quetiapine-fumarate and Tachycardia

This is the first investigation of the pharmacokinetics, tolerability, and efficacy of quetiapine fumarate in adolescents with chronic or intermittent psychotic disorders.. Ten patients with DSM-IV chronic or intermittent psychotic disorders (ages 12.3 through 15.9 years) participated in an open-label, rising-dose trial and received oral doses of quetiapine twice daily (b.i.d.), starting at 25 mg b.i.d. and reaching 400 mg b.i.d. by day 20. The trial ended on day 23. Key assessments were pharmacokinetic analysis of plasma quetiapine concentrations and neurologic, safety, and efficacy evaluations.. No statistically significant differences were observed between 100-mg b.i.d. and 400-mg b.i.d. quetiapine regimens for total body clearance, dose-normalized area under the plasma concentration-time curve, or dose-normalized premorning- or postmorning-dose trough plasma values obtained under steady-state conditions after multiple-dose regimens. No unexpected side effects occurred with quetiapine therapy, and no statistically significant changes from baseline were observed for the UKU Side Effect Rating Scale items that were rated. No serious adverse events or clinically important changes in hematology or clinical chemistry variables were reported. The most common adverse events were postural tachycardia and insomnia. Extrapyramidal side effects improved, as evidenced by significant (p < .05) decreases from baseline to endpoint in the mean Simpson-Angus Scale total scores and Barnes Akathisia Scale scores. Quetiapine improved positive and negative symptoms, as shown by significant (p < .05) decreases from baseline to endpoint in the mean Brief Psychiatric Rating Scale total score, the Clinical Global Impressions-Severity of Illness scale, and the Modified Scale for the Assessment of Negative Symptoms summary score.. Quetiapine pharmacokinetics were dose proportional in adolescents and were similar to those previously reported for adults. Quetiapine was well tolerated and effective in the small number of adolescents studied.

Topics: Adolescent; Adult; Age Factors; Antipsychotic Agents; Basal Ganglia Diseases; Brief Psychiatric Rating Scale; Child; Dibenzothiazepines; Drug Administration Schedule; Humans; Psychotic Disorders; Quetiapine Fumarate; Schizophrenia; Schizophrenic Psychology; Sleep Initiation and Maintenance Disorders; Tachycardia; Treatment Outcome

Duloxetine is a commonly used antidepressant that is a serotonin and norepinephrine reuptake inhibitor. We aimed to investigate the frequency and severity of clinical effects following duloxetine overdose.. We undertook a retrospective review of duloxetine overdoses (>120 mg) admitted to two tertiary toxicology units between March 2007 and May 2021. Demographic information, details of ingestion (dose, co-ingestants), clinical effects, investigations (ECG parameters including QT interval), complications (coma [GCS < 9], serotonin toxicity, seizures and cardiovascular effects), length of stay [LOS] and intensive care unit [ICU] admission were extracted from a clinical database.. There were 241 duloxetine overdoses (>120 mg), median age 37 years (interquartile range [IQR]: 25-48 years) and there were 156 females (65%). The median dose was 735 mg (IQR: 405-1200 mg). In 177 patients, other medications were co-ingested, most commonly alcohol, paracetamol, quetiapine, diazepam, ibuprofen, pregabalin and oxycodone. These patients were more likely to be admitted to ICU (12 [7%] vs. none;. Duloxetine overdose most commonly caused sympathomimetic effects and serotonin toxicity, consistent with its pharmacology, and did not result in coma, arrhythmias or intensive care admission, when taken alone in overdose.

Topics: Acetaminophen; Adult; Antidepressive Agents; Arrhythmias, Cardiac; Coma; Diazepam; Droperidol; Drug Overdose; Duloxetine Hydrochloride; Female; Humans; Hypotension; Ibuprofen; Middle Aged; Norepinephrine; Oxycodone; Pregabalin; Quetiapine Fumarate; Seizures; Serotonin; Sympathomimetics; Tachycardia

Quetiapine is a low-affinity dopamine D2 receptor antagonist, approved for the treatment of bipolar disorder and schizophrenia in children and adolescents by the Food and Drug Administration, but not by European Medicine Agency. Although knowledge of adverse drug reactions in children and adolescents is scarce, quetiapine is increasingly being used for youth in Denmark. The aim of this case study is to discuss adverse drug events (ADEs) spontaneously reported to the Danish Medicines Agency on quetiapine used in the pediatric population in relation to adversive drug reactions (ADRs) reported in the European Summary of Product Characteristics (SPCs). The ADE report database at Danish Medicines Agency was searched for all quetiapine ADRs involving individuals (<18 years) in the period 1997-2015. Fifteen ADE case reports were retrieved, scrutinized, and categorized. The average age was 14.8 years (range 10-17 years) and six patients were boys. The main reported ADEs were (i) endocrine, for example, hyperprolactinemia and hyperthyroidism, (ii) cardiac, for example, tachycardia and QT prolongation, (iii) neurological, for example, seizures and cerebral hemorrhage, and (iv) psychiatric, for example, hallucinations. As some of the reported ADEs are life threatening and not listed as ADRs in the SPCs, off-label use of quetiapine in children and adolescents gives rise to safety concerns.

Topics: Adolescent; Adverse Drug Reaction Reporting Systems; Age Factors; Antipsychotic Agents; Case-Control Studies; Child; Databases, Factual; Denmark; Drug-Related Side Effects and Adverse Reactions; Dystonia; Female; Humans; Hypotension, Orthostatic; Male; Quetiapine Fumarate; Tachycardia; Treatment Outcome

Detailed data on severe overdoses with quetiapine are relatively sparsely reported in the literature.. To describe a cohort of 20 acute quetiapine overdoses and provide additional data on the pharmacokinetics and clinical features of intoxication with this drug.. A retrospective study was conducted on patients with quetiapine poisoning admitted to our institution. We included moderate to severe overdoses between 2005-2011 who required admission to ICU.. Predominantly female patients (n = 17) ingested a median dose of 9.8 g quetiapine. Poison Severity Score was moderate in 9 patients, severe in 10 patients and in one case fatal. Quetiapine was analytically confirmed in all cases. Clinical manifestations included drowsiness or coma (all patients), tachycardia (12 patients) and hypotension (10 patients). Seizures and arrhythmia occurred in 4 patients, each. Intubation and mechanical ventilation was required in 14 patients due to seizures, respiratory depression or loss of airway protection and 15 patients developed pneumonia. Hypokalaemia and hyperglycaemia were present at admission in 10 and 5 patients, respectively. Despite frequent prolongation of the QT(c) in 13 patients, QT interval was normal in most cases and QRS-interval was prolonged in only one patient. Presumably anticholinergic delirium was recognised in 8 patients and 6 patients received physostigmine with good clinical response. In 13 cases quetiapine was analysed quantitatively in serum with a relevantly prolonged half-life (16 ± 12 h) and a median peak serum concentration of 3074 ng/mL. In 4 of these 13 patients we observed an increase of quetiapine serum concentration in the further course.. In this study, quetiapine overdoses were associated with significant toxicity and a fairly high number of complications. A careful and often prolonged clinical observation in the more severe cases of overdose seems mandatory.

Topics: Adult; Antipsychotic Agents; Arrhythmias, Cardiac; Cohort Studies; Coma; Dibenzothiazepines; Drug Overdose; Female; Half-Life; Humans; Hypotension; Intensive Care Units; Male; Middle Aged; Pneumonia; Quetiapine Fumarate; Retrospective Studies; Tachycardia

Quetiapine is an atypical antipsychotic agent increasingly used to treat schizophrenia and bipolar disorder in pediatric patients. Few published data exist concerning quetiapine's effects in therapeutic settings or short-term overdose in pediatric and adolescent populations. In this report, we describe a 15-year-old adolescent girl who experienced continued delirium 5 days after an overdose of quetiapine, trazodone, and clonidine. The patient initially presented with sedation and stable vital signs. After 3 days of gradual improvement, she experienced episodes of delirium coinciding with an increase in resting heart rate. On the basis of suspicion for quetiapine-associated antimuscarinic effects, the patient was administered intravenously with physostigmine on the fifth day after ingestion. Treatment resulted in a brief resolution of symptoms. Serum quetiapine levels measured 1 day and 5 days after ingestion were 3400 and 4800 ng/mL, respectively. The use of physostigmine and interpretation of serum levels are discussed further.

Topics: Adolescent; Antipsychotic Agents; Cholinergic Antagonists; Clonidine; Cytochrome P-450 CYP3A; Delirium; Depression; Dibenzothiazepines; Drug Interactions; Emergencies; Female; Heart Block; Humans; Hypotension; Physostigmine; Quetiapine Fumarate; Self-Injurious Behavior; Suicide, Attempted; Tachycardia; Time Factors; Trazodone

Topics: Aged; Alzheimer Disease; Anti-Anxiety Agents; Antipsychotic Agents; Benzodiazepines; Delirium; Depressive Disorder; Diagnosis, Differential; Dibenzothiazepines; Hallucinations; Humans; Male; Olanzapine; Oxazepam; Psychotic Disorders; Quetiapine Fumarate; Tachycardia

Data on quetiapine overdosage are only sparsely available in the literature. This study provides additional data on the pharmacokinetics and clinical effects of intoxication with this atypical antipsychotic drug. The authors performed a retrospective analysis of all quetiapine intoxications reported to and screened by the toxicological laboratory of the Central Hospital Pharmacy The Hague between January 1999 and December 2003. Cases with known suggested amount of intake and medical outcome were included. From the patient's medical record and from the toxicological laboratory findings, patient demographic characteristics (gender, age), details of quetiapine intoxication (estimated time of ingestion, estimated amount of ingestion, and coingested drugs) and clinical parameters were obtained. Severity of intoxication was graded by the Poisoning Severity Score (PSS). Individual pharmacokinetic parameter values were calculated using a one-compartment open model and a Bayesian fitting procedure. Out of a total of 21 intoxications with quetiapine, 14 fulfilled the inclusion criteria. The ingested dose ranged from 1200 to 18,000 mg. The blood concentration ranged from 1.1 to 8.8 mg/L with a lag time of 1 to 26.2 hours between time of ingestion and blood sampling at the emergency ward. The most frequent findings were somnolence and tachycardia. The PSS was minor in 6 patients (43%), moderate in 5 patients (36%), and severe in 3 patients (21%). Severity of intoxication was not associated with a higher amount of quetiapine intake. The authors found no correlation between the serum concentration of quetiapine and the amount ingested. Elimination t(1/2) was not prolonged. It can be concluded that quetiapine intoxications appear to proceed mildly. Tachycardia and somnolence were the main clinical symptoms in our case series. No fatalities occurred. The severity of clinical symptoms was not associated with either a high serum concentration or the suggested amount ingested of quetiapine.

Topics: Administration, Oral; Adult; Antipsychotic Agents; Coma; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Overdose; Emergency Treatment; Female; Half-Life; Humans; Male; Medical Records; Middle Aged; Quetiapine Fumarate; Recovery of Function; Retrospective Studies; Severity of Illness Index; Tachycardia

Although the new atypical antipsychotic, quetiapine fumarate, is growing in popularity over its progenitor, clozapine, clinical experience with overdose of this agent remains limited. Observation of an overdose situation provided a unique opportunity to define the safety, clinical effects, and pharmacokinetics of this medication more clearly.. A patient admitted immediately after ingesting an overdose of 30 tablets of 100 mg of quetiapine was observed carefully to document effects of the medication. These observations were compared with the only two other published cases of overdose, to the known pharmacology of the drug, and to serial measurements of serum drug concentrations obtained to document the time course of elimination of the drug.. Consistent with the two previously published cases, the main clinical effects of overdose were hypotension, tachycardia, and somnolence as predicted by its known alpha-adrenergic receptor and histamine receptor blockade. These effects were managed with fluid resuscitation and supportive measures. No cardiac arrhythmias other than tachycardia have been reported, but the tachycardia was of an unexpectedly long duration in this case. Decline in serum quetiapine concentration followed a biexponential pattern with a terminal elimination half-life of 22 hours. Unexpectedly low peak serum concentrations in three patients with overdose suggest that absorption is highly reduced, either by the effects of the overdose or by the activated charcoal administered.. Quetiapine appears to have greater safety in overdose than traditional antipsychotic agents. Its toxicity is consistent with its receptor pharmacology. Elevated serum concentrations associated with this overdose remained above the limit of detection long enough to document a terminal elimination half-life of 22 hours in this patient. This is much more consistent with previously noted duration of clinical effects and detectable serum concentrations after overdose than the published half-life of 6 hours. Physicians should be aware that any new drug that is active at low concentrations may have had its half-life underestimated during preclinical development because of the difficulty in detecting the drug after the distribution phase has ended.

Topics: Adrenergic alpha-Antagonists; Adult; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Drug Overdose; Female; Half-Life; Humans; Hypotension; Quetiapine Fumarate; Sleep Stages; Tachycardia