Possible association of QTc interval prolongation with co-administration of quetiapine and lovastatin.

BACKGROUND: 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. METHODS: 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. RESULTS: QTc returned to baseline when the lovastatin dose was reduced. CONCLUSIONS: 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.     

Analysis of the QTc interval during olanzapine treatment of patients with schizophrenia and related psychosis

BACKGROUND: 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. METHOD: 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. RESULTS: The incidence of maximum QTc > or = 450 msec during treatment was approximately equal to the incidence of QTc > or =450 msec at baseline. CONCLUSION: 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.     

New Generation Antipsychotic Drugs and QTc Interval Prolongation

BACKGROUND: Recent regulatory and clinical concerns have brought into sharp focus antipsychotic drug-induced QTc interval prolongation, torsades de pointes, and sudden cardiac death. Several new generation (atypical) antipsychotic drugs have either been withdrawn from clinical use or delayed in reaching the marketplace due to these concerns. Because torsades de pointes is rarely found, QTc interval prolongation serves as a surrogate marker for this potentially life-threatening arrhythmia. Current methods of calculating this electrocardiographic parameter have limitations. The primary care physician is a key member of the team managing a patient who requires administration of antipsychotic drugs. This article focuses on new generation antipsychotic drugs and principles useful to both the primary care physician and the psychiatrist. METHOD: PubMed was searched in September 2002 using the terms antipsychotic drug and QT interval. References were examined from review articles describing antipsychotic drugs and the QT interval. The author's files gathered over the past 20 years on the QT interval were also reviewed. RESULTS: Nine cases were available in which drug-induced QTc interval prolongation was associated with new generation antipsychotic drug administration. Eight cases were taken from the literature, and the author added one additional report. The newer agents involved were risperidone, quetiapine, and ziprasidone. In at least 8 cases, there was evidence of other risk factors associated with QTc interval prolongation. In one case frequently referenced in the literature, the authors misunderstood their own data showing that QTc interval prolongation did not relate to delayed ventricular repolarization. In another instance, 2 authors reported on the same patient, with important information missing from both articles. No evidence of torsades de pointes appeared in any of the 9 cases. CONCLUSIONS: No evidence is currently available in the literature implicating new generation antipsychotic drugs in the production of torsades de pointes. However, the absence of such evidence does not prove that newer antipsychotic drugs do not cause torsades de pointes. Among patients free of risk factors for QTc interval prolongation and torsades de pointes, current literature does not dictate any specific consultative or laboratory intervention before administering new generation antipsychotic drugs. When risk factors are present, evaluation and intervention specific to those risk factors should dictate the clinician's course of action. More specific guidelines for monitoring the QT interval and risk of torsades de pointes await improved methods of measuring the QTc interval relevant to each patient.     

Impact of Age and Sex on QT Prolongation in Patients Receiving Psychotropics

Objective:

To assess older age and female sex, 2 of the major risk factors for potentially fatal cardiac arrhythmias or sudden cardiac death in patients prescribed psychotropics, within the context of electrocardiographic evidence of time between start of Q wave and end of T wave (QT) interval prolongation, which is an indicator of an increased risk for potentially fatal cardiac arrhythmias.

Method:

The literature on the relation between age, sex, and QT interval with respect to psychotropic drugs was reviewed.

Results:

The QT interval must be corrected (QTc) for heart rate. Because slower heart rates prolong and faster heart rates shorten the QT interval, people with faster heart rates may have a prolonged QT interval that is not apparent until the correction is performed. QTc values for apparently healthy post-pubertal people are less than 450 ms for males and less than 470 ms for females. The longer QT intervals in women may account for their increased risk of potentially fatal cardiac arrhythmias on psychotropics. QTc increases with increasing age. Assessment of QTc in older people is especially important to identify people with a longer QTc who are more likely to attain a serious QT level with drugs that prolong QTc. The age-related increase in QTc is more evident in men than women, suggesting that male sex does not afford protection against potentially fatal arrhythmias at older age.

Conclusion:

The association of increasing age and female sex with greater QT intervals indicates the need to have an increased awareness of the QTc prior to use of these psychotropics and to evaluate the QTc after initiation of therapy.     

QTc-interval abnormalities in a forensic population

Background Antipsychotic drugs have been linked to sudden death among psychiatric patients, with a suggestion that prolongation of the QT‐interval detectable on a standard electrocardiogram may be linked to fatal cardiac arrhythmias in these circumstances. Patients in secure forensic psychiatric facilities may be particularly likely to be on high‐dose antipsychotic medication, and yet, as far as the authors are aware, no study of QT‐intervals among such patients has been reported. Aim To investigate the prevalence of QT‐interval abnormalities and associated known risk factors for fatal cardiac arrhythmias in a sample of forensic patients. Method Participants had a 12‐lead electrocardiogram taken at 50 mm/s. Information was collected on their age, gender, psychiatric diagnosis, history of cardiovascular, liver and kidney diseases, and smoking, on all medications and on history of seclusion over the previous 12 months. Analysis was carried out using binary logistic regression. Results Lower rates of QT‐interval abnormalities than might be expected for this population were found. It was also found that a high dose of antipsychotics was associated with QTc prolongation (Adjusted OR = 9.5, 95% CI 2.6–34.2), a result consistent with previous literature. Conclusion Forensic patients need not be at increased risk of QTc abnormality provided risk factors are properly managed. A high dose of antipsychotic medication increases the risk of QTc prolongation. Copyright © 2007 John Wiley & Sons, Ltd.     

Antipsychotics and QT prolongation

OBJECTIVE: To evaluate literature relating to cardiac QT prolongation and the use of antipsychotic drugs. METHOD: Literature searches of EMBASE, Medline, PsychLIT were performed in December 2001 and reference sections of retrieved papers scrutinized for further relevant reports. RESULTS: The Cardiac QTc interval is difficult to measure precisely or accurately but appears to be a useful predictor of risk of dysrhythmia (specifically torsade de pointes) and sudden death. It is less clear that drug-induced QTc prolongation gives rise to similar risks but data are emerging, linking antipsychotic use to increased cardiac mortality. Many antipsychotics have been clearly associated with QTc prolongation. Methodological considerations arguably preclude assuming that any antipsychotic is free of the risk of QTc prolongation and dysrhythmia. CONCLUSION: Available data do not allow assessment of relative or absolute risk of dysrhythmia or sudden death engendered by antipsychotics but caution is advised. Risk of dysrhythmia can very probably be reduced by careful prescribing of antipsychotics in low doses in simple drug regimens which avoid metabolic interactions. Electrocardiographic monitoring may also help to reduce risk but review by specialist cardiologist may be necessary.     

QTc interval measurement and metabolic parameters in psychiatric patients taking typical or atypical antipsychotic drugs: a preliminary study

BACKGROUND: Antipsychotic drugs have been associated with prolongation of the QTc interval on the electrocardiogram, and QTc prolongation is, in turn, associated with an increased risk of cardiac arrhythmias and sudden death. Antipsychotic polypharmacy has been implicated in reduced survival, possibly secondary to cardiotoxic effects of antipsychotic medication. Abnormalities of glucose homeostasis, which may be more common in individuals with major mood disorders and schizophrenia, also affect the QTc interval. METHOD: We performed detailed assessment of metabolic parameters in 103 psychiatric out-patients, from across the diagnostic spectrum, who had been taking antipsychotic medication (typical, atypical, or a combination thereof) for a minimum of 6 months. We measured the QTc interval in a subset of these patients (N = 65). RESULTS: Only 2 patients (3%) had a prolonged QTc interval. There was a statistical trend (p = .08) toward a lower QTc interval in patients receiving antipsychotic polypharmacy. QTc interval was associated with age (p = .04) but not with any metabolic parameter. CONCLUSION: QTc prolongation in this population is uncommon. There was a significant association between increasing age and QTc interval, but cardiac repolarization was not related to any metabolic parameter. Further large prospective studies of similar patients are needed to confirm these findings.     

Torsade de pointes in a patient with complex medical and psychiatric conditions receiving low-dose quetiapine

OBJECTIVE: Describe potential cardiac complications of low-dose quetiapine and other atypical antipsychotic drugs. METHOD: We present a case report of a 45-year-old Black woman with multiple medical and psychiatric problems taking low-dose quetiapine. RESULTS: Coincident with a generalized seizure, the patient developed 'ventricular fibrillation'. She was countershocked with restoration of normal sinus rhythm. The initial electrocardiogram showed QT interval prolongation. Shortly thereafter, classical torsade de pointes appeared, lasted 10 min, and resolved spontaneously. Hypomagnesemia was present. A cardiac electrophysiologist was concerned that the very slow shortening of the prolonged QTc interval after magnesium replacement implicated quetiapine as a risk factor for QTc interval prolongation and torsade de pointes. A psychosomatic medicine consultant asserted that the fragmented medical and psychiatric care almost certainly contributed to the patient's medical problems. We discuss other cases of QT interval prolongation by newer antipsychotic drugs and previous reports by our group concerning the association of psychotropic drugs, QT interval prolongation, and torsade de pointes. CONCLUSION: Atypical antipsychotic drug administration, when accompanied by risk factors, may contribute to cardiac arrhythmias including torsade de pointes.     

抗精神病药致首发精神疾病QTc 间期变化的相关 因素分析

目的 调查抗精神病药致首发精神疾病QTc间期延长的影响因素.方法 对服用稳定剂量抗精神病药治疗1月的309例首发精神疾病患者进行回顾性调查,收集人口学资料、空腹血糖、血压、血脂等生化指标、心电图资料,以QTc≥440ms作为QTc间期延长的标准,分析QTc间期延长的状况及其相关因素.结果 QTc间期延长的发生率为10.6%.药物治疗组QTc间期均值大于基线期,差异有统计学意义(P<0.05);药物联合电休克治疗组以及药物联合脑电治疗组QTc间期与基线期相比,差异无统计学意义(P>0.05).单一抗精神病药治疗组QTc间期与基线期差异无统计学意义(P>0.05);而抗精神病药联用以及抗精神病药联用抗抑郁药/心境稳定剂组QTc间期均值大于基线期,差异有统计学意义(P<0.05).抗精神病药等效氯丙嗪剂量<1000mg/d组别QTc间期与基线期相比差异有统计学意义(P<0.05).抗精神病药剂量与QTc间期没有相关性.女性是QTc间期延长的风险因素(OR=3.26,95%CI=1.050~10.094),其他因素未进入回归方程.结论 首发精神疾病患者抗精神病药治疗期间QTc间期延长存在性别差异,女性发生QTc间期延长的风险是男性的3.26倍.药物联用延长的QTc间期并未达到异常值.抗精神病药剂量与QTc间期没有相关性.除了性别因素外,其他指标不是QTc间期延长的风险因素.     

Antipsychotic Polypharmacy and Corrected QT Interval: A Systematic Review

Objective:

It remains unclear whether antipsychotic polypharmacy, a common clinical practice, is related to an increased risk of corrected time between start of Q wave and end of T wave (QTc) interval prolongation. We conducted a systematic review of the literature to address this important issue.

Method:

A systematic literature search was conducted in October 2014, using MEDLINE, Embase, and PsycINFO. Studies and case reports were included if they reported QTc intervals or QTc interval changes before and after antipsychotic polypharmacy or QTc intervals in both antipsychotic polypharmacy and monotherapy groups.

Results:

A total of 21 articles (10 clinical trials, 4 observational studies, and 7 case reports) met inclusion criteria. The clinical trials have shown that a combination treatment with risperidone or pimozide is not obviously related to an increase in QTc interval, whereas ziprasidone or sertindole combined with clozapine may prolong QTc interval. Among the 4 observational studies, antipsychotic polypharmacy was not clearly associated with QTc prolongation in 3 studies, each cross-sectional. In contrast, one prospective study showed a significant increase in QTc interval following antipsychotic coadministration. The case reports indicated an increased risk of QTc prolongation in at least some patients receiving antipsychotic polypharmacy.

Conclusions:

Currently available evidence fails to confirm that antipsychotic polypharmacy worsens QTc prolongation in general, although the evidence is scarce and inconsistent. Clinicians are advised to remain conservative in resorting to antipsychotic polypharmacy, as a combination of some QTc-prolongation liable antipsychotics may further prolong QTc interval, and efficacy supporting the clinical benefits of antipsychotic polypharmacy is equivocal, at best.     

Coronary heart disease and cardiac conduction abnormalities in persons with psychotic disorders in a general population

We investigated the prevalence of coronary heart disease (CHD) and myocardial infarction (MI) in persons with DSM-IV psychotic disorders. We also examined cardiac conduction abnormalities, and the role of antipsychotic medication in them. The study was based on a nationally representative survey of 8028 persons aged 30 years or over from Finland. Diagnoses of CHD and MI were based on electrocardiographic findings, health examination, and register information. QTc was calculated using the Bazett formula, and Minnesota classification was used for conduction abnormalities. We found that large Q-waves suggesting past MI were significantly more frequent in persons with schizophrenia, while the prevalence of CHD in persons with psychotic disorders did not differ significantly from the remaining study sample. Prevalence of prolonged QTc interval was significantly increased in persons with schizophrenia and in users of typical antipsychotics. However, low-potency antipsychotic use but not diagnosis of schizophrenia remained an independent predictor of prolonged QTc interval in a logistic regression. Low-potency antipsychotic use was associated with ventricular conduction defects, and high-potency antipsychotic use with premature beats. Symptoms and signs of CHD should be actively monitored patients with schizophrenia, and the electrocardiogram should be monitored for all types of changes in persons receiving antipsychotic medication.     

Pediatric case report of quetiapine overdose and QTc prolongation.

BACKGROUND: Consideration of the risk of QTc interval prolongation associated with atypical antipsychotic administration is mounting, as this can lead to sudden cardiac death. METHODS: This is a case report of a 14-year-old boy with a history of major depressive disorder with psychotic features, post-traumatic stress disorder, oppositional defiant disorder, and polysubstance abuse who ingested 1900 mg of quetiapine. RESULTS: One and one half hours after ingestion, the QTc interval lengthened from 453 msec to 618 msec on the printout (manual calculation was 444 msec to 500 msec, respectively). On the baseline EKG, the QTc interval was 411 msec (manual calculation of 416 msec). CONCLUSION: This report presents an association between higher doses of quetiapine, resulting in higher serum levels and QTc interval prolongation. Also, this report demonstrates the importance of manually calculating the QTc interval to ensure accuracy of the measurement. A review of the literature revealed two case reports and a study where quetiapine was associated with an increase in QTc interval. Further studies are necessary to understand the relationship between higher doses of quetiapine, resulting in higher serum levels, and the propensity for QTc interval prolongation to ensure safe clinical use of this medication.     

Low-dose escitalopram for 2 days associated with corrected QT interval prolongation in a middle-aged woman: a case report and literature review

Prolongation of the corrected QT interval (QTc) on the electrocardiography is an important clinical condition because it increases the risk of torsade de pointes, a medical emergency that can cause sudden cardiac death. QTc prolongation can be induced by many drugs, including antipsychotics and tricyclic antidepressants (TCAs). Compared with TCAs, use of selective serotonin reuptake inhibitors (SSRIs) was less likely to cause severe cardiac adverse effects. Escitalopram, one of the SSRIs, has shown significant antidepressant efficacy and well tolerability. Here, we present one female patient showing QTc prolongation induced by low-dose (5 mg/day) treatment of escitalopram for 2 days. The QTc returned to normal soon after discontinuation of escitalopram. Clinicians should be cautious about cardiac effects when using a SSRI, even in a low dose.     

The QTc interval and its dispersion in patients receiving two atypical antipsychotics

Objective  Treatment with atypical antipsychotics may prolong the rate-corrected Q–T interval (QTc) on electrocardiogram and increase the risk of dangerous ventricular arrhythmias. Polytherapy with atypical antipsychotics is becoming common, but the effect of this practice on the QTc has not been explored in detail. Methods  Among 364 adults treated with atypical antipsychotics randomly selected from consecutive admissions to a single hospital, electrocardiograms with measurable Q–T intervals in at least six leads were available for 38 of 49 patients receiving polytherapy with two atypical antipsychotics. Daily chlorpromazine equivalent, QTc duration and QTc dispersion were assessed in this group and in 73 closely matched patients receiving atypical antipsychotic monotherapy. Results  The daily chlorpromazine equivalent of atypical antipsychotics was significantly greater in the polytherapy group (525.2 vs. 244.7 mg, P = 0.0003). Polytherapy and monotherapy patients were similar with regard to QTc duration, QTc dispersion and proportion of patients with gender-adjusted QTc prolongation (7.9% vs. 9.6%). The QTc duration had only a modest correlation with the total antipsychotic dose (P = 0.064). The presence of hypokalemia (3.0–3.5 mEq/l) was not associated with longer QTc intervals. Conclusions  The common practice of polytherapy with two atypical antipsychotics does not seem to lead to significant QTc prolongation compared to monotherapy. Grant Support: The Zucker Hillside Hospital Advanced Center for Intervention and Services Research for the Study of Schizophrenia (MH074543-01) from the National Institute of Mental Health, Bethesda, Maryland.     

QTc prolongation and antipsychotic medications in a sample of 1017 patients with schizophrenia

Many antipsychotic drugs cause QT prolongation, although the effect differs based on the particular drug. We sought to determine the potential for antipsychotic drugs to prolong the QTc interval (> 470 ms in men and > 480 ms in women) using the Bazett formula in a “real-world” setting by analyzing the electrocardiograms of 1017 patients suffering from schizophrenia. Using logistic regression analysis to calculate the adjusted relative risk (RR), we found that chlorpromazine (RR for 100 mg = 1.37, 95% confidence interval (CI) = 1.14 to 1.64; p < .005), intravenous haloperidol (RR for 2 mg = 1.29, 95% CI = 1.18 to 1.43; p < .001), and sultopride (RR for 200 mg = 1.45, 95% CI = 1.28 to 1.63; p < .001) were associated with an increased risk of QTc prolongation. Levomepromazine also significantly lengthened the QTc interval. The second-generation antipsychotic drugs (i.e., olanzapine, quetiapine, risperidone, and zotepine), mood stabilizers, benzodiazepines, and antiparkinsonian drugs did not prolong the QTc interval. Our results suggest that second-generation antipsychotic drugs are generally less likely than first-generation antipsychotic drugs to produce QTc interval prolongation, which may be of use in clinical decision making concerning the choice of antipsychotic medication.     

Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death.

OBJECTIVE: The authors review the mechanisms and establish the risk of torsade de pointes and sudden death with antipsychotic drugs. METHOD: They present a review of original concepts, the distinction between familial and drug-induced cases of torsade de pointes, and the recognition of the role of noncardiac drugs in torsade de pointes and sudden death. They review the evidence linking QTc interval prolongation, potassium channels, and torsade de pointes from both the long QT syndrome and drugs. They examine the risk for torsade de pointes from antipsychotic drugs and estimate the frequency of sudden death on the basis of epidemiological data in normal and schizophrenic populations. RESULTS: All drugs that cause torsade de pointes prolong the QTc interval and bind to the potassium rectifier channel, but the relationships are not precise. Prediction of torsade de pointes and sudden death can be improved by examining dose dependency, the percent of QTc intervals higher than 500 msec, and the risk of drug-drug interactions. Although sudden unexpected death occurs almost twice as often in populations treated with antipsychotics as in normal populations, there are still only 10-15 such events in 10,000 person-years of observation. CONCLUSIONS: Although pimozide, sertindole, droperidol, and haloperidol have been documented to cause torsade de pointes and sudden death, the most marked risk is with thioridazine. There is no association with olanzapine, quetiapine, or risperidone. Ziprasidone does prolong the QT interval, but there is no evidence to suggest that this leads to torsade de pointes or sudden death. Only widespread use will prove if ziprasidone is entirely safe. To date, all antipsychotic drugs have the potential for serious adverse events. Balancing these risks with the positive effects of treatment poses a challenge for psychiatry.     

Clinical profile of clozapine: Adverse reactions and agranulocytosis

The arrival of clozapine has been one of the most significant developments in antipsychotic drug treatment since the advent of chlorpromazine ushered in the psychopharmacologic era. However, its utilization has been significantly limited and complicated by its potential to cause adverse effects and agranulocytosis in particular. It must be emphasized that clozapine has a side effect profile that is in many ways distinct from standard typical antipsychotic drugs. Side effects with clozapine are common and range from the benign to the potentially lethal. The most common side effects include sedation, dizziness, and sialorrhea during sleep; the most serious are agranulocytosis, seizures and respiratory depression. Although side effects from clozapine are not necessarily preventable, they are for the most part manageable. Even with the most serious adverse effects, proper knowledge of the medication's actions, clinical vigilance, and prompt intervention can prevent the occurrence of significant morbidity and mortality as a consequence of clozapine treatment.     

QTc interval in a sample of long-term schizophrenia inpatients

This naturalistic study attempted to determine the prevalence of prolonged QTc interval in a relatively large population of inpatients hospitalized with chronic schizophrenia, and to explore QTc relationship with demographic variables, metabolic parameters and prescribed treatments. All inpatients from a Spanish long-term psychiatric hospital were cross-sectionally investigated to determine the prevalence of QTc prolongation and metabolic syndrome. The sample with a DSM-IV diagnosis of schizophrenia included 171 Caucasian inpatients, all of Spanish origin. A prolonged QTc interval was defined as >450 ms in men and >470 ms in women. The relationships between QTc and other continuous variables were assessed using a linear regression model with QTc as the dependent variable. Only 10 patients (6%) had a prolonged QTc interval; one case was possibly explained by hypokalemia. Three patients (2%) had a QTc > 500 ms. Gender, old age (≥50 years old), current smoking, systolic blood pressure, HDL cholesterol and history of arrhythmia were found to have significant effects on QTc interval in a linear regression analysis. After controlling for significant variables, the mean QTc interval was not significantly influenced by antipsychotic dose, type of antipsychotic treatment, the use of depot antipsychotics, or the number of different antipsychotics prescribed. Our study focused on long-term schizophrenia inpatients with frequent antipsychotic polypharmacy and high antipsychotic doses, and suggested that after excluding the case with hypokalemia length of QTc was associated with history of arrhythmias and with metabolic factors, while the effects of antipsychotic compound or class were not so evident.     

Antipsychotic drugs and QT interval prolongation

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 I_Kr 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 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.     

Subarachnoid hemorrhage: frequency and severity of cardiac arrhythmias. A survey of 70 cases studied in the acute phase

The frequency and severity of cardiac arrhythmias were studied in 70 patients with spontaneous subarachnoid hemorrhage investigated prospectively with 24-hour Holter monitoring. Patients were less than 70 years old and without clinical and/or ECG signs of previous heart disease; Holter monitoring was initiated within 48 hours of subarachnoid hemorrhage. Arrhythmias were detected in 64 of the 70 patients (91%). Twenty-nine of the 70 patients (41%) showed serious cardiac arrhythmias; malignant ventricular arrhythmias, i.e., torsade de pointe and ventricular flutter or fibrillation, occurred in 3 cases. Serious ventricular arrhythmias were associated with QTc prolongation and hypokalemia. No correlation was found between the frequency and severity of cardiac arrhythmias and the neurologic condition, the site and extent of intracranial blood on computed tomography scan, or the location of ruptured malformation. The extremely high incidence of cardiac arrhythmias, sometimes serious, in the acute period after subarachnoid hemorrhage and the absence of clinical and radiologic predictors make systematic continuous ECG monitoring compulsory to improve the overall results of subarachnoid hemorrhage, irrespective of early or delayed surgical treatment.