Olanzapine Overdose Research Articles

Olanzapine overdose in a 1-year-old male

Olanzapine overdose in a 1-year-old male

Olanzapine overdose in a 1-year-old male

Olanzapine overdose in a 1-year-old male

Olanzapine Overdose Mimicking Opioid Intoxication

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 α 2 -adrenergic agonist intoxication in the differential diagnosis of the patient with depressed mental status and miosis. [O’Malley GF, Seifert S, Heard K, Daly F, Dart RC: Olanzapine overdose mimicking opioid intoxication. Ann Emerg Med August 1999;34:279-281.]

MONITORING OF OLANZAPINE IN SERUM BY LIQUID CHROMATOGRAPHY-ATMOSPHERIC PRESSURE CHEMICAL IONIZATION MASS SPECTROMETRY.

Abstract A selective assay of olanzapine with liquid chromatography atmospheric pressure chemical ionization (LC–APCI–MS, positive ions) is described. The drug and internal standard (ethyl derivative of olanzapine) were isolated from serum using a solid-phase extraction procedure (C 18 cartridges). The separation was performed on ODS column in acetonitrile–50 m M ammonium formate buffer, pH 3.0 (25:75). After analysis of mass spectra taken in full scan mode, a selected-ion monitoring detection (SIM) was applied with the following ions: m/z 313 and 256 for olanzapine and m/z 327 and 270 for the internal standard for quantitation. The limit of quantitation was 1 μg/l, the absolute recovery was above 80% at concentration level of 10 to 100 μg/l. The method tested linear in the range from 1 to 1000 μg/l and was applied for therapeutic monitoring of olanzapine in the serum of patients receiving (Zyprexa™) and in one case of olanzapine overdose. Olanzapine in frozen serum samples and in frozen extracts was stable over at least four weeks. The examinations of urine extracts from patients receiving olanzapine revealed peaks of postulated metabolites (glucuronide and N -desmethylolanzapine).

Acute olanzapine overdose

Olanzapine, a thiobenzodiazepine derivate, is a recently released novel antipsychotic medication. The authors report the first case of overdose of olanzapine in an apparent suicide attempt. A 38-year-old schizophrenic patient was brought to a hospital emergency room following the ingestion of 12 10-mg tablets of olanzapine. There were no serious clinical adverse effects. Copyright © 1999 John Wiley & Sons, Ltd.

Olanzapine Overdose Cause of Acute Extrapyramidal Symptoms

Back to table of contents Previous article Next article Letter to the EditorFull AccessOlanzapine Overdose Cause of Acute Extrapyramidal SymptomsR. ANDREW CHAMBERS, M.D., ANNMARIE CARACANSI, M.D., and GORDON WEISS, M.D., R. ANDREW CHAMBERSSearch for more papers by this author, M.D., ANNMARIE CARACANSISearch for more papers by this author, M.D., and GORDON WEISSSearch for more papers by this author, M.D., New Haven, Conn.Published Online:1 Nov 1998https://doi.org/10.1176/ajp.155.11.1626hAboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: As one of the atypical antipsychotic agents, olanzapine has been considered to be similar to clozapine but free of the risk of agranulocytosis. The in vitro binding of olanzapine to dopamine (D1, D2, D4), serotonin (5-HT2a, 5-HT2c), a-adrenergic, histamine, and muscarinic receptors is comparable to the binding of clozapine (1). Neuroimaging studies have shown that the D2-receptor binding of olanzapine in therapeutic doses is similar to that of clozapine (2). Such preclinical studies would predict that olanzapine and clozapine are similar in their lack of propensity to cause extrapyramidal symptoms. Broad-based clinical trials have found that olanzapine, in doses up to 20 mg/day, produces extrapyramidal symptoms at rates approximating those of placebo (3). Sheitman et al. recently reported that olanzapine becomes more distinct from clozapine and is associated with more extrapyramidal symptoms at doses above those most often prescribed (20mg/day) (4). We present the first reported case in which an overdose of olanzapine produced acute extrapyramidal symptoms.Quentin, a 9-year-old boy who weighed 64 lb and had no prior exposure to psychotropic medication, took 100 mg of his mother"s olanzapine and an indeterminate amount of acetominophen in an apparent suicide attempt. At presentation in the emergency department about 2 hours after ingestion, Quentin was combative and unable to follow commands. He also had tachycardia, hypotension, and decreased gastrointestinal motility. He was treated with elective intubation for airway management and with intravenous fluids and norepinephrine for pressure support. Activated charcoal and n-acetyl cysteine were used to prevent further drug toxicity. Cisapride, ondansetron, and metoclopramide were given for promotility effects. Significant laboratory abnormalities during his hospitalization included peak levels of the following: acetaminophen (158 mg/ml), aspartate aminotransferase (93 U/liter), alanine aminotransferase (47 U/liter), and lactate dehydrogenase (434 U/liter). Quentin’s platelets were elevated (502,000/mm3). Quentin did well with treatment and was extubated within 15 hours of admission. By about 36 hours after ingestion and after resolution of his presenting symptoms Quentin developed “jitteriness” and hyperreflexia followed by tremors of the extremities, cogwheel rigidity, a stiff jaw, oculogyric signs, and severe dystonia of the neck. These symptoms were treated with intravenous diphenhydramine for 24 hours and then with oral diphenhydramine for 9 days thereafter. During the course of this treatment, his extrapyramidal symptoms improved significantly. At 13 days after ingestion, Quentin had only a slight upper extremity tremor and no subjective complaints. Hoffman and Donovan have found that in rats, olanzapine, like risperidone, loses its atypical properties in higher doses by producing catalepsy, not unlike haloperidol at therapeutic doses (5). This effect was not observed with clozapine at any dose, suggesting that clozapine remains unique in its lack of association with extrapyramidal symptoms relative even to the newer atypical antipsychotics.