[The clinical picture of acute olanzapine poisonings].

BACKGROUND 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. AIM OF THE STUDY Evaluation of incidence and intensity of clinical symptoms in patients with of acute olanzapine intoxication. The pathophysiological mechanisms of particular symptoms are also described. MATERIAL 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. METHODS 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). RESULTS 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). CONCLUSIONS 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.