olanzapine and Coma

Olanzapine is a thienobenzodiazepine class antipsychotic that strongly antagonises the 5-HT2A serotonin receptor, but acute poisonings are reported rarely. Symptoms of an overdose include disorder of consciousness, hypersalivation, myosis, and coma. Serum concentration higher than 0.1 mg/L is toxic, while concentration above 1 mg/L can be fatal. Here we report key data about 61 patients admitted to the National Poison Control Centre in Belgrade, Serbia over olanzapine poisoning in 2017 and 2018. The ingested doses ranged from 35 to 1680 mg, and time from ingestion to determination from two to 24 hours. In 34 patients olanzapine serum concentrations were in the therapeutic range and in 27 in the toxic range. In five patients they were higher than fatal, but only one patient died. The most common symptoms of poisoning were depressed consciousness (fluctuating from somnolence to coma), tachycardia, hypersalivation, hypotension, myosis, and high creatine kinase. All patients but one recovered fully after nonspecific detoxification and symptomatic and supportive therapy.. Olanzapin je antipsihotik koji pripada grupi tienobenzodiazepina. Kao i drugi atipični antipsihotici, olanzapin je jak antagonist 5-HT2A serotoninskih receptora. Akutna trovanja olanzapinom su rijetka. Simptomi predoziranja uključuju duboki ili fluktuirajući poremećaj stanja svijesti s hipersalivacijom i miozom, kao i komu i smrt u slučaju ingestije velikih doza. Koncentracije olanzapina u serumu veće od 0,1 mg/L smatraju se toksičnima, a letalnima veće od 1 mg/L. U radu su prikazana akutna trovanja olanzapinom zabilježena u Nacionalnom centru za kontrolu trovanja u Beogradu tijekom dvije godine. Koncentracije olanzapina u serumu pacijenata akutno otrovanih olanzapinom određene su pouzdanom metodom tekuće kromatografije s masenom spektrometrijom. Registriran je 61 pacijent s predoziranjem olanzapinom: u njih 34 koncentracije olanzapina bile su u terapijskom opsegu, a u njih 27 zabilježene su toksične koncentracije. Pet pacijenata imalo je koncentracije veće od letalnih, a zabilježen je i jedan smrtni ishod. Najčešći simptomi trovanja bili su hipotenzija, tahikardija i povećanje aktivnosti enzima kreatin kinaze. Nakon primjene nespecifičnog detoksikacijskog simptomatskog i potpornog liječenja svi pacijenti osim jednog su se potpuno oporavili.

Topics: Benzodiazepines; Coma; Humans; Olanzapine; Poison Control Centers; Serbia; Sialorrhea

BACKGROUND Olanzapine is an antipsychotic drug and is used in critical care to treat delirium. There is no known antidote to olanzapine intoxication. Overdosing olanzapine can cause, tremor, bradykinesia, hypotension somnolence, coma, and miosis. CASE REPORT We present the case of a previously healthy 69-year-old man who after routine mitral valve surgery developed pneumonia and severe sepsis requiring several weeks on a ventilator in the Intensive Care Unit. He developed delirium and paranoia and was prescribed olanzapine. After 4 doses, he became hypotensive and nonresponsive and developed pinpoint pupils. The symptoms were reversed minutes after administration of flumazenil. The clinical picture in this case corresponds well with an olanzapine intoxication. No other drugs, such as benzodiazepines or opioids, had been administered that could explain the reaction. Olanzapine intoxication is known to present with hypotension, coma, and miosis. The doses given were normal starting doses for olanzapine in the outpatient setting but much higher than recommended doses in the intensive care setting. CONCLUSIONS This case illustrates a risk for severe adverse effects, even within normal prescription range, when olanzapine is used in the intensive care setting. Finally, it is intriguing that the symptoms were reversed after administration of flumazenil, a selective competitive antagonist of the GABA receptor. Olanzapine mainly effects dopamine, serotonin, a1-adrenergic, histamine, and muscarinic receptors, but a low affinity to GABA and benzodiazepine sites can perhaps explain the observed effect.

Topics: Aged; Benzodiazepines; Coma; Delirium; Flumazenil; Humans; Hypotension; Intensive Care Units; Male; Miosis; Olanzapine

Topics: Antipsychotic Agents; Benzodiazepines; Coma; Delirium; Humans; Injections, Intravenous; Male; Middle Aged; Olanzapine; Schizophrenia

Recommended doses for olanzapine long-acting injection (olanzapine LAI) are 150 mg/2 weeks, 210 mg/2 weeks, 300 mg/2 or 4 weeks, and 405 mg/4 weeks. This analysis evaluated the dosing and interval patterns to compare the actual dosing patterns with the recommended dosing strategy.. These data, from March 2010 through September 2011, were collected as part of a Risk Evaluation and Mitigation Strategy mandatory patient registry that captures all post-approval olanzapine injections in the US. This registry includes both active and inactive (60 + days since last injection) patients.. All patients with at least one olanzapine injection were included (n = 1694). The mean number of injections received was 6.6 (range of 1-40). The most frequent numbers of injections were one (26.3%) and two (12.9%). For the 11,228 olanzapine injections, the most common doses were 300 mg and 405 mg, accounting for 92.9% of injections. Although the most common time intervals between injections was about 14 days for 150 mg, 210 mg, and 300 mg, and about 28 days for 405 mg, the intervals ranged from less than 10 to more than 60 days for all doses. Among active patients (48.2% of registry), 68.2% had >120 days of treatment with any dose, and the number of days since the last injection was around 2 weeks or less for 61.2% of patients, around 3 weeks for 16.5% of patients, and around 4 weeks for 7.1% of patients. Among inactive patients (51.8% of registry), 48.6% had <30 days of treatment. For the pattern of the first five injections, most patients (70.9%) received four subsequent injections of the same dose as their initial injection.. This registry will continue to change. There is a broad range in time between injections. Most patients continue to receive the same initial dose instead of switching to a maintenance dose. This may suggest that some clinicians are not reassessing the dose after the initial starting dose because the patient was stabilized on olanzapine oral before beginning olanzapine long-acting injection. The study is limited by a database that does not include reasons for dose and dosing interval decisions or reasons for delaying or discontinuing treatment.

Topics: Antipsychotic Agents; Benzodiazepines; Coma; Deep Sedation; Delirium; Humans; Injections; Olanzapine; Schizophrenia; Treatment Outcome; United States

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

We report a case of severe neuroleptic malignant syndrome developing in a 28-year-old female patient following deliberate self-poisoning with atypical antipsychotic drugs and serotonin reuptake inhibitors. Because of an increasing loss of consciousness she was rapidly transferred to an Intensive Care Unit. Following this, she became progressively febrile associated with rhabdomyolysis and life-threatening organ dysfunctions. Due to fast diagnosis and immediate therapy the patient was treated successfully. This article describes etiology, pathophysiology and symptoms of neuroleptic malignant syndrome. In addition therapeutic options are discussed.

Topics: Adult; Antidepressive Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Coma; Creatine Kinase; Critical Care; Dantrolene; Female; Humans; Muscle Relaxants, Central; Myoglobin; Neuroleptic Malignant Syndrome; Olanzapine; Sertraline; Treatment Outcome

Topics: Adult; Antiphospholipid Syndrome; Antipsychotic Agents; Benzodiazepines; Coma; Drug Overdose; Epilepsy, Complex Partial; Humans; Male; Olanzapine; Pulmonary Embolism; Schizophrenia, Paranoid; Thrombophilia; Venous Thrombosis

Olanzapine is an atypical antipsychotic drug that is increasingly used in intentional drug overdoses. Although acute olanzapine overdose is predominantly associated with anticholinergic symptoms and central nervous system depression, miosis and unpredictable fluctuations between somnolence/coma and agitation/ aggression have been suggested as typical signs of olanzapine intoxication in single case reports.. To confirm the suggestion that fluctuating central nervous system changes and miosis are characteristic signs of olanzapine intoxication. To estimate the dose-response relationship as a guide for the provision of optimal management of olanzapine intoxicated patients.. Retrospective analysis of all well-documented cases of olanzapine intoxication reported to the Swiss Toxicological Information Centre between January 1997 and October 2001. Inclusion criteria for detailed analysis were patient age > or = 16 yr, acute olanzapine monointoxication, ingested dose > 20 mg, and a causal relationship between olanzapine overdose and clinical effects. The Poisoning Severity Score of the European Association of Poison Centres and Clinical Toxicologists (EAPCCT) assessed the intoxication severity.. Out of a total of 131 cases of olanzapine overdose, 26 cases fulfilled the inclusion criteria. The ingested olanzapine doses ranged from 30 to 840 mg. The most frequent findings were somnolence (77%), agitation (42%), and miosis (31%). The Poisoning Severity Score was "minor" in 14 (54%), "moderate" in 11 (42%), and "severe" in 1 (4%) patients. Nine patients (35% of all patients) with moderate olanzapine poisoning (120-840 mg) showed unpredictable fluctuations between somnolence and agitation. Five of these patients also demonstrated marked miosis. All patients recovered within 48h. One patient with severe poisoning (560 mg) had coma and convulsions. Moderate (and severe) symptoms occurred only at ingested doses above 120 mg. There was a statistically significant association between increasing ingested olanzapine doses and poisoning severity.. Although olanzapine is tolerated relatively well in acute overdose, unpredictable and transient fluctuations between central nervous system depression and agitation, frequently associated with miosis, appear to be characteristic findings in moderate to high olanzapine overdoses. They are transient in nature and require careful clinical monitoring but rarely require specific therapeutic interventions.

Topics: Activity Cycles; Adolescent; Adult; Aggression; Antipsychotic Agents; Benzodiazepines; Coma; Disorders of Excessive Somnolence; Drug Overdose; Female; Humans; Male; Middle Aged; Nervous System Diseases; Olanzapine; Psychomotor Agitation; Retrospective Studies; Severity of Illness Index

Topics: Aged; Aged, 80 and over; Benzodiazepines; Coma; Female; Humans; Hypoglycemia; Olanzapine; Pirenzepine; Psychomotor Agitation; Selective Serotonin Reuptake Inhibitors

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Coma; Drug Overdose; Female; Humans; Naloxone; Narcotic Antagonists; Olanzapine; Pirenzepine