olanzapine 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

Clozapine (Clozaril) and olanzapine (Zyprexa) are two relatively new atypical antipsychotics that are structurally and pharmacologically related. There are currently no therapeutic indications for these pharmaceuticals in infants and toddlers.Presumably, as the usage of these medications in adults increases, the frequency of unintentional pediatric ingestions will increase. In 2001 the annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System included a separate subcategory for atypical antipsychotics under the heading of sedatives/hypnotics/antipsychotics. The toxidrome resulting from these drugs is predominately central nervous system depression and anticholinergic effects. Although the desirable lack of extrapyramidal symptoms in adults results in their greatest clinical utility, several reports of toxic ingestions in small children are noteworthy for having extrapyramidal manifestations. We review here the available reported clinical experience with toxic doses of these medications that in small children may amount to as little as a single tablet. Although such doses may be lethal, supportive care and gastrointestinal decontamination in this population will generally lead to a good outcome.

Topics: Antipsychotic Agents; Benzodiazepines; Child, Preschool; Clozapine; Dose-Response Relationship, Drug; Humans; Infant; Olanzapine; Poisoning

Oxcarbazepine is a carbamazepine pre-drug with less drug interactions. Its adverse effects, including hyponatremia, somnolence and ataxia, are dose dependent. Olanzapine is an atypical antipsychotic drug most commonly used to manage psychoses and symptoms of irritability and aggressive behavior. Main side effects include extrapyramidal and anticholinergic symptoms, weight gain, and hyperglycemia.. In this manuscript a case of oxcarbazepine and olanzapine intoxication is discussed. A 45-year-old woman, previously diagnosed with bipolar disorder and chronic alcoholism, was presented two hours after ingestion of 30,000mg of oxcarbazepine and 140 mg of olanzapine, combined with alcohol. She was immediately treated with gastric lavage and administration of activated charcoal. During her hospitalization she was hemodynamically and respiratory stable with no neurological signs and symptoms except for somnolence. Another side effect was hyponatremia. She was discharged from our department in stable clinical condition after being evaluated by a psychiatrist.. Early approach is crucial for the management of drug intoxication. Late symptoms can be avoided through close monitoring of vital signs, mental status and laboratory values. Psychiatric consultation is essential for a better long-term outcome.

Topics: Antipsychotic Agents; Bipolar Disorder; Female; Greece; Humans; Middle Aged; Olanzapine; Oxcarbazepine; Poisoning; Treatment Outcome

A 19-year-old male came to the Emergency Room of our hospital due to an episode of dystonic movements and disorientation 4 days after consuming methamphetamine, which evolved to a catatonic frank syndrome and eventually to status epilepticus. Definitive diagnosis was anti-NMDA receptor encephalitis, an acute inflammation of the limbic area of autoimmune origin in which early diagnosis and treatment are key elements for the final outcome. In this case, initial normal tests and previous methamphetamine poisoning delayed diagnosis, because inhaled-methamphetamine poisoning causes similar clinical symptoms to anti-NMDA receptor encephalitis. Methamphetamine poisoning may have caused an immune response in the patient, bringing on the progress of the pathology.

Topics: Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Anticonvulsants; Autoantibodies; Benzodiazepines; Catatonia; Delayed Diagnosis; Diagnosis, Differential; Diagnostic Errors; Diazepam; Electroconvulsive Therapy; Emergencies; Epilepsies, Partial; Hallucinations; Humans; Infectious Encephalitis; Male; Methamphetamine; Olanzapine; Poisoning; Receptors, N-Methyl-D-Aspartate; Status Epilepticus; Young Adult

Olanzapine is an atypical antipsychotic with multireceptor affinity and different pharmacological effects, which can result with abnormalities in laboratory investigations.. To assess the nature and frequency of laboratory tests abnormalities in patients with an acute olanzapine poisoning.. 26 adult cases (mean age 37.7 +/- 15.3 years) of an acute olanzapine poisoning (serum level above 100 ng/mL). Group consisted of 11 men and 13 women, but 1 man and 1 woman were poisoned twice.. Prospective analysis of the following laboratory parameters: complete blood count (CBC), coagulation tests (APTT, INR), serum concentration of sodium, potassium, chlorides, glucose, BUN, creatinine and bilirubin, serum activity of AST, ALT, GGTP and CPK, urinalysis.. The most common laboratory abnormalities in the study group were: hyperglycaemia (96%), hyper-prolactinaemia (83%), elevated CPK (80%), hypokalaemia (75%), hyperbilirubinaemia (60%), leukocytosis (55%). Less frequent parameters were: elevated AST (20%), hyponatraemia (15%), elevated ALT(10%) and thrombocytopenia (5%). The onset of some parameters was as follows: 1st day of hospitalization hyperglycaemia, leukocytosis and hypokalaemia, 2nd - hyperbilirubinaemia and elevated CPK, and 3rd - hyperprolactinaemia.. In acute olanzapine poisonings: (1) muscle and liver injury, serum glucose and electrolytes abnormalities, and changes in CBC can be present; (2) the valuable parameters for the monitoring of the course of poisonings are: serum activity of CPK and transaminases (AST, ALT), serum level of bilirubin, glucose, potassium and sodium, and CBC; (3) hyperprolactinaemia probably lacks of practical importance, but the further investigations are needed in this area.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Female; Humans; Incidence; Male; Middle Aged; Olanzapine; Poisoning; Prospective Studies

Olanzapine is a second generation antipsychotic of thienobenzodiazepin group, which is used in the treatment of schizophrenia, bipolar disorder, and others, mainly psychiatric. Its multireceptor action (antagonism to dopaminergic D1, D2, D4, serotoninergic 5-HT2A, 5-HT2C, histaminergic H1, cholinergic M1-5, and a1--adrenergic receptors) results in multiple clinical symptoms in the course of acute poisoning.. Evaluation of incidence and intensity of clinical symptoms in patients with of acute olanzapine intoxication. The pathophysiological mechanisms of particular symptoms are also described.. 26 patients (mean age 37.7 +/- 15.3 years) hospitalized in 2005-2008 in toxicological centers in Krakow and Gdansk because of acute olanzapine poisoning (all patients had the toxic serum level of olanzapine above 100 ng/mL). The study group consisted of 11 men (29.3 +/- 8.5 years) and 13 women (44.9 +/- 16.4 years); 1 man and 1 woman were poisoned twice.. Prospective analysis (using descriptive statistics) of data taken from medical anamnesis and results of physical examination, considering the following ones: consciousness disturbances (Glasgow Coma Scale, Matthew's scale, qualitative disturbances), vital signs (arterial blood pressure, heart rate, breathing rate, temperature), neurological findings (muscular tension, tendon reflexes, extrapyramidal symptoms, pupils) and others (oral and bronchial secretion, Poisoning Severity Score).. The mean dose of ingested olanzapine in the study group was 352.5 +/- 220.0 mg, while the mean time since ingestion to hospital admission was 4.4 +/- 3.5 h. The half of the patients took other medicines together with olanzapine, and 23% consumed alcohol, as well. The following intensity of quantitative consciousness disturbances according to Matthew's scale were observed: grade 0 - 8%, I - 15%, II - 23%, III - 50%, and IV - 4%. The minimal and maximal values of blood pressure were: 102/63 +/- 16/14 and 163/ 97 +/- 27/18 mmHg, respectively; heart rate: 77 +/- 15 and 138 +/- 22 beats/min; temperature: 36.3 +/- 0.5 and 37.9 +/- 0.8 degrees C; breathing rate in non-intubated patients: 14 +/- 2 and 22 +/- 7 breaths/min. The mean duration of consciousness disturbances, endotracheal intubation and mechanical ventilation were: 44.9 +/- 31.3; 22.0 +/- 33.3 and 7.0 +/- 25.9 h, respectively. The study revealed tachycardia (85%), psychomotor agitation (81%), hypertension (73%), miosis (65%), and coma (54%) as the most common symptoms of poisoning. The hospitalization of poisoned patients lasted on average 5.7 +/- 3.6 days and the half of them were poisoned severely (PSS 3).. In the course of acute olanzapine poisoning: (1) the prevailing symptoms come from circulatory and central nervous systems; (2) some symptoms are mutually opposed, eg.: coma - psychomotor agitation, hypertension - hypotension, tachycardia - bradycardia, hyperthermia - hypothermia, miosis - mydriasis; (3) rarely consciousness disturbances may persist for up to 6 days after olanzapine overdose; (4) the course of poisoning can be severe, sometimes complicated, but fatal outcomes are rare.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Coma; Drug Overdose; Female; Hospitalization; Humans; Hypertension; Male; Miosis; Olanzapine; Poisoning; Poland; Psychomotor Agitation; Tachycardia

Acute cocaine poisoning causes neuroexcitation and can be fatal. The toxic effects of cocaine can be attenuated by antagonists of serotonin, muscarinic cholinergic, and dopamine receptors. Olanzapine, an atypical antipsychotic medication, is an antagonist of these receptors. The objective of this study is to evaluate the efficacy of olanzapine pretreatment for attenuation of acute cocaine toxicity using a mouse model.. Eighty male CF-1 mice were randomly assigned to olanzapine (1 mg/kg) or placebo pretreatment. Fifteen minutes later, all animals received 103 mg/kg intraperitoneal cocaine.. Overall mortality was 11% for olanzapine-treated animals and 45% for placebo. Olanzapine also appeared to alter the characteristics of seizures due to cocaine.. In this model of acute cocaine toxicity, olanzapine pretreatment attenuated acute cocaine toxicity. Olanzapine should be evaluated further as a potential treatment for acute cocaine poisoning.

Topics: Animals; Benzodiazepines; Cocaine; Cocaine-Related Disorders; Disease Models, Animal; Drug Antagonism; Injections, Intraperitoneal; Longevity; Male; Mice; Mice, Inbred Strains; Olanzapine; Poisoning; Seizures; Selective Serotonin Reuptake Inhibitors; Vasoconstrictor Agents

Topics: Aged; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Citalopram; Female; Fluoxetine; Humans; Mianserin; Myoclonus; Olanzapine; Poisoning; Seizures; Selective Serotonin Reuptake Inhibitors; Unconsciousness

Olanzapine is a new atypical antipsychotic drug acting on different receptors. A variety of pharmacologic effects are responsible for toxicity and the variety of clinical symptoms seen in overdose: tachycardia, agitation or aggression, dysarthria, extrapyramidal dystonic effects, sedation or coma, small pupils, blurred vision, respiratory depression, hypotension. A retrospective analysis of clinical course of eight acute olanzapine intoxication treated at the Department of Clinical Toxicology Jagiellonian University Medical College is presented. CNS symptoms manifested in fluctuations between somnolence/coma and agitation/aggression and miosis were observed in most of the patients. Increased CPK activity was stated in the most of patients. All of the patients recovered, poisoning severity according PSS was moderate and severe.

Topics: Acute Disease; Adolescent; Adult; Antipsychotic Agents; Benzodiazepines; Drug Overdose; Female; Humans; Male; Nervous System Diseases; Olanzapine; Poisoning; Retrospective Studies; Severity of Illness Index