowest MSR.. The misuse of opioids, both alone and in conjunction with another drug, deserves continued surveillance. In addition, common prescription drugs with less appreciated misuse potential, especially carisoprodol, amitriptyline, and quetiapine, require greater attention for their ability to enhance the effects of other drugs.

Topics: Amitriptyline; Analgesics, Opioid; Carisoprodol; Central Nervous System Stimulants; Drug Overdose; Hallucinogens; Humans; Maine; Prescription Drug Misuse; Quetiapine Fumarate

Quetiapine is a psychotropic drug. Excessive use of quetiapine may lead to drowsiness, blurred vision, respiratory depression, hypotension and extrapyramidal reactions. Acute respiratory distress syndrome (ARDS) is rare due to overdose of quetiapine. On 14 February 2020, a patients with coma, respiratory arrest and hypotension due to overdose of quetiapine were admitted to our hospital. After receiving mechanical ventilation、plasma adsorption and anti-inflammatory treatment, the patient's consciousness turned clear, the machine was successfully removed and extubated, and the patient's condition was improved and discharged from hospital. We analyzed the clinical data of the patient with quetiapine poisoning, and discussed the clinical symptoms and chest CT characteristics of ARDS caused by quetiapine poisoning, in order to improve the understanding of quetiapine poisoning and improve the success rate of rescue.. 喹硫平是一种精神类药品，过量服用可能会出现嗜睡、视物模糊、呼吸抑制、低血压和锥体外系反应，因过量服用引起的急性呼吸窘迫综合征（ARDS）较为罕见。我们于2020年2月14日收治一例因服用过量喹硫平后出现昏迷、呼吸停止、低血压的患者，入院给予机械通气、血浆吸附、抗炎等治疗后，患者意识转清，顺利撤机拔管，病情好转出院。我们对该例喹硫平中毒患者的临床资料进行分析，探讨喹硫平中毒致ARDS的临床表现及胸部CT特点，旨在提高对喹硫平中毒的认识，提高抢救成功率。.

Topics: Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Humans; Quetiapine Fumarate; Respiratory Distress Syndrome

Topics: Antipsychotic Agents; Drug Overdose; Humans; Myoclonus; Quetiapine Fumarate

Duloxetine is a commonly used antidepressant that is a serotonin and norepinephrine reuptake inhibitor. We aimed to investigate the frequency and severity of clinical effects following duloxetine overdose.. We undertook a retrospective review of duloxetine overdoses (>120 mg) admitted to two tertiary toxicology units between March 2007 and May 2021. Demographic information, details of ingestion (dose, co-ingestants), clinical effects, investigations (ECG parameters including QT interval), complications (coma [GCS < 9], serotonin toxicity, seizures and cardiovascular effects), length of stay [LOS] and intensive care unit [ICU] admission were extracted from a clinical database.. There were 241 duloxetine overdoses (>120 mg), median age 37 years (interquartile range [IQR]: 25-48 years) and there were 156 females (65%). The median dose was 735 mg (IQR: 405-1200 mg). In 177 patients, other medications were co-ingested, most commonly alcohol, paracetamol, quetiapine, diazepam, ibuprofen, pregabalin and oxycodone. These patients were more likely to be admitted to ICU (12 [7%] vs. none;. Duloxetine overdose most commonly caused sympathomimetic effects and serotonin toxicity, consistent with its pharmacology, and did not result in coma, arrhythmias or intensive care admission, when taken alone in overdose.

Topics: Acetaminophen; Adult; Antidepressive Agents; Arrhythmias, Cardiac; Coma; Diazepam; Droperidol; Drug Overdose; Duloxetine Hydrochloride; Female; Humans; Hypotension; Ibuprofen; Middle Aged; Norepinephrine; Oxycodone; Pregabalin; Quetiapine Fumarate; Seizures; Serotonin; Sympathomimetics; Tachycardia

Calcium-channel blocker overdose can result in profound vasoplegia and cardiogenic shock, which can quickly spiral into multi-organ failure and death. In this case report, we discuss two separate cases of massive amlodipine overdose with polydrug intoxication (Patient A: amlodipine and quetiapine; Patient B: amlodipine, fluoxetine and zopiclone), both of which were complicated by life-threatening vasoplegic shock refractory to supportive therapy (endotracheal intubation, fluid resuscitation, activated charcoal, vasopressors and inotropes), multimodal antidotes (calcium and hyper-insulinemic euglycemic therapy) and even second-line treatment (methylene blue and therapeutic plasma exchange). Despite exhausting all therapeutic options, resuscitation remained futile with no clinical response elicited until veno-arterial extracorporeal membrane oxygenation (ECMO) salvage therapy was initiated in both cases as a bridge-to-recovery. Albumin dialysis was also commenced to further enhance elimination of amlodipine given its high plasma protein-binding properties. Both patients improved drastically once perfusion to vital organs was maintained by ECMO and eventually survived with good neurological outcomes and preserved cardiac contractility on discharge. This case report supports the growing evidence that although ECMO support represents a potentially life-saving salvage therapy for refractory poisoning-induced shock, escalation to ECMO must be considered and instituted early before irreversible multi-organ failure sets in to ensure good clinical outcomes.

Topics: Albumins; Amlodipine; Antidotes; Calcium; Calcium Channel Blockers; Charcoal; Drug Overdose; Extracorporeal Membrane Oxygenation; Fluoxetine; Humans; Methylene Blue; Quetiapine Fumarate

This study aimed to compare whole blood and serum concentrations of quetiapine in acute poisoning cases. Authentic whole blood and respective serum samples were routinely collected from patients diagnosed with blood poisoning at our University Hospital. Accordingly, whole blood and serum paired samples from nine patients (one male and eight female patients) were analyzed for quetiapine using liquid chromatography-mass spectrometry (LC-MS). Quetiapine concentrations in whole blood and serum samples ranged widely from 5.4 to 2780 ng/mL and 9.9 to 2500 ng/mL, respectively. The whole blood/serum concentration ratio was 0.5-1.1 and increased together with an increase in whole blood and serum quetiapine concentrations. The ratio was reversed at around 2500 ng/mL to > 1. Our findings suggest that whole blood concentrations are more useful than serum concentrations in diagnosing quetiapine poisonings.

Topics: Bacteremia; Drug Overdose; Female; Humans; Male; Quetiapine Fumarate; Sepsis; Toxemia

Topics: Antipsychotic Agents; Cardiotoxicity; Cyclohexanols; Dibenzothiazepines; Drug Overdose; Humans; Quetiapine Fumarate; Venlafaxine Hydrochloride

Hypotension is a common presentation following an overdose of quetiapine. Adrenaline is often used as the vasopressor of choice for hypotension not responding to intravenous fluids. We present a case of quetiapine overdose with hypotension unresponsive to high-dose adrenaline. The patient was commenced on noradrenaline and made a full recovery. We highlight learning points about vasopressor therapy for atypical antipsychotic overdose. Quetiapine-induced hypotension is thought to be mediated by α1-receptor antagonism. Adrenaline is unlikely to improve blood pressure, as it is an agonist at both α- and β-receptors. Alpha-2- and β2-agonism can reduce sympathetic outflow and cause vasodilation, respectively, further exacerbating the hypotension. Noradrenaline is the preferred vasopressor of choice for hypotension caused by quetiapine overdose, as it has less affinity for α2- and β2-receptors, but maintains α1-receptor agonism. Drugs with a similar mechanism of inducing hypotension should also be treated with noradrenaline as the vasopressor of choice.

Topics: Antipsychotic Agents; Drug Overdose; Epinephrine; Female; Humans; Hypotension; Norepinephrine; Quetiapine Fumarate; Treatment Outcome; Vasoconstrictor Agents; Young Adult

Here, we review the case of a 26 1/7 weeks' gestation premature female infant born to a mother who intentionally ingested a large quantity of Tylenol, aspirin, quetiapine, and prenatal vitamins. The neonate subsequently had markedly elevated levels of both Tylenol and aspirin when checked on the first day of life. While overall clinically stable, the neonate did demonstrate coagulopathy as evidenced by abnormal coagulation studies. Both poison control and a pediatric gastroenterologist/hepatologist were consulted. She successfully tolerated a course of N-acetylcysteine; her subsequent Tylenol level was markedly decreased and the neonate exhibited no further effects of toxicity. The salicylate level decreased on its own accord. To our knowledge, this is the first report of a neonate at 26 weeks' gestation that has been successfully managed for supratherapeutic concentrations of acetaminophen and acetylsalicylic acid secondary to maternal ingestion. While rare, this case may serve as a reference for the effectiveness of N-acetylcysteine in premature infants in such instances.

Topics: Acetaminophen; Antidepressive Agents; Antidotes; Aspirin; Cystine; Drug Overdose; Female; Humans; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Maternal Exposure; Poisoning; Pregnancy; Quetiapine Fumarate; Sodium Bicarbonate; Suicide, Attempted

There are currently no studies comparing toxicity after extended-release (XR) and immediate-release (IR) quetiapine overdose. To compare the time course of toxicity of XR and IR quetiapine overdose.. Retrospective analysis of toxicology unit consultations from July 2013 to April 2016. Information extracted included demographics, type of ingestion (IR, XR, mixed formulation, dose, tablet count, time to presentation, sedative co-ingestants), lowest Glasgow coma score (GCS), time to lowest GCS, fastest pulse, lowest systolic blood pressure, and time to recovery from sedation.. There were 256 presentations in 210 patients. Females 86% (n = 181), median age 30.5 years (IQR 23-43). Median quetiapine dose for the whole cohort was 2 g (IQR 1-5). Sedating co-ingestants were seen in 61% of presentations. Comparison of IR (n = 43) and XR quetiapine (n = 23) ingestions without sedating co-ingestants revealed a larger median ingested dose for XR formulation: 5.7 g versus 1.75 g (P = 0.004) and larger median tablet strength (XR 200 mg vs IR 100 mg, P < 0.001). Median time to lowest GCS: XR 7 h (IQR 4.9-11) versus IR 3.8 h (IQR 2.4-5.7), P < 0.001. Median time to peak pulse: XR 9 h (IQR 3-12) versus IR 2.5 h (IQR 1.5-5), P = 0.01. Median time to recovery from sedation: XR quetiapine 20 h (IQR 12-39) versus 12 h (IQR 5.5-22), P < 0.05. Median duration of intubation: XR 47 h versus 17 h for IR, P = 0.04).. XR quetiapine overdoses without sedating co-ingestants were associated with a doubling of time to peak sedation and pulse, and had longer recovery from sedation. The absence of sedation or tachycardia 12 h post-overdose of XR quetiapine seems a reasonable timeframe to rule out significant poisoning.

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Drug Overdose; Female; Glasgow Coma Scale; Humans; Male; Quetiapine Fumarate; Retrospective Studies; Young Adult

Kratom is a plant with dose-dependent mixed stimulant and opioid properties whose pharmacologic characteristics and social impact continue to be described. The main active isolate of kratom is mitragynine, an indole-containing alkaloid with opioid-like effects. Kratom toxicity and kratom-associated fatalities have been described, including those in association with additional drugs. In this paper we describe the case of a 27-year-old man who was found deceased with a toxic blood concentration of quetiapine in conjunction with the qualitative presence of mitragynine. Investigative and autopsy findings suggested perimortem hyperthermia and seizure-like activity. Kratom toxicity and kratom-associated fatalities are being increasingly reported. Experiments with kratom extracts have shown inhibitory effects upon hepatic CYP enzymes, leading to previous speculation of the potential for clinically significant interactions between kratom and a wide array of medications. Herein is described a fatal case of quetiapine toxicity complicated by mitragynine use. The potential ability of mitragynine to alter the pharmacokinetics of a prescription medication via inhibition of its hepatic metabolism is discussed.

Topics: Adult; Antipsychotic Agents; Drug Overdose; Herb-Drug Interactions; Humans; Male; Quetiapine Fumarate; Secologanin Tryptamine Alkaloids

Quetiapine overdose, although rare, is mainly linked with tachycardia, QTc-interval prolongation, somnolence, coma, hyperglycemia, and eventually hepatotoxicity and myocarditis. Extracorporeal techniques for quetiapine removal might be helpful, but only a few cases are reported in the literature. We here describe the case of a 27-year-old healthy woman, admitted to our Intensive Care Unit after voluntary quetiapine intake and successfully treated with CytoSorb hemoperfusion in combination with continuous renal replacement therapy (CRRT), in order to accelerate quetiapine elimination. This is the first published experience about the potential application of hemoadsorption therapies, as CytoSorb sorbent, in large overdoses of quetiapine and this approach might be feasible to rapidly remove the substance from blood, stabilizing the patient condition.

Topics: Adult; Antipsychotic Agents; Drug Overdose; Female; Humans; Intensive Care Units; Quetiapine Fumarate; Renal Replacement Therapy; Sorption Detoxification; Suicide, Attempted

A 25-year-old patient was admitted urgently due to mixed amitriptyline/quetiapine intoxication at a potentially lethal dose. Alongside severe anticholinergic toxidrome, she presented with antiadrenergic and quinidin-like cardiotoxic findings, including ventricular tachycardia. In the present case, arrhythmia and circulatory shock responded neither to alkalization and elevated sodium levels after infusion of sodium bicarbonate, nor to any other established therapies. Following the lipid rescue paradigm, bolus infusion of a 20% lipid emulsion led to rapid stabilization and continued reversal of all intoxication features.

Topics: Adrenergic Uptake Inhibitors; Adult; Amitriptyline; Arrhythmias, Cardiac; Drug Overdose; Female; Humans; Lipids; Quetiapine Fumarate; Tachycardia, Ventricular

Quetiapine is misused due to its anxiolytic and hedonic effects and has been associated with deliberate self-harm. This study analyzed quetiapine-related calls to the Victorian Poisons Information Centre (VPIC), coronial data from Victorian Institute of Forensic Medicine (VIFM) and prescribed data from the Pharmaceutical Benefits Scheme (PBS) to determine current trends in overdose, misuse and mortality.. This was a retrospective review of multiple databases. Calls to VPIC and coronial data from the VIFM were reviewed from 2006 to 2016. PBS prescription data from 2000 to 2015 was obtained from the Australian Statistics on Medicines website.. VPIC data indicated a 6-fold increase in the number of quetiapine-related calls over the 11-year period of which most were overdose-related (77%). Overdose and misuse calls increased by 6-fold and 6.6-fold, respectively. Coronial data also indicated a rise in quetiapine-related harm; a 7.4-fold increase in quetiapine-related deaths was recorded for the same period. Similarly, Australian PBS data showed that quetiapine prescriptions increased 285-fold since 2000. There was a significant positive correlation between the increase in prescribing and overdose (r = 0.75, p < 0.001), and prescribing and mortality (r = 0.82, p < 0.01).. This study revealed an increasing trend of misuse, non-fatal and fatal overdoses in Victoria over the last decade. The increasing rates of prescriptions in Australia and thus increased quetiapine availability are likely to have contributed to increased poisoning and mortality. Further research is warranted to explore the reasons behind increased prescribing, including off-label use.

Topics: Adult; Antipsychotic Agents; Drug Overdose; Female; Humans; Male; Prescription Drug Overuse; Quetiapine Fumarate; Retrospective Studies; Victoria

We report the case of an 18-year-old woman with personality disorders who was hospitalized a few hours after suicidal ingestion of acetaminophen, quetiapine, acetylsalicylic acid, and ethanol. Twelve hours after admission, severe liver damage was evident, but the patient was stable and awaiting hepatic transplantation. Electrolytes were successfully controlled. The condition of the liver stabilized. Cardiac biomarkers then deteriorated unexpectedly. Localized ST-segment elevations were noted on electrocardiogram, but angiography ruled out myocardial infarction. A computed tomographic scan ruled out cerebral edema. The patient died of irreversible cardiac arrest 40 hours after admission. Heart failure remained unexplained, and the body underwent forensic autopsy.At autopsy, histologic findings were indicative of acute toxic myocarditis and were concluded to be caused by acetaminophen intoxication. Acetaminophen overdose is common and typically leads to liver failure requiring supportive treatment and emergency liver transplantation. Toxic myocarditis is an extremely rare complication of acetaminophen overdose. It has only been reported 4 times in the literature despite the widespread use and misuse of acetaminophen. Toxic myocarditis remains a possibility in many cases of overdose but can be overlooked in a clinical picture dominated by hepatorenal failure and encephalopathy. Clinicians and forensic pathologists should be aware of this rare potential complication.

Topics: Acetaminophen; Adolescent; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Antipsychotic Agents; Aspirin; Borderline Personality Disorder; Central Nervous System Depressants; Drug Overdose; Ethanol; Female; Gas Chromatography-Mass Spectrometry; Heart Failure; Humans; Myocarditis; Quetiapine Fumarate; Suicide

Brugada pattern can be found on the electrocardiogram (ECG) of patients with altered mental status, usually with fever or drug intoxication. Diagnosis remains challenging, because the ECG changes are dynamic and variable. In addition, triggers are not always clearly identified. In patients with atrial fibrillation (AF), the use of class IC antidysrhythmic drugs can unmask a Brugada pattern on the ECG, especially if combined with other medications acting on sodium channels.. A 62-year-old man with a medical history of AF was admitted to our emergency department for altered mental status. The ECG at the time of admission showed a Brugada pattern, triggered by a flecainide overdose (about 1 g), in association with an unknown dose of lamotrigine and quetiapine. After discontinuation of all medications, the Brugada pattern disappeared and his ECG showed no abnormalities. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: In patients with AF, the use of class IC antidysrhythmic drugs, if overdosed, can trigger a Brugada ECG pattern, and therefore it can increase the risk for malignant dysrhythmias. It is important to provide, to all patients with a Brugada ECG pattern, a list of drugs to avoid, and to underline the synergistic interplay between drugs, taking into consideration all patients' comorbidities.

Topics: Atrial Fibrillation; Bipolar Disorder; Brugada Syndrome; Consciousness Disorders; Drug Overdose; Electrocardiography; Emergency Service, Hospital; Flecainide; Humans; Lamotrigine; Male; Middle Aged; Quetiapine Fumarate; Sodium Channel Blockers; Stroke; Suicide, Attempted; Triazines

Carisoprodol, a centrally acting muscle relaxant with a high abuse potential, has barbiturate-like properties at the GABA-A receptor, leading to central nervous system depression and desired effects. Its tolerance and dependence has been previously demonstrated in an animal model, and withdrawal has been described in several recent case reports. Many cases can be effectively managed with a short course of benzodiazepines or antipsychotic agents. However, abrupt cessation in a patient with a history of long-term and high-dose carisoprodol abuse may result in symptoms that are more difficult for providers to treat.. We present a case of a 34-year-old man with a long history of carisoprodol abuse who was found unresponsive after having ingested 7.5 grams of carisoprodol. He was intubated and admitted to the intensive care unit. He was given propofol, dexmedetomidine, fentanyl, ketamine, lorazepam, midazolam, quetiapine, and haloperidol, some at high-dose infusions, before his agitation and ventilator asynchrony could be controlled. His improvement coincided with the addition of carisoprodol and phenobarbital to his treatment regimen. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Trends show increasing emergency department presentations for drug-related disorders and treatment. This case highlights an uncommon case of carisoprodol withdrawal that may be encountered by emergency physicians, and demonstrates that benzodiazepines may not be sufficient to suppress severe withdrawal symptoms. Treatment with carisoprodol and phenobarbital provided additional benefit and can be considered in cases of severe carisoprodol withdrawal.

Topics: Adult; Carisoprodol; Dexmedetomidine; Drug Overdose; Fentanyl; Haloperidol; Humans; Hypnotics and Sedatives; Intensive Care Units; Ketamine; Lorazepam; Male; Midazolam; Propofol; Quetiapine Fumarate; Respiration, Artificial; Substance Withdrawal Syndrome; Substance-Related Disorders

The treatment of quetiapine and/or citalopram poisoning is mainly supportive and involves gastric lavage, activated charcoal, intubation, and mechanical ventilation. Recently, however, there were reports of successful treatment with intravenous lipid emulsion. Here we report a case of a 19-year-old Caucasian girl who ingested approximately 6000 mg of quetiapine, 400 mg of citalopram, and 45 mg of bromazepam in a suicide attempt. The patient developed ventricular tachycardia and epileptic seizures 12 h after admission to the hospital. As the patient's condition deteriorated, we combined standard therapy (intubation, mechanical ventilation, and vasopressors) with low-dose intravenous lipid emulsion (ILE) (a total of 300 mL of 20 % lipid emulsion) and normalised her heart rhythm and stopped the seizures. She was discharged to the psychiatric ward after 48 h and home after a prolonged (2-month) psychiatric rehabilitation. Intravenous lipid emulsion turned out to be effective even in the lower dose range than previously reported for quetiapine poisoning in patients presenting with seizure and ventricular arrhythmia. To our knowledge, there are no case reports describing the use of ILE in treating citalopram poisoning.

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Bromazepam; Citalopram; Drug Overdose; Fat Emulsions, Intravenous; Female; Humans; Quetiapine Fumarate; Slovenia; Suicide, Attempted; Treatment Outcome; Young Adult

Topics: Adult; Drug Overdose; Female; Humans; Pregnancy; Pregnancy Complications; Psychotic Disorders; Quetiapine Fumarate; Suicide, Attempted

Brain tissue is a useful alternative to blood in postmortem forensic investigations, but scarcity of information on reference concentrations in brain tissue makes interpretation challenging. Here we present a study of 43 cases where the antipsychotic drug quetiapine was quantified in brain tissue and related to concentrations in postmortem blood. For cases, where quetiapine was unrelated to the cause of death (N = 36), the 10-90 percentiles for quetiapine concentrations in brain tissue were 0.030-1.54 mg/kg (median 0.48 mg/kg, mean 0.79 mg/kg). Corresponding blood 10-90 percentile values were 0.007-0.39 mg/kg (median 0.15 mg/kg, mean 0.19 mg/kg), giving brain-blood ratio 10-90 percentiles of 2.31-6.54 (median 3.87, mean 4.32). Both correspond well to the limited amount of data found in the literature. For cases where quetiapine was a contributing factor to death (N = 5), the median value in brain tissue of 8.02 mg/kg (range 2.69-22.98 mg/kg) was more than 15 times higher than the median of the nontoxic values, and about the same relationship occurred for blood with a median of 3.19 mg/kg (range 1.00-6.90 mg/kg). The brain-blood ratios for toxic concentrations were in the range of 2.08-6.05, which correspond to those of the nontoxic concentrations. A single case, where quetiapine was ruled as the sole cause of death, a suicide by quetiapine overdose, had an even higher value of 25.74 mg/kg in brain tissue. The blood concentration was 8.99 mg/kg, giving a brain-blood ratio of 2.86. Thus, on average the brain concentrations were about four times the blood concentrations. The brain concentrations of quetiapine observed in cases, where quetiapine was unrelated to death, may serve as a reference, when evaluating postmortem cases with no blood available. The recorded concentrations, where quetiapine was contributing to death, give an indication of likely toxic concentrations.

Topics: Antipsychotic Agents; Autopsy; Brain; Calibration; Cause of Death; Chromatography, High Pressure Liquid; Drug Overdose; Forensic Toxicology; Humans; Predictive Value of Tests; Quetiapine Fumarate; Reference Standards; Substance Abuse Detection; Suicide; Tandem Mass Spectrometry

Intravenous lipid emulsion (ILE) is a lifesaving treatment of lipophilic drug intoxications. Not only does ILE have demonstrable efficacy as an antidote to local anesthetic toxicity, it is also effective in lipophilic drug intoxications. Our case series involved 10 patients with ingestion of different types of lipophilic drugs. Intravenous lipid emulsion treatment improved Glasgow Coma Scale or blood pressure and pulse rate or both according to the drug type. Complications were observed in 2 patients (minimal change pancreatitis and probable ILE treatment-related fat infiltration in lungs). In our case series, ILE was used for different lipophilic drug intoxications to improve cardiovascular and neurologic symptoms. According to the results, it was found that ILE treatment is a lifesaving agent in lipophilic drug intoxications and it can be used in unconscious patients who have cardiac and/or neurologic symptoms but no history of a specific drug ingestion.

Topics: Adolescent; Adult; Alprazolam; Amitriptyline; Antidotes; Blood Pressure; Dibenzothiazepines; Drug Overdose; Fat Emulsions, Intravenous; Female; Fluoxetine; Glasgow Coma Scale; Heart Rate; Humans; Lamotrigine; Lipid Metabolism; Male; Metoprolol; Middle Aged; Nifedipine; Quetiapine Fumarate; Triazines; Young Adult

We report the case of a 29-year-old woman who attempted suicide by oral ingestion of potentially fatal doses of multiple drugs including quetiapine. Intravenous lipid emulsion (ILE) was administered at a dose higher than that used in the standard management of toxicity. Rapid improvement was observed in the patient's status, and no additional treatment was required during the period of observation. No adverse effect of lipid administration was observed. ILE treatment seems to have great potential in the management of lipophilic drug toxicity in the future.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Fat Emulsions, Intravenous; Female; Humans; Quetiapine Fumarate; Suicide, Attempted; Treatment Outcome

Quetiapine is an atypical antipsychotic medication that is increasingly being used in the treatment of psychotic disorders and depression. An overdose of quetiapine is associated with hypotension, sinus tachycardia, and sedation. The clinical effects of its overdose are often mild to moderate, but a severe overdose can cause cardiovascular collapse and death.Intravenous lipid emulsion (ILE) is a proposed treatment for potentially lethal cardiotoxicity after severe overdoses with lipophilic drugs, such as quetiapine, mainly by the sequestration of the lipophilic toxin to an expanded intravascular lipid phase.. To report a case where ILE was successfully used in the resuscitation of a patient with cardiovascular collapse after a severe quetiapine overdose.. A 42-year-old woman was admitted to the Emergency Department after being found unconscious at home, due to an estimated ingestion of 24 g of quetiapine (Seroquel). She was initially cardiorespiratory stable and unresponsive with a Glasgow Coma Scale of 3. The woman was immediately admitted to the Intensive Care Unit, where her condition quickly deteriorated. She was intubated, due to loss of airway. In addition, a gastric lavage was performed and activated charcoal was administered. The patient presented with cardiovascular collapse refractory to vasopressor treatment and volume resuscitation. ILE bolus followed by continuous infusion was administered. Her blood pressure started increasing 5 min after ILE was initiated and within an hour circulation was stabilized. The patient recovered completely without any residual symptoms, after 3 days in the ICU.. ILE may potentially be life-saving in cases of severe quetiapine poisoning and should be considered as a treatment for severe cardiovascular instability resulting from quetiapine poisoning refractory to maximum conventional therapy.

Topics: Adult; Antipsychotic Agents; Blood Pressure; Coma; Dibenzothiazepines; Drug Overdose; Fat Emulsions, Intravenous; Female; Humans; Quetiapine Fumarate; Resuscitation; Shock

Although extended-release (XR) formulations are recognized to bear some risk of pharmacobezoar formation in overdose, there are no previously documented reports of this phenomenon with quetiapine. We describe nine cases of pharmacobezoar formation in acute quetiapine XR overdose.. Observational case series of all patients who underwent gastroscopy after quetiapine XR overdose, which were reported by physicians to the Swiss Toxicological Information Centre between January 2010 and December 2012, with detailed analysis of cases with documented pharmacobezoar.. Gastric pharmacobezoars were detected in 9 out of 19 gastroscopic evaluations performed during the study period. All these patients ingested a large dose of quetiapine XR (10-61 tablets; 6-24.4 g quetiapine). All patients but one also coingested at least one other substance, and in three cases another XR drug formulation. Gastroscopic pharmacobezoar removal was achieved without complications in all patients, but was difficult due to the particular "gelatinous-sticky-pasty" consistency of the concretion. The subsequent clinical course was favorable.. The possibility of pharmacobezoar formation following a large quetiapine XR overdose should be considered, as this may influence acute patient management. Complete endoscopic pharmacobezoar removal may be a promising approach in selected cases, but further studies are needed to define its role.

Topics: Adult; Antipsychotic Agents; Bezoars; Chemistry, Pharmaceutical; Delayed-Action Preparations; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Overdose; Female; Humans; Male; Middle Aged; Quetiapine Fumarate; Stomach; Tablets; Young Adult

The use of quetiapine in Australia has increased rapidly in recent years. Anecdotal and post-marketing surveillance reports indicate an increase in quetiapine misuse in prisons as well as an increase in its availability on the black-market. This study examined a cohort of quetiapine-associated deaths occurring in Victoria, Australia, between 2001 and 2009, to determine the prevalence of deaths associated with this drug and to determine whether misuse represents a legitimate concern. Case details were extracted from the National Coronial Information System. There were 224 cases with an average age of 43 years of age (range 15-87 years). The cause of death was mostly drug toxicity (n = 114, 51 %), followed by natural disease (n = 60, 27 %), external injury (n = 31, 14 %) and unascertained causes (n = 19, 8 %). Depression and/or anxiety were common, observed in over a third of the cohort (80 cases, 36 %). About 20 % of cases did not mention a psychiatric diagnosis at all which raises the question of whether quetiapine had been prescribed correctly in these cases. Cardiovascular disease was the most commonly reported illness after mental disease. Quetiapine ranged in concentration from the limit of reporting (0.01 mg/L) to 110 mg/L. The median concentration of quetiapine was much lower in the natural disease deaths (0.25 mg/L) compared with drug caused deaths (0.7 mg/L). The most commonly co-administered drug was diazepam in 81 (36 %) cases. There were a small number of cases where quetiapine contributed to a death where it had not apparently been prescribed, including the death of a 15 year old boy and one of a 34 year old female. Overall, misuse of quetiapine did not appear to be a significant issue in this cohort; use of the drug only occasionally led to fatalities when used in excess or concomitantly with interacting drugs. However, considering that it is a recent social concern, it is possible that analysis of cases post 2009 would reveal more cases of quetiapine abuse. Close monitoring of quetiapine is therefore advised to prevent adverse outcomes, particularly in vulnerable populations such as substance abusers.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Cause of Death; Comorbidity; Dibenzothiazepines; Drug Interactions; Drug Overdose; Female; Forensic Toxicology; Humans; Male; Middle Aged; Polypharmacy; Prescription Drug Misuse; Prevalence; Quetiapine Fumarate; Risk Factors; Victoria; Young Adult

Cervical and thoracic flexion myelopathy are uncommon causes of spinal cord injury that can lead to irreversible paralysis, autonomic dysfunction, and death. To the authors' knowledge, this report is the first to describe the natural history of flexion myelopathy and the simultaneous occurrence of cervical and thoracic flexion myelopathy in the setting of drug overdose.. To report the association of cervical and thoracic flexion myelopathy and drug overdose; to describe the subacute natural history of flexion myelopathy in the setting of drug overdose; to emphasize the need for first responders to document positioning of unresponsive individuals; and to suggest careful neurological examination and early spinal cord imaging in appropriately identified patients at risk of flexion myelopathy.. We describe the case of a 34-year-old woman who developed flexion myelopathy resulting in severe quadriparesis after overdose of quetiapine fumarate, oxycodone/acetaminophen, and chloral hydrate.. Flexion myelopathy in the setting of drug overdose is a subacute injury. Early intervention may limit neurological disability. However, the clinical diagnosis of flexion myelopathy is inevitably delayed by the patient's altered level of consciousness or mental status at presentation, and concurrent multiple organ failure.

Topics: Acetaminophen; Adult; Analgesics, Non-Narcotic; Antipsychotic Agents; Chloral Hydrate; Dibenzothiazepines; Drug Combinations; Drug Overdose; Female; Humans; Hypnotics and Sedatives; Magnetic Resonance Imaging; Neck; Oxycodone; Posture; Quadriplegia; Quetiapine Fumarate; Range of Motion, Articular; Spinal Cord Diseases

Quetiapine overdose is a clinical entity commonly encountered in emergency departments. Quetiapine is a drug with many mechanisms, including antimuscarinic effects. Traditionally, treatment of quetiapine toxicity has been primarily supportive care. Case reports exist documenting improvement in mental status in these patients after administration of physostigmine, a carbamate capable of reversing antimuscarinic toxicity. In this descriptive case series, 3 patients with quetiapine toxicity treated with physostigmine are reported. In each case, the patient had significant altered mental status that was rapidly reversed with administration of physostigmine. In all 3 cases, patient disposition was changed to a lower level of care, requiring less invasive monitoring. In 1 case, intubation was prevented. Because quetiapine toxicity is commonly encountered and the use of physostigmine in this setting is a potentially practice-altering treatment, emergency physicians should be aware of this phenomenon.

Topics: Adult; Antipsychotic Agents; Cholinesterase Inhibitors; Consciousness Disorders; Dibenzothiazepines; Drug Overdose; Emergency Service, Hospital; Female; Glasgow Coma Scale; Humans; Male; Physostigmine; Quetiapine Fumarate; Young Adult

Quetiapine is a second-generation antipsychotic drug, used mainly in the treatment of psychotic disorders. Overdose is associated with sedation, tachycardia and a prolonged QT-interval on the ECG. Cardiovascular symptoms are uncommon but in severe cases profound cardiovascular depression may occur.. To report a case where extracorporeal circulatory support (ECCS) was used successfully in severe quetiapine overdose.. A 40-year-old woman was admitted to the emergency department (ED) with reduced consciousness apparently due to intoxication. She had a history of schizophrenia and was treated with 900 mg of quetiapine daily. In the ED, she presented with immeasurable low blood pressure, irregular bradycardia, hypothermia and a Glasgow Coma Scale (GCS) of 8. An immunoassay test for tricyclic antidepressive agents (TCA) was positive. Despite resuscitation with intravenous fluids, intensive vasopressor treatment and renal replacement therapy (CRRT) the patient's condition deteriorated. The patient was quickly moved to an intensive care unit where ECCS could be instituted. The patient subsequently recovered after 4 days in the ICU without any residual symptoms. Further laboratory analysis did not confirm the immunoassay finding.. Severe poisoning with quetiapine may imitate tricyclic antidepressant poisoning, and drug screening methods may be falsely positive for TCA. In case of cardiovascular collapse due to quetiapine overdose, ECCS may be life saving.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Electrocardiography; Extracorporeal Circulation; Female; Humans; Quetiapine Fumarate

We present the case of a 26-year-old man with schizoid personality disorder who suffered from a very focal and transparietal necrosis of the sigmoid after an overdose of atypical neuroleptics. This is a singular, rather unknown and potentially lethal side effect of these drugs. The physiopathology of this complication is multifactorial.

Topics: Adult; Anti-Anxiety Agents; Anticonvulsants; Antidepressive Agents; Antipsychotic Agents; Citalopram; Clopenthixol; Dibenzothiazepines; Drug Overdose; Enterocolitis, Necrotizing; Humans; Lamotrigine; Lorazepam; Male; Quetiapine Fumarate; Schizoid Personality Disorder; Trazodone; Triazines

Topics: Antipsychotic Agents; Death, Sudden, Cardiac; Dibenzothiazepines; Drug Overdose; Fatal Outcome; Gas Chromatography-Mass Spectrometry; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia

Quetiapine is a second-generation antipsychotic drug approved for the treatment of bipolar disorders and schizophrenia. Acute quetiapine overdose is rare, and quetiapine has long been thought to be safer than other antipsychotics. Nevertheless, as reported in the literature, the severity of the effect of quetiapine overdose has not been associated with a high serum concentration of the drug or with the reported ingested dose. In this article, we report a case of survival from coma induced by a massive extended-release (XR) quetiapine ingestion at a dose greater than reported in some previous fatal cases. A 34-year-old woman with chronic schizophrenia ingested 36 g of quetiapine fumarate XR for attempted suicide. She was initially lethargic, but her clinical conditions rapidly deteriorated and she collapsed unconscious. The woman was taken to the nearest hospital, where the medical emergency team found her in deep coma with response only to deep painful stimuli (Glasgow Coma Scale 9). An endotracheal tube was inserted for airway protection, and the patient was transferred to a critical care area for ventilatory support and maintenance of hydration status and electrolytic balance. Spontaneous breathing was restored in approximately 36 hours, and a few days later, she was discharged without reporting clinical complications. This is the first case of coma induced by an intentional 36-g overdose of quetiapine XR. Given the widespread use of quetiapine and the lack of information about its toxicity in overdose, this case report reinforces the importance of closely monitoring patients taking quetiapine and helps to better define the safety of this drug.

Topics: Adult; Antipsychotic Agents; Coma; Delayed-Action Preparations; Dibenzothiazepines; Drug Overdose; Female; Humans; Quetiapine Fumarate; Suicide, Attempted; Treatment Outcome

Detailed data on severe overdoses with quetiapine are relatively sparsely reported in the literature.. To describe a cohort of 20 acute quetiapine overdoses and provide additional data on the pharmacokinetics and clinical features of intoxication with this drug.. A retrospective study was conducted on patients with quetiapine poisoning admitted to our institution. We included moderate to severe overdoses between 2005-2011 who required admission to ICU.. Predominantly female patients (n = 17) ingested a median dose of 9.8 g quetiapine. Poison Severity Score was moderate in 9 patients, severe in 10 patients and in one case fatal. Quetiapine was analytically confirmed in all cases. Clinical manifestations included drowsiness or coma (all patients), tachycardia (12 patients) and hypotension (10 patients). Seizures and arrhythmia occurred in 4 patients, each. Intubation and mechanical ventilation was required in 14 patients due to seizures, respiratory depression or loss of airway protection and 15 patients developed pneumonia. Hypokalaemia and hyperglycaemia were present at admission in 10 and 5 patients, respectively. Despite frequent prolongation of the QT(c) in 13 patients, QT interval was normal in most cases and QRS-interval was prolonged in only one patient. Presumably anticholinergic delirium was recognised in 8 patients and 6 patients received physostigmine with good clinical response. In 13 cases quetiapine was analysed quantitatively in serum with a relevantly prolonged half-life (16 ± 12 h) and a median peak serum concentration of 3074 ng/mL. In 4 of these 13 patients we observed an increase of quetiapine serum concentration in the further course.. In this study, quetiapine overdoses were associated with significant toxicity and a fairly high number of complications. A careful and often prolonged clinical observation in the more severe cases of overdose seems mandatory.

Topics: Adult; Antipsychotic Agents; Arrhythmias, Cardiac; Cohort Studies; Coma; Dibenzothiazepines; Drug Overdose; Female; Half-Life; Humans; Hypotension; Intensive Care Units; Male; Middle Aged; Pneumonia; Quetiapine Fumarate; Retrospective Studies; Tachycardia

Topics: Anticonvulsants; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Cyclohexanols; Dibenzothiazepines; Drug Overdose; Fatal Outcome; Female; Fructose; Humans; Quetiapine Fumarate; Seizures; Time Factors; Topiramate; Venlafaxine Hydrochloride; Young Adult

A 47-year-old woman ingested an overdose of 8000 mg quetiapine. The treatment had been initiated 3 weeks before. The current medications were lamuvidine, ritonavir, atazanavir and tenofovir for an HIV infection. The patient presented a deep coma and sustained hypotension as main complications. The toxicokinetic data revealed a markedly prolonged elimination half-life for quetiapine (62.4 hours) and the relationship with antiretroviral therapy is discussed.

Topics: Anti-HIV Agents; Antipsychotic Agents; Coma; Dibenzothiazepines; Drug Interactions; Drug Overdose; Female; Half-Life; HIV Infections; Humans; Hypotension; Middle Aged; Quetiapine Fumarate

Topics: Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Fat Emulsions, Intravenous; Humans; Quetiapine Fumarate

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Humans; Male; Quetiapine Fumarate; Rhabdomyolysis; Suicide, Attempted

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Humans; Male; Quetiapine Fumarate

We describe the initial management and subsequent recovery of a 61 year-old male patient following attempted suicide by oral ingestion of a potentially fatal overdose of quetiapine and sertraline. Intravenous Intralipid was given soon after initiation of basic resuscitation. There was a rapid improvement in the patient's level of consciousness. No other clinical signs of drug toxicity were observed. Intralipid may have reversed the deep coma associated with ingestion and prevented other manifestations of drug toxicity occurring, thus expediting this patient's recovery.

Topics: Antidepressive Agents; Antipsychotic Agents; Coma; Dibenzothiazepines; Drug Overdose; Fat Emulsions, Intravenous; Humans; Male; Middle Aged; Quetiapine Fumarate; Sertraline; Suicide, Attempted

Quetiapine, a second-generation antipsychotic, acts at multiple brain neurotransmitter receptors and has the potential for serious complications. Although seizures have been described in the literature, delayed seizure onset has not been reported. We report the first case of delayed seizures after a significant quetiapine overdose.. A 27-year-old female presented to the emergency department following an overdose of approximately 30 g of quetiapine. Twenty-four hours after arrival, the patient had 2 seizures. The patient was then intubated and remained in the ICU for four days. EEG was negative for epileptiform activity. The serum quetiapine levels (MedTox, St. Paul, MN) were 8.67 mg/L on hospital day one and 3.28 mg/L on hospital day three.. Quetiapine poisoning, with serum levels, associated with seizures has been reported in one prior case. Our case report represents late-onset seizures with serum levels above therapeutic range (>1 mg/L). The serum concentrations of quetiapine in this case were consistent with those in postmortem case reports.

Topics: Adult; Anticonvulsants; Antipsychotic Agents; Critical Care; Dibenzothiazepines; Drug Overdose; Electrocardiography; Electroencephalography; Female; Humans; Quetiapine Fumarate; Recurrence; Seizures; Time Factors; Treatment Outcome

Second-generation antipsychotics (SGAs) are far more commonly used in the United States compared to first-generation antipsychotics (FGAs), but the relative safety of SGAs compared to FGAs following acute toxic ingestions has not been studied.. A retrospective cohort study was performed by chart review of the California Poison Control System electronic database of 1975 cases from the 10-year period 1997 to 2006 involving patients aged 18 to 65 years who ingested a single SGA or FGA. Cases were coded for overall severity of adverse outcome as defined by the American Association of Poison Control Centers criteria and for presence of specific symptoms and treatments. Odds ratios were calculated between SGAs and FGAs for various symptoms, treatments, and outcome severity.. Odds of a major adverse outcome or death were significantly higher for SGAs than FGAs (OR = 1.71, 95% CI = 1.09 to 2.71). Patients taking SGAs had higher odds of respiratory depression (OR = 2.39, 95% CI = 1.09 to 5.26), coma (OR = 2.18, 95% CI = 1.30 to 3.65), and hypotension (OR = 1.80, 95% CI = 1.23 to 2.63) compared to those taking FGAs but lower odds of dystonia (OR = 0.12, 95% CI = 0.08 to 0.19) or rigidity (OR = 0.30, 95% CI = 0.10 to 0.90).. SGAs appear no safer than FGAs in acute overdose. While neuromuscular symptoms appear less frequently with SGAs compared to FGAs, the relatively greater rates of central nervous system depression associated with SGA overdose may be more dangerous.

Topics: Antipsychotic Agents; Cause of Death; Cohort Studies; Coma; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Overdose; Dyskinesia, Drug-Induced; Follow-Up Studies; Humans; Hypotension; Long QT Syndrome; Neuroleptic Malignant Syndrome; Odds Ratio; Poison Control Centers; Quetiapine Fumarate; Respiratory Insufficiency; Retrospective Studies; Risk Factors; Schizophrenia; Survival Analysis

We report the case of a patient who presented with coma in the context of baclofen and quetiapine overdose. While the clinical picture was largely in keeping with previous descriptions of baclofen and quetiapine toxicity, the patient went on to exhibit clinical and biochemical features of cranial diabetes insipidus, a finding which has not previously been described in this context.

Topics: Baclofen; Diabetes Insipidus; Dibenzothiazepines; Drug Overdose; Humans; Male; Middle Aged; Quetiapine Fumarate

Topics: Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Epinephrine; Fat Emulsions, Intravenous; Humans; Hypotension; Infusions, Intravenous; Quetiapine Fumarate; Vasoconstrictor Agents

To investigate factors that predict the probability and duration of mechanical ventilation in quetiapine overdose, and if cardiac toxicity occurs, this cohort study involved 176 patients presenting to a toxicology unit on 286 occasions with quetiapine overdose. Patient demographics, dose, coingestants, single dose activated charcoal (SDAC) administration, requirement for and duration of mechanical ventilation and electrocardiogram parameters (heart rate, QT, QRS) were obtained. A fully Bayesian approach using logistic regression and time-to-event analysis was undertaken to investigate the relationship between predictor variables and the requirement for and duration of intubation. QT versus heart rate was plotted on a QT nomogram to investigate QT prolongation. The commonest clinical effects were central nervous system depression on 136 occasions (48%) and tachycardia (67%). There were no malignant arrhythmias and an abnormal QT occurred in only 24 admissions (8.4%), all with tachycardia. Hypotension (systolic blood pressure <90 mmHg) occurred on 35 occasions (12%). The logistic regression model supported dose and SDAC (<2 h) influencing the probability of intubation, but not age, sex, therapeutic use of quetiapine or coingestants. The probability of intubation was 10% after 2 g, 22% after 5 g, 37% after 10 g and 55% after 20 g and SDAC resulted in a reduced probability of intubation of 7% for 2 g ingestion. The median duration of ventilation was 22 h (interquartile: 19-28 h), which was not affected by SDAC. Ingested dose can inform early decision making about requirements for intensive care unit admission and intubation. SDAC seems to have only modest effects on outcomes but may be considered within 2 h for large ingestions. Electrocardiogram monitoring is unlikely to be necessary.

Topics: Adult; Antipsychotic Agents; Cardiovascular Diseases; Charcoal; Cohort Studies; Dibenzothiazepines; Drug Interactions; Drug Overdose; Female; Humans; Intubation, Intratracheal; Male; Models, Statistical; Quetiapine Fumarate; Respiration, Artificial; Time Factors

Topics: Antipsychotic Agents; Delirium; Dibenzothiazepines; Drug Overdose; Female; Humans; Quetiapine Fumarate; Suicide, Attempted; Young Adult

Topics: Acetaminophen; Adult; Antipsychotic Agents; Diazepam; Dibenzothiazepines; Drug Overdose; Fat Emulsions, Intravenous; Female; Humans; Lipids; Middle Aged; Quetiapine Fumarate

We present a case of massive overdose with the atypical antipsychotic quetiapine in a 34-year-old woman (body weight 65 kg). At admission, approximately 2 to 4 hours after ingestion of approximately 24 g of quetiapine, the patient was comatose (Glasgow Coma Scale score 5), requiring orotracheal intubation and transfer to the intensive care unit. Because of myoclonic jerks and generalized seizures, benzodiazepines were administered. In addition to transient mild hypotension after intubation, the main cardiovascular manifestation was sinus tachycardia. The QT interval was normal, and the QTc interval (Bazett's correction) was maximally prolonged to 620 ms. However, no malignant arrhythmias were observed. The patient recovered within 2 days but remained agitated and aggressive, for which she was transferred to the psychiatric clinic. The pharmacokinetics of quetiapine in such a large overdose could not be described by simple first-order kinetics. The initially observed rapid decline of the plasma concentrations of quetiapine could be simulated by first-order kinetics (half life = 4.1 hr) and can most probably be explained by rapid distribution into tissues. The final elimination of the drug from the body occurred after approximately 34 hours at much slower rate, most probably reflecting redistribution from tissues into blood and consecutive hepatic clearance of the drug.

Topics: Adult; Antipsychotic Agents; Autonomic Nervous System Diseases; Chromatography, High Pressure Liquid; Coma; Depressive Disorder, Major; Dibenzothiazepines; Drug Overdose; Female; Glasgow Coma Scale; Half-Life; Humans; Long QT Syndrome; Parasympathetic Nervous System; Quetiapine Fumarate; Schizophrenia; Seizures; Suicide, Attempted

Atypical antipsychotics (quetiapine, olanzapine, risperidone and clozapine) are increasingly prescribed in Australia, and emergency departments report growing rates of overdose of these agents. As these drugs are comparatively new, the spectrum of toxicity may be unfamiliar to critical care physicians. Severe hypotension is a recognised consequence of quetiapine poisoning. We describe three patients with massive quetiapine overdose who developed significant hypotension resistant to fluid resuscitation. In each case, blood pressure fell dramatically after commencement of adrenaline infusions. Haemodynamic stability was restored when noradrenaline was substituted for adrenaline. The pharmacodynamics of quetiapine and the literature on overdose are reviewed. We present these cases to broaden the knowledge of physicians treating quetiapine overdose and to publicise the potential deleterious interaction with adrenaline. We recommend use of noradrenaline in preference to adrenaline in pharmacological management of shock in these patients.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Epinephrine; Female; Humans; Hypotension; Male; Middle Aged; Norepinephrine; Quetiapine Fumarate; Vasoconstrictor Agents

Topics: Adult; Anti-Bacterial Agents; Antipsychotic Agents; Clarithromycin; Dibenzothiazepines; Drug Interactions; Drug Overdose; Humans; Male; Metabolic Syndrome; Psychotic Disorders; Quetiapine Fumarate

Topics: Acetaminophen; Antidotes; Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Female; Humans; Lorazepam; Middle Aged; Neuroleptic Malignant Syndrome; Quetiapine Fumarate; Treatment Outcome

To describe clinical effects and outcome after acute quetiapine overdose in adults and compare these with overdose by all other antipsychotic drugs as a group.. We performed a 5-year (2002 to 2006) retrospective case series by chart review of the California Poison Control System database for adult patients with acute ingestion of quetiapine. Patients with coingestants were excluded. Symptoms, signs, and medical outcomes were extracted from the database and also by direct chart review for some variables (QRS- and QT-interval prolongation, torsades de pointes).. We found 945 cases meeting criteria for analysis. Intentional ingestions accounted for 87% of cases. Patient ages ranged from 18 to 84 years, with a median of 35 years. There were 3 deaths, all of whom had coma, tachycardia, and respiratory depression requiring ventilatory support. Clinical manifestations included drowsiness (76%), coma (10%), seizures (2%), tachycardia (56%), hypotension (18%), and respiratory depression (5%). There were insufficient data to determine the incidence of QRS or QT prolongation in our study group, but only 2 patients were reported to have ventricular tachycardia and neither was described as having torsades de pointes. Compared with overdose by all other antipsychotic agents as a group, quetiapine was more likely to cause hypotension (odds ratio [OR] 2.05; 95% confidence interval [CI] 1.52 to 2.76), coma (OR 2.16; 95% CI 1.46 to 3.20), and respiratory depression (OR 2.49; 95% CI 1.40 to 4.41); require tracheal intubation (OR 1.92; 95% CI 1.41 to 2.61); and result in death or a major medical outcome (OR 2.62; 95% CI 1.78 to 3.85).. Consequences of acute quetiapine overdose included coma, respiratory depression, and hypotension, and these complications were more common compared with overdose by all other antipsychotic agents as a group.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antipsychotic Agents; California; Dibenzothiazepines; Drug Overdose; Female; Humans; Male; Medical Records; Middle Aged; Poison Control Centers; Quetiapine Fumarate; Retrospective Studies; United States

The aim of the study was to investigate the pharmacokinetics of quetiapine overdose and the effect of charcoal. The data set included 204 concentration-time points from 54 quetiapine overdose events (median dose 2,700 mg (300-24,000 mg)). Charcoal was administered 0.5-6 h after 19 overdoses. A fully Bayesian methodology for population pharmacokinetic analysis was used and data were modelled using WinBUGS. Uncertainty in the dose history was considered in model building by estimating dose amount and dose time within a possible range. Inclusion of informative priors stabilized the model and population parameter values could be estimated well. A one-compartment model with first-order input and first-order elimination described the data. The final model included uncertainty in dose time. The median and interquartile range of the half-life for individual patients was 6.6 h (4.9-8.4 h). Charcoal was estimated to reduce fraction absorbed by 35%. Co-ingested CYP3A4 inhibitors appeared to decrease clearance and CYP3A4 inducers increase clearance. Charcoal administration may be beneficial after quetiapine overdose.

Topics: Adolescent; Adult; Antidotes; Antipsychotic Agents; Bayes Theorem; Charcoal; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Overdose; Enzyme Activators; Female; Half-Life; Humans; Male; Metabolic Clearance Rate; Middle Aged; Models, Biological; Quetiapine Fumarate; Uncertainty

Topics: Adult; Antipsychotic Agents; Creatine Kinase; Dibenzothiazepines; Drug Overdose; Humans; Male; Quetiapine Fumarate; Rhabdomyolysis; Schizophrenia

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Emergency Nursing; Humans; Male; Quetiapine Fumarate; Treatment Outcome

A 41-year-old man with bipolar disorder came to the emergency department with mental status changes, prolonged rate-corrected QT interval, and myoclonus after ingesting 4500 mg of quetiapine, an atypical antipsychotic drug. Within 24 hours, respiratory failure ensued, requiring intubation and mechanical ventilation. Chest radiograph demonstrated bilateral infiltrates consistent with acute respiratory distress syndrome (ARDS). To our knowledge, this is the first report of ARDS resulting from quetiapine overdose. Clinicians should be aware that in cases of large overdoses of quetiapine, patients should be closely monitored if mental status changes, electro-cardiographic changes, or hypoxia occur, preferably in an intensive care unit.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Electrocardiography; Humans; Male; Mental Health; Myoclonus; Quetiapine Fumarate; Respiratory Distress Syndrome

Data on quetiapine overdosage are only sparsely available in the literature. This study provides additional data on the pharmacokinetics and clinical effects of intoxication with this atypical antipsychotic drug. The authors performed a retrospective analysis of all quetiapine intoxications reported to and screened by the toxicological laboratory of the Central Hospital Pharmacy The Hague between January 1999 and December 2003. Cases with known suggested amount of intake and medical outcome were included. From the patient's medical record and from the toxicological laboratory findings, patient demographic characteristics (gender, age), details of quetiapine intoxication (estimated time of ingestion, estimated amount of ingestion, and coingested drugs) and clinical parameters were obtained. Severity of intoxication was graded by the Poisoning Severity Score (PSS). Individual pharmacokinetic parameter values were calculated using a one-compartment open model and a Bayesian fitting procedure. Out of a total of 21 intoxications with quetiapine, 14 fulfilled the inclusion criteria. The ingested dose ranged from 1200 to 18,000 mg. The blood concentration ranged from 1.1 to 8.8 mg/L with a lag time of 1 to 26.2 hours between time of ingestion and blood sampling at the emergency ward. The most frequent findings were somnolence and tachycardia. The PSS was minor in 6 patients (43%), moderate in 5 patients (36%), and severe in 3 patients (21%). Severity of intoxication was not associated with a higher amount of quetiapine intake. The authors found no correlation between the serum concentration of quetiapine and the amount ingested. Elimination t(1/2) was not prolonged. It can be concluded that quetiapine intoxications appear to proceed mildly. Tachycardia and somnolence were the main clinical symptoms in our case series. No fatalities occurred. The severity of clinical symptoms was not associated with either a high serum concentration or the suggested amount ingested of quetiapine.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Coma; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Overdose; Emergency Treatment; Female; Half-Life; Humans; Male; Medical Records; Middle Aged; Quetiapine Fumarate; Recovery of Function; Retrospective Studies; Severity of Illness Index; Tachycardia

Quetiapine fumarate (Seroquel) is a dibenzothiazepine psychotropic agent that was introduced in 1997 for treating psychoses. Quetiapine is being found with increasing frequency in postmortem cases in Virginia. We report the postmortem results and histories of 20 quetiapine cases from the Office of the Chief Medical Examiner in Virginia covering the period 1999 through 2004. Quetiapine was extracted from blood using a basic drug solid-phase extraction (SPE) and identified by full scan electron impact gas chromatography-mass spectrometry (GC-MS). Quetiapine quantification was accomplished by forming the trimethylsilyl derivative with bis(trimethylsilyl)trifluoracetamide/trimethylchlorosilane and using selected ion monitoring GC-MS. The quetiapine trimethylsilyl derivative ions acquired were m/z 210, 239, and 322. Methapyrilene was the internal standard, and ions m/z 97 and 58 were monitored. The method was linear from 0.1 to 5.0 mg/L with a limit of quantitation of 0.1 mg/L. The quetiapine mean and range of concentrations found in each tissue are as follows: peripheral blood, 7.7 mg/L (0.14-37 mg/L, n = 17); heart blood, 23.63 mg/L (0.53-76 mg/L, n = 4); liver, 91 mg/Kg (1.1-510 mg/Kg, n = 19); bile, 44 mg/L (6.0-96 mg/L, n = 4); urine, 15 mg/L (1.9-37 mg/L, n = 8); gastric, 897 mg total (3.5-3960 mg, n = 7); and vitreous, 1.4 mg/L (0.2-3.2 mg/L, n = 5). The average of all blood concentrations in 18 cases in which quetiapine contributed to the cause of death was 7.95 mg/L (0.4-76 mg/L). The manner of death in 13 of those cases was suicide, two were undetermined, and three were accidents. In two cases in which quetiapine was an incidental finding, the blood concentrations were 0.14 and 1.0 mg/L. Quetiapine and other toxicological findings are presented with the cause and manner of death to assist in interpreting future quetiapine findings in postmortem samples.

Topics: Adolescent; Adult; Antipsychotic Agents; Autopsy; Bile; Bipolar Disorder; Depressive Disorder; Dibenzothiazepines; Drug Overdose; Female; Gas Chromatography-Mass Spectrometry; Gastric Juice; Humans; Liver; Male; Middle Aged; Quetiapine Fumarate; Suicide; Tissue Distribution; Virginia

To report a case of quetiapine/venlafaxine intoxication associated with multiple complications and to review their possible relationship with these 2 drugs.. A 53-year-old white man was admitted to the hospital for loss of consciousness secondary to voluntary intoxication with venlafaxine and quetiapine. Several complications were attributable to this intoxication including seizures, prolonged coma, respiratory depression, neuroleptic malignant syndrome, prolonged QRS and QTc intervals, and a possible venlafaxine withdrawal syndrome.. Quetiapine could be responsible for the neuroleptic malignant syndrome presented in this case. Moreover, venlafaxine intoxication, fever, autonomic instability, and myoclonus presented serotonin syndrome as a differential diagnosis. Potential causes of seizures and prolongation of the QRS and QTc intervals are reviewed. Finally, prolonged coma and late venlafaxine withdrawal are discussed with regard to the pharmacodynamics and pharmacokinetics of drug elimination in the context of intoxication.. Clinicians should be aware of possible complications following intoxication with atypical antipsychotics and anti-depressants, including protracted altered mental status.

Topics: Coma; Cyclohexanols; Diagnosis, Differential; Dibenzothiazepines; Drug Overdose; Electrocardiography; Humans; Male; Middle Aged; Neuroleptic Malignant Syndrome; Quetiapine Fumarate; Respiratory Insufficiency; Seizures; Serotonin Agents; Serotonin Syndrome; Substance Withdrawal Syndrome; Venlafaxine Hydrochloride

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Humans; Hypokalemia; Male; Quetiapine Fumarate; Risperidone

Topics: Adult; Dibenzothiazepines; Drug Overdose; Humans; Male; Quetiapine Fumarate; Rhabdomyolysis

We present a case of acute oxcarbazepine and atomoxetine overdose combined with excess quetiapine in a 19-y-old male. The patient ingested approximately 36 g oxcarbazepine (514 mg/kg), 1.2 g atomoxetine (17 mg/kg), and 9 mg Quetiapine (128 mg/kg). Central nervous system (CNS) depression with initial unresponsiveness developed within 1 h of ingestion, necessitating intubation for airway protection. Despite aggressive therapy with whole bowel irrigation and charcoal administration, the patient's somnolence persisted for 4 d, punctuated by occasional violent outbursts. Prolonged QTc was noted initially, but normalized within 4 d. This case suggests that acute overdose of oxcarbazepine and atomoxetine combined with quetiapine is associated with rapid and prolonged CNS depression.

Topics: Adult; Antipsychotic Agents; Atomoxetine Hydrochloride; Carbamazepine; Diagnosis, Differential; Dibenzothiazepines; Drug Overdose; Emergency Treatment; Humans; Male; Oxcarbazepine; Propylamines; Quetiapine Fumarate; Suicide, Attempted

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Female; Heart Conduction System; Humans; Long QT Syndrome; Quetiapine Fumarate; Sleep Stages

Quetiapine (Seroquel) is an atypical antipsychotic drug belonging to a new chemical class, the benzothiazepine derivatives. We present three cases from the Provincial Toxicology Center of British Columbia, Canada in which suicidal overdose deaths were associated with quetiapine. The blood specimens were initially subjected to a thorough qualitative analysis. Basic drugs were screened for by liquid-liquid extraction followed by gas chromatography-nitrogen-phosphorus (GC-NPD) and gas chromatography-mass spectrometry-electron impact detection utilizing both in-house and commercial search libraries. Acidic and neutral drugs were screened for by liquid-liquid extraction followed by high-performance liquid chromatography-diode-array detection. Volatiles were assayed by gas chromatography-flame-ionization detection. Quetiapine was assayed in biological specimens by basic extraction with n-butyl chloride and derivatized with 50 microL of MTBSTFA and separation by GC-NPD. Linearity was observed up to 2.0 mg/L. Samples with concentrations exceeding the linearity were diluted. These cases were chosen for study because they were all deaths as a result of suicidal ingestion of drugs in which quetiapine was considered a significant factor. The concentrations of quetiapine in these cases are 6-16 times greater than the upper reported therapeutic range (0.1-1.0 mg/L). In case #1, the concentrations of quetiapine found were 7.20 mg/L (19 micromol/L) in blood and 0.93 mg/L (2.4 micromol/L) in vitreous fluid. In case #2, the concentrations of quetiapine found were 16 mg/L in blood (42 micromol/L), 120 mg/kg (310 micromol/kg) in liver, and 1.8 mg/L (4.6 micromol/L) in vitreous fluid. In case #3, the concentrations of quetiapine found in femoral blood was 5.90 mg/L (15 micromol/L). In all cases, drugs in addition to quetiapine were detected, but in cases #1 and #2, the cause of death was considered to be a quetiapine overdose and the other drugs were not considered to be contributory. Case #3 was considered a mixed drug overdose.

Topics: Adult; Antipsychotic Agents; Bipolar Disorder; Dibenzothiazepines; Drug Overdose; Fatal Outcome; Female; Gas Chromatography-Mass Spectrometry; Humans; Middle Aged; Quetiapine Fumarate; Schizophrenia; Suicide

Quetiapine is an atypical antipsychotic agent with structural similarities to the tricyclic antidepressants (TCA). We report a case of quetiapine overdose that was initially clinically similar to that of a TCA overdose and caused a false-positive TCA immunoassay. We then analyzed three common TCA immunoassays [Microgenics (formerly Diagnostic Reagents, Inc.) Tricyclics Serum Tox EIA Assay, Syva RapidTest d.a.u., and Biosite Triage Panel for Drugs of Abuse] with quetiapine in solution as well as urine from both an overdose patient and a therapeutic patient. There was significant variation of the cutoff of false-positivity in all three immunoassays. Both the Syva and Microgenics immunoassays tested positive in both the overdose and therapeutic samples and were positive at urine levels of 100 microg/mL and 10 microg/mL, respectively. The Triage immunoassay was negative in solutions up to 1000 microg/mL and negative in both the therapeutic and overdose urine samples. Quetiapine may cause false-positive TCA immunoassay with both therapeutic use and in overdose. Significant variation exists between immunoassays to detect quetiapine as a false-positive test.

Topics: Adult; Antibody Specificity; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Chromatography, Gas; Cross Reactions; Dibenzothiazepines; Drug Overdose; Electrocardiography; False Positive Reactions; Female; Humans; Immunoassay; Long QT Syndrome; Quetiapine Fumarate; Suicide, Attempted

We describe the effects of quetiapine in overdose.. Quetiapine poisonings were identified from a prospective database of poisoning admissions to a regional toxicology service. Data extracted included details of ingestion, clinical features, investigations (including ECG), and other outcomes (length of stay and ICU admission rate).. There were 45 cases of quetiapine overdose, of which 18 patients with quetiapine assay results were included. Median length of stay was 35 hours (interquartile range [IQR] 14 to 42 hours) for the 18 patients, and 9 were admitted to the ICU. The median ingested dose was 3.5 g (IQR 1.7 to 6.2 g), and reported ingested dose was highly correlated with estimated peak drug concentration (r(2)=0.84; P<.0001), confirming patient-provided history of ingestion. Seizures occurred in 2 patients, delirium occurred in 3 patients, and mechanical ventilation was required in 4 patients. No arrhythmias or deaths occurred. Six of the 18 patients ingested quetiapine alone, with a median length of stay of 35 hours, and 3 were admitted to the ICU. In 1 patient who ingested 24 g, hypotension and seizures occurred. For 10 patients for whom ECGs were available and who had ingested no cardiotoxic drugs, tachycardia occurred in 8 patients. For these 10 patients, the mean corrected QT (QTc) interval was increased at 487 ms, but the mean uncorrected QT interval was 349 ms. Reported dose and peak quetiapine concentrations were significantly associated with ICU admission and length of stay more than 24 hours. A reported dose less than 3 g and a Glasgow Coma Scale score not less than 15 predicted patients not requiring ICU admission or length of stay more than 24 hours.. Quetiapine overdose causes central nervous system depression and sinus tachycardia. In large overdoses, patients may require intubation and ventilation for associated respiratory depression. Although a prolonged QTc occurs, its clinical significance is unclear because it is most likely caused by an overcorrection caused by the tachycardia. In our experience, a reported dose of less than 3 g for patients who are not drowsy (with a Glasgow Coma Scale score of 15) at least 4 hours after ingestion and who did not coingest another toxic agent defined a group not requiring ICU admission or inpatient admission greater than 24 hours.

Topics: Adult; Antipsychotic Agents; Central Nervous System Diseases; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Overdose; Drug Therapy, Combination; Female; Glasgow Coma Scale; Humans; Intensive Care Units; Length of Stay; Male; Quetiapine Fumarate; Respiratory Insufficiency; Retrospective Studies; Seizures

Previous reports of gabapentin overdose have described mild symptoms of somnolence, ataxia and slurred speech. Quetiapine has produced a false positive for cyclic antidepressants on immunoassay drugscreens. Quetiapine overdose is associated with coma, QTc prolongation and hypotension. We report a case of massive gabapentin and presumptive quetiapine overdose with the highest recorded serum gabapentin concentration (104.5 u/ml) associated with coma, respiratory depression requiring mechanical ventilation, and hypotension.

Topics: Acetates; Amines; Anti-Anxiety Agents; Antipsychotic Agents; Coma; Cyclohexanecarboxylic Acids; Dibenzothiazepines; Drug Overdose; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Hypotension; Middle Aged; Quetiapine Fumarate; Respiration, Artificial; Respiratory Insufficiency; Suicide, Attempted

Topics: Dibenzothiazepines; Drug Overdose; Fatal Outcome; Humans; Male; Middle Aged; Quetiapine Fumarate; Schizophrenia; Self Administration

We present a case of acute Quetiapine (SeroQuel) overdose in an 11-y-old girl who ingested 1,300 mg (22.2 mg/kg bw). Initial lethargy developed within I h followed by an episode of agitation and combativeness 3 h after ingestion. After treatment with lorazepam the patient experienced extended somnolence followed by return to normal mental status 16 h after ingestion. No cardiotoxic or laboratory abnormalities were found. This is the first report of acute Quetiapine overdose in an adolescent and suggests a relatively benign clinical course.

Topics: Acute Disease; Antipsychotic Agents; Child; Diagnosis, Differential; Dibenzothiazepines; Drug Overdose; Emergency Treatment; Female; Humans; Quetiapine Fumarate

We report a case of priapism occurring after an overdose of the newly approved atypical antipsychotic quetiapine. A review of its previously published receptor-binding studies suggests that alpha-adrenergic blockade may be the responsible mechanism. To our knowledge, this is the first report of priapism associated with quetiapine, and we recommend the inclusion of priapism in its list of potential adverse effects in cases of overdose.

Topics: Adrenergic alpha-Antagonists; Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Humans; Male; Middle Aged; Priapism; Quetiapine Fumarate; Receptors, Adrenergic, alpha; Suicide, Attempted

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Female; Humans; Quetiapine Fumarate

Although the new atypical antipsychotic, quetiapine fumarate, is growing in popularity over its progenitor, clozapine, clinical experience with overdose of this agent remains limited. Observation of an overdose situation provided a unique opportunity to define the safety, clinical effects, and pharmacokinetics of this medication more clearly.. A patient admitted immediately after ingesting an overdose of 30 tablets of 100 mg of quetiapine was observed carefully to document effects of the medication. These observations were compared with the only two other published cases of overdose, to the known pharmacology of the drug, and to serial measurements of serum drug concentrations obtained to document the time course of elimination of the drug.. Consistent with the two previously published cases, the main clinical effects of overdose were hypotension, tachycardia, and somnolence as predicted by its known alpha-adrenergic receptor and histamine receptor blockade. These effects were managed with fluid resuscitation and supportive measures. No cardiac arrhythmias other than tachycardia have been reported, but the tachycardia was of an unexpectedly long duration in this case. Decline in serum quetiapine concentration followed a biexponential pattern with a terminal elimination half-life of 22 hours. Unexpectedly low peak serum concentrations in three patients with overdose suggest that absorption is highly reduced, either by the effects of the overdose or by the activated charcoal administered.. Quetiapine appears to have greater safety in overdose than traditional antipsychotic agents. Its toxicity is consistent with its receptor pharmacology. Elevated serum concentrations associated with this overdose remained above the limit of detection long enough to document a terminal elimination half-life of 22 hours in this patient. This is much more consistent with previously noted duration of clinical effects and detectable serum concentrations after overdose than the published half-life of 6 hours. Physicians should be aware that any new drug that is active at low concentrations may have had its half-life underestimated during preclinical development because of the difficulty in detecting the drug after the distribution phase has ended.

Topics: Adrenergic alpha-Antagonists; Adult; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Drug Overdose; Female; Half-Life; Humans; Hypotension; Quetiapine Fumarate; Sleep Stages; Tachycardia

Topics: Adult; Antipsychotic Agents; Charcoal; Dibenzothiazepines; Drug Overdose; Fluoxetine; Gastric Lavage; Humans; Male; Quetiapine Fumarate; Suicide, Attempted

Quetiapine (Seroquel) is a new atypical antipsychotic agent developed for the treatment of schizophrenia. This dibenzothiazepine derivative possesses high affinity for 5-HT2 receptors with lower affinity for D1 and D2 dopamine receptors. In comparison to other antipsychotic agents, quetiapine has less antimuscarinic and alpha1 antagonist receptor activity. Overdose reports outside of clinical trials are limited. We report an intentional overdose of quetiapine by a schizophrenic.. A 26-year-old female presented to the emergency department following an alleged ingestion of greater than 10,000 mg of quetiapine. At 1 1/2 hours postingestion, the patient was awake, ambulatory, and responded to verbal stimuli. At 2 1/2 hours postingestion, the patient experienced a decreased level of consciousness and responded only to deep pain. Physical findings included sinus tachycardia, pupils 3-4 mm and sluggish, and BP 135/70. Within 16 hours, the patient became awake and alert and was subsequently extubated. Serum electrolytes and blood count were unremarkable. The electrocardiogram at 18 hours postingestion showed a sinus tachycardia, which lasted for approximately 40 hours postingestion. A follow-up electrocardiogram at 42 hours postingestion was normal.. This ingestion resulted in the loss of consciousness with need for airway protection and persistent tachycardia. Major overdoses of quetiapine warrant close observation in an intensive care setting.

Topics: Adult; Antipsychotic Agents; Blood Pressure; Dibenzothiazepines; Drug Overdose; Electrocardiography; Female; Humans; Pupil; Quetiapine Fumarate; Schizophrenia, Paranoid; Tachycardia, Sinus; Unconsciousness