quetiapine-fumarate and Central-Nervous-System-Diseases

Adverse effects of antipsychotics often lead to noncompliance. Thus, clinicians should address patients' concerns about adverse effects and attempt to choose medications that will improve their patients' quality of life as well as overall health. The side effect profiles of the atypical antipsychotics are more advantageous than those of the conventional neuroleptics. Conventional agents are associated with unwanted central nervous system effects, including extrapyramidal symptoms (EPS), tardive dyskinesia, sedation, and possible impairment of some cognitive measures, as well as cardiac effects, orthostatic hypotension, hepatic changes, anticholinergic side effects, sexual dysfunction, and weight gain. The newer atypical agents have a lower risk of EPS, but are associated in varying degrees with sedation, cardiovascular effects, anticholinergic effects, weight gain, sexual dysfunction, hepatic effects, lowered seizure threshold (primarily clozapine), and agranulocytosis (clozapine only). Since the incidence and severity of specific adverse effects differ among the various atypicals, the clinician should carefully consider which side effects are most likely to lead to the individual's dissatisfaction and noncompliance before choosing an antipsychotic for a particular patient.

Topics: Agranulocytosis; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Central Nervous System Diseases; Clozapine; Dibenzothiazepines; Drug Interactions; Dyskinesia, Drug-Induced; Health Status; Humans; Hypotension, Orthostatic; Olanzapine; Pirenzepine; Quality of Life; Quetiapine Fumarate; Receptors, Cholinergic; Risperidone; Schizophrenia; Sexual Dysfunctions, Psychological; Sleep Wake Disorders; Treatment Refusal; Weight Gain

We describe the effects of quetiapine in overdose.. Quetiapine poisonings were identified from a prospective database of poisoning admissions to a regional toxicology service. Data extracted included details of ingestion, clinical features, investigations (including ECG), and other outcomes (length of stay and ICU admission rate).. There were 45 cases of quetiapine overdose, of which 18 patients with quetiapine assay results were included. Median length of stay was 35 hours (interquartile range [IQR] 14 to 42 hours) for the 18 patients, and 9 were admitted to the ICU. The median ingested dose was 3.5 g (IQR 1.7 to 6.2 g), and reported ingested dose was highly correlated with estimated peak drug concentration (r(2)=0.84; P<.0001), confirming patient-provided history of ingestion. Seizures occurred in 2 patients, delirium occurred in 3 patients, and mechanical ventilation was required in 4 patients. No arrhythmias or deaths occurred. Six of the 18 patients ingested quetiapine alone, with a median length of stay of 35 hours, and 3 were admitted to the ICU. In 1 patient who ingested 24 g, hypotension and seizures occurred. For 10 patients for whom ECGs were available and who had ingested no cardiotoxic drugs, tachycardia occurred in 8 patients. For these 10 patients, the mean corrected QT (QTc) interval was increased at 487 ms, but the mean uncorrected QT interval was 349 ms. Reported dose and peak quetiapine concentrations were significantly associated with ICU admission and length of stay more than 24 hours. A reported dose less than 3 g and a Glasgow Coma Scale score not less than 15 predicted patients not requiring ICU admission or length of stay more than 24 hours.. Quetiapine overdose causes central nervous system depression and sinus tachycardia. In large overdoses, patients may require intubation and ventilation for associated respiratory depression. Although a prolonged QTc occurs, its clinical significance is unclear because it is most likely caused by an overcorrection caused by the tachycardia. In our experience, a reported dose of less than 3 g for patients who are not drowsy (with a Glasgow Coma Scale score of 15) at least 4 hours after ingestion and who did not coingest another toxic agent defined a group not requiring ICU admission or inpatient admission greater than 24 hours.

Topics: Adult; Antipsychotic Agents; Central Nervous System Diseases; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Overdose; Drug Therapy, Combination; Female; Glasgow Coma Scale; Humans; Intensive Care Units; Length of Stay; Male; Quetiapine Fumarate; Respiratory Insufficiency; Retrospective Studies; Seizures