quetiapine-fumarate and Arrhythmias--Cardiac

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

Behavioral and psychological symptoms of dementia pose management challenges for caregivers and clinicians. Firstline nonpharmacologic treatments include eliminating physical and emotional stressors, modifying the patient's environment, and establishing daily routines. Family members and caregivers benefit from education about dementia symptoms and reminders that the behaviors are normal and unintentional. Cognitive and emotion-oriented interventions, sensory stimulation interventions, behavior management techniques, and other psychosocial interventions are modestly effective. In refractory cases, physicians may choose to prescribe off-label antipsychotics. Aripiprazole has the most consistent evidence of symptom improvement; however, this improvement is small. Olanzapine, quetiapine, and risperidone have inconsistent evidence of benefit. Physicians should use the smallest effective dose for the shortest possible duration to minimize adverse effects, most notably an increased mortality risk. Other adverse effects include anticholinergic and antidopaminergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, postural hypotension, metabolic syndrome, cardiac arrhythmia, and sedation. Patients should be monitored for these effects while receiving treatment; however, laboratory monitoring may be limited to patients receiving long-term therapy.

Topics: Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Basal Ganglia Diseases; Behavior Therapy; Benzodiazepines; Cognitive Behavioral Therapy; Dementia; Emotions; Humans; Hypotension, Orthostatic; Metabolic Syndrome; Neuroleptic Malignant Syndrome; Olanzapine; Practice Guidelines as Topic; Psychotic Disorders; Quetiapine Fumarate; Risperidone

Topics: Animals; Antipsychotic Agents; Arrhythmias, Cardiac; Cardiotonic Agents; Dibenzothiazepines; Drug Interactions; Drug Labeling; Humans; Quetiapine Fumarate

Management of bipolar disorder (BPD) may require multiple medications, including lithium, anticonvulsants, and antipsychotics (both conventional and atypical). Updated treatment guidelines reflect an expanded role for atypical antipsychotics (AAPs) in BPD treatment. Five AAPs--olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole--are approved by the US Food and Drug Administration (FDA) as monotherapy for first-line treatment of acute manic and (except for quetiapine) mixed episodes. Two AAPs--olanzapine (in fixed-dose combination with fluoxetine) and quetiapine--are also FDA approved for bipolar depression. For long-term maintenance therapy, one option is to continue effective, well-tolerated acute phase treatment; however, only olanzapine and aripiprazole are FDA approved for maintenance, based on evidence from randomized, placebo-controlled clinical trials. Although head-to-head comparisons are scarce, meta-analysis data suggest that olanzapine, risperidone, quetiapine, ziprasidone, and aripiprazole have similar antimanic efficacy; therefore, AAP selection for this indication should be guided by other considerations such as safety, tolerability, and cost. Safety and tolerability issues to consider when selecting an AAP include metabolic dysfunction (weight gain, type 2 diabetes, and dyslipidemia); hyperprolactinemia; extrapyramidal symptoms; QTc prolongation; and pharmacokinetic drug interactions.

Topics: Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Benzodiazepines; Bipolar Disorder; Diabetes Mellitus, Type 2; Dibenzothiazepines; Drug Evaluation; Drug Interactions; Drug Therapy, Combination; Dyslipidemias; Humans; Hyperprolactinemia; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Thiazoles; Treatment Outcome; Weight Gain

There are now five new-generation atypical psychiatric medications currently available. As these new treatments have become more common, they have grown to account for a significant percentage of all psychiatric medications prescribed. This is because of their efficacy in the treatment of several psychiatric disorders, ease of administration, and absence of the well-known extrapyramidal adverse effects long-attributed to the standard dopamine blocking anti-psychotic medications. As these medications have become treatments of choice, we have discovered additional information about their respective side effects. Issues such as bone marrow suppression, endocrine abnormalities, and most recently cardiac arrhythmia have produced concern. This paper will address all in an attempt to inform the primary care physician of the most prominent and clinically relevant adverse effects of these agents. A particular focus will address the increasing concern that these new medications can produce hyperglycemia and diabetes mellitus.

Topics: Adult; Aged; Antipsychotic Agents; Arrhythmias, Cardiac; Benzodiazepines; Black or African American; Bone Marrow Diseases; Child; Dibenzothiazepines; Endocrine System Diseases; Humans; Mental Disorders; Nervous System Diseases; Olanzapine; Piperazines; Pirenzepine; Primary Health Care; Quetiapine Fumarate; Risperidone; Thiazoles

An assessment of the effects of asenapine on QTc interval in patients with schizophrenia revealed a discrepancy between the results obtained by two different methods: an intersection-union test (IUT) (as recommended in the International Conference on Harmonisation E14 guidance) and an exposure-response (E-R) analysis. Simulations were performed in order to understand and reconcile this discrepancy. Although estimates of the time-matched, placebo-corrected mean change in QTc from baseline (ddQTc) at peak plasma concentrations from the E-R analysis ranged from 2 to 5 ms per dose level, the IUT applied to simulated data from the E-R model yielded maximum ddQTc estimates of 7-10 ms for the various doses of asenapine. These results indicate that the IUT can produce biased estimates that may induce a high false-positive rate in individual thorough QTc trials. In such cases, simulations from an E-R model can aid in reconciling the results from the two methods and may support the use of E-R results as a basis for labeling.

Topics: Antipsychotic Agents; Arrhythmias, Cardiac; Bias; Computer Simulation; Data Interpretation, Statistical; Dibenzocycloheptenes; Dibenzothiazepines; Dose-Response Relationship, Drug; False Positive Reactions; Heterocyclic Compounds, 4 or More Rings; Humans; Models, Biological; Pharmacology, Clinical; Practice Guidelines as Topic; Quetiapine Fumarate; Schizophrenia; Toxicity Tests

Delirium is a common complication of critical illness, with a prevalence of 25% among pediatric intensive care unit (ICU) patients. Pharmacological treatment options for ICU delirium are limited to off-label use of antipsychotics, but their benefit remains uncertain.. The purpose of this study was to evaluate quetiapine effectiveness for the treatment of delirium in critically ill pediatric patients and to describe the safety profile of quetiapine.. A single-center, retrospective review of patients aged ≤ 18 years who screened positive for delirium via the Cornell Assessment of Pediatric Delirium (CAPD ≥ 9) and received ≥ 48 hours of quetiapine therapy was conducted. The relationship between quetiapine and deliriogenic medication doses was evaluated.. This study included 37 patients who received quetiapine for the treatment of delirium. The change in sedation requirements before quetiapine initiation to 48 hours after the highest quetiapine dose demonstrated a downward trend; 68% of patients had a decrease in opioid requirements and 43% of patients had a decrease in benzodiazepine requirements. The median CAPD score at baseline was 17 and the median CAPD score at 48 hours after the highest dose was 16. Three patients experienced QTc prolongation (defined as a QTc ≥ 500), although none developed dysrhythmias.. Quetiapine did not have a statistically significant impact on deliriogenic medication doses. There were minimal changes in QTc and dysrhythmias were not identified. Therefore, quetiapine can be safe to use in our pediatric patients but further studies are needed to find an effective dose.

Topics: Antipsychotic Agents; Arrhythmias, Cardiac; Child; Critical Illness; Delirium; Humans; Intensive Care Units; Quetiapine Fumarate; Retrospective Studies

Torsade de pointes is a potentially lethal polymorphic ventricular tachyarrhythmia that can occur in the setting of long QT syndrome (LQTS). LQTS is multi-hit in nature and multiple factors combine their effects leading to increased arrhythmic risk. While hypokalemia and multiple medications are accounted for in LQTS, the arrhythmogenic role of systemic inflammation is increasingly recognized but often overlooked. We tested the hypothesis that the inflammatory cytokine interleukin(IL)-6 will significantly increase the incidence of arrhythmia when combined with other pro-arrhythmic conditions (hypokalemia and the psychotropic medication, quetiapine).. Guinea pigs were injected intraperitoneally with IL-6/soluble IL-6 receptor and QT changes were measured in vivo. Subsequently, hearts were cannulated via Langendorff perfusion for ex vivo optical mapping measurements of action potential duration (APD. IL-6 prolonged QTc in vivo guinea pigs from 306.74 ± 7.19 ms to 332.60 ± 8.75 ms (n = 8, p = .0021). Optical mapping on isolated hearts demonstrated APD prolongation in IL-6- vs saline groups (3Hz APD. Our experimental observations strongly suggest that controlling inflammation, specifically IL-6, could be a viable and important route for reducing QT prolongation and arrhythmia incidence in the clinical setting.

Topics: Animals; Arrhythmias, Cardiac; Cytokines; Electrocardiography; Guinea Pigs; Hypokalemia; Inflammation; Interleukin-6; Long QT Syndrome; Quetiapine Fumarate; Torsades de Pointes

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

A 25-year-old patient was admitted urgently due to mixed amitriptyline/quetiapine intoxication at a potentially lethal dose. Alongside severe anticholinergic toxidrome, she presented with antiadrenergic and quinidin-like cardiotoxic findings, including ventricular tachycardia. In the present case, arrhythmia and circulatory shock responded neither to alkalization and elevated sodium levels after infusion of sodium bicarbonate, nor to any other established therapies. Following the lipid rescue paradigm, bolus infusion of a 20% lipid emulsion led to rapid stabilization and continued reversal of all intoxication features.

Topics: Adrenergic Uptake Inhibitors; Adult; Amitriptyline; Arrhythmias, Cardiac; Drug Overdose; Female; Humans; Lipids; Quetiapine Fumarate; Tachycardia, Ventricular

In 2012, the Food and Drug Administration issued Drug Safety Communications on several drugs associated with QT prolongation and fatal ventricular arrhythmias. Among these was citalopram, a selective serotonin reuptake inhibitor (SSRI) approved for depression and commonly used for posttraumatic stress disorder (PTSD). Evaluation of the risk for QT prolongation among other psychotropic drugs for individuals with PTSD remains limited.. Explore psychotropic drugs associated with QT prolongation among veterans with PTSD.. Patients in the Veterans Health Administration in 2006-2009 with PTSD and QT prolongation (176 cases) were matched 1:4 on age, gender, visit date and setting, and physical comorbidity. Classification trees assessed QT prolongation risk among prescribed medications (n=880).. Receipt of any drug with known risk of QT prolongation varied by group (23% QT cases vs 15% control, p<0.01). Psychotropic medications conferring significant risks included ziprasidone (3% vs 1%, p=0.02) and buspirone (6% vs 2%, p=0.01). Increased risk was not observed for the SSRIs, citalopram and fluoxetine. Classification trees found that sotalol and amitriptyline carried greater risk among cardiac patients and methadone, especially if prescribed with quetiapine, among noncardiac patients. Per adjusted survival model, patients with QT prolongation were at increased risk for death (hazard ratio=1.60; 95% CI=1.04-2.44).. Decision models are particularly advantageous when exploring nonlinear relationships or nonadditive interactions. These findings may potentially affect clinical decision-making concerning treatment for PTSD. For patients at higher risk of QT prolongation, antidepressants other than amitriptyline should be considered. Medications for comorbid conditions should also be closely monitored for heightened QT prolongation risk.

Topics: Adult; Aged; Aged, 80 and over; Amitriptyline; Arrhythmias, Cardiac; Buspirone; Female; Humans; Male; Methadone; Middle Aged; Piperazines; Psychotropic Drugs; Quetiapine Fumarate; Sotalol; Stress Disorders, Post-Traumatic; Thiazoles; Veterans; Young Adult

The purpose of the study was to determine the downstream implications of atypical antipsychotic (AAP) prescribing in the intensive care unit (ICU), including discharge prescribing practices, monitoring, and attributable adverse drug events.. This retrospective cohort study included patients at least 18 years of age admitted to an ICU that received at least 2 doses of an AAP for documented delirium or avoidance of a deliriogenic medication. Exclusion criteria were documentation of an AAP as a home medication or initiation for a psychiatric indication unrelated to delirium (eg, schizophrenia).. During the 8-month study period, 156 patients were included and 133 (85.2%) patients survived to hospital discharge. Of the survivors, AAP therapy was continued for 112 (84.2%) patients upon ICU transfer and for 38 (28.6%) patients upon hospital discharge. A majority of these patients had evidence of delirium resolution or no indication for continuation documented at discharge. Of the 127 patients with an electrocardiogram ordered during AAP therapy, QTc prolongation occurred in 49 (31.4%) patients. An adverse drug event leading to drug discontinuation was documented in 16 (10.2%) patients.. Because of significant patient-centered implications, AAPs initiated in the ICU require continued evaluation for indication to avoid prolonged and possibly unnecessary use.

Topics: Adult; Aged; Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Basal Ganglia Diseases; Benzodiazepines; Cohort Studies; Delirium; Disorders of Excessive Somnolence; Female; Humans; Inappropriate Prescribing; Intensive Care Units; Male; Middle Aged; Olanzapine; Patient Discharge; Piperazines; Quetiapine Fumarate; Retrospective Studies; Risperidone; Survivors; Thiazoles

The treatment of bipolar disorders is based on the concomitant use of the mood stabilizers and antipsychotics. In the first case carbamazepine is frequently used, in the second case second-generation (atypical) neuroleptics like quetiapine. This drug combination in a significant number of cases prevent recurrence of mania and depression, normalizes mood and emotion and improves lifestyle. However, this treatment is related to increased interactions and risk of the side effects. Even greater risks involve mixed drug intoxications with these groups of drugs. In this paper we present acute poisoning with carbamazepine and quetiapine complicated cardiotoxic effects in the form of arrhythmias and conduction disorders of the heart. This symptoms disappeared spontaneously after resolution of the poisoning.

Topics: Antidepressive Agents; Antimanic Agents; Antipsychotic Agents; Arrhythmias, Cardiac; Bipolar Disorder; Carbamazepine; Dibenzothiazepines; Drug Interactions; Female; Heart Conduction System; Humans; Middle Aged; Mood Disorders; Quetiapine Fumarate

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

Acquired long QT interval has been widely reported to be a consequence of drug therapy and electrolyte disturbances. We describe two cases of multifactorial acquired QT interval prolongation and torsades de pointes. In the first case, the drugs venlafaxine, amiodarone and domperidone may have contributed to QT interval prolongation in a patient with hypokalemia and hypomagnesaemia. In the second case, QT interval prolongation occurred in a patient taking quetiapine and citalopram, and whose use of hydrocholorothiazide and history of chronic alcohol abuse likely contributed by rendering the patient hypokalemic. These cases highlight the potential risks associated with polypharmacy and demonstrate that though torsades de pointes is an uncommon arrhythmia, the combination of multiple factors known to prolong QT interval may precipitate this life-threatening arrhythmia.

Topics: Alcoholism; Amiodarone; Antipsychotic Agents; Arrhythmias, Cardiac; Biomarkers; Citalopram; Cyclohexanols; Dibenzothiazepines; Diuretics; Domperidone; Dopamine Antagonists; Electrocardiography; Female; Humans; Hydrochlorothiazide; Hypokalemia; Magnesium; Middle Aged; Polypharmacy; Quetiapine Fumarate; Risk Factors; Selective Serotonin Reuptake Inhibitors; Torsades de Pointes; Treatment Outcome; Venlafaxine Hydrochloride

Topics: Administration, Oral; Aged; Antipsychotic Agents; Aripiprazole; Arrhythmias, Cardiac; Benzodiazepines; Clozapine; Databases, Factual; Dementia; Dibenzothiazepines; Drug Utilization Review; Health Services for the Aged; Humans; Olanzapine; Pharmaceutical Services; Piperazines; Quetiapine Fumarate; Quinolones; Risk Assessment; Risperidone; Stroke; Thiazoles; Treatment Outcome