quetiapine-fumarate and Poisoning

Use of second generation antipsychotics in England and Wales has increased in recent years whilst prescription of first generation antipsychotics has decreased.. 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 entirel. 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.

Topics: Antipsychotic Agents; Benzodiazepines; Chlorpromazine; Clozapine; Drug Recalls; England; Heroin; Humans; Methadone; Morphine; Olanzapine; Poisoning; Quetiapine Fumarate; Thioridazine; Wales

The aim of this review was to determine the spectrum and severity of effects of unintentional antipsychotic poisoning in children. A computerised literature search of MEDLINE (1966 to February 2005) and EMBASE (1980 to February 2005) was undertaken. The Internet was searched using URL: www.google.com. The proceedings of the North American Congress of Clinical Toxicology (NACCT) and the European Association of Poisons Centres and Clinical Toxicologists (EAPCCT) were hand searched. All cases of unintentional antipsychotic (all classes) poisoning in children aged 0-6 years were included. The data extracted included the age, weight, antipsychotic, dose, clinical effects, treatment and outcomes. The toxic dose was estimated as the lowest dose causing objective adverse effects.Sixty-eight reports were identified. Few contained all of the required information. Most of the case series included multiple antipsychotics with limited information on individual drugs or all ages with limited paediatric information. For most antipsychotics the ingestion of one tablet caused symptoms that were sometimes severe and usually lasted from 1 to 3 days. Extrapyramidal symptoms (EPS) were often delayed for up to 12-24 hours. Chlorpromazine caused CNS depression, hypotension and miosis; EPS and cardiac effects were rare, and the toxic dose was estimated to be 15 mg/kg. Haloperidol caused drowsiness (rarely coma) and over one-half of patients had neuromuscular effects (mainly EPS), with a toxic dose estimated at 0.15 mg/kg. Thioridazine caused CNS depression and potentially cardiac effects, with a toxic dose of 1.4 mg/kg. Atypical antipsychotics caused significant CNS depression (except risperidone); EPS were less common. Toxic doses were clozapine 2.5 mg/kg, olanzapine 0.5 mg/kg and aripiprazole 3 mg/kg. EPS responded to anticholinergic drug treatment. In summary, unintentional antipsychotic ingestion in children can cause severe effects that last 1-3 days, often with one tablet. Children potentially ingesting a toxic dose or who are symptomatic should be considered for assessment in hospital. Most cases resolve with good supportive care. Toxic doses are only estimates that are based on limited data and should be used with caution until prospective studies are undertaken.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Child; Child, Preschool; Chlorpromazine; Clozapine; Dibenzothiazepines; Haloperidol; Humans; Infant; Infant, Newborn; Olanzapine; Pimozide; Piperazines; Poisoning; Quetiapine Fumarate; Quinolones; Risperidone

Poisonings contribute significantly to morbidity and mortality of patients. Some patients have numerous contacts to a poison information center, indicating repeated poisoning exposures. Information on the involved substances is necessary to explore methods to prevent self-harm and reduce mortality. The objective of this study was to characterize the patient population with repeated poison exposures in Denmark and identify the substances involved.. This study was a retrospective cohort study of enquiries to the nationwide Danish Poison Information Centre and the Danish National Patient Registry. The databases were used to identify patients with more than five individual poisoning episodes within a 12-month-period between 1 January 2013, and 31 December 2017.. One hundred and thirty-seven patients and 995 patients met the inclusion criteria in the Danish Poison Information Centre and the Danish National Patient Registry, respectively. The majority were women (82.5% and 66.3% for the Danish Poison Information Centre and the Danish National Patient Registry cohorts, respectively). The mean age was 24.7 and 29.5 years. Psychiatric comorbidities were frequent with 74.5% and 67.0% suffering from personality disorders and 70.1% and 54.5% from affective disorders in the Danish Poison Information Centre and the Danish National Patient Registry cohorts, respectively. One thousand seven hundred and fifty-two poisoning episodes were identified in the Danish Poison Information Centre database, and the most common types of substance were 'pharmaceuticals' (1,420 episodes). The most common medications ingested were quetiapine, paracetamol and cyclizine. Median number of contacts to the Danish Poison Information Centre was 10. Patients with one or more poisoning episodes involving cyclizine had on average 11.4 poisoning episodes involving cyclizine. In the Danish National Patient Registry cohort 80.9% were alive after 10 years compared to 97.7% in the background population.. Most poisonings were intentional and occurred among younger women. Psychiatric comorbidity was frequent. Most often, pharmaceuticals were the toxic substance, mainly quetiapine, paracetamol and cyclizine. Changing the status of cyclizine from over the counter to prescription only medication, and implementing stricter rules for prescribing quetiapine, could limit future poisoning incidences.

Topics: Acetaminophen; Adult; Cyclizine; Denmark; Female; Humans; Male; Poison Control Centers; Poisoning; Poisons; Prescription Drugs; Quetiapine Fumarate; Retrospective Studies; 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

A rapid, sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination and quantification of 12 psychotropic drugs and metabolites in hair was developed and validated. After freeze grinding with methanol, the supernatant was determined by LC-MS/MS using an Allure PFPPropyl column (100 × 2.1 mm, 5 μm) with a gradient elution of acetonitrile and 10 mmol/L ammonium acetate with 0.1% formic acid, and in the subsequent analysis using multiple reaction monitoring (MRM) mode, two ion transitions were monitored for each analyte. The limits of detection ranged from 0.002 to 0.05 ng/mg, and the limits of quantitation were in the range of 0.005-0.1 ng/mg. Good linearity (r > 0.995) was observed for all analytes over the linear range. Acceptable intraday and interday precision (RSD ≤ 20%) and accuracy (85.3%-112.9%) were achieved. This method of detection was applied to the analysis of guinea pig hair roots after a single dose of quetiapine. Quetiapine and 7-hydroxyquetiapine were both detected in guinea pig hair roots from 5 min post administration. The concentration of quetiapine (10.3-1733.8 ng/mg) was much higher than that of 7-hydroxyquetiapine (0.1-40.6 ng/mg) in the hair roots of guinea pigs, and higher concentrations of quetiapine and 7-hydroxyquetiapine occurred in black hair root than in that of white and brown. The animal experiment demonstrated that hair roots may be a good specimen for proving acute quetiapine poisoning when other biological matrices are not available.

Topics: Animals; Chromatography, Liquid; Dibenzothiazepines; Forensic Toxicology; Guinea Pigs; Hair; Limit of Detection; Models, Animal; Poisoning; Psychotropic Drugs; Quetiapine Fumarate; Substance Abuse Detection; Tandem Mass Spectrometry

A 13-year-old boy was presented to the emergency department with a presumed intoxication with quetiapine, an antipsychotic. The tablets turned out to be peppermints, used as advertisement gift from the pharmaceutical industry. This misunderstanding could have led to unnecessary treatment and observation of the patient in hospital, for a moderately serious intoxication.

Topics: Adolescent; Advertising; Antipsychotic Agents; Candy; Dibenzothiazepines; Humans; Male; Poisoning; Quetiapine Fumarate