olanzapine and Miosis

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

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

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

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