Vasopressor therapy in atypical antipsychotic overdose.

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 ß-receptors. Alpha-2- and ß2-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 ß2-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.

Quetiapine Poisoning and Factors Influencing Severity.

PURPOSE/BACKGROUND: Quetiapine is a relatively new atypical antipsychotic with fewer adverse effects. It is increasingly prescribed to patients. The purpose of this study was to describe the cases of poisoning observed at the western France Poison Control Centre and identify potential risk factors that increase the severity of the cases. METHODS: This was a retrospective study of self-poisoning with quetiapine as reported by the western France Poison Control Centre between 2007 and 2017. RESULTS: There were 372 cases of quetiapine poisoning. Circumstances are known in 367 of 372 cases. There were 75 cases of null severity (grade 0), 133 cases of mild severity (grade 1), 85 cases of moderate severity (grade 2), and 79 cases of high severity (grade 3). Five deaths were listed in this series. The most commonly observed symptoms were neurological and cardiovascular in nature (drowsiness, coma, tachycardia, hypotension). Of these cases, 79.8% included voluntary ingestions. Among 302 cases with coagents, the most common coagents were benzodiazepines (56%), other psychotropic drugs (41%), and antidepressants (37%). An evaluated ingested dose 1500 mg or greater and 2 or more coagents increase the risk of severe poisoning. In particular, concomitant ingestion of benzodiazepines and antidepressants with quetiapine was associated with high severity (odds ratio, 2.478 [confidence interval, 1.3-4.723]; odds ratio, 1.820 [confidence interval, 1.010-3.316]). CONCLUSIONS: Quetiapine may lead to severe poisoning for which there is currently no specific treatment. Patients and practitioners should be aware of this when quetiapine is prescribed, particularly when used in combination with other medications, and in order to deal with cases of poisoning.

Extended-release quetiapine overdose is associated with delayed onset of toxicity compared to immediate-release quetiapine overdose.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Fatal combination of mitragynine and quetiapine - a case report with discussion of a potential herb-drug interaction.

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.

Acetaminophen and Acetylsalicylic Acid Exposure in a Preterm Infant after Maternal Overdose.

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.

[Successful lipid rescue therapy in a case of severe amitriptyline/quetiapine intoxication]. / Erfolgreiche "Lipidrescuetherapie" bei Amitriptylin-Quetiapin-Mischintoxikation in mehrfach letaler Dosis.

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.

Brugada Pattern Caused by a Flecainide Overdose.

BACKGROUND: 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. CASE REPORT: 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.

Seizure due to multiple drugs intoxication: a case report / Convulsão por causa de intoxicação por múltiplas drogas: relato de caso

Abstract The mechanism of the antidepressant effect of bupropion is not fully understood. Besides, using it in the treatment of depression, it is found to be effective in reducing withdrawal symptoms due to smoking cessation. A 28-year-old female patient with a history of depression was admitted to emergency department an hour after ingestion of bupropion, quetiapine, and levothyroxine in high doses to commit suicide. While accepting her into the Intensive Care Unit, she was awake, alert, disoriented and agitated. After 2 h, the patient had a generalized tonic-clonic seizure. The necessary treatment was given and 9 h later with hemodynamic improvement, the patients’ mental status improved. Bupropion may cause unusual behaviors such as delusions, paranoia, hallucinations, or confusion. The risk of seizure is strongly dose-dependent. We want to emphasize the importance of early gastric lavage and administration of activated charcoal.

Resumo O mecanismo do efeito antidepressivo de bupropiona ainda não está bem esclarecido. Contudo, seu uso no tratamento de depressão revelou ser eficaz para reduzir os sintomas de abstinência relacionados à cessação do tabagismo. Uma paciente do sexo feminino, 28 anos, com história de depressão, deu entrada no setor de emergência uma hora após a ingestão de bupropiona, quetiapina e levotiroxina em doses elevadas para cometer suicídio. Ao ser internada em unidade de terapia intensiva, estava acordada, alerta, desorientada e agitada. Após duas horas, apresentou uma crise tônico-clônica generalizada. O tratamento necessário foi administrado e nove horas mais tarde, com a estabilização hemodinâmica, o estado mental da paciente melhorou. Bupropiona pode causar comportamentos incomuns, incluindo delírios, paranoia, alucinações ou confusão mental. O risco de convulsão é altamente dependente da dose. Queremos enfatizar a importância da lavagem gástrica precoce e da administração de carvão ativado.

Seizure due to multiple drugs intoxication: a case report.

The mechanism of the antidepressant effect of bupropion is not fully understood. Besides, using it in the treatment of depression, it is found to be effective in reducing withdrawal symptoms due to smoking cessation. A 28-year-old female patient with a history of depression was admitted to emergency department an hour after ingestion of bupropion, quetiapine, and levothyroxine in high doses to commit suicide. While accepting her into the Intensive Care Unit, she was awake, alert, disoriented and agitated. After 2h, the patient had a generalized tonic-clonic seizure. The necessary treatment was given and 9h later with hemodynamic improvement, the patients' mental status improved. Bupropion may cause unusual behaviors such as delusions, paranoia, hallucinations, or confusion. The risk of seizure is strongly dose-dependent. We want to emphasize the importance of early gastric lavage and administration of activated charcoal.

Low-dose intravenous lipid emulsion for the treatment of severe quetiapine and citalopram poisoning.

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.

Antipsychotic-related fatal poisoning, England and Wales, 1993-2013: impact of the withdrawal of thioridazine.

CONTEXT: Use of second generation antipsychotics in England and Wales has increased in recent years whilst prescription of first generation antipsychotics has decreased. METHODS: To evaluate the impact of this change and of the withdrawal of thioridazine in 2000 on antipsychotic-related fatal poisoning, we reviewed all such deaths in England and Wales 1993-2013 recorded on the Office for National Statistics drug poisoning deaths database. We also reviewed antipsychotic prescribing in the community, England and Wales, 2001-2013. Use of routine mortality data: When an antipsychotic was recorded with other drug(s), the death certificate does not normally say if the antipsychotic caused the death rather than the other substance(s). A second consideration concerns intent. A record of "undetermined intent" is likely to have been intentional self-poisoning, the evidence being insufficient to be certain that the individual intended to kill. A record of drug abuse/dependence, on the other hand, is likely to have been associated with an unintentional death. Accuracy of the diagnosis of poisoning: When investigating a death in someone prescribed antipsychotics, toxicological analysis of biological samples collected post-mortem is usually performed. However, prolonged attempts at resuscitation, or diffusion from tissues into blood as autolysis proceeds, may serve to alter the composition of blood sampled after death from that circulating at death. With chlorpromazine and with olanzapine a further factor is that these compounds are notoriously unstable in post-mortem blood. Deaths from antipsychotics: There were 1544 antipsychotic-related poisoning deaths. Deaths in males (N = 948) were almost twice those in females. For most antipsychotics, the proportion of deaths in which a specific antipsychotic featured either alone, or only with alcohol was 30-40%, but for clozapine (193 deaths) such mentions totalled 66%. For clozapine, the proportion of deaths attributed to either intentional self-harm, or undetermined intent was 44%, but for all other drugs except haloperidol (20 deaths) the proportion was 56% or more. The annual number of antipsychotic-related deaths increased from some 55 per year (1.0 per million population) between 1993 and 1998 to 74 (1.5 per million population) in 2000, and then after falling slightly in 2002 increased steadily to reach 109 (1.9 per million population) in 2013. Intent: The annual number of intentional and unascertained intent poisoning deaths remained relatively constant throughout the study period (1993: 35 deaths, 2013: 38 deaths) hence the increase in antipsychotic-related deaths since 2002 was almost entirely in unintentional poisoning involving second generation antipsychotics. Clozapine, olanzapine, and quetiapine were the second generation antipsychotics mentioned most frequently in unintentional poisonings (99, 136, and 99 deaths, respectively). Mentions of diamorphine/morphine and methadone (67 and 99 deaths, respectively) together with an antipsychotic were mainly (84 and 90%, respectively) in either unintentional or drug abuse-related deaths. Deaths and community prescriptions: Deaths involving antipsychotics (10 or more deaths) were in the range 11.3-17.1 deaths per million community prescriptions in England and Wales, 2001-2013. Almost all (96%) such deaths now involve second generation antipsychotics. This is keeping with the increase in annual numbers of prescriptions of these drugs overall (<1 million in 2000, 7 million in 2013), largely driven by increases in prescriptions for olanzapine and quetiapine. In contrast, deaths involving thioridazine declined markedly (from 40 in 2000 to 10 in 2003-2013) in line with the fall in prescriptions for thioridazine from 2001. CONCLUSIONS: The removal of thioridazine has had no apparent effect on the incidence of antipsychotic-related fatal poisoning in England and Wales. That such deaths have increased steadily since 2001 is in large part attributable to an increase in unintentional deaths related to (i) clozapine, and (ii) co-exposure to opioids, principally diamorphine and methadone.

Postmortem Quetiapine Reference Concentrations in Brain and Blood.

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.