quetiapine-fumarate and Hypotension

Opioid poisoning is a frequent cause of death in drug addicts and occurs with opioid treatment. Quetiapine is often found in forensic autopsies and may increase the risk of fatal opioid poisoning by enhancing sedation, respiratory depression, hypotension and QT prolongation. We systematically searched for studies of acute toxicity of quetiapine or other antipsychotics combined with morphine or methadone. Case reports describing toxicity of quetiapine combined with morphine or methadone were also included. We retrieved one human study that observed pharmacokinetic interaction between quetiapine and methadone, and 16 other human studies. Fourteen investigated the combination of droperidol and morphine in treatment doses, and some indicated an additive sedative effect. Five animal studies with acepromazine in combination with morphine or methadone were located and indicated an additive effect on sedation and hypotension. Six forensic case reports in which death could have been caused solely by quetiapine, the opioid, or other drugs were found. Thus, acute toxicity of quetiapine combined with morphine or methadone has not been studied. Because of quetiapine's effects on alpha-adrenoceptors, muscarinic and histamine receptors, human ether-a-go-go-channels and methadone kinetics, we suggest further research to clarify if the indicated additive effects of opioids and droperidol or acepromazine are also true for quetiapine.

Topics: Adolescent; Adult; Analgesics, Opioid; Animals; Antipsychotic Agents; Arrhythmias, Cardiac; Autopsy; Cause of Death; Consciousness; Drug Interactions; Drug Overdose; Female; Forensic Toxicology; Humans; Hypotension; Male; Methadone; Middle Aged; Morphine; Opioid-Related Disorders; Quetiapine Fumarate; Respiratory Insufficiency; Risk Assessment; Risk Factors

Atypical antipsychotic medications (second-generation antipsychotics) have been increasingly used in the treatment of a number of psychotic disorders since their introduction in 1988, with the newest medication introduced in 2002. Justification for their use includes claims of equal or improved antipsychotic activity over first-generation antipsychotics, increased tolerability, and decreased side effects. However, there are still significant adverse effects and toxicities with this class of medications. Toxicologic exposures and fatalities associated with atypical antipsychotics continue to increase in the United States, with 32,422 exposures and 72 deaths in 2003. There have also been Food and Drug Administration warnings in the past year about how some atypical antipsychotics have been marketed to minimize the potentially fatal risks and claiming superior safety to other atypical antipsychotics without adequate substantiation, indicating the toxicologic potential of these agents may be underestimated.. Continued research to evaluate adverse effects and tolerability of atypical antipsychotics compared with first-generation antipsychotics and each other is reviewed. This article also reviews the pharmacodynamics, pharmacokinetics, and drug interactions with these medications. New therapeutic monitoring recommendations for this class of medications have also been proposed. Finally, clinical toxicity in overdose and management are reviewed.. While new atypical antipsychotic medications may have a safer therapeutic and overdose profile than first-generation antipsychotic medications, many adverse and toxic effects still need to be considered in therapeutic monitoring and overdose management.

Topics: Antipsychotic Agents; Aripiprazole; Basal Ganglia Diseases; Benzodiazepines; Cardiomyopathies; Child; Clozapine; Diabetes Mellitus; Dibenzothiazepines; Drug Interactions; Drug Overdose; Dry Eye Syndromes; Humans; Hyperlipidemias; Hypotension; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Seizures; Thiazoles

Quetiapine is an atypical antipsychotic used in the treatment of depressive, schizophrenic, or bipolar disorders. It acts on dopamine D

Topics: Antipsychotic Agents; Dibenzothiazepines; Dopamine; Humans; Hypotension; Quetiapine Fumarate

Atypical antipsychotics are used in cardiac intensive care units (CICU) to treat delirium despite limited data on safety in patients with acute cardiovascular conditions. Patients treated with these agents may be at higher risk for adverse events such as QTc prolongation and arrhythmias. We performed a retrospective cohort study of 144 adult patients who were not receiving antipsychotics before admission and received olanzapine (n = 50) or quetiapine (n = 94) in the Michigan Medicine CICU. Data on baseline characteristics, antipsychotic dose and duration, length of stay, and adverse events were collected. Adverse events included ventricular tachycardia (sustained ventricular tachycardia attributed to the medication), hypotension (systolic blood pressure <90 mm Hg attributed to the medication), and QTc prolongation (QTc increase by ≥60 ms or to an interval ≥500 ms). Twenty-six patients (18%) experienced an adverse event. Of those adverse events, 20 patients (14%) experienced QTc prolongation, 3 patients (2%) had ventricular tachycardia, and 3 patients (2%) had hypotension. Patients who received quetiapine had a higher rate of adverse events (25% vs 6%, p = 0.01) including QTc prolongation (18% vs 6%, p = 0.046). Intensive care unit length of stay was shorter in patients who received olanzapine (6.5 vs 9.5 days, p = 0.047). Eighteen patients (13%) had their antipsychotic continued at discharge from the hospital. In conclusion, QTc prolongation was more common in patients treated with quetiapine versus olanzapine although the number of events was relatively low with both agents in a CICU cohort.

Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Arrhythmias, Cardiac; Coronary Care Units; Delirium; Endocarditis; Female; Heart Arrest; Heart Failure; Humans; Hypotension; Length of Stay; Long QT Syndrome; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Respiratory Insufficiency; Retrospective Studies; Shock, Cardiogenic; ST Elevation Myocardial Infarction; Tachycardia, Ventricular

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

Hypotension is a common presentation following an overdose of quetiapine. Adrenaline is often used as the vasopressor of choice for hypotension not responding to intravenous fluids. We present a case of quetiapine overdose with hypotension unresponsive to high-dose adrenaline. The patient was commenced on noradrenaline and made a full recovery. We highlight learning points about vasopressor therapy for atypical antipsychotic overdose. Quetiapine-induced hypotension is thought to be mediated by α1-receptor antagonism. Adrenaline is unlikely to improve blood pressure, as it is an agonist at both α- and β-receptors. Alpha-2- and β2-agonism can reduce sympathetic outflow and cause vasodilation, respectively, further exacerbating the hypotension. Noradrenaline is the preferred vasopressor of choice for hypotension caused by quetiapine overdose, as it has less affinity for α2- and β2-receptors, but maintains α1-receptor agonism. Drugs with a similar mechanism of inducing hypotension should also be treated with noradrenaline as the vasopressor of choice.

Topics: Antipsychotic Agents; Drug Overdose; Epinephrine; Female; Humans; Hypotension; Norepinephrine; Quetiapine Fumarate; Treatment Outcome; Vasoconstrictor Agents; Young Adult

Methylene blue inhibits the nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway, decreasing vasodilation and increasing responsiveness to vasopressors. It is reported to improve haemodynamics in distributive shock from various causes including septicaemia and post-cardiac surgery. Reports of use in overdose are limited. We describe the use of methylene blue to treat a case of refractory distributive shock following a mixed drug poisoning.. A 41-year-old male presented following reported ingestion of 18 g extended-release quetiapine, 10 g controlled-release carbamazepine, 240 mg fluoxetine, 35 g enteric-coated sodium valproate and 375 mg oxazepam. He was comatose and intubated on presentation. Progressive hypotension developed. Echocardiogram revealed a hyperdynamic left ventricle, suggesting distributive shock. The patient remained hypotensive despite intravenous fluid boluses, escalating vasopressor infusions. Arterial blood gas revealed metabolic acidaemia and high lactate. Methylene blue was administered as loading-dose of 1.5 mg/kg and continuous infusion (1.5 mg/kg/h for 12 h, then 0.75 mg/kg/h for 12 h) resulting in rapid improvement in haemodynamic parameters and weaning of vasopressors. Serum quetiapine concentration was 18600 ng/mL (30-160 ng/mL), collected at the time of peak toxicity.. Severe quetiapine poisoning produces hypotension primarily from alpha-adrenoreceptor antagonism. Methylene blue may have utility in the treatment of distributive shock resulting from poisoning refractory to standard vasopressor therapy.

Topics: Adult; Anticonvulsants; Antidepressive Agents, Second-Generation; Antidotes; Antipsychotic Agents; Blood Gas Analysis; Blood Pressure; Carbamazepine; Dibenzothiazepines; Electrocardiography; Fluid Therapy; Fluoxetine; Humans; Hypnotics and Sedatives; Hypotension; Male; Methylene Blue; Oxazepam; Quetiapine Fumarate; Shock; Valproic Acid; Vasoconstrictor Agents

Several adverse outcomes attributed to atypical antipsychotic drugs, specifically quetiapine, risperidone, and olanzapine, are known to cause acute kidney injury (AKI). Such outcomes include hypotension, acute urinary retention, and the neuroleptic malignant syndrome or rhabdomyolysis.. To investigate the risk for AKI and other adverse outcomes associated with use of atypical antipsychotic drugs versus nonuse.. Population-based cohort study.. Ontario, Canada, from 2003 to 2012.. Adults aged 65 years or older who received a new outpatient prescription for an oral atypical antipsychotic drug (n=97,777) matched 1:1 with those who did not receive such a prescription.. The primary outcome was hospitalization with AKI (assessed by using a hospital diagnosis code and, in a subpopulation, serum creatinine levels) within 90 days of prescription for atypical antipsychotic drugs.. Atypical antipsychotic drug use versus nonuse was associated with a higher risk for hospitalization with AKI (relative risk [RR], 1.73 [95% CI, 1.55 to 1.92]). This association was consistent when AKI was assessed in a subpopulation for which information on serum creatinine levels was available (5.46% vs. 3.34%; RR, 1.70 [CI, 1.22 to 2.38]; absolute risk increase, 2.12% [CI, 0.80% to 3.43%]). Drug use was also associated with hypotension (RR, 1.91 [CI, 1.60 to 2.28]), acute urinary retention (RR, 1.98 [CI, 1.63 to 2.40]), and all-cause mortality (RR, 2.39 [CI, 2.28 to 2.50]).. Only older adults were included in the study.. Atypical antipsychotic drug use is associated with an increased risk for AKI and other adverse outcomes that may explain the observed association with AKI. The findings support current safety concerns about the use of these drugs in older adults.. Academic Medical Organization of Southwestern Ontario.

Topics: Acute Kidney Injury; Age Factors; Aged; Aged, 80 and over; Antipsychotic Agents; Benzodiazepines; Cause of Death; Creatinine; Dibenzothiazepines; Female; Hospitalization; Humans; Hypotension; Male; Olanzapine; Ontario; Quetiapine Fumarate; Retrospective Studies; Risk Factors; Risperidone; Urinary Retention

Quetiapine is an atypical antipsychotic with known α-adrenergic antagonism. We present a case of refractory hypotension that occurred after induction of general anesthesia in a patient being treated with quetiapine. This patient was not currently taking antihypertensives and had no known cardiovascular abnormalities. We observed that the hypotension was most responsive to vasopressin. We recommend further investigation regarding the interaction of quetiapine and general anesthesia.

Topics: Adult; Anesthesia, General; Antidepressive Agents, Second-Generation; Antimanic Agents; Antipsychotic Agents; Blood Pressure; Carbon Dioxide; Cardiac Surgical Procedures; Cyclohexanols; Dibenzothiazepines; Electronic Health Records; Ephedrine; Female; Humans; Hypotension; Intraoperative Complications; Lamotrigine; Obesity, Morbid; Operating Rooms; Oxygen; Phenylephrine; Quetiapine Fumarate; Triazines; Vasoconstrictor Agents; Vasopressins; Venlafaxine Hydrochloride

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

A 47-year-old woman ingested an overdose of 8000 mg quetiapine. The treatment had been initiated 3 weeks before. The current medications were lamuvidine, ritonavir, atazanavir and tenofovir for an HIV infection. The patient presented a deep coma and sustained hypotension as main complications. The toxicokinetic data revealed a markedly prolonged elimination half-life for quetiapine (62.4 hours) and the relationship with antiretroviral therapy is discussed.

Topics: Anti-HIV Agents; Antipsychotic Agents; Coma; Dibenzothiazepines; Drug Interactions; Drug Overdose; Female; Half-Life; HIV Infections; Humans; Hypotension; Middle Aged; Quetiapine Fumarate

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

Second-generation antipsychotics (SGAs) are far more commonly used in the United States compared to first-generation antipsychotics (FGAs), but the relative safety of SGAs compared to FGAs following acute toxic ingestions has not been studied.. A retrospective cohort study was performed by chart review of the California Poison Control System electronic database of 1975 cases from the 10-year period 1997 to 2006 involving patients aged 18 to 65 years who ingested a single SGA or FGA. Cases were coded for overall severity of adverse outcome as defined by the American Association of Poison Control Centers criteria and for presence of specific symptoms and treatments. Odds ratios were calculated between SGAs and FGAs for various symptoms, treatments, and outcome severity.. Odds of a major adverse outcome or death were significantly higher for SGAs than FGAs (OR = 1.71, 95% CI = 1.09 to 2.71). Patients taking SGAs had higher odds of respiratory depression (OR = 2.39, 95% CI = 1.09 to 5.26), coma (OR = 2.18, 95% CI = 1.30 to 3.65), and hypotension (OR = 1.80, 95% CI = 1.23 to 2.63) compared to those taking FGAs but lower odds of dystonia (OR = 0.12, 95% CI = 0.08 to 0.19) or rigidity (OR = 0.30, 95% CI = 0.10 to 0.90).. SGAs appear no safer than FGAs in acute overdose. While neuromuscular symptoms appear less frequently with SGAs compared to FGAs, the relatively greater rates of central nervous system depression associated with SGA overdose may be more dangerous.

Topics: Antipsychotic Agents; Cause of Death; Cohort Studies; Coma; Dibenzothiazepines; Dose-Response Relationship, Drug; Drug Overdose; Dyskinesia, Drug-Induced; Follow-Up Studies; Humans; Hypotension; Long QT Syndrome; Neuroleptic Malignant Syndrome; Odds Ratio; Poison Control Centers; Quetiapine Fumarate; Respiratory Insufficiency; Retrospective Studies; Risk Factors; Schizophrenia; Survival Analysis

Topics: Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Epinephrine; Fat Emulsions, Intravenous; Humans; Hypotension; Infusions, Intravenous; Quetiapine Fumarate; Vasoconstrictor Agents

Atypical antipsychotics (quetiapine, olanzapine, risperidone and clozapine) are increasingly prescribed in Australia, and emergency departments report growing rates of overdose of these agents. As these drugs are comparatively new, the spectrum of toxicity may be unfamiliar to critical care physicians. Severe hypotension is a recognised consequence of quetiapine poisoning. We describe three patients with massive quetiapine overdose who developed significant hypotension resistant to fluid resuscitation. In each case, blood pressure fell dramatically after commencement of adrenaline infusions. Haemodynamic stability was restored when noradrenaline was substituted for adrenaline. The pharmacodynamics of quetiapine and the literature on overdose are reviewed. We present these cases to broaden the knowledge of physicians treating quetiapine overdose and to publicise the potential deleterious interaction with adrenaline. We recommend use of noradrenaline in preference to adrenaline in pharmacological management of shock in these patients.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Epinephrine; Female; Humans; Hypotension; Male; Middle Aged; Norepinephrine; Quetiapine Fumarate; Vasoconstrictor Agents

The case of a 44-year-old female patient is reported, who ingested trimipramine and quetiapine in a suicide attempt. Initially sinus tachycardia and hypotension were seen, which resulted in a hypotensive cardio-circulatory failure despite fluid therapy and administration of catecholamines. Because of the life-threatening situation and the fact that the ingestion was 2 h prior to admission, a rapid transport to the next hospital was preferred to treatment with active charcoal. Intoxication with tricyclic antidepressants are very common in Europe and have a mortality of up to 15% in severe cases. The specific therapy consists of airway management, hemodynamic stabilization and primary elimination of the poison. Secondary detoxication is less important. The administration of the antidote physostigmine is controversial but carbo medicinalis should be given orally or via a gastric tube.

Topics: Adult; Antidepressive Agents; Antidotes; Antipsychotic Agents; Charcoal; Dibenzothiazepines; Electrocardiography; Female; Heart Failure; Humans; Hypotension; Quetiapine Fumarate; Shock; Suicide, Attempted; Trimipramine

Previous reports of gabapentin overdose have described mild symptoms of somnolence, ataxia and slurred speech. Quetiapine has produced a false positive for cyclic antidepressants on immunoassay drugscreens. Quetiapine overdose is associated with coma, QTc prolongation and hypotension. We report a case of massive gabapentin and presumptive quetiapine overdose with the highest recorded serum gabapentin concentration (104.5 u/ml) associated with coma, respiratory depression requiring mechanical ventilation, and hypotension.

Topics: Acetates; Amines; Anti-Anxiety Agents; Antipsychotic Agents; Coma; Cyclohexanecarboxylic Acids; Dibenzothiazepines; Drug Overdose; Female; Gabapentin; gamma-Aminobutyric Acid; Humans; Hypotension; Middle Aged; Quetiapine Fumarate; Respiration, Artificial; Respiratory Insufficiency; Suicide, Attempted

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