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.

Toxic leukoencephalopathy in the intensive care unit.

In this article, we report two cases of acute toxic leukoencephalopathy to highlight this acute clinicoradiological syndrome as an important, although uncommon, consideration in the undifferentiated comatose patient who fails to wake following drug overdose or has unexplained neurology with a history of drug exposure. We then review the current literature and discuss potential differential diagnoses in this setting, along with proposed treatments for this condition. The cases presented demonstrate a more fulminant onset than previously well-defined acute toxic leukoencephalopathy subtypes and highlight the prognostic importance of magnetic resonance imaging in diagnosing a condition from which significant functional recovery seems possible.

Intralipid emulsion treatment as an antidote in lipophilic drug intoxications.

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.

Rapid determination of quetiapine in blood by gas chromatography-mass spectrometry. Application to post-mortem cases.

A simple, fast and sensitive method for the determination of quetiapine in human blood has been developed and validated. The method involved a basic liquid-liquid extraction procedure and subsequent analysis by gas chromatography-mass spectrometry, previous derivatization with bis(trimethylsilyl)-trifluoro-acetamide and chorotrimethylsilane (99 : 1). The methods of validation included linearity with a correlation coefficient > 0.99 over the range 0.02-1 µg ml(-1), intra- and interday precision (always < 12%) and accuracy (mean relative error always < 12%) to meet the bioanalytical acceptance criteria. The limit of detection was 0.005 µg ml(-1). The procedure was further applied to post mortems from the Institute of Legal Medicine, University of Santiago de Compostela.

Methylene blue used in the treatment of refractory shock resulting from drug poisoning.

BACKGROUND: Methylene blue inhibits the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, decreasing vasodilation and increasing responsiveness to vasopressors. It is reported to improve haemodynamics in distributive shock from various causes including septicaemia and post-cardiac surgery. Reports of use in overdose are limited. We describe the use of methylene blue to treat a case of refractory distributive shock following a mixed drug poisoning. CASE DETAILS: A 41-year-old male presented following reported ingestion of 18 g extended-release quetiapine, 10 g controlled-release carbamazepine, 240 mg fluoxetine, 35 g enteric-coated sodium valproate and 375 mg oxazepam. He was comatose and intubated on presentation. Progressive hypotension developed. Echocardiogram revealed a hyperdynamic left ventricle, suggesting distributive shock. The patient remained hypotensive despite intravenous fluid boluses, escalating vasopressor infusions. Arterial blood gas revealed metabolic acidaemia and high lactate. Methylene blue was administered as loading-dose of 1.5 mg/kg and continuous infusion (1.5 mg/kg/h for 12 h, then 0.75 mg/kg/h for 12 h) resulting in rapid improvement in haemodynamic parameters and weaning of vasopressors. Serum quetiapine concentration was 18600 ng/mL (30-160 ng/mL), collected at the time of peak toxicity. CONCLUSION: Severe quetiapine poisoning produces hypotension primarily from alpha-adrenoreceptor antagonism. Methylene blue may have utility in the treatment of distributive shock resulting from poisoning refractory to standard vasopressor therapy.

Gastric pharmacobezoars in quetiapine extended-release overdose: a case series.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

The toxicology and comorbidities of fatal cases involving quetiapine.

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.

Focal parietal necrosis of the sigmoid due to atypical neuroleptics: a case report.

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.

Severe overdose of quetiapine treated successfully with extracorporeal life support.

BACKGROUND: 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. OBJECTIVES: To report a case where extracorporeal circulatory support (ECCS) was used successfully in severe quetiapine overdose. CASE REPORT: 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. CONCLUSIONS: 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.

Window of opportunity: flexion myelopathy after drug overdose.

BACKGROUND: 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. OBJECTIVES: 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. CASE REPORT: 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. CONCLUSION: 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.

Survival from coma induced by an intentional 36-g overdose of extended-release quetiapine.

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.

Prolonged delirium after quetiapine overdose.

Quetiapine is an atypical antipsychotic agent increasingly used to treat schizophrenia and bipolar disorder in pediatric patients. Few published data exist concerning quetiapine's effects in therapeutic settings or short-term overdose in pediatric and adolescent populations. In this report, we describe a 15-year-old adolescent girl who experienced continued delirium 5 days after an overdose of quetiapine, trazodone, and clonidine. The patient initially presented with sedation and stable vital signs. After 3 days of gradual improvement, she experienced episodes of delirium coinciding with an increase in resting heart rate. On the basis of suspicion for quetiapine-associated antimuscarinic effects, the patient was administered intravenously with physostigmine on the fifth day after ingestion. Treatment resulted in a brief resolution of symptoms. Serum quetiapine levels measured 1 day and 5 days after ingestion were 3400 and 4800 ng/mL, respectively. The use of physostigmine and interpretation of serum levels are discussed further.

Convulsiones tardías tras intoxicación por topiramato, venlafaxina y quetiapina / Delayed seizures afte topiramate, venlafaxine and quetiapine overdose

No disponible

No disponible