quetiapine-fumarate and Long-QT-Syndrome

QT prolongation can occur with both first- (FGA) and second-generation antipsychotics (SGA). QT prolongation was identified in an adult patient who presented to the emergency room with schizophrenia, fluid and electrolyte imbalances, and pneumonia. Quetiapine, an SGA, was a component of the pharmacotherapy regimen. Based on the Naranjo adverse drug reaction probability scale rating criteria, a probable causal association was made.. PubMed and Ovid were searched using the terms antipsychotic, psychotropic, QT interval, corrected QT interval (QTc) prolongation, and quetiapine. References were examined for additional articles related to antipsychotic drugs and the QT interval.. In this patient, the use of quetiapine was identified as a contributing factor in QT prolongation. Prior QT prolongation was experienced with ziprasidone, another SGA. The antidepressant and dose remained consistent throughout the inpatient course of treatment. Other risk factors in this patient included hypokalemia, dehydration, pneumonia, age, gender, and concurrent usage of an antidepressant. Dual psychiatric diagnoses, preexisting cardiovascular disease, and electrolyte disturbances may increase this risk potential.. Psychiatric patients may be more at risk of cardiovascular complications, such as QT interval prolongation. The pharmacist can help evaluate risk factors and provide input into the care of all patients, particularly those identified as at risk.

Topics: Antipsychotic Agents; Dibenzothiazepines; Female; Humans; Long QT Syndrome; Middle Aged; Quetiapine Fumarate; Risk Factors; Schizophrenia

Quetiapine has been reported to prolong the QT interval, and has been used as a positive control in thorough QT studies. The objective of the present study was to evaluate, in the late stages of clinical development, the QT-prolongation effects of the extended-release (XR) formulation of quetiapine at the approved dose in Japanese patients with bipolar disorder, using concentration-QT modeling and simulation.. Plasma concentrations of quetiapine and 4 of its metabolites (M1, M2, M4, and M5), and the QT interval corrected using the Fridericia formula (QTcF), were used for the concentration-QT analysis. Data from intensive electrocardiogram monitoring at predose and at 4, 6, 10, and 24 h after the administration of the last dose were pooled from a Phase I trial (6949-CL-0006) and from sparse sampling in late-stage clinical trials (6949-CL-0005, -0021, -0022, and -0023) in Japanese patients (N = 505). The upper limit of 1-sided 95% confidence interval (CI) of the changes from baseline in QTcF (ΔQTcF) at the geometric mean Cmax of a therapeutic dose of 300 mg once daily was predicted using a linear mixed-effects model, with the intercept as a random effect specifying a subject effect.. For quetiapine and M2, but not M1, M4, or M5, positive slopes were observed between ΔQTcF and concentration. The predicted upper limits of the 1-sided 95% CIs did not exceed the regulatory threshold of 10 msec. Therefore, QTc prolongation is unlikely to be clinically relevant at the approved dose of quetiapine XR.. In this pooled data analysis of the QT-prolongation effects of the quetiapine XR, positive relationships between ΔQTcF and quetiapine and M2 concentrations were observed. However, the predicted upper limits of the 1-sided 95% CIs did not exceed 10 msec. Therefore, QTc prolongation is unlikely to be clinically relevant at the approved dose. ClinicalTrials.gov identifiers: NCT01725282, NCT01919008, NCT01725308, NCT01737268, and NCT02362412.

Topics: Adult; Aged; Aged, 80 and over; Asian People; Bipolar Disorder; Computer Simulation; Cross-Over Studies; Delayed-Action Preparations; Double-Blind Method; Electrocardiography; Female; Heart Rate; Humans; Long QT Syndrome; Male; Middle Aged; Models, Biological; Quetiapine Fumarate; Young Adult

Prescriptions of antipsychotic drugs (AP) in children and adolescents have significantly increased in Europe as well as in the United States. However, there is limited evidence of the cardiac safety of second-generation antipsychotics (SGA) in the pediatric population.. The aim of the study is to evaluate the cardiac side effects of SGA in children and adolescents, and how they are influenced by clinical, demographic, and treatment factors.. This article presents a naturalistic, longitudinal, multicenter study conducted in 216 treatment-naïve or quasi-naïve children and adolescents receiving AP treatment. It analyzed the possible influence of AP treatment on variables such as corrected QT (QTc) intervals and heart rate for a period of 12 months (baseline, 3 months, 6 months, and 12 months). Differences among the three main prescribed drugs used in the sample (risperidone, quetiapine, and olanzapine) were assessed.. A total of 211 received one of the three most prescribed AP (quetiapine, risperidone or olanzapine). There were no significant QTc variations in the sample during follow-up (p = 0.54). There were no differences in QTc rates between the different SGA (risperidone-olanzapine p = 0.43; risperidone-quetiapine p = 0.42; olanzapine-quetiapine p = 0.23). When demographic, clinical, or concomitant treatment variables were considered, only baseline overweight correlated with QTc prolongation (p = 0.003). The heart rate in the whole sample tended to decrease during follow-up (p = 0.054). However, patients on quetiapine showed increased heart rate compared with those on risperidone (p = 0.04).. In this sample, SGA seem to have a safe heart side effect profile in the child and adolescent population. There was no observed mean increase in QTc or in heart rate.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Biomarkers, Pharmacological; Child; Child, Preschool; Electrocardiography; Female; Heart Rate; Humans; Long QT Syndrome; Longitudinal Studies; Male; Olanzapine; Prospective Studies; Quetiapine Fumarate; Risperidone

The QT interval is the most widely used surrogate marker for predicting TdP; however, several alternative surrogate markers, such as Tpeak-Tend (TpTe) and a quantitative T-wave morphology combination score (MCS) have emerged. This study investigated the cardiac effects of sertindole and quetiapine using the QTc interval and newer surrogate markers. Data were derived from a 12 week randomized double-blind study comparing flexible dosage of sertindole 12-20mg and quetiapine 400-600mg in patients with schizophrenia. ECGs were recorded digitally at baseline and after 3, 6 and 12 weeks. Between group effects were compared by using a mixed effect model, whereas assessment within group was compared by using a paired t-test. Treatment with sertindole was associated with QTcF and QTcB interval prolongation and an increase in MCS, T-wave asymmetry, T-wave flatness and TpTe. The mean increase in QTcF from baseline to last observation was 12.1ms for sertindole (p<0.001) and -0.5ms for quetiapine (p=0.8). Quetiapine caused no increase in MCS, T-wave asymmetry, T-wave flatness or TpTe compared to baseline. In the categorical analysis, there were 11 patients (9.6%) receiving quetiapine who experienced more than 20ms QTcF prolongation compared with 36 patients (33.3%) in the sertindole group. Sertindole (12-20mg) was associated with moderate QTc prolongation and worsening of T-wave morphology in a study population of patients with schizophrenia. Although, quetiapine (400-600mg) did not show worsening of repolarization measures some individual patients did experience significant worsening of repolarization. Clinical Trials NCT00654706.

Topics: Antipsychotic Agents; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Female; Follow-Up Studies; Heart Rate; Humans; Imidazoles; Indoles; Long QT Syndrome; Male; Principal Component Analysis; Quetiapine Fumarate; Schizophrenia

We examined sex differences in the effect of olanzapine (OLZ), risperidone (RIS), aripiprazole (ARP), or quetiapine (QTP) on mean corrected QT (QTc) intervals among 222 patients with schizophrenia.. Subjects were patients with schizophrenia who were treated with either OLZ (n = 69), RIS (n = 60), ARP (n = 62), or QTP (n = 31). Electrocardiographic measurements were conducted, and the QT interval was corrected using Bazett's correction formula.. The mean QTc interval of the QTP group was significantly longer than that of the RIS group (p = 0.002) or ARP group (p = 0.029). The mean QTc interval of the OLZ group was also significantly longer than that of the RIS group (p = 0.006). In female participants, the difference in the mean QTc interval among the four second-generation antipsychotic (SGA) groups was statistically significant (p = 0.002), whereas in male patients, there was no significant difference in the mean QTc interval among the four SGA groups. Post hoc analyses showed that sex differences in QTc interval were observed only in OLZ treatment group (p = 0.007).. To our knowledge, this is the first study to demonstrate sex differences in the effect of four SGAs on the QTc interval.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Dibenzothiazepines; Electrocardiography; Female; Humans; Long QT Syndrome; Male; Middle Aged; Olanzapine; Piperazines; Quetiapine Fumarate; Quinolones; Risperidone; Schizophrenia; Sex Factors; Young Adult

The potential for iloperidone, a D2/5-HT2A antipsychotic, to affect the heart rate-corrected QT interval (QTc) was assessed in the absence and presence of metabolic inhibitors in a randomized, open-label, multicenter study. QT interval prolongation by medications, including both conventional and atypical antipsychotic drugs, can predispose patients to cardiac arrhythmias and result in sudden death. Adults with schizophrenia or schizoaffective disorder and normal electrocardiograms at baseline (N = 188) were randomized 1:1:1:1:1 to iloperidone, 8 mg twice daily (BID), 12 mg BID, 24 mg once daily (QD); quetiapine, 375 mg BID; or ziprasidone, 80 mg BID during period 1 (no metabolic inhibitors present). Iloperidone BID produced mean changes in QTc Fridericia correction (QTcF) interval (8.5-9.0 milliseconds [ms]) similar to those produced by ziprasidone (9.6 ms) and higher than those produced by quetiapine (1.3 ms). Iloperidone, 24 mg QD, produced a mean QTcF change of 15.4 ms. Coadministration of metabolic inhibitors with iloperidone during periods 2 (paroxetine) and 3 (paroxetine and ketoconazole) resulted in greater increases in the QTc interval. Increased QTc was observed in individuals with specific cytochrome P450 2D6 polymorphisms. Up to 10% of patients on iloperidone experienced QTc intervals of 60 ms or longer in the presence of metabolic inhibition and QD dosing. However, no patients experienced QTc changes of clinical concern (QTc ≥ 500 ms). The most common adverse events with iloperidone were headache, anxiety, and dyspepsia. The only cardiovascular adverse events with iloperidone were non-concentration-dependent tachycardia that was mild in most patients and did not lead to further sequelae. Pharmacogenetics and recommendations are discussed.

Topics: Adolescent; Adult; Aged; Antipsychotic Agents; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP2D6 Inhibitors; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inhibitors; Dibenzothiazepines; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Electrocardiography; Enzyme Inhibitors; Female; Genotype; Heart Rate; Humans; Isoxazoles; Ketoconazole; Linear Models; Long QT Syndrome; Male; Middle Aged; Paroxetine; Pharmacogenetics; Phenotype; Piperazines; Piperidines; Quetiapine Fumarate; Thiazoles; United States; Young Adult

The effect of two atypical antipsychotics on QTc intervals (heart rate-corrected QT interval) was evaluated. Patients (N=109) with schizophrenia (79%) or schizoaffective disorder (21%) were randomly assigned in 2 : 2 : 1 ratio to paliperidone extended release (ER), quetiapine, or placebo. Doses of 12 and 18 mg/day of paliperidone ER were compared with quetiapine 800 mg/day. Least-squares mean change from baseline in population-specific linear-derived correction method from baseline to days 6-7 at individual tmax was 5.1 ms less [90% confidence interval: -9.2 to -0.9] with paliperidone ER 12 mg/day than with quetiapine 800 mg/day. On the basis of a prespecified 10-ms noninferiority margin, paliperidone ER was thus declared noninferior to quetiapine (primary analysis). Mean change in population-specific linear-derived correction method from baseline to days 11-12 at individual tmax was 2.3 ms less (90% confidence interval: -6.8 to 2.3) with paliperidone ER 18 mg/day than with quetiapine 800 mg/day. Treatment-emergent adverse events occurred in 36 (82%) patients treated with paliperidone ER, 41 (95%) patients treated with quetiapine, and 14 (64%) patients treated with placebo. No adverse events of a proarrhythmic nature were noted. The effect on the QTc interval in patients with schizophrenia or schizoaffective disorder was comparable between paliperidone ER 12 mg/day (maximum recommended dose), paliperidone ER 18 mg/day (supratherapeutic dose), and quetiapine 800 mg/day.

Topics: Adult; Antipsychotic Agents; Delayed-Action Preparations; Dibenzothiazepines; Double-Blind Method; Electrocardiography; Female; Humans; Isoxazoles; Long QT Syndrome; Male; Middle Aged; Paliperidone Palmitate; Pyrimidines; Quetiapine Fumarate; Schizophrenia; Treatment Outcome

Many drugs have been associated with QTc prolongation and, in some cases, this is augmented by concomitant administration with metabolic inhibitors. The effects of 6 antipsychotics on the QTc interval at and around the time of estimated peak plasma/serum concentrations in the absence and presence of metabolic inhibition were characterized in a prospective, randomized study in which patients with psychotic disorders reached steady-state on either haloperidol 15 mg/d (n = 27), thioridazine 300 mg/d (n = 30), ziprasidone 160 mg/d (n = 31), quetiapine 750 mg/d (n = 27), olanzapine 20 mg/d (n = 24), or risperidone 6-8 mg/d increased to 16 mg/d (n = 25/20). Electrocardiograms (ECGs) were done at estimated Cmax at steady-state on both antipsychotic monotherapy and after concomitant administration of appropriate cytochrome P-450 (CYP450) inhibitor(s). Mean QTc intervals did not exceed 500 milliseconds in any patient taking any of the antipsychotics studied, in the absence or presence of metabolic inhibition. The mean QTc interval change was greatest in the thioridazine group, both in the presence and absence of metabolic inhibition. The presence of metabolic inhibition did not significantly augment QTc prolongation associated with any agent. Each of the antipsychotics studied was associated with measurable QTc prolongation at steady-state peak plasma concentrations, which was not augmented by metabolic inhibition. The theoretical risk of cardiotoxicity associated with QTc prolongation should be balanced against the substantial clinical benefits associated with atypical antipsychotics and the likelihood of other toxicities.

Topics: Adolescent; Adult; Antipsychotic Agents; Aryl Hydrocarbon Hydroxylases; Benzodiazepines; Biotransformation; Clozapine; Dibenzothiazepines; Electrocardiography; Female; Haloperidol; Heart Conduction System; Humans; Long QT Syndrome; Male; Middle Aged; Olanzapine; Quetiapine Fumarate; Risperidone; Thioridazine

Dear Doctor Letters (DDLs, Direct Healthcare Professional Communications) from 2011 provided guidance regarding QTc-prolonging effects with risk of torsade de pointes during treatment with citalopram and escitalopram. This study examines the DDLs' effects on prescription behavior. Data from 8842 inpatients treated with citalopram or escitalopram with a primary diagnosis of major depressive disorder (MDD) were derived from a European pharmacovigilance study (Arzneimittelsicherheit in der Psychiatrie, AMSP) from 2001 to 2017. It was examined to what extent new maximum doses were adhered to and newly contraindicated combinations with QTc-prolonging drugs were avoided. In addition, the prescriptions of psychotropic drugs before and after DDLs were compared in all 43,480 inpatients with MDD in the data set. The proportion of patients dosed above the new limit decreased from 8 to 1% in patients ≤ 65 years and from 46 to 23% in patients > 65 years old for citalopram versus 14-5% and 47-31% for escitalopram. Combinations of es-/citalopram with other QTc-prolonging psychotropic drugs reduced only insignificantly (from 35.9 to 30.9%). However, the proportion of patients with doses of quetiapine > 150 mg/day substantially decreased within the combinations of quetiapine and es-/citalopram (from 53 to 35%). After the DDLs, prescription of citalopram decreased and of sertraline increased. The DDLs' recommendations were not entirely adhered to, particularly in the elderly and concerning combination treatments. This might partly be due to therapeutic requirements of the included population. Official warnings should consider clinical needs.

Topics: Aged; Citalopram; Depressive Disorder, Major; Escitalopram; Humans; Long QT Syndrome; Psychotropic Drugs; Quetiapine Fumarate

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

Quetiapine, an atypical antipsychotic drug, is used for the treatment of schizophrenia and acute mania. Although a previous report showed that quetiapine blocked hERG potassium current, quetiapine has been considered relatively safe in terms of cardiovascular side effects. In the present study, we used the whole-cell patch-clamp technique to investigate the effect that quetiapine and its major metabolite norquetiapine can exert on human cardiac sodium channels (hNa

Topics: Action Potentials; Dibenzothiazepines; Heart; HEK293 Cells; Humans; Long QT Syndrome; Membrane Potentials; Myocardium; NAV1.5 Voltage-Gated Sodium Channel; Patch-Clamp Techniques; Quetiapine Fumarate; Sodium Channel Blockers

Quetiapine is an atypical antipsychotic commonly utilized for the management of delirium in critically ill patients. The impact of quetiapine on QTc in the critically ill population is largely unknown.. The purpose of this study was to evaluate QTc prolongation following administration of quetiapine for the management of delirium in critically ill patients.. This was a single-center prospective, observational cohort study. QTc measurements of patients who received at least one dose of quetiapine were compared with a control group receiving melatonin. The primary outcome was mean change in QTc from baseline to maximum serum drug concentration after the first dose of quetiapine.. No significant change in QTc was observed from baseline to post-quetiapine administration, with a mean change in QTc of 2.7 ms (438.4 ± 43.2 ms vs 441.1 ± 36.4 ms; P = 0.50). When comparing mean change in QTc between the quetiapine group and melatonin group, the difference was not significant (2.7 ± 37.8 ms vs -0.18 ± 32.0 ms, P = 0.73). Conclusion and Relevance: This study represents one of the first prospective studies evaluating the impact of quetiapine on QTc. The results of this study demonstrate a nonsignificant statistical and clinical change in the QTc following quetiapine administration in critically ill patients utilizing telemetry measurements. Routine QTc monitoring with formal electrocardiogram(s) following quetiapine administration may not be warranted.

Topics: Adult; Antipsychotic Agents; Cohort Studies; Critical Illness; Delirium; Electrocardiography; Female; Humans; Long QT Syndrome; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Telemetry

Quetiapine, an atypical antipsychotic used in the intensive care unit (ICU) to manage delirium, has a possible adverse effect of corrected QT (QTc) interval prolongation. The objective of this analysis was to describe the impact of quetiapine on QTc interval prolongation in critically ill patients. This was a single-center, prospective cohort analysis of ICU patients who received quetiapine between October 2015 and February 2016. The major end point was the incidence of QTc prolongation greater than 60 milliseconds above baseline during therapy. Minor end points included median change in QTc interval and incidence of Torsades de Pointes (TdP). Univariate and multivariable analyses were performed to determine variables associated with higher risk of QTc prolongation. During the study period, 103 patients were enrolled in the analysis. QTc interval prolongation greater than 60 milliseconds occurred in 14 (13.6%) patients. The median change in QTc interval was 20 milliseconds. There were no cases of TdP. On multivariable analysis, the only variable associated with higher incidence of QTc prolongation was administration of a concomitant medication known to prolong the QTc interval ( P = .046). QTc prolongation was relatively uncommon among critically ill patients utilizing quetiapine. Patients receiving concomitant medications known to prolong the QTc interval may be at an increased risk.

Topics: Aged; Antipsychotic Agents; Cohort Studies; Critical Illness; Delirium; Electrocardiography; Female; Humans; Long QT Syndrome; Male; Middle Aged; Prospective Studies; Quetiapine Fumarate; Treatment Outcome

Topics: Adult; Antipsychotic Agents; Electrocardiography; Female; Humans; Long QT Syndrome; Quetiapine Fumarate; Risk Factors; Torsades de Pointes

Topics: Antipsychotic Agents; Depressive Disorder, Major; Dose-Response Relationship, Drug; Electrocardiography; Humans; Long QT Syndrome; Male; Middle Aged; Quetiapine Fumarate

Topics: Animals; Antipsychotic Agents; Dibenzothiazepines; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; Evidence-Based Medicine; Heart Conduction System; Humans; Long QT Syndrome; Potassium Channel Blockers; Quetiapine Fumarate; Risk Assessment; Risk Factors; Torsades de Pointes

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

We present a case of massive overdose with the atypical antipsychotic quetiapine in a 34-year-old woman (body weight 65 kg). At admission, approximately 2 to 4 hours after ingestion of approximately 24 g of quetiapine, the patient was comatose (Glasgow Coma Scale score 5), requiring orotracheal intubation and transfer to the intensive care unit. Because of myoclonic jerks and generalized seizures, benzodiazepines were administered. In addition to transient mild hypotension after intubation, the main cardiovascular manifestation was sinus tachycardia. The QT interval was normal, and the QTc interval (Bazett's correction) was maximally prolonged to 620 ms. However, no malignant arrhythmias were observed. The patient recovered within 2 days but remained agitated and aggressive, for which she was transferred to the psychiatric clinic. The pharmacokinetics of quetiapine in such a large overdose could not be described by simple first-order kinetics. The initially observed rapid decline of the plasma concentrations of quetiapine could be simulated by first-order kinetics (half life = 4.1 hr) and can most probably be explained by rapid distribution into tissues. The final elimination of the drug from the body occurred after approximately 34 hours at much slower rate, most probably reflecting redistribution from tissues into blood and consecutive hepatic clearance of the drug.

Topics: Adult; Antipsychotic Agents; Autonomic Nervous System Diseases; Chromatography, High Pressure Liquid; Coma; Depressive Disorder, Major; Dibenzothiazepines; Drug Overdose; Female; Glasgow Coma Scale; Half-Life; Humans; Long QT Syndrome; Parasympathetic Nervous System; Quetiapine Fumarate; Schizophrenia; Seizures; Suicide, Attempted

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Child; Child, Preschool; Dibenzothiazepines; Electrocardiography; Female; Follow-Up Studies; Humans; Long QT Syndrome; Male; Olanzapine; Quetiapine Fumarate; Risperidone

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Drug Overdose; Female; Heart Conduction System; Humans; Long QT Syndrome; Quetiapine Fumarate; Sleep Stages

Ziprasidone, a novel antipsychotic agent for the treatment of schizophrenia, undergoes partial metabolism by cytochrome P450 3A4. It is associated with moderate prolongation of QT interval, but no increased risk for ventricular tachyarrhythmia or sudden death was demonstrated.. A 70-year-old male was initiated on quetiapine therapy for an acute exacerbation of chronic schizophrenia. The baseline electrocardiogram (ECG) showed a normal QT interval (QTc: 417 ms). In combination therapy of quetiapine and ziprasidone the patient developed suddenly cardiac arrhythmia with extrasystoles and the ECG revealed a prolonged QTc interval of 482 ms. After breaking off treatment with quetiapine and reduction of ziprasidone a normalized QT interval (QTc: 428 ms) was measured.. We suppose a potential of pharmacokinetic interaction between quetiapine and ziprasidone because of the same metabolic pathway by CYP3A4. Combining treatment of quetiapine and ziprasidone is therefore contraindicated. In addition we suggest caution using ziprasidone with any potential 3A4 substrate or inhibitor.

Topics: Acute Disease; Aged; Antipsychotic Agents; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Electrocardiography; Hallucinations; Humans; Long QT Syndrome; Male; Piperazines; Quetiapine Fumarate; Schizophrenia, Paranoid; Thiazoles

Quetiapine is an atypical antipsychotic agent with structural similarities to the tricyclic antidepressants (TCA). We report a case of quetiapine overdose that was initially clinically similar to that of a TCA overdose and caused a false-positive TCA immunoassay. We then analyzed three common TCA immunoassays [Microgenics (formerly Diagnostic Reagents, Inc.) Tricyclics Serum Tox EIA Assay, Syva RapidTest d.a.u., and Biosite Triage Panel for Drugs of Abuse] with quetiapine in solution as well as urine from both an overdose patient and a therapeutic patient. There was significant variation of the cutoff of false-positivity in all three immunoassays. Both the Syva and Microgenics immunoassays tested positive in both the overdose and therapeutic samples and were positive at urine levels of 100 microg/mL and 10 microg/mL, respectively. The Triage immunoassay was negative in solutions up to 1000 microg/mL and negative in both the therapeutic and overdose urine samples. Quetiapine may cause false-positive TCA immunoassay with both therapeutic use and in overdose. Significant variation exists between immunoassays to detect quetiapine as a false-positive test.

Topics: Adult; Antibody Specificity; Antidepressive Agents, Tricyclic; Antipsychotic Agents; Chromatography, Gas; Cross Reactions; Dibenzothiazepines; Drug Overdose; Electrocardiography; False Positive Reactions; Female; Humans; Immunoassay; Long QT Syndrome; Quetiapine Fumarate; Suicide, Attempted

Topics: Antipsychotic Agents; Dibenzothiazepines; Electroencephalography; Equipment Failure; Female; Humans; Long QT Syndrome; Middle Aged; Psychotic Disorders; Quetiapine Fumarate

Topics: Aged; Antipsychotic Agents; Clozapine; Dibenzothiazepines; Electrocardiography; Female; Humans; Long QT Syndrome; Psychotic Disorders; Quetiapine Fumarate; Ventricular Premature Complexes

Topics: Antipsychotic Agents; Dibenzothiazepines; Drug Interactions; Drug Therapy, Combination; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Long QT Syndrome; Lovastatin; Quetiapine Fumarate

QTc interval prolongation can occur as a result of treatment with both conventional and novel antipsychotic medications and is of clinical concern because of its association with the potentially fatal ventricular arrhythmia, torsade de pointes.. One case is described in which a patient with schizophrenia, who was being treated for dyslipidemia, developed a prolonged QTc interval while taking quetiapine and lovastatin.. QTc returned to baseline when the lovastatin dose was reduced.. QTc prolongation associated with antipsychotic medication occurs in a dose-dependent manner. We therefore hypothesize that the addition of lovastatin caused an increase in plasma quetiapine levels through competitive inhibition of the cytochrome P(450) (CYP) isoenzyme 3A4. Our case highlights the potential for a drug interaction between quetiapine and lovastatin leading to QTc prolongation during the management of dysipidemia in patients with schizophrenia.

Topics: Anticholesteremic Agents; Antipsychotic Agents; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Dibenzothiazepines; Electrocardiography; Female; Humans; Hyperlipidemias; Long QT Syndrome; Lovastatin; Middle Aged; Mixed Function Oxygenases; Quetiapine Fumarate; Schizophrenia; Time Factors; Triglycerides

We report a patient who ingested a 2000-mg overdose of quetiapine fumarate (Seroquel). Her maintenance medications also included risperidone, venlafaxine, topiramate, and clonazepam. On presentation, she was drowsy, but had no other significant CNS signs and no cardiac symptoms or abnormal physical signs. Approximately 2 h after the quetiapine ingestion, an electrocardiogram (ECG) showed normal sinus rhythm at 95 beats/min with a corrected QT (QTc) interval of 537 ms (upper limit of normal = 440 ms). Plasma quetiapine concentration at that time was 1800 ng/ml. Continuous ECG monitoring for the subsequent 18 h did not reveal any episode of ventricular tachycardia. A 12-lead ECG 18 h post-overdose was normal with a QTc interval of 401 ms and the corresponding plasma quetiapine concentration was 160 ng/ml. She made an uneventful medical recovery from the toxic ingestion. This case suggests that when patients overdose on quetiapine while taking therapeutic doses of risperidone, such overdoses, even if not massive, can cause considerable QTc interval prolongation. We recommend that quetiapine overdose patients undergo continuous ECG monitoring for 12-18 h post-ingestion.

Topics: Adult; Antipsychotic Agents; Dibenzothiazepines; Female; Follow-Up Studies; Humans; Long QT Syndrome; Quetiapine Fumarate; Risperidone; Time Factors