scholarly journals QTc interval in patients with schizophrenia receiving antipsychotic treatment as monotherapy or polypharmacy

CNS Spectrums ◽  
2017 ◽  
Vol 23 (4) ◽  
pp. 278-283 ◽  
Author(s):  
Anja Elliott ◽  
Thibault Johan Mørk ◽  
Mikkel Højlund ◽  
Thomas Christensen ◽  
Rasmus Jeppesen ◽  
...  
Keyword(s):  
Small Sample Size ◽  
Torsades De Pointes ◽  
Small Sample ◽  
Polymorphic Ventricular Tachycardia ◽  
Antipsychotic Treatment ◽  
Qtc Interval ◽  
Qtc Prolongation ◽  
Worst Case ◽  
Clinical Interviews ◽  
Observational Cohort

ObjectiveAntipsychotics are associated with a polymorphic ventricular tachycardia, torsades de pointes, which, in the worst case, can lead to sudden cardiac death. The QT interval corrected for heart rate (QTc) is used as a clinical proxy for torsades de pointes. The QTc interval can be prolonged by antipsychotic monotherapy, but it is unknown if the QTc interval is prolonged further with antipsychotic polypharmaceutical treatment. Therefore, this study investigated the associations between QTc interval and antipsychotic monotherapy and antipsychotic polypharmaceutical treatment in schizophrenia, and measured the frequency of QTc prolongation among patients.MethodsWe carried out an observational cohort study of unselected patients with schizophrenia visiting outpatient facilities in the region of Central Jutland, Denmark. Patients were enrolled from January of 2013 to June of 2015, with follow-up until June of 2015. Data were collected from clinical interviews and clinical case records.ResultsElectrocardiograms were available for 65 patients, and 6% had QTc prolongation. We observed no difference in average QTc interval for the whole sample of patients receiving no antipsychotics, antipsychotic monotherapy, or antipsychotic polypharmaceutical treatment (p=0.29). However, women presented with a longer QTc interval when receiving polypharmacy than when receiving monotherapy (p=0.01). A limitation of this study was its small sample size.ConclusionsWe recommend an increased focus on monitoring the QTc interval in women with schizophrenia receiving antipsychotics as polypharmacy.

QTc Interval in individuals with schizophrenia receiving antipsychotic as monotherapy or polypharmacy

2017 ◽  
Vol 41 (S1) ◽  
pp. S194-S195
Author(s):  
A. Elliott ◽  
M. Højlund ◽  
T.J. Mørk ◽  
T. Christensen ◽  
R. Jeppesen ◽  
...  
Keyword(s):  
Polymorphic Ventricular Tachycardia ◽  
Antipsychotic Treatment ◽  
Qtc Interval ◽  
Worst Case ◽  
Clinical Interviews ◽  
Schizophrenic Patients ◽  
Observational Cohort ◽  
Competing Interest ◽  
The Impact

IntroductionAntipsychotics are associated with the polymorphic ventricular tachycardia, Torsade's de pointes, which in worst case can lead to sudden cardiac death. The QTc interval is used as a clinical proxy for Torsade's de pointes. QTc interval is prolonged by monotherapy with antipsychotic, but it is unknown if the QTc interval is prolonged further with antipsychotic polypharmacy.ObjectivesTo investigate the associations between QTc interval and antipsychotic mono- and polypharmaceutical treatment, respectively, in schizophrenic patients.AimsTo learn more about the impact of antipsychotics on the QTc interval.MethodsAn observational cohort study of unselected patients with schizophrenia visiting outpatient facilities in the Region of Central Jutland, Denmark. Patients were enrolled from January 2013 through March 2015 with follow-up until June 2015. Data was collected from clinical interviews and clinical case records.ResultsECGs were available in 58 patients receiving antipsychotic treatment. We observed no difference in average QTc interval for the whole sample of patients receiving monotherapy or polypharmacy (P = 0.29). However, women presented longer QTc-interval on polypharmacy than on monotherapy (P = 0.01).ConclusionWe recommend an increased focus on monitoring the QTc interval in woman with schizophrenia receiving antipsychotics as polypharmacy.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Risk of QTc Interval Prolongation Associated With Circulating Anti‐Ro/SSA Antibodies Among US Veterans: An Observational Cohort Study

2021 ◽  
Vol 10 (4) ◽  
Author(s):  
Pietro Enea Lazzerini ◽  
Gabriele Cevenini ◽  
Yongxia Sarah Qu ◽  
Frank Fabris ◽  
Nabil El‐Sherif ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cohort Study ◽  
Small Sample ◽  
Observational Cohort Study ◽  
Current Evidence ◽  
Qtc Interval ◽  
Qtc Prolongation ◽  
Increased Risk ◽  
Observational Cohort ◽  
Us Veterans

Background Anti‐Sjögren's syndrome‐related antigen A‐antibodies (anti‐Ro/SSA‐antibodies) are responsible for a novel form of acquired long‐QT syndrome, owing to autoimmune‐mediated inhibition of cardiac human ether‐a‐go‐go‐related gene‐potassium channels. However, current evidence derives only from basic mechanistic studies and relatively small sample‐size clinical investigations. Hence, the aim of our study is to estimate the risk of QTc prolongation associated with the presence of anti‐Ro/SSA‐antibodies in a large population of unselected subjects. Methods and Results This is a retrospective observational cohort study using the Veterans Affairs Informatics and Computing Infrastructure. Participants were veterans who were tested for anti‐Ro/SSA status and had an ECG. Descriptive statistics and univariate and multivariate logistic regression analyses were performed to identify risk factors for heart rate‐corrected QT interval (QTc) prolongation. The study population consisted of 7339 subjects (61.4±12.2 years), 612 of whom were anti‐Ro/SSA‐positive (8.3%). Subjects who were anti‐Ro/SSA‐positive showed an increased prevalence of QTc prolongation, in the presence of other concomitant risk factors (crude odds ratios [OR], 1.67 [1.26–2.21] for QTc >470/480 ms; 2.32 [1.54–3.49] for QTc >490 ms; 2.77 [1.66–4.60] for QTc >500 ms), independent of a connective tissue disease history. Adjustments for age, sex, electrolytes, cardiovascular risk factors/diseases, and medications gradually attenuated QTc prolongation estimates, particularly when QT‐prolonging drugs were added to the model. Nevertheless, stepwise‐fully adjusted OR for the higher cutoffs remained significantly increased in anti‐Ro/SSA‐positive subjects, particularly for QTc >500 ms (2.27 [1.34–3.87]). Conclusions Anti‐Ro/SSA‐antibody positivity was independently associated with an increased risk of marked QTc prolongation in a large cohort of US veterans. Our data suggest that within the general population individuals who are anti‐Ro/SSA‐positive may represent a subgroup of patients particularly predisposed to ventricular arrhythmias/sudden cardiac death.

scholarly journals Incidence of Corrected QT Prolongation With Concomitant Methadone and Atypical Antipsychotics in Critically Ill Children

2021 ◽  
Vol 26 (3) ◽  
pp. 271-276
Author(s):  
Kaitlin M. Hughes ◽  
Anne Thorndyke ◽  
Emma M. Tillman
Keyword(s):  
Atypical Antipsychotic ◽  
Atypical Antipsychotics ◽  
Pilot Trial ◽  
Critically Ill Children ◽  
Qtc Interval ◽  
Qtc Prolongation ◽  
Significant Difference ◽  
Before And After ◽  
Observational Cohort ◽  
Clinically Significant

OBJECTIVE To evaluate the safety of the combination of methadone and an atypical antipsychotic in PICU patients. METHODS This was a retrospective observational cohort pilot study in a single-center PICU in an academic children's hospital. Children 1 month to 18 years of age were included if they received methadone, were then initiated on an atypical antipsychotic (i.e., quetiapine or risperidone), and had EKG monitoring before and after medication initiation. RESULTS Prolongation of the corrected QT (QTc) interval occurred in 5 of the 34 included patients when an atypical antipsychotic was added to methadone. Of the 5 patients who had a prolonged QTc interval, 4 (80%) were older than 12 years and had a median weight of 91.3 kg. There were statistical differences between age and weight when comparing patients who experienced QTc prolongation, but no differences in sex, ethnicity, electrolyte deficiencies, number of additional QTc-prolonging medications, and number of additional drug-drug interactions were identified. When comparing atypical antipsychotics, 9.5% of patients receiving risperidone had a prolonged QTc interval, versus 23% of patients receiving quetiapine (p = 0.04). The net change in QTc interval after initiation of methadone was 0.19 milliseconds (IQR: −3, 15), which increased after atypical antipsychotic initiation to 4 milliseconds (IQR: −16, 15). CONCLUSIONS Our pilot trial suggests there is no clinically significant difference in incidence of QTc prolongation with addition of atypical antipsychotics to methadone.

Role of Co-occurring Alcohol and Substances Abuse on QTc Interval Prolongation Among Psychiatric Patients: A Cross-sectional National Survey

2017 ◽  
Vol 41 (S1) ◽  
pp. S201-S202
Author(s):  
M. Corbo ◽  
T. Acciavatti ◽  
F. Fiori ◽  
R. Santacroce ◽  
A. Aguglia ◽  
...  
Keyword(s):  
National Survey ◽  
Psychotropic Drugs ◽  
Polymorphic Ventricular Tachycardia ◽  
Qtc Interval ◽  
Interval Prolongation ◽  
Qtc Prolongation ◽  
Cross Sectional ◽  
Star Network ◽  
Qtc Interval Prolongation

IntroductionQTc interval prolongation is considered a risk factor for fatal polymorphic ventricular tachycardia, which can result in sudden cardiac death. Most psychotropic drugs have a dose-dependent potential to prolong the QTc interval. However, other factors require appropriate consideration, including: age; gender; other medications; electrolyte abnormalities; severe comorbid conditions, such as co-occurring alcohol or substances abuse/dependence.ObjectivesThe objective was to study the potential mediating roles of alcohol/substances abuse on QTc prolongation.AimsThe Italian research group STAR Network, in collaboration with the Young Italian Psychiatrists Association, aimed to evaluate the frequency of QTc interval prolongation in a sample of patients under treatment with psychotropic drugs through a cross-sectional national survey.MethodsA sample of 2411 unselected patients were enrolled after performing an ECG during the recruitment period. Sociodemographic and clinical characteristics were collected from medical records. Collected data underwent statistical analysis.ResultsA total of 11.2% of patients reported alcohol abuse, and only 8.9% psychotropic substances. According to the threshold, less than 20% of patients had a borderline value of QTc, and 1% a pathological value. Patients with co-occurring alcohol misuse and drug abuse were more likely to have longer QTc interval.ConclusionsThe present study describes the frequency of QTc prolongation in real-world clinical practice. Before prescribing a psychotropic drug, the physician should carefully assess its risks and benefits to avoid this type of adverse reaction, particularly when additional risk factors are present. The potential role of alcohol and substances on QTc length could be particularly useful in emergency settings.Disclosure of interestThe authors have not supplied their declaration of competing interest.

QTc Prolongation and Torsades de Pointes

2020 ◽  
pp. 137-142
Author(s):  
Ankur Srivastava ◽  
James E. Littlejohn
Keyword(s):  
Qt Interval ◽  
Torsades De Pointes ◽  
Hemodynamic Instability ◽  
Polymorphic Ventricular Tachycardia ◽  
Stable Patient ◽  
Qtc Prolongation ◽  
Preventative Measures ◽  
Drug Classes ◽  
Alternative Medications ◽  
Primary Management

This chapter looks at QTc prolongation and torsades de pointes (Tdp). In cases of recurrent polymorphic ventricular tachycardia, Tdp should be an immediate consideration. Tdp appears like a “twisting of points” of the cardiac axis, which is most often due to acquired QTc prolongation. The QT interval is inversely related to heart rate; therefore, it is corrected (QTc) using formulas such as Bazett's, Fridericia, and Framingham. There are several congenital and acquired causes of QTc prolongation. The congenital long QT syndrome, Romano-Ward syndrome, and Jervell and Lange-Nielsen syndrome are commonly associated with QTc prolongation and Tdp. Drug classes such as anti-arrhythmics, antidepressants, antipsychotics, antibiotics, and antihistamines are the other common cause of acquired QTc prolongation. Primary management of QTc prolongation and Tdp consists of minimizing risk factors like alternative medications and correcting electrolyte abnormalities. In a hemodynamically stable patient with QTc prolongation, treatment should focus on discontinuing the possible offending medications and correcting electrolyte levels. Meanwhile, patients with Tdp and hemodynamic instability require emergent electrical cardioversion in conjunction with preventative measures.

scholarly journals Torsades de pointes in SARS-CoV-2 (COVID-19) pneumonia: medicine reconciliation and careful monitoring of QTc interval may help prevent cardiac complications

2021 ◽  
Vol 14 (3) ◽  
pp. e239963
Author(s):  
Waqas Aslam ◽  
Carla R Lamb ◽  
Nadia Ali
Keyword(s):  
Sinus Rhythm ◽  
Normal Sinus Rhythm ◽  
Torsades De Pointes ◽  
Normal Serum ◽  
Cardiac Complications ◽  
Qtc Interval ◽  
Careful Monitoring ◽  
Qtc Prolongation ◽  
Serum Electrolytes ◽  
Normal Sinus

Hydroxychloroquine has been widely prescribed to treat patients with COVID-19 pneumonia. A 73-year-0ld woman with COVID-19 pneumonia was treated with dexamethasone and hydroxychloroquine. Her home medications, citalopram and donepezil, were continued. The ECG prior to starting hydroxychloroquine showed normal sinus rhythm with prolonged corrected QT (QTc) of 497 ms, due to citalopram and donepezil therapy. Repeat ECG on days 3 and 4 of hydroxychloroquine therapy showed significantly prolonged QTc of 557 ms and 538 ms, respectively, despite normal serum electrolytes. All QT-prolonging medications including hydroxychloroquine were discontinued on day 4; however, she suffered a transient torsades de pointes lasting for about 15 s, which resolved before any intervention. QTc improved to 477 ms, after discontinuation of QT-prolonging medications. The patient had QTc prolongation and torsades de pointes due to therapy with multiple QT-prolonging medications. Medicine reconciliation and careful monitoring of QTc may help prevent cardiac complications in patients with COVID-19 treated with hydroxychloroquine.

scholarly journals Donepezil-induced QTc prolongation: A case report

2019 ◽  
Vol 9 (3) ◽  
pp. 128-132 ◽  
Author(s):  
Samantha M. Vogel ◽  
Lisa M. Mican ◽  
Tawny L. Smith
Keyword(s):  
Cognitive Rehabilitation ◽  
Case Reports ◽  
Torsades De Pointes ◽  
African American Female ◽  
Qtc Interval ◽  
Qtc Prolongation ◽  
Geriatric Population ◽  
Normal Limits ◽  
Neurocognitive Rehabilitation

Abstract Background Several psychoactive medications are known to cause QTc prolongation. Patient factors also increase the risk for QTc prolongation, including bradycardia, female sex, older age, metabolic abnormalities, and polypharmacy. Donepezil, a cholinesterase inhibitor, prolongs the QTc interval through a multimodal mechanism. Patient History A 26-year-old African American female was admitted to the inpatient psychiatric hospital following a suicide attempt that was not an overdose. Past medical history was significant for major depression, traumatic brain injury, seizures, hemiplegia, gastroesophageal reflux disease, and tachycardia. Two baseline electrocardiograms (EKGs) were obtained showing normal QTc intervals. After several weeks, donepezil (5 mg by mouth once daily) was initiated for cognitive rehabilitation and titrated over 3 weeks to a dose of 20 mg. An EKG performed after the last dose change showed a prolonged QTc of 463 ms. Another follow-up EKG performed 9 days later showed further prolongation to 528 ms. Laboratory values were within normal limits during her hospital stay. Donepezil was discontinued completely, leading to normalization of the QTc interval. Discussion QTc prolongation and torsades de pointes have been identified in postmarketing case reports of donepezil. Instances of QTc prolongation have predominantly been documented in the geriatric population, primarily in those with additional risk factors. Additionally, current literature does not support the use of donepezil for neurocognitive rehabilitation in daily doses exceeding 10 mg. A temporal and causal relationship was observed between the initiation and titration of donepezil and development of QTc prolongation.

Risk of hepatotoxicity with concurrent statin and tyrosine kinase inhibitor (TKI) or mTOR inhibitor (mTORi) in patients with metastatic renal cell carcinoma (mRCC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 610-610
Author(s):  
Trang H. Au ◽  
Erin B. Bailey ◽  
Shiven B. Patel ◽  
Srinivas Kiran Tantravahi ◽  
Neeraj Agarwal ◽  
...  
Keyword(s):  
Liver Enzyme ◽  
Kinase Inhibitor ◽  
Competitive Inhibition ◽  
Small Sample Size ◽  
Small Sample ◽  
Exact Test ◽  
Treatment Line ◽  
Concurrent Use ◽  
Additive Risk ◽  
Observational Cohort

610 Background: TKIs and statins alone can cause liver injury. When used together, there is additive risk for hepatotoxicity, as seen with pazopanib and simvastatin, and the potential for discontinuing TKI therapy. Liver enzyme abnormalities are also associated with mTORi. Hepatotoxicity from concurrent use of statins as a class with TKI or mTORi as a class in real world practice in mRCC has not been reported. Methods: This observational cohort study included adult patients treated with a TKI or mTORi for mRCC at the Huntsman Cancer Institute from 2004-2014. We performed a treatment line analysis. For each treatment line, CTCAE criteria were used to categorize maximum AST, ALT, and total bilirubin. Highest grade of any liver enzyme was compared between TKI with and without statin and between mTORi with and without statin (Fisher’s Exact test). Results: A total of 162 treatment lines were included. For TKI and statin, the three most common treatment line combinations were sunitinib and simvastatin (7), sunitinib and atorvastatin (4), and pazopanib and simvastatin (3). For mTORi and statin, the three most common treatment line combinations involved simvastatin with temsirolimus (7) and everolimus (3). Prevalence of hepatotoxicity is shown in the table. Conclusions: Our results show a trend toward significance in the prevalence of hepatotoxicity with concomitant mTORi and statin versus mTORi alone, perhaps explained by mTORi-mediated competitive inhibition of simvastatin (sensitive CYP 3A4 substrate). There was no difference in hepatotoxicity for TKI with or without statin, although there were few pazopanib and simvastatin combinations. Study limitations include the small sample size, limited number of TKI or mTORi and statin combinations, and retrospective study design. A larger study is needed to validate these findings. [Table: see text]

Evaluation of QTc Interval Prolongation Among Patients With Cancer Using Enteral Methadone

2018 ◽  
Vol 36 (3) ◽  
pp. 177-184 ◽  
Author(s):  
Amanda G. Lovell ◽  
Bridget McCrate Protus ◽  
Maureen L. Saphire ◽  
Sachin S. Kale ◽  
Amy Lehman ◽  
...  
Keyword(s):  
Low Dose ◽  
Torsades De Pointes ◽  
High Dose ◽  
Qtc Interval ◽  
Moderate Dose ◽  
Qtc Prolongation ◽  
Patients With Cancer ◽  
Qtc Interval Prolongation ◽  
High Incidence ◽  
Clinically Significant

Context: The effect of methadone on corrected QT interval (QTc) in patients with cancer pain is not well-known. Objectives: To describe and characterize the effect of low-, moderate-, and high-dose enteral methadone on QTc interval in patients with cancer. Methods: Retrospective cohort study including patients prescribed enteral methadone during the 27-month study period. Participants were divided into 3 methadone daily dose groups: <30 (low dose), 30 to 59 (moderate dose), ≥60 (high dose) mg. The primary outcome was the incidence of QTc prolongation (>450 ms for females and >430 ms for males). Secondary outcomes included the magnitude of change in QTc after starting methadone, the incidence of clinically significant QTc prolongation (>500 ms) and the prevalence of torsades de pointes and syncope. Results: Two hundred three patients met study inclusion criteria: 91 (45%) low dose, 52 (26%) moderate dose, and 60 (29%) high dose. Incidence of QTc prolongation for low-, moderate-, and high-dose groups was 50 (55%), 37 (71%), and 43 (72%), respectively ( P = .039, low vs high dose). Incidence of clinically significant QTc prolongation was 10 (11%), 4 (8%), and 7 (12%) for low-, moderate-, and high-dose groups. For patients without QTc prolongation prior to initiating methadone, 62% of moderate-dose patients and 67% of high-dose patients had QTc prolongation, while taking methadone. Conclusion: This study found a notably high incidence of QTc prolongation in patients with cancer using enteral methadone. Future studies should aim to determine the risk of adverse cardiac effects in the cancer population and determine appropriate monitoring of methadone for pain management.

Effect of concomitant proton pump inhibitor (PPI) on effectiveness of tyrosine kinase inhibitor (TKI) in patients with metastatic renal cell carcinoma (mRCC).

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 608-608
Author(s):  
Trang H. Au ◽  
Erin B. Bailey ◽  
Shiven B. Patel ◽  
Srinivas Kiran Tantravahi ◽  
Neeraj Agarwal ◽  
...  
Keyword(s):  
Kinase Inhibitor ◽  
Small Sample Size ◽  
Small Sample ◽  
Kaplan Meier ◽  
Observational Cohort ◽  
Retrospective Study Design ◽  
Tki Treatment ◽  
Lost To Follow Up ◽  
Tki Discontinuation

608 Background: PPIs may reduce TKI bioavailability resulting in reduced efficacy, shortened time on TKI treatment, and disease progression. Axitinib, sorafenib, and pazopanib exhibit pH-dependent solubility. Esomeprazole reduced the AUC and Cmax of pazopanib by 40%, but there was no significant interaction for sorafenib with omeprazole or axitinib with rabeprazole. In real world practice, the effect of PPIs as a class on the efficacy of TKIs as a class in mRCC has not been reported. Methods: This observational cohort study evaluated adult patients treated with a TKI for mRCC. Time on TKI treatment was defined as TKI initiation date to date of discontinuation, change in therapy, lost to follow-up, or death. We performed a treatment line analysis. Time on TKI treatment was compared between patients with and without concurrent PPI (Kaplan-Meier, log-rank). Results: Analysis included 128 treatment lines, including 49 TKI with PPI and 79 TKI with no PPI treatment lines. TKIs included sunitinib, pazopanib, sorafenib, and axitinib. PPIs included omeprazole, lansoprazole, esomeprazole, pantoprazole, and rabeprazole. The three most common TKI/PPI combinations involved omeprazole with sunitinib (26), pazopanib (13), and axitinib (3). No difference in time on TKI treatment with PPI (median 8.7 months) and with no PPI (median 7.0 months, p = 0.41) was observed. In pazopanib treatment lines, no difference in time on treatment was observed in those treated with omeprazole or esomeprazole (n = 14, median 4.8 months) compared to those without PPI (n = 18, median 1.7 months, p = 0.22). Conclusions: Among the TKI/PPI combinations evaluated, there was no difference in time to TKI discontinuation with or without concurrent PPI. This suggests that concurrent PPI does not affect time to discontinuation of TKI. Study limitations include the small sample size, limited number of TKI/PPI combinations, and retrospective study design. A larger study is needed to validate these findings.

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