olanzapine and Drug-Overdose

An advance in the treatment of schizophrenia is the development of long-acting intramuscular formulations of antipsychotics, such as olanzapine long-acting injection (LAI). During clinical trials, a post-injection syndrome characterized by signs of delirium and/or excessive sedation was identified in a small percentage of patients following injection with olanzapine LAI.. Safety data from all completed and ongoing trials of olanzapine LAI were reviewed for possible cases of this post-injection syndrome. Descriptive analyses were conducted to characterize incidence, clinical presentation, and outcome. Regression analyses were conducted to assess possible risk factors.. Based on approximately 45,000 olanzapine LAI injections given to 2054 patients in clinical trials through 14 October 2008, post-injection delirium/sedation syndrome occurred in approximately 0.07% of injections or 1.4% of patients (30 cases in 29 patients). Symptomatology was consistent with olanzapine overdose (e.g., sedation, confusion, slurred speech, altered gait, or unconsciousness). However, no clinically significant decreases in vital signs were observed. Symptom onset ranged from immediate to 3 to 5 hours post injection, with a median onset time of 25 minutes post injection. All patients recovered within 1.5 to 72 hours, and the majority continued to receive further olanzapine LAI injections following the event. No clear risk factors were identified.. Post-injection delirium/sedation syndrome can be readily identified based on symptom presentation, progression, and temporal relationship to the injection, and is consistent with olanzapine overdose following probable accidental intravascular injection of a portion of the olanzapine LAI dose. Although there is no specific antidote for olanzapine overdose, patients can be treated symptomatically as needed. Special precautions include use of proper injection technique and a post-injection observation period.. ClinicalTrials.gov ID; URL: http://http//www.clinicaltrials.gov/: NCT00094640, NCT00088478, NCT00088491, NCT00088465, and NCT00320489.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Cognition Disorders; Delayed-Action Preparations; Delirium; Drug Administration Schedule; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Humans; Incidence; Injections, Intramuscular; Olanzapine; Risk Factors; Schizophrenia; Sleep; Syndrome; Treatment Outcome

As the use of atypical antipsychotic medications (AAPMs) increases, the number of overdoses continues to grow. Cardiovascular toxicity was common with older psychiatric medications but seems uncommon with AAPM. We conducted a systematic literature review to describe the cardiovascular effects reported after overdose of 5 common AAPM: aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone. We included case reports and case series describing overdose of these 5 medications identified in a search of MEDLINE, EMBASE, and abstracts from major toxicology meetings. We found 13 pediatric cases (age, <7 years), 22 adolescent cases (age, 7-16 years), and 185 adult cases. No pediatric case described a ventricular dysrhythmia or a cardiovascular death. In the adolescent and adult cases, we found numerous reports of prolonged corrected QT interval and hypotension, but there were only 3 cases of ventricular dysrhythmia and 3 deaths that may have been due to direct cardiovascular toxicity. The results from case series reports were similar to the single case report data. Our review suggests that overdose of AAPM is unlikely to cause significant cardiovascular toxicity.

Topics: Antipsychotic Agents; Aripiprazole; Benzodiazepines; Cardiovascular System; Dibenzothiazepines; Drug Overdose; Humans; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles

Atypical antipsychotic medications (second-generation antipsychotics) have been increasingly used in the treatment of a number of psychotic disorders since their introduction in 1988, with the newest medication introduced in 2002. Justification for their use includes claims of equal or improved antipsychotic activity over first-generation antipsychotics, increased tolerability, and decreased side effects. However, there are still significant adverse effects and toxicities with this class of medications. Toxicologic exposures and fatalities associated with atypical antipsychotics continue to increase in the United States, with 32,422 exposures and 72 deaths in 2003. There have also been Food and Drug Administration warnings in the past year about how some atypical antipsychotics have been marketed to minimize the potentially fatal risks and claiming superior safety to other atypical antipsychotics without adequate substantiation, indicating the toxicologic potential of these agents may be underestimated.. Continued research to evaluate adverse effects and tolerability of atypical antipsychotics compared with first-generation antipsychotics and each other is reviewed. This article also reviews the pharmacodynamics, pharmacokinetics, and drug interactions with these medications. New therapeutic monitoring recommendations for this class of medications have also been proposed. Finally, clinical toxicity in overdose and management are reviewed.. While new atypical antipsychotic medications may have a safer therapeutic and overdose profile than first-generation antipsychotic medications, many adverse and toxic effects still need to be considered in therapeutic monitoring and overdose management.

Topics: Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Cardiomyopathies; Child; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Drug Interactions; Drug Overdose; Dry Eye Syndromes; Humans; Hyperlipidemias; Hypotension; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Seizures; Thiazoles

Although the atypical antipsychotic olanzapine is increasingly being used in child and adolescent psychiatry, reports of olanzapine overdose in this young population are scarce. We report on two cases of adolescents who attempted suicide with an overdose of olanzapine: (1) A 14-year-old female ingested 275 mg olanzapine, which produced the highest reported nonlethal serum level (1503 ng/mL) and caused somnolence, agitation (acutely), and extrapyramidal symptoms (EPS; after 54 hours) but no major clinical complications. The serum olanzapine level dropped to 129 ng/mL within 48 hours; and (2) a 17-year-old male ingested 400 mg olanzapine, the highest reported nonlethal dose of olanzapine in adolescents, which produced respiratory suppression requiring intubation and mechanical ventilation; he recovered after 3 days. Based on clinical monitoring and postmortem data, the 2 patients survived the ingestion of high doses of olanzapine. We also provide a review of the literature, encompassing all reported cases of olanzapine overdose in children and adolescents and discuss symptoms, diagnosis, and treatment options, based on pharmacokinetic and pharmacodynamic considerations.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Dose-Response Relationship, Drug; Drug Overdose; Female; Follow-Up Studies; Humans; Male; Metabolic Clearance Rate; Olanzapine; Respiratory Insufficiency; Suicide, Attempted

Given the increasing use of atypical antipsychotics in psychiatric populations and the very limited data concerning the safety of such drugs, we examined the available data on olanzapine in untreated overdose situations.. Available toxicity data concerning olanzapine were obtained from the Offices of the Medical Examiners of Canada, the Canadian Adverse Drug Reaction Monitoring Program and a review of the literature.. Despite the complexities and limitations of postmortem data analysis, 29 deaths were identified where an overdose of olanzapine was either the principal cause of toxicity or a significant contributor in combined toxicity.. Olanzapine is associated with toxicity in certain overdose situations, but evidence of any relation is limited and likely influenced by the higher rates of cardiovascular disease and sudden death in subjects with schizophrenia.. Similar toxicity data reviews should be conducted for all commonly prescribed psychotropics. Early signal detection and effective notification processes are crucial in the event that serious adverse effects do occur.

Topics: Antipsychotic Agents; Benzodiazepines; Drug Overdose; Humans; Mental Disorders; Olanzapine; Pirenzepine; Risk Factors

Olanzapine is an atypical antipsychotic medication that was approved for use in the United States in 1996. While it is a widely used medication in adults, there has been minimal investigation into its effect on children. We present the case of an 18-month-old boy who ingested 30-40 mg of olanzapine, which resulted in significant symptoms, including respiratory distress and mental status changes. Previously reported pediatric cases of olanzapine ingestion have described similar symptoms. Therefore, the pediatric population should be monitored closely when ingestions of olanzapine occur.

Topics: Antipsychotic Agents; Benzodiazepines; Child, Preschool; Drug Overdose; Humans; Male; Olanzapine; Pirenzepine

We aimed to investigate the frequency of serotonin toxicity following overdose of antidepressants that inhibit serotonin reuptake and the factors that influence the probability of serotonin toxicity occurring.. This was a retrospective cohort study of overdoses that included selective serotonin reuptake inhibitors (SSRIs) (70%) and serotonin norepinephrine reuptake inhibitors (SNRIs) (30%) admitted to a tertiary toxicology unit over 23 years. A multivariate mixed effects logistic regression model using NONMEM (7.2.0) was used to determine factors that influenced the probability of serotonin toxicity occurring.. There were 1978 overdoses in 1520 patients; median age 33 y (range: 13-86 years) and 64% female. Median defined daily dose equivalent (DDD) was 15 (1-420). Co-ingestants were taken in 1678/1978 (85%) overdoses: 11 co-ingested the monoamine oxidase-A inhibitor (MAOI) moclobemide, 99 (5%) co-ingested olanzapine, 58 (3%) co-ingested risperidone and 417 co-ingested a benzodiazepine (21%). Serotonin toxicity occurred in 269 overdoses (13.6%). The probability of serotonin toxicity increased slightly per 10 DDD units dose [OR, 1.01; 95% confidence intervals (CIs): 0.93-1.10], increased for an SNRI. Serotonin toxicity is common following SSRI/SNRI overdose. Although dose increases probability, this was only a small effect. Co-ingestion with olanzapine or risperidone reduced the risk 2-6-fold, and moclobemide increased the risk 5-fold.

Topics: Adult; Drug Overdose; Female; Humans; Male; Moclobemide; Olanzapine; Retrospective Studies; Risperidone; Selective Serotonin Reuptake Inhibitors; Serotonin; Serotonin and Noradrenaline Reuptake Inhibitors

BACKGROUND Serotonin syndrome is a condition characterized predominantly by neuromuscular symptoms and altered thermoregulation in response to serotonergic overtone. Treatment is focused on withdrawal of serotonergic agents, which leads to resolution in the majority of cases. In the setting of serotonergic overdose, the onset of serotonin syndrome is usually within 4 to 13 h. Here, we report a case of delayed-onset serotonin syndrome in a patient who ingested a mixture of longer-acting serotonin agonists with serotonin antagonists. CASE REPORT A 24-year-old male was transferred to our medical intensive care unit with hypotension and altered mental status after an overdose of fluoxetine, cyproheptadine, trazodone, olanzapine, risperidone, and bupropion. After approximately 72 h, the patient developed symptoms of fever, lower leg clonus, hyperreflexia, and agitation. He was diagnosed with delayed-onset serotonin syndrome, which responded well to re-administration of cyproheptadine, leading to resolution of symptoms by day 5 of his stay. CONCLUSIONS In this present case, our patient presented with the longest reported delay in the onset of serotonin syndrome after intentional ingestion. This was likely secondary to co-ingestion of long-acting serotonin agonists with protective shorter-acting serotonin antagonists (cyproheptadine and olanzapine). Clinicians should consider delayed-onset serotonin syndrome when patients ingest longer-acting serotonergic agents with serotonin antagonists.

Topics: Benzodiazepines; Bupropion; Cyproheptadine; Dopamine Uptake Inhibitors; Drug Overdose; Fluoxetine; Humans; Male; Olanzapine; Risperidone; Selective Serotonin Reuptake Inhibitors; Serotonin Agents; Serotonin Antagonists; Serotonin Receptor Agonists; Serotonin Syndrome; Time Factors; Trazodone; Young Adult

Olanzapine is an antipsychotic drug used in psychiatric diseases. At high doses it exhibits cardiovascular and neurological sideeffects in particular. Lipid emulsion therapy for the removal of medication from plasma in high-dose lipophilic drug use has recently become very widespread. In the light of current literature, this report discusses the successful treatment of a patient within 4 hrs of olanzapine overdose as an attempted suicide, who presented with agitation and clouded consciousness.

Topics: Antipsychotic Agents; Benzodiazepines; Drug Overdose; Fat Emulsions, Intravenous; Humans; Olanzapine; Suicide, Attempted

We report a case of delirium with anticholinergic symptoms in a 19-year-old female patient with schizophrenia. On the day the symptoms emerged, the patient received olanzapine long-acting injection and a higher dose of paliperidone. We observed symptoms ranging from confusion to delirium as well as some anticholinergic symptoms. The delirium lasted 24 hours and was managed by intravenous fluid substitution and oral benzodiazepines. Olanzapine pamoate, paliperidone and cannabis are central nervous system (CNS) depressants, and their combination can increase the risks of CNS depression. In this case report, we review the symptoms of delirium in a case of antipsychotic overdose and provide general guidelines for managing these symptoms. We also review possible complications in combined use of cannabis, olanzapine and paliperidone.

Topics: Antipsychotic Agents; Benzodiazepines; Cannabis; Central Nervous System; Cholinergic Antagonists; Delirium; Drug Overdose; Female; Humans; Olanzapine; Paliperidone Palmitate; Schizophrenia; Treatment Outcome; Young Adult

Olanzapine is widely used in the treatment of schizophrenia and it is becoming more frequently responsible for overdoses. Standard pharmacokinetic models do not fit to the toxic concentration data.. The aim of present study is to investigate the reasons for an abnormal olanzapine plasma concentration time curve in the range of toxic concentrations. Two hypotheses were verified: entering the enterohepatic cycle, and drug deposition and its desorption from activated charcoal used for gastrointestinal decontamination.. One-hundred thirty-five plasma concentration data from 21 patients hospitalized for acute olanzapine poisoning were analyzed with the use of the population pharmacokinetic approach. A non-linear mixed-effects modeling approach with Monolix 4.3.1 was employed.. A model assuming gallbladder emptying at irregular intervals was developed. Also, a model that describes desorption of olanzapine from the charcoal surface, in which the dose is divided into two absorbed fractions, was constructed. The analysis has found gastrointestinal decontamination and previous olanzapine treatment, as the significant covariates for toxicokinetic parameters of olanzapine.. Our study provides interesting models for investigation of toxic concentration of olanzapine, which may also be used as the basis for further model development for other drugs as well. The investigated population was not large enough to reliably confirm any of the proposed models. It would be well worth continuing this study with more substantial data. Also, any additional information about olanzapine metabolite concentration could be vital.

Topics: Absorption, Physicochemical; Adolescent; Adult; Aged; Antipsychotic Agents; Benzodiazepines; Charcoal; Drug Overdose; Enterohepatic Circulation; Female; Hospitalization; Humans; Male; Middle Aged; Models, Biological; Nonlinear Dynamics; Olanzapine; Stochastic Processes; Toxicokinetics; Young Adult

Topics: Benzodiazepines; Charcoal; Combined Modality Therapy; Depressive Disorder; Drug Overdose; Female; Flumazenil; Hemoperfusion; Humans; Hyperammonemia; Middle Aged; Naloxone; Olanzapine; Paranoid Disorders; Psychotropic Drugs; Respiration, Artificial; Suicide, Attempted; Valproic Acid

In 2012, Danish psychiatrist raised concerns regarding the use of high-dose olanzapine in the treatment of patients. The present study was part of an audit carried out by the Mental Health Services of the Capitol Region of Denmark regarding this topic. Objective. To assess the potential risks associated with high-dose olanzapine treatment (> 40 mg daily) in inpatient psychiatric units.. The study was an observational case series based on review of patient charts. The main inclusion criterion was treatment with at least one daily dose > 40 mg olanzapine during the index admission in the period between 1st of January and 15th of March 2012. Six additional criteria were applied in order to target the subgroup of patients most likely to have experienced an adverse event due to treatment with olanzapine. The physician order entry system and the central patient register containing patient specific information about diagnoses and treatments were used for identification of study population.. The 91 patients included in the study received maximum daily doses of olanzapine ranging from 45 to 160 mg and in 25% of patients, the total antipsychotic load exceeded 2000 mg of chlorpromazine equivalents. Extrapyramidal symptoms and sedation were the most frequent adverse events with frequencies of 27% and 25%, respectively. Furthermore, other well-known adverse events such as weight gain (14%), hypotension (2%), neuroleptic malignant syndrome (2%) and corrected QT-interval (QTc) prolongation (1%) were also observed in some patients. Five patients died and in two of these cases, olanzapine was concluded to be a possible contributing cause of death.. Increased frequency of extrapyramidal symptoms and sedation as well as severe toxicity was observed in patients treated with up to 160 mg olanzapine per day. In order to prevent harmful outcomes, the clinicians should be ready to act appropriately if toxic effects of olanzapine occur. Treatment cessation should be immediate if serious adverse events such as neuroleptic malignant syndrome arise.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Central Nervous System; Denmark; Depression, Chemical; Drug Overdose; Electrocardiography; Female; Hospitals, Psychiatric; Humans; Inpatients; Long QT Syndrome; Male; Neuroleptic Malignant Syndrome; Olanzapine; Psychotic Disorders; Retrospective Studies; Risk Assessment

The PDSS is a potential side-effect of the intramuscular injection of olanzapine pamoate. We saw the typical symptoms develop in a 46-year-old man 4 hours after the injection. The syndrome is caused by a toxic concentration of olanzapine, and is possibly the result of the direct injection of the substance in the bloodstream. The most important measures that can be taken to prevent such an emergency are: a careful injection procedure, a 3-hour observation period following the injection and good counselling of the patient and his family. The treatment is conservative.

Topics: Antipsychotic Agents; Benzodiazepines; Delayed-Action Preparations; Delirium; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Humans; Injections, Intramuscular; Male; Middle Aged; Olanzapine; Schizophrenia; Syndrome; Treatment Outcome

Physostigmine effectively reverses anticholinergic delirium. However, continuous IV infusion of physostigmine is rarely used due to concern for cardiotoxicity and signs of cholinergic excess such as seizures, nausea, and vomiting. We report the successful use of continuous IV physostigmine in a 6-year-old boy with anticholinergic delirium. A 6-year-old, 30-kg boy with attention deficit hyperactivity disorder (ADHD) ingested 15-20 olanzapine (5 mg) tablets. He was agitated and was treated with lorazepam at a local hospital. His heart rate was 148 beats per min; respiratory rate, 32 breaths per minute; blood pressure, 111/70 mmHg; temperature, 96.8°F, and O2 saturation of 98% on room air. His pupils were 5-6 mm, and his skin was warm and initially flushed. Blood chemistry results were normal. A 12-lead ECG showed sinus tachycardia with normal QRS and QT intervals. The agitation worsened and did not respond to benzodiazepines. The patient was then given a dose of 0.6 mg physostigmine (0.02 mg/kg) intravenously with reversal of the agitation. But the effect only lasted 45 min requiring administration of a second bolus of 0.6 mg (0.02 mg/kg). A physostigmine intravenous infusion was administered at a rate of 0.5 mg/h (0.0167 mg/kg/h). Overnight, the patient became more agitated. The physostigmine was discontinued, and IV dexmedetomidine (0.2 μg/kg/h) was started at 21:00. The patient became over-sedated with pinpoint pupils resulting in discontinuation of the dexmedetomidine at 04:00. The patient again became agitated and developed visual hallucinations. Three 1-mg (0.03 mg/kg) boluses of physostigmine were administered over 45 min, and the physostigmine infusion was restarted at a rate of 1 mg/h (0.03 mg/kg/h) for 16.5 h. He received 19.5 mg of physostigmine with no return of anticholinergic symptoms and no signs of cholinergic excess except for a tremor that resolved when the infusion was stopped. He was discharged home without further sequelae. There are few publications describing a continuous infusion of physostigmine to reverse anticholinergic delirium. Our patient received a total dose of 25.5 mg with complete resolution of symptoms. We report the successful use of continuous infusion of physostigmine to reverse anticholinergic delirium in a pediatric patient who unintentionally ingested olanzapine.

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Child; Cholinesterase Inhibitors; Delirium; Drug Overdose; Heart Rate; Humans; Infusions, Intravenous; Male; Olanzapine; Physostigmine

This is a case of a citalopram and olanzapine overdose causing seizures and severe cardiotoxicity.. A 21-year-old man presented unresponsive, with seizures, to an Emergency Department. The patient's initial electrocardiogram demonstrated a widened QRS of 160 ms and a normal QT/QTc interval of 400/487 ms consistent with cardiac sodium channel blockade. Within 30 min of arrival, peak citalopram and olanzapine levels were measured to be 522 ng/mL and 505 ng/mL, respectively. Measured levels remained supratherapeutic until 13.6 h and 42.6 h after arrival for citalopram and olanzapine, respectively. The patient developed bradycardia and hypotension that required multimodal therapies including sodium bicarbonate boluses, vasopressors, and transvenous pacing. Seizures and cardiotoxicity continued while citalopram, but not olanzapine, was supratherapeutic.. This case describes cardiotoxicity directly correlated with supratherapeutic citalopram levels in overdose.

Topics: Adult; Benzodiazepines; Bradycardia; Citalopram; Drug Overdose; Electrocardiography; Humans; Hypotension; Male; Olanzapine; Seizures; Selective Serotonin Reuptake Inhibitors; Young Adult

We describe a 17-month-old female presented with an acute overdose of olanzapine, an atypical antipsychotic. She displayed prolonged extrapyramidal symptoms as compared with that in previous reports and prolactin levels above the upper limits of normal ranges. This is the first report to measure serum prolactin levels in an olanzapine-overdosed toddler and the second to calculate olanzapine's elimination half-life.

Topics: Antipsychotic Agents; Benzodiazepines; Drug Overdose; Female; Half-Life; Humans; Infant; Olanzapine; Prolactin

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Drug Overdose; Female; Humans; Olanzapine; Tablets, Enteric-Coated; Valproic Acid

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Consciousness; Drug Overdose; Fat Emulsions, Intravenous; Female; Glasgow Coma Scale; Humans; Olanzapine

The atypical antipsychotic olanzapine is increasingly being used for various psychiatric conditions. There are few reports of olanzapine overdose in adolescent population. We report a case of 16-year-old adolescent who ingested 750 mg olanzapine, the highest reported nonlethal dose of olanzapine in adolescents. He presented with tachycardia, hypotension, generalized myoclonus, hyperpyrexia, muscular rigidity, leukocytosis and elevated creatine phosphokinase (CPK) levels. He recovered from the toxicity with minimal intervention.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Drug Overdose; Humans; Male; Olanzapine; Suicide, Attempted

Topics: Adult; Antipsychotic Agents; Atrial Fibrillation; Benzodiazepines; Drug Overdose; Female; Humans; Olanzapine

Olanzapine is a second-generation atypical antipsychotic agent approved for the treatment of psychotic disorders and mania. The effects of olanzapine intoxication include central nervous system depression, hyperthermia, myosis, tachycardia, and orthostatic hypotension. Heretofore, only one case has been reported to develop polyuria after olanzapine overdose (560 mg). We describe a case that developed diabetes insipidus following massive olanzapine ingestion and returned to normal after desmopressin treatment.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Diabetes Insipidus; Drug Overdose; Humans; Male; Olanzapine; Time Factors

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

Olanzapine long-acting injection (LAI) is a salt-based depot antipsychotic combining olanzapine and pamoic acid. The slow intramuscular dissolution of this practically insoluble salt produces an extended release of olanzapine lasting up to 4 weeks. However, in a small number of injections (< 0.1%), patients experienced symptoms suggestive of olanzapine overdose, a phenomenon that has been termed "post-injection delirium/sedation syndrome" (PDSS). The authors conducted a series of parallel investigations into the possible reasons PDSS events occur.. Healthcare providers involved in the PDSS cases were queried for clinical information around the events. Plasma samples from patients experiencing PDSS were collected when possible (12/30 cases) and olanzapine concentrations compared with the known pharmacokinetic profile for olanzapine LAI. Product batches and used vials from the PDSS cases were evaluated for compliance with established manufacturing standards and/or possible user error. Because this depot formulation depends upon slow dissolution at the intramuscular injection site, in-vitro experiments were conducted to assess solubility of olanzapine pamoate in various media.. Injection administrators reported no unusual occurrences during the injection. No anomalies were found with the product batches or the remaining suspension in the used vials. Olanzapine concentrations during PDSS events were higher than the expected 5-73 ng/mL range, with concentrations exceeding 100 ng/mL and in some cases reaching >600 ng/mL during the first hours after injection but then returning to the expected therapeutic range within 24 to 72 hours. Solubility and dissolution rate of olanzapine pamoate were also found to be substantially greater in plasma than in other media such as those approximating the environment in muscle tissue.. Manufacturing irregularities, improper drug reconstitution, and inappropriate dosing were ruled out as possible causes of PDSS. In-vitro solubility and in-vivo pharmacokinetic investigations suggest that PDSS is related to exposure of the injected product to a substantial volume of blood. This exposure is most likely the result of unintended partial intravascular injection or blood vessel injury during the injection (occurring even with proper injection technique) with subsequent seepage of the medication into the vasculature, which would produce higher than intended olanzapine concentrations and symptoms consistent with PDSS.. ClinicalTrials.gov ID; URL: http://http//www.clinicaltrials.gov/: NCT00094640, NCT00088478, NCT00088491, NCT00088465, and NCT00320489.

Topics: Antipsychotic Agents; Benzodiazepines; Clinical Trials as Topic; Delayed-Action Preparations; Drug Overdose; Drug-Related Side Effects and Adverse Reactions; Humans; Injections, Intramuscular; Olanzapine; Schizophrenia; Syndrome; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Drug Overdose; Humans; Injections; Olanzapine; Schizophrenia

This case report describes the history and hospital course of an otherwise healthy 20-year-old male with bipolar I disorder who developed symptoms of severe lithium toxicity, culminating in a seizure, despite a level of lithium of only 0.8 mEq/L, within the usual therapeutic range. The discussion emphasizes that lithium toxicity is diagnosed by clinical symptoms and can occur even at usual therapeutic blood levels.

Topics: Antimanic Agents; Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Drug Overdose; Humans; Lithium Carbonate; Male; Olanzapine; Seizures; Suicide, Attempted; Young Adult

Neuroleptic malignant syndrome (NMS) is a relatively uncommon side effect that may develop after a recent increase in the therapeutic dose of an antipsychotic medication or the addition of a new agent in therapeutic doses.. We report a case of NMS developing in a 36-year-old female patient 2 days following deliberate self-poisoning with 30 x 10-mg olanzapine tablets, 7 x 100-mg chlorpromazine tablets and an unknown amount of escitalopram. These were the patient's own medications. She had not been taking these for several weeks. The patient initially presented with sedation from her overdose which resolved over the next 24 hours. Following this, over the subsequent 24 hours, she became progressively confused, ataxic, hypertonic, ferbrile and tachycardic, with marked lead pipe rigidity of the limbs. Head CT, lumbar puncture and septic screen were all negative. She was treated with intravenous midazolam infusion, nasogastrically administered bromocriptine, external cooling and was mechanically ventilated. She gradually improved over a period of 10 days, with residual confusion lasting another week, and was discharged well with no deterioration from her premorbid neurologic state.. To our knowledge, although there are numerous cases reported with therapeutic use, NMS has not been reported to develop following acute olanzapine overdose. Clinicians should be aware that this may be an uncommon side effect of antipsychotic medication.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Bromocriptine; Chlorpromazine; Citalopram; Combined Modality Therapy; Dopamine Agonists; Drug Overdose; Female; Humans; Hypnotics and Sedatives; Hypothermia, Induced; Infusions, Intravenous; Midazolam; Neuroleptic Malignant Syndrome; Olanzapine; Respiration, Artificial; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Bromocriptine; Chlorpromazine; Disease Progression; Dopamine Agonists; Drug Overdose; Humans; Neuroleptic Malignant Syndrome; Olanzapine; Serotonin Receptor Agonists; Treatment Outcome

Olanzapine is a second-generation atypical antipsychotic that is increasingly used in preference to older antipsychotic agents. Limited data is available concerning the toxic effects of olanzapine after deliberate overdose. Two patients presented to our institution after massive olanzapine ingestion, and required prolonged ventilatory support due to the development of coma and respiratory depression. Serum olanzapine concentrations were orders of magnitude higher than those associated with therapeutic doses, and remained elevated for several days after ingestion. Both patients made a full recovery with only supportive care, despite having initial serum drug concentrations > 2500 microg/l. These reports indicate the potential for olanzapine ingestion to cause coma that may persist for several days after overdose.

Topics: Antipsychotic Agents; Benzodiazepines; Drug Overdose; Female; Humans; Middle Aged; Olanzapine

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Depressive Disorder, Major; Drug Overdose; Female; Humans; Olanzapine; Risk Factors; Suicide, Attempted

To describe the spectrum of clinical effects in olanzapine overdose and investigate the factors that predict severe outcomes. We analysed olanzapine-overdose events confirmed by drug analysis. Demographic, clinical and outcome data were recorded for each presentation. The relationship between dose and therapeutic olanzapine use, and outcomes (length of hospital stay, intensive care unit admission, mechanical ventilation, Glasgow coma score <9 and delirium) were investigated. Thirty-seven olanzapine overdose admissions were included. Median age was 30 years (interquartile range: 24-40 years), 24 women and 27 taking olanzapine therapeutically. Median ingested dose was 150 mg (range: 10-1600 mg). Olanzapine overdose was characterized by tachycardia (73%), central nervous system depression (43%), miosis (39%) and delirium (54%), which were either present on admission or developed within 6 h. There was no relationship between the dose and length of hospital stay, intensive care unit admission, Glasgow coma score <9 or delirium, but there was a trend towards more severe outcomes in patients not taking olanzapine therapeutically. Patients with delirium had an increased length of hospital stay and intensive care unit admission rate (50%) and 70% of them required physical or chemical restraint. Olanzapine overdose causes a high rate of delirium and central nervous system sedation that requires significant inpatient resources. Olanzapine overdoses should be initially observed for 6 h and patients not taking olanzapine regularly may have more severe effects.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Brain; Central Nervous System Depressants; Critical Care; Delirium; Dose-Response Relationship, Drug; Drug Overdose; Female; Glasgow Coma Scale; Humans; Length of Stay; Male; Middle Aged; Miosis; Olanzapine

Olanzapine is a second-generation atypical antipsychotic agent approved for the treatment of psychotic disorders and mania. While olanzapine overdoses are common, cases with whole blood concentrations are less so. We describe here a well-documented case of a pure olanzapine overdose in which whole blood concentrations were determined, and compared with other concentrations in the literature.. A 58-year-old woman with a 10-year history of paranoid schizophrenia and poor therapeutic compliance was found unconscious with two empty 28-tablet vials of Zyprexa (olanzapine) 10 mg tablets. Her initial vital signs were blood pressure 110/70 mmHg, pulse rate 82 beats/minute (sinus rhythm), respirations 20 breaths/minute, and the Glasgow Coma Scale score was 7. In the Intensive Care Unit, her pulse rate was 160 beats/minute, in sinus rhythm, and QTc 0.423 seconds (normal <0.4 seconds). Relevant analytical findings were metabolic acidosis, leukocytosis, creatine phosphokinase 1992 mg/dL, and glucose 207 mg/dL. Ten hours after being found, her blood sugar was 350 mg/dL and became normal at 25 hours. The patient needed intubation and insulin.. Olanzapine was detected and quantitated by gas chromatography with nitrogen-phosphorus detector and confirmed by gas chromatography-mass spectrometry using a validated analytical method. At approximately 4, 8, and 12 hours post-ingestion, whole blood concentrations of olanzapine were 0.41, 0.34, and 0.38 mg/L, respectively.. This study reports an acute olanzapine monointoxication with severe toxicity and high whole blood olanzapine concentrations. Clinical and analytical data of similar samples obtained in non-fatal life-threatening cases can be very useful when interpreting postmortem cases.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Antipsychotic Agents; Benzodiazepines; Blood Pressure; Drug Overdose; Female; Glasgow Coma Scale; Humans; Hypoglycemic Agents; Insulin; Middle Aged; Olanzapine; Respiration, Artificial; Suicide, Attempted

Olanzapine is a widely used second generation antipsychotic drug. Case reports of intoxications have been published, but reports in the literature of non-fatal intoxications of olanzapine containing repeated measurements of serum levels are scarce. Therefore, this case of non-fatal olanzapine intoxication is presented, in which 19 blood samples were drawn during 2 weeks. The highest (initial) measured value was estimated at 800 pg/L. This patient ingested 550 mg of olanzapine resulting in clinical signs of intoxication, including seizures. Because the patient was found the day after the intoxication, the initial concentration had probably been higher. The pharmacokinetics of olanzapine has been described as linear and dose-proportional throughout the therapeutic dosing range. Large overdoses, however, have been described to show non-linear pharmacokinetics. In this study's series of serum concentrations, a two-phase elimination was seen, with an initial elimination half-life of about 24 h during the first 3 days, followed by a second phase with a half-life of about 2.5 days. The patient in this case recovered completely. Because the elimination time after intoxication can be considerably longer than expected, it is recommended that the patient's serum concentrations after intoxication be monitored.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chemical and Drug Induced Liver Injury; Chromatography, High Pressure Liquid; Drug Overdose; Half-Life; Humans; Liver Diseases; Liver Function Tests; Male; Olanzapine; Seizures; Suicide, Attempted

Olanzapine, an atypical antipsychotic of the thienobenzodiazepine class, has been on the market since 1996. Its popularity has increased over recent years because of excellent clinical results as well as a favourable side effect profile. Mirroring this increased olanzapine use has been a rise in the number of non-accidental overdoses. The clinical picture of olanzapine overdose can be surprisingly variable. In the case presented, the patient's low Glasgow Coma Score prevented an accurate history being taken. Examination revealed bilateral upgoing plantars, pinpoint pupils, increased tone, and brisk reflexes; however initial investigations, including an urgent CT head, were normal. The patient required 24 hours of intensive care before he regained consciousness and admitted to the overdose. Although there are several reports of olanzapine mimicking opiate intoxication in overdose, this is one of the first cases where overdose has mimicked an intracerebral event. The authors highlight some of the literature regarding clinical presentation and treatment options, and discuss the relation between olanzapine therapy and diabetes.

Topics: Antipsychotic Agents; Benzodiazepines; Cerebral Hemorrhage; Diagnosis, Differential; Drug Overdose; Humans; Male; Middle Aged; Olanzapine; Pons

Topics: Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Bupropion; Chemistry, Pharmaceutical; Drug Overdose; Drug Stability; Embalming; Forensic Medicine; Formaldehyde; Humans; Indicators and Reagents; Olanzapine; Quality Control; Reference Standards; Reproducibility of Results; Solutions; Suicide

The patient with acute extrapyramidal signs and symptoms presents a significant clinical challenge. We present the case of a young man who developed an acute akathisia and dystonia after inadvertent overdose of olanzapine (Zyprexa) in the setting of a recent discontinuation of fluoxetine. The receptor chemistry and mechanisms pertinent to his presentation are reviewed. An analysis of the literature indicates that a broad incidence range is cited for the extrapyramidal effects of these medications. We suggest a diagnostic and therapeutic approach to the undifferentiated patient presenting with extrapyramidal signs and symptoms. The possibility of neuroleptic malignant syndrome (NMS), serotonin syndrome (SS), tricyclic overdose, and cocaine abuse should be considered in a patient with extrapyramidal signs and symptoms, given the potential for complications. An emphasis is placed on the need for carefully verbalized discharge instructions to avoid a potential untoward outcome.

Topics: Accidents; Acute Disease; Adult; Akathisia, Drug-Induced; Benzodiazepines; Drug Overdose; Dystonia; Emergency Service, Hospital; Fluoxetine; Humans; Male; Olanzapine; Selective Serotonin Reuptake Inhibitors

Olanzapine is commonly prescribed to patients with schizophrenia. One retrospective study demonstrates the efficacy of physostigmine in reversing mental status changes induced by olanzapine. We report two patients with delirium due to confirmed olanzapine overdose treated with physostigmine. One patient's mental status transiently returned to normal. The other patient completely recovered. CASE 1: A 25-year-old man ingested 300 mg of olanzapine. On presentation, he was agitated, delirious, tachycardic, had dry skin and mucous membranes, and dilated pupils (6 mm) minimally reactive to light. Physostigmine, 0.5 mg, was given intravenously (IV) without effect. Additional physostigmine doses of 1.5 mg IV administered 5 minutes later and then 1 mg IV resulted in the patient having a clear sensorium and normal mentation. The patient's mental status continued to remain normal for the duration of his hospital stay. Olanzapine was identified in the urine by high performance liquid chromatography. CASE 2: A 20-year-old female ingested 600 mg of olanzapine. On presentation, she was tachycardic, obtunded, and minimally responsive to painful stimuli, with decreased bowel sounds, dry skin and dry mucous membranes. Physostigmine, 2 mg, was given IV. Shortly thereafter she regained full consciousness and began speaking coherently. She remained in this condition for approximately 30 minutes, and then became obtunded. Her serum olanzapine concentration was 1230 ng/mL. No further doses of physostigmine were administered. On day 3 of admission her mental status returned to normal.. We report two cases of olanzapine-induced mental status changes treated with physostigmine. The utility of physostigmine as a safe or necessary antidote in the setting of olanzapine overdose remains to be determined.

Topics: Acetylcholinesterase; Adult; Benzodiazepines; Delirium; Drug Administration Schedule; Drug Overdose; Female; Humans; Injections, Intravenous; Male; Olanzapine; Physostigmine; Treatment Outcome

Olanzapine is an atypical antipsychotic that is reported to cause myopathy and raised creatine kinase (CK) levels. The prevalence and severity of acute myopathy after deliberate olanzapine ingestion are unclear. Therefore, we reviewed case notes from 64 consecutive patients admitted to our institution after olanzapine overdose. Overall, serum CK was higher than five times the upper limit of normal in 17% of patients. The prevalence of raised CK values was positively correlated with the stated quantity of olanzapine ingested, suggesting a dose-dependent relationship for acute muscle toxicity. There was an apparent delay of 12 hours or more between olanzapine ingestion and the occurrence of maximum CK. Despite the high prevalence of acute muscle toxicity after olanzapine ingestion, none of the patients developed renal failure.

Topics: Acute Disease; Adult; Antipsychotic Agents; Benzodiazepines; Creatine Kinase, MM Form; Dose-Response Relationship, Drug; Drug Overdose; Female; Humans; Male; Middle Aged; Muscle, Skeletal; Muscular Diseases; Olanzapine; Retrospective Studies; Rhabdomyolysis; Scotland

Topics: Antipsychotic Agents; Athetosis; Basal Ganglia Diseases; Benzodiazepines; Brain; Chorea; Diffusion Magnetic Resonance Imaging; Drug Overdose; Fatal Outcome; Humans; Male; Middle Aged; Olanzapine

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

A 40-year-old white male was found dead in bed in a group home for mentally ill adults. The decedent had been diagnosed a paranoid schizophrenic. An autopsy was performed at the Office of the Cuyahoga County Coroner in Cleveland, Ohio. Toxicological testing detected olanzapine and citalopram in post mortem specimens. Multiple fluids and tissues were assayed by liquid-liquid extraction followed by gas chromatography with nitrogen phosphorus detection, and qualitative confirmation by electron impact gas chromatography/mass spectrometry. Drug concentrations [olanzapine: citalopram; mg/L or mg/Kg] determined in this case are the highest reported to date involving these drugs- 1.38:3.35 heart blood, 1.11:1.65 femoral blood, 60.24:32.43 urine, 6.47:10:71 liver, and 38.36:49.16 lung, respectively. Drug concentrations in tissues were found to be the highest in lung for both drugs and lowest in the heart. Citalopram but not olanzapine was detected in bone. The cause of death was ruled acute intoxication by the combined effects of olanzapine and citalopram and the manner, accident.

Topics: Adult; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Autopsy; Benzodiazepines; Citalopram; Drug Overdose; Humans; Male; Olanzapine; Postmortem Changes; Schizophrenia, Paranoid; Tissue Distribution

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

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: Adolescent; Benzodiazepines; Borderline Personality Disorder; Diabetes Insipidus; Dose-Response Relationship, Drug; Drug Overdose; Humans; Male; Olanzapine; Polyuria; Prazepam; Suicide, Attempted

We describe a case of delirium due to olanzapine overdose. After ingestion of 280 mg of olanzapine, a 19-year-old schizophrenic patient developed a delirium (ICD-10: F 05.0) with consciousness disturbance, disorientation in time, space, and situation, acoustic and visual hallucinations, and agitation. The symptoms lasted for approximately 36 h. Blood pressure, temperature, and heart frequency showed no disturbance. There were no abnormalities in ECG, EEG, or routine blood tests. Approximately 36 h after the intoxication, the patient recovered fully. Until now, there have been no reports of delirium from this cause.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Delirium; Drug Overdose; Female; Humans; Olanzapine; Schizophrenia

Topics: Adrenergic alpha-Agonists; Adult; Antipsychotic Agents; Benzodiazepines; Drug Overdose; Humans; Male; Norepinephrine; Obsessive-Compulsive Disorder; Olanzapine; Pirenzepine

Atypical antipsychotics are increasingly used for the treatment of elderly patients. However, there are only few studies on their efficacy and side effects in this patient group. The case of a 67-year old patient is presented, in whom under treatment with olanzapine in usual dosage, serum level increased into the toxic range. This olanzapine overdosage was accompanied by severe impairments in visual and verbal memory and by an increase of slow-frequency activity in the EEG. Both alterations may be attributed to the anticholinergic effects of olanzapine and reversed rapidly after dose reduction and normalization of the olanzapine serum level.

Topics: Aged; Amnesia; Antipsychotic Agents; Benzodiazepines; Chronic Disease; Dose-Response Relationship, Drug; Drug Overdose; Electroencephalography; Humans; Male; Mental Recall; Neuropsychological Tests; Olanzapine; Pirenzepine; Risk Factors; Schizophrenia, Paranoid

This paper reports a case of an olanzapine overdose in a 12-year-old boy. An opioid-like presentation was noted. Despite a high serum level of olanzapine, the patient made a complete recovery and showed no sequelae at follow-up.

Topics: Amphetamines; Antipsychotic Agents; Benzodiazepines; Central Nervous System Stimulants; Child; Drug Overdose; Glasgow Coma Scale; Humans; Male; Olanzapine; Pirenzepine

Olanzapine is a relatively new antipsychotic drug used in the United States for the treatment of schizophrenia. Since its release in the United States market in 1996, few cases of fatal acute intoxication have been reported in the literature. This article describes the case of a 25-year-old man found dead at home who had been prescribed olanzapine for schizophrenia. This case is unique because of the measurement of olanzapine in brain tissue obtained from seven regions in addition to the commonly collected biologic matrices. Olanzapine was detected and quantitated by basic liquid-liquid extraction followed by dual-column gas chromatographic analysis with nitrogen phosphorus detection. The assay had a limit of detection of 0.05 mg/L and an upper limit of linearity of 2 mg/L. The presence of olanzapine was confirmed by gas chromatography-mass spectrometry by use of electron impact ionization. The concentrations of olanzapine measured in this case were as follows (mg/L or mg/kg): 0.40 (heart blood), 0.27 (carotid blood), 0.35 (urine), 0.61 (liver), negative (cerebrospinal fluid), 0.33 mg in 50 ml (gastric contents). In the brain, the following distribution of olanzapine was determined (mg/kg): negative (cerebellum), 0.22 (hippocampus), 0.86 (midbrain), 0.16 (amygdala), 0.39 (caudate/putamen), 0.17 (left frontal cortex), and 0.37 (right frontal cortex). The cause of death was determined to be acute intoxication by olanzapine, and the manner of death was accidental.

Topics: Adult; Antipsychotic Agents; Autopsy; Benzodiazepines; Drug Overdose; Forensic Anthropology; Gas Chromatography-Mass Spectrometry; Humans; Male; Olanzapine; Pirenzepine; Postmortem Changes; Schizophrenia; Tissue Distribution

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Diabetes Mellitus, Type 1; Dose-Response Relationship, Drug; Drug Overdose; Humans; Insulin; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Risk Factors; Suicide, Attempted

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Drug Overdose; Humans; Male; Olanzapine; Pirenzepine; Schizophrenia; Schizophrenic Psychology; Severity of Illness Index; Suicide, Attempted

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Drug Overdose; Humans; Male; Olanzapine; Pirenzepine; Schizophrenia

Olanzapine is an antipsychotic drug that has been on the market since 1996. Olanzapine-related deaths are very rare; the literature reports only one. However, in a recent 5-month period one medical examiner's office found two such cases that are reported in this paper. One is a suicide and the other is not. The toxicologic and anatomic findings for each are described. Blood olanzapine concentrations ranged from 0.237 microg/ml for one to 0.675 microg/ml for the other. Gastric content concentrations also exhibited a wide range, varying from 0.197 microg/ml to 17.400 microg/ml for the other. Distribution studies of the liver, kidney, and brain produced nondetectable concentrations for the drug. There were no consistent pathologic anatomic findings for cause of death except for moderate coronary atherosclerosis in the nonsuicide case. Both deaths were attributed to olanzapine toxicity.

Topics: Adult; Antipsychotic Agents; Autopsy; Benzodiazepines; Coronary Disease; Drug Overdose; Fatal Outcome; Humans; Male; Middle Aged; Olanzapine; Pirenzepine; Schizophrenia, Paranoid

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Drug Overdose; Female; Hallucinations; Humans; Olanzapine; Pirenzepine; Schizophrenia; Schizophrenic Psychology

Olanzapine, a new atypical antipsychotic drug, has been prescribed in the treatment of schizophrenia and psychotic mood disorders for approximately 2.3 million patients worldwide. Considering the increase in olanzapine prescriptions and the increased risk of suicide in this patient population, the number of reported cases of olanzapine overdose may be expected to increase. This report describes the clinical course and serum concentrations in a patient who consumed an olanzapine overdose (800 mg). Profound central nervous system depression and tachycardia without arrhythmia occurred within 2 hours after the ingestion. Additional clinical findings (ie, fever, mutism, agitation, dystonia, akathisia, elevated creatine kinase, and increased leukocyte count) were similar to those of neuroleptic malignant syndrome. After intubation, gut decontamination, and supportive care, the patient recovered and was discharged.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Drug Overdose; Female; Humans; Olanzapine; Pirenzepine

We report significant central nervous system depression and the previously unreported phenomenon of pupillary constriction after acute overdose of olanzapine (Zyprexa) in 4 patients. Phase 2 trials describe a typically benign course in overdose, and published abstracts note a wide spectrum of clinical effects with supratherapeutic ingestion of olanzapine. Our patients demonstrated profound central nervous system depression, and 2 required advanced airway support. All 4 patients recovered with supportive care. Olanzapine should be added to opioid and alpha(2)-adrenergic agonist intoxication in the differential diagnosis of the patient with depressed mental status and miosis.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Central Nervous System; Central Nervous System Depressants; Drug Overdose; Female; Humans; Male; Middle Aged; Miosis; Narcotics; Olanzapine; Pirenzepine; Pupil

Topics: Anti-Allergic Agents; Antipsychotic Agents; Asthma; Benzodiazepines; Cetirizine; Child; Drug Overdose; Female; Humans; Medication Errors; Olanzapine; Pirenzepine

Topics: Akathisia, Drug-Induced; Antipsychotic Agents; Benzodiazepines; Drug Overdose; Humans; Infant; Male; Olanzapine; Pirenzepine; Sleep Stages

An ingestion of an unknown quantity of Zyprexa (olanzapine) tablets in a suicide is described. Biological fluid samples obtained at autopsy were analyzed for the presence of olanzapine by gas chromatography equipped with nitrogen-phosphorous detector and gas chromatography/mass spectroscopy. The blood concentration of olanzapine was 490 micrograms/dl and the concentration in gastric contents was 4100 micrograms/dl.

Topics: Antipsychotic Agents; Benzodiazepines; Blood Chemical Analysis; Drug Overdose; Fatal Outcome; Female; Gas Chromatography-Mass Spectrometry; Gastric Juice; Humans; Middle Aged; Olanzapine; Pirenzepine; Suicide

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

Topics: Acute Disease; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Child; Drug Overdose; Humans; Male; Olanzapine; Pirenzepine; Suicide, Attempted

A 43-year-old male psychiatric outpatient died within hours of ingesting as much as 600 mg of olanzapine, a newer antipsychotic agent related to clozapine. Analysis of postmortem blood and urine by gas chromatography with nitrogen-selective detection yielded olanzapine concentrations of 1238 and 6987 micrograms/L, respectively, greatly in excess of levels expected following therapeutic administration of the drug. Based on the toxicology findings, the decedent's known history of suicide attempts, and the circumstances surrounding the death, this case was ruled a suicide by olanzapine overdosage.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Chromatography, Gas; Drug Overdose; Fatal Outcome; Forensic Medicine; Humans; Male; Olanzapine; Pirenzepine; Suicide