olanzapine and Long-QT-Syndrome

The QTc prolongation by antipsychotic drugs is of major concern, especially in light of the data indicating an increased risk of sudden death in psychiatric patients taking these drugs. Sudden death in psychiatric patients could be partially attributed to drug-induced torsades de pointes and for this reason careful evaluation of QTc prolonging properties of antipsychotic drugs is needed. Antipsychotic drugs prolong QT interval usually by blocking the potassium IKr current. Improved understanding of ion channel structure and kinetics and its role in repolarization has tremendous impact on understanding of the mechanisms of drug-induced QT prolongation and torsades de pointes. Proarrhythmia caused by a QT-prolonging drug occurs infrequently, and usually multiple factors need to operate to precipitate such an event including a combination of two or more drugs affecting the same pathway, hypokalemia, and possibly genetic predisposition. Currently prescribed antipsychotics might cause QT prolongation ranging from 4-6 ms for haloperidol and olanzapine to 35 ms for thioridazine. The response of a patient to a drug is very individual and therefore an individualized system of drug administration and monitoring needs to be developed which takes into account baseline QTc duration and its changes after a drug was introduced. A systematic approach while stratifying psychiatric patients as those with short QTc (QTc < or = 0.41 sec), borderline QTc (QTC = 0.42-0.44 sec), and prolonged QTc (0.45 sec) is being proposed to improve the safety of administering antipsychotic drugs and to decrease the risk of drug-related sudden death in psychiatric patients.

Topics: Age Factors; Algorithms; Antipsychotic Agents; Benzodiazepines; Death, Sudden, Cardiac; Dopamine Antagonists; Drug Labeling; Haloperidol; Humans; Long QT Syndrome; Olanzapine; Pirenzepine; Sex Factors; Thioridazine; Torsades de Pointes

Alterations of electrocardiogram results and cases of sudden cardiac death have been reported since the beginning of neuroleptic treatment. In particular, a temporal association exists between some antipsychotics and prolongation of the heart rate-corrected QT interval (QTc), an event that may increase the risk for developing a potentially fatal ventricular tachycardia arrhythmia known as torsades de pointes if it significantly exceeds normal intraindividual and interindividual variation. Although the incidence of serious adverse cardiac events in response to antipsychotic medications is relatively low, any possibility for the occurrence of cardiotoxicity warrants continued study. The present article reviews important differences among antipsychotic drugs in the potential for, and occurrence of, serious adverse cardiac outcomes and suggests that olanzapine, as therapeutically administered to patients with schizophrenia and related psychoses, does not contribute significantly to a QTc prolongation that could result in potentially fatal ventricular arrhythmias.

Topics: Acute Disease; Antipsychotic Agents; Arrhythmias, Cardiac; Benzodiazepines; Death, Sudden; Female; Humans; Long QT Syndrome; Male; Olanzapine; Pirenzepine; Psychotic Disorders; Schizophrenia; Schizophrenic Psychology; Torsades de Pointes

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

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

Most antipsychotic agents can cause QT prolongation, which causes torsades de pointes. The QT interval in healthy subjects is longer during nighttime than during daytime. The QT interval of patients treated with antipsychotics may be prolonged during nighttime, and the effects of antipsychotics on the QT interval may differ between antipsychotics. This study investigated the circadian dynamics of the QT interval in patients treated with antipsychotics and healthy controls, using a 24-hour Holter electrocardiogram in a clinical setting. Sixty-six patients with a diagnosis of schizophrenia that were treated with risperidone or olanzapine and 40 healthy volunteers were enrolled. The QT intervals were corrected using the Fridericia formula (QTcF = QT / RR). Mean ± SD nighttime QTcFs were 411.6 ± 29.0, 395.9 ± 21.2, and 387.8 ± 19.0 milliseconds (ms) in the risperidone, olanzapine, and control groups, respectively. The mean daytime QTcFs were 397.7 ± 23.4, 392.4 ± 18.9, and 382.6 ± 17.3 ms, respectively. The mean nighttime QTcF of the risperidone group was significantly longer than that of the olanzapine and control groups, although there was no significant difference in the mean daytime QTcF between the risperidone and olanzapine groups. The current study used 24-hour Holter electrocardiograms to reveal significantly longer QT intervals in the risperidone group especially during nighttime. In clinical practices, evaluations of the QT interval have been conducted over short periods in the daytime, but it is believed that such methods may not be able to fully elucidate the effects of antipsychotics on the QT interval.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Circadian Rhythm; Death, Sudden, Cardiac; Electrocardiography, Ambulatory; Female; Humans; Long QT Syndrome; Male; Middle Aged; Olanzapine; Risperidone; Schizophrenia; Schizophrenic Psychology; Signal Processing, Computer-Assisted; Torsades de Pointes

The authors compared 1-year mortality rates associated with ziprasidone and olanzapine in real-world use.. The Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC) was an open-label, randomized, postmarketing large simple trial that enrolled patients with schizophrenia (N=18,154) in naturalistic practice in 18 countries. The primary outcome measure was nonsuicide mortality in the year after initiation of assigned treatment. Patients were randomly assigned to receive treatment with either ziprasidone or olanzapine and followed for 1 year by unblinded investigators providing usual care. A physician-administered questionnaire was used to collect baseline demographic information, medical and psychiatric history, and concomitant medication use. Follow-up information on hospitalizations and emergency department visits, patients' vital status, and current antipsychotic drug status was collected and reported by treating psychiatrists. Post hoc analyses of sudden death, a secondary endpoint, were also conducted.. The incidence of nonsuicide mortality within 1 year of initiating pharmacotherapy was 0.91 for ziprasidone (N=9,077) and 0.90 for olanzapine (N=9,077). The relative risk was 1.02 (95% CI=0.76-1.39). This finding was confirmed in numerous secondary and sensitivity analyses.. Despite the known risk of QTc prolongation with ziprasidone treatment, the findings of this study failed to show that ziprasidone is associated with an elevated risk of nonsuicidal mortality relative to olanzapine in real-world use; the study excludes a relative risk larger than 1.39 with a high probability. However, the study was neither powered nor designed to examine the risk of rare events like torsade de pointes.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Cause of Death; Cross-Sectional Studies; Death, Sudden, Cardiac; Diabetic Ketoacidosis; Female; Hospitalization; Humans; Incidence; Kaplan-Meier Estimate; Long QT Syndrome; Male; Middle Aged; Myocardial Infarction; Olanzapine; Piperazines; Product Surveillance, Postmarketing; Prospective Studies; Risk; Schizophrenia; Suicide; Thiazoles

There have been few reports regarding olanzapine (OLZ)-related QT prolongation and hyperprolactinemia. This study evaluated the dose-dependent effect of OLZ on QT interval and plasma prolactin (PRL) level in a single sample of patients with schizophrenia.. Twenty-six subjects treated with varying starting doses of OLZ were enrolled in the study. Following baseline assessments, which included completion of the Brief Psychiatric Rating Scale (BPRS), measurements of Body Mass Index (BMI), QT interval, electrolytes, fasting plasma glucose, PRL, hemoglobin A1c (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), and low density lipoprotein (LDL), the dose of OLZ was increased for each subject. The same parameters were evaluated following the increased dose treatment.. A significant decrease was observed in BPRS score (p = 0.01) following treatment with an increased dose of OLZ. Significant increases were observed in BMI (p = 0.032), QTc (p = 0.031), and plasma PRL level (p = 0.028). The mean values of electrolytes, fasting plasma glucose, HbA1c, TC, TG, HDL and LDL treatment were unchanged by the switch to increased-dose OLZ treatment.. We have demonstrated the dose-dependent effect of OLZ on the QT interval and the plasma PRL level of patients with schizophrenia.

Topics: Adolescent; Antipsychotic Agents; Benzodiazepines; Body Mass Index; Dose-Response Relationship, Drug; Female; Humans; Japan; Long QT Syndrome; Male; Olanzapine; Prolactin; Psychiatric Status Rating Scales; Schizophrenia; Young Adult

Topics: Adult; Benzodiazepines; Cross-Over Studies; Electrocardiography; Female; Humans; Long QT Syndrome; Male; Middle Aged; Olanzapine; Risperidone; Schizophrenia

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

Prolongation of the QTc interval has been reported during treatment with oral antipsychotic agents and may be more pronounced during parenteral administration. Pooled QTc interval data from acutely agitated patients across four double-blind trials were compared. Databases included: placebo-controlled [two schizophrenia, one bipolar mania trials (n=565)]; haloperidol-controlled [two schizophrenia trials (n=482)]; geriatric placebo-controlled [1 dementia trial (n=204)]. Patients received 1-3 injections of intramuscular (IM) olanzapine (2.5-10 mg/injection), IM haloperidol (7.5 mg/injection), or IM placebo. At 2 and 24 h after IM olanzapine treatment, the mean QTc interval decreased approximately 3 ms from baseline in the placebo- and haloperidol-controlled databases. When there was a statistically significant difference between IM olanzapine and IM placebo, QTc intervals decreased during treatment with IM olanzapine and increased with IM placebo. The incidences of prolonged (endpoint >/=99th percentile of healthy adults or >/=500 ms) or lengthened (increase >/=60 ms) QTc intervals during treatment with IM olanzapine (<3% placebo- and haloperidol-controlled databases, <12% geriatric placebo-controlled database) were never significantly greater than with comparators. These data suggest that IM olanzapine has a favorable QTc interval profile in acutely agitated patients with schizophrenia, bipolar mania, or dementia.

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Dementia; Dose-Response Relationship, Drug; Double-Blind Method; Electrocardiography; Haloperidol; Humans; Injections, Intramuscular; Long QT Syndrome; Olanzapine; Psychomotor Agitation; Schizophrenia

There may be a temporal association between some antipsychotics and prolongation of the heart-rate-corrected QT interval (QTc) representing a delay in ventricular repolarization. QTc prolongation significantly exceeding normal intra-individual and interindividual variation may increase the risk of ventricular tachydysrhythmias, especially torsade de pointes, and therefore, sudden cardiac death.. Electrocardiogram recordings obtained as part of the safety assessment of olanzapine in 4 controlled, randomized clinical trials (N = 2,700) were analyzed. These analyses were conducted to characterize any change in QTc temporally associated with olanzapine, compared with placebo, haloperidol, and risperidone, in acutely psychotic patients (DSM-III-R and DSM-IV) and to characterize variability and temporal course of the QTc in this patient population. Changes from baseline to minimum and maximum QTc were tested for significance, and baseline to acute-phase endpoint change in mean QTc was tested for significance within treatments and for differences between olanzapine and comparators. The possibility of a linear relationship between dose of olanzapine and mean change in QTc, as well as incidence of treatment-emergent prolongation of QTc (change from < 430 msec at baseline to > or =430 msec at endpoint), was tested.. The incidence of maximum QTc > or = 450 msec during treatment was approximately equal to the incidence of QTc > or =450 msec at baseline.. Results of these analyses suggest that olanzapine, as therapeutically administered to patients with schizophrenia and related psychoses, does not contribute to QTc prolongation resulting in potentially fatal ventricular arrhythmias.

Topics: Acute Disease; Adolescent; Adult; Adverse Drug Reaction Reporting Systems; Aged; Antipsychotic Agents; Arrhythmias, Cardiac; Benzodiazepines; Electrocardiography; Female; Haloperidol; Humans; Incidence; Long QT Syndrome; Male; Middle Aged; Olanzapine; Pirenzepine; Placebos; Risperidone; Schizophrenia

Current palliative care guidelines lack a specific treatment algorithm for nausea and emesis. Olanzapine is an atypical antipsychotic with antiemetic activity that's recommended in the guidelines for the treatment of chemotherapy induced nausea and vomiting, but outside of oncologic indications there is a lack of research.. To describe the safety and efficacy of olanzapine for nausea and emesis in the palliative care domain, excluding patients actively undergoing chemotherapy or radiation.. This retrospective chart review encompassed hospitalized adult patients from six hospitals across a large health system admitted from August 2020 through August 2021, with a palliative care consult, and being treated with olanzapine for nausea or emesis. Data was collected on antiemetic therapy affordability, the ability for patients to tolerate medications by mouth, and safety outcomes such as QTc prolongation and increased liver function tests.. A total of 78 patients were included in the study. Olanzapine decreased the number of doses required of antiemetic medications, the median doses of antiemetic medications pre-olanzapine was 1.6 (IQR 0.8-2.8) and post-olanzapine was 0.6 (IQR 0-2.4) (P = 0.0006). After olanzapine was initiated, appetite was improved (P < 0.001), cost of antiemetic therapy was reduced by 65 cents per day (P = 0.059) and olanzapine was prescribed at discharge in 69% of patients. QTc prolongation was observed in 19% of patients, and increased ALT and AST were observed in 4.3% and 0%, respectively.. This retrospective review demonstrated benefit to utilizing olanzapine for nausea and emesis in palliative care patients and should be considered to aid in symptom management.

Topics: Adult; Antiemetics; Antineoplastic Agents; Gastrointestinal Agents; Humans; Long QT Syndrome; Nausea; Olanzapine; Palliative Care; Retrospective Studies; Vomiting

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

Domperidone, ondansetron and olanzapine can prolong the QT interval. The clinical use of combinations of these drugs is not uncommon. Our study aimed to determine the presence of any QTc prolonging effect of the combination when used as antiemetic in patients receiving cancer chemotherapy. We carried out a prospective, observational study of patients with malignancy who were to receive domperidone, ondansetron and olanzapine-containing antiemetic regimen. Electrocardiograms were recorded before and during the administration of antiemetics, for three consecutive days. A blinded assessor determined the QTc interval using Bazett and Fridericia formulae. Thirty-six patients completed the study; 23 (63.9%) were females. There was a statistically significant change in QTc with time (Fridericia, χ

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Antineoplastic Agents; Domperidone; Drug Combinations; Electrocardiography; Female; Humans; Long QT Syndrome; Male; Middle Aged; Nausea; Neoplasms; Olanzapine; Ondansetron; Prospective Studies; Single-Blind Method; Young Adult

Topics: Female; Humans; Long QT Syndrome; Middle Aged; Olanzapine

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Electrocardiography; Electroencephalography; Female; Follow-Up Studies; Heart Rate; Humans; Long QT Syndrome; Male; Olanzapine; Psychiatric Status Rating Scales; Schizophrenia; Young Adult

In 2012, Danish psychiatrist raised concerns regarding the use of high-dose olanzapine in the treatment of patients. The present study was part of an audit carried out by the Mental Health Services of the Capitol Region of Denmark regarding this topic. Objective. To assess the potential risks associated with high-dose olanzapine treatment (> 40 mg daily) in inpatient psychiatric units.. The study was an observational case series based on review of patient charts. The main inclusion criterion was treatment with at least one daily dose > 40 mg olanzapine during the index admission in the period between 1st of January and 15th of March 2012. Six additional criteria were applied in order to target the subgroup of patients most likely to have experienced an adverse event due to treatment with olanzapine. The physician order entry system and the central patient register containing patient specific information about diagnoses and treatments were used for identification of study population.. The 91 patients included in the study received maximum daily doses of olanzapine ranging from 45 to 160 mg and in 25% of patients, the total antipsychotic load exceeded 2000 mg of chlorpromazine equivalents. Extrapyramidal symptoms and sedation were the most frequent adverse events with frequencies of 27% and 25%, respectively. Furthermore, other well-known adverse events such as weight gain (14%), hypotension (2%), neuroleptic malignant syndrome (2%) and corrected QT-interval (QTc) prolongation (1%) were also observed in some patients. Five patients died and in two of these cases, olanzapine was concluded to be a possible contributing cause of death.. Increased frequency of extrapyramidal symptoms and sedation as well as severe toxicity was observed in patients treated with up to 160 mg olanzapine per day. In order to prevent harmful outcomes, the clinicians should be ready to act appropriately if toxic effects of olanzapine occur. Treatment cessation should be immediate if serious adverse events such as neuroleptic malignant syndrome arise.

Topics: Adult; Antipsychotic Agents; Basal Ganglia Diseases; Benzodiazepines; Central Nervous System; Denmark; Depression, Chemical; Drug Overdose; Electrocardiography; Female; Hospitals, Psychiatric; Humans; Inpatients; Long QT Syndrome; Male; Neuroleptic Malignant Syndrome; Olanzapine; Psychotic Disorders; Retrospective Studies; Risk Assessment

QTc prolongation is associated with arsenic trioxide (ATO) treatment of acute promyelocytic leukemia (APL). Olanzapine was safely co-administered with ATO to treat co-morbid psychiatric diagnoses. It is important to closely monitor for drug-drug interactions and cumulative drug adverse effects in patients receiving oncology agents and psychotropics. Further research is indicated to determine risk/benefit profiles of psychotropics co-administered with ATO. In light of current limited data, co-administration of psychotropics with ATO should be reported presenting both instances wherein no interactions are noted and those with adverse effects.

Topics: Adult; Antineoplastic Agents; Antipsychotic Agents; Arsenic Trioxide; Arsenicals; Benzodiazepines; Drug Administration Schedule; Drug Interactions; Drug Monitoring; Electrocardiography; Humans; Leukemia, Promyelocytic, Acute; Long QT Syndrome; Male; Mental Disorders; Olanzapine; Oxides; Patient Safety; Risk Factors

We report on a 76 year old woman who fainted on her way to the restroom during the night. At the emergency department, a prolonged QT-interval was noticed in addition to sinusbradycardia and marginal hypokalemia. The QT-interval normalized promptly after citalopram was discontinued. Taking into account the clinical picture and the ascertained orthostatic dysregulation, a diagnosis of orthostatic syncope was made. Because of the lengthened QT-interval, drug-induced torsade de pointes ventricular arrhythmia was considered as a differential diagnosis. We describe that citalopram was most probably the cause for the prolonged QT-interval. In our article we discuss the pathophysiology of drug-induced long QT syndrome (LQTS), the most important drugs involved, and finally the prophylaxis and treatment of a TdP ventricular arrhythmia.

Topics: Aged; Antidepressive Agents, Second-Generation; Antipsychotic Agents; Benzodiazepines; Citalopram; Depressive Disorder; Diagnosis, Differential; Drug Interactions; Drug Therapy, Combination; Electrocardiography; Female; Humans; Long QT Syndrome; Olanzapine; Schizophrenia, Paranoid; Syncope, Vasovagal

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

Several non-antiarrhythmic drugs including antibiotic and antipsychotic agents have been shown to prolong cardiac repolarization predisposing to torsade de pointes ventricular tachycardia. Blockade of the delayed rectifier (repolarising) potassium current and drug interactions with inhibitors of the CYP-mediated metabolism are the most common underlying mechanisms. In the present case report, an elderly woman receiving a long-term medication with azathioprine, olanzapine and valsartan developed a marked QT interval prolongation after intravenous administration of ciprofloxacin.

Topics: Aged; Anti-Infective Agents; Antipsychotic Agents; Benzodiazepines; Bundle-Branch Block; Ciprofloxacin; Drug Synergism; Electrocardiography; Female; Humans; Long QT Syndrome; Olanzapine

A case of a 53 year old female with olanzapine-induced QT interval prolongation and ventricular fibrillation is described. The relationship between neuroleptic drugs and the risk of sudden cardiac death is discussed.

Topics: Antipsychotic Agents; Benzodiazepines; Electrocardiography; Female; Humans; Long QT Syndrome; Middle Aged; Olanzapine; Potassium; Schizophrenia; Torsades de Pointes; Treatment Outcome

Topics: Antipsychotic Agents; Benzodiazepines; Bipolar Disorder; Female; Humans; Long QT Syndrome; Middle Aged; Olanzapine; Wolff-Parkinson-White Syndrome

The case of a 73-year-old male with delusions of parasitosis (DP) is presented. He complained about severe itching of the limbs and the genital region as well as abnormal body and pubic hair that he believed to be parasites. The symptoms occurred over the course of several years together with severe heart diseases (New York Heart Association class III, atrial fibrillation, tricuspid regurgitation) and chronic edema of the lower leg. The pruritus was also based on chronic, self-induced skin lesions due to aggressive disinfection and tearing out of body hair. After ruling out true infection, a multimodal DP therapy was initiated. Instead of the standard neuroleptic drug pimozide, olanzapine was used because of its better tolerability in patients with increased cardiac risk (i.e., borderline prolonged QTc time). At discharge, the DP had partially remitted. Substantial improvement in the heart and skin diseases under specific treatment contributed substantially to the success of the therapeutic regimen. This case hints at (1) the effectiveness of olanzapine in DP and (2) the importance of general medical conditions in the therapeutic approach to DP.

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Comorbidity; Delusions; Dementia, Vascular; Drug Interactions; Ectoparasitic Infestations; Electrocardiography; Heart Failure; Humans; Long QT Syndrome; Male; Olanzapine; Patient Care Team; Pirenzepine; Pruritus; Self-Injurious Behavior

Topics: Aged; Antipsychotic Agents; Benzodiazepines; Dose-Response Relationship, Drug; Female; Health Status; Humans; Long QT Syndrome; Olanzapine; Pirenzepine; Psychotic Disorders; Severity of Illness Index

We report the case of a patient on antipsychotic medication, who developed an abnormal QTc interval, which normalized following treatment with oral magnesium sulphate.

Topics: Adult; Antipsychotic Agents; Benzodiazepines; Clonazepam; Electrocardiography; Humans; Long QT Syndrome; Magnesium; Male; Olanzapine

Many antipsychotic drugs produce QT interval prolongation on the electrocardiogram (ECG). Blockade of the human cardiac K(+) channel known as human ether-a-go-go-related gene (HERG) often underlies such clinical findings. In fact, HERG channel inhibition is now commonly used as a screen to predict the ability of a drug to prolong QT interval. However, the exact relationship between HERG channel blockade, target receptor binding affinity and clinical QT prolongation is not known. Using patch-clamp electrophysiology, we examined a series of seven antipsychotic drugs for their ability to block HERG, and determined their IC(50) values. We then compared these results to their binding affinities (K(i) values) for the dopamine D(2) receptor, the 5-HT(2A) receptor and, where available, to clinical QT prolongation data. We found that sertindole, pimozide and thioridazine displayed little (<10-fold) or no selectivity for dopamine D(2) or 5-HT(2A) receptors relative to their HERG channel affinities. This lack of selectivity likely underlies the significant QT interval prolongation observed with administration of these drugs. Of the other drugs tested (ziprasidone, quetiapine, risperidone and olanzapine), olanzapine displayed the greatest selectivity for dopamine D(2) and 5-HT(2A) receptor binding (100-1000-fold) compared to its HERG channel IC(50). We also compared these HERG channel IC(50) values to QT interval prolongation and plasma drug levels obtained in a recent clinical study. We found that the ratio of total plasma drug concentration to HERG IC(50) value was indicative of the degree of QT prolongation observed. Target receptor affinity and expected clinical plasma levels are important parameters to consider for the interpretation of HERG channel data.

Topics: Animals; Antipsychotic Agents; Cation Transport Proteins; Cell Line; Clinical Trials as Topic; Cricetinae; DNA-Binding Proteins; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; Humans; Long QT Syndrome; Patch-Clamp Techniques; Potassium Channel Blockers; Potassium Channels; Potassium Channels, Voltage-Gated; Radioligand Assay; Receptor, Serotonin, 5-HT2A; Receptors, Dopamine D2; Receptors, Serotonin; Trans-Activators; Transcriptional Regulator ERG

Topics: Aged; Antiparkinson Agents; Antipsychotic Agents; Benzodiazepines; Carbidopa; Electrocardiography; Female; Humans; Levodopa; Long QT Syndrome; Olanzapine; Pirenzepine; Psychoses, Substance-Induced; Risk Factors

Sertindole (Serdolect), an atypical antipsychotic, was voluntarily suspended in the European Union in 1998 following regulatory concerns over reports of serious cardiac dysrhythmias and sudden unexpected deaths. The reported causes of death, their frequency, prolongation of the rate corrected QT interval (QTc) and cardiac dysrhythmias in patients prescribed sertindole were compared with those for patients treated with two other atypical antipsychotics. All patients in England, prescribed atypical antipsychotics by general practitioners during each drug's immediate post-marketing period, were identified using an observational cohort technique, prescription-event monitoring. Mortality rates in the sertindole cohort were compared with those in a comparator cohort using standardized mortality ratios and incidence rate ratios. Cardiovascular events were reviewed and followed up to identify cases of prolongation of QTc interval. There was no statistically significant difference in mortality rates between sertindole and the comparator cohort, although confidence intervals (CI) were wide due to small numbers in the sertindole cohort. A much smaller number of patients were prescribed sertindole than the other antipsychotics. Six cases of prolongation of QTc interval were identified in 462 patients (1.3%, 95% CI 0.5-2.8) treated with sertindole and one with unspecified electrocardiogram changes in the comparator cohort of 16,542 patients. This study contributes to the understanding of the occurrence of prolongation of QTc interval during clinical use of sertindole, the incidence of which was similar to that in clinical trials. Although no statistically significant difference was shown in mortality rates between sertindole and comparator cohort, the sertindole cohort was too small to rule out an association between the use of this drug and cardiovascular deaths.

Topics: Adult; Aged; Aged, 80 and over; Antipsychotic Agents; Arrhythmias, Cardiac; Benzodiazepines; Cohort Studies; Death, Sudden; Electrocardiography; European Union; Female; Humans; Imidazoles; Indoles; Long QT Syndrome; Male; Middle Aged; Olanzapine; Pirenzepine; Product Surveillance, Postmarketing; Risperidone; Sex Factors