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 Several new generation (atypical) antipsychotic drugs have either been withdrawn from clinical use or delayed in reaching the marketplace due to these concerns.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.     

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.     

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.     

Cardiac safety parameters of olanzapine: comparison with other atypical and typical antipsychotics

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.     

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.     

A retrospective study of the safety of intramuscular ziprasidone in agitated elderly patients

OBJECTIVE: Authors evaluated the safety of intramuscular ziprasidone for use in acute agitation in an elderly population. METHOD: Medical records were reviewed retrospectively to identify consecutive patients who were admitted to our neuropsychiatry service with the presenting complaint of dementia (DSM-IV) with agitation and who were given intramuscular ziprasidone and then administered an electrocardiogram (ECG) (N = 23). Some patients also had a baseline ECG (N = 14). QTc intervals were recorded, and significance was defined as a QTc of > or =450 ms or a 10% prolongation from baseline. A paired-samples t test was performed to compare the baseline and postmedication QTc intervals. Confounding factors were examined, and cardiac events (torsades de pointes, cardiac arrest) were recorded. RESULTS: There was no significant difference in the QTc interval between the baseline and the post-ziprasidone values. One patient had a QTc greater than 500 ms and 25% over baseline, and therefore the medication was discontinued. The mean prolongation of the QTc interval was only 0.5 ms. There were no episodes of torsades de pointes. Other medications that the patients were taking did not appear to affect the QTc interval in an expected manner. CONCLUSION: Larger studies need to be done to evaluate the safety of intramuscular ziprasidone in agitated elderly patients, a population with an increased risk of QT prolongation and torsades de pointes because of their age, comorbid conditions, and concomitant use of multiple medications.     

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.     

Cardiac adverse reactions associated with psychotropic drugs

Rates of cardiovascular morbidity and mortality in psychiatric patients are higher than in the general population: it is estimated that those who suffer from schizophrenia have a life expectancy approximately 20 % shorter than those who do not, and this difference is not fully accounted for by suicide or accidental death.¹ Cardiovascular adverse effects of psychotropic drugs are common, and potentially harmful.² The most serious cardiovascular consequences of psychotropic drugs are arrhythmias and sudden death, which principally result from torsades de pointes following progressive QT intervall prolongation. Less severe cardiac adverse drug reactions are extremely common. Orthostatic hypotension, vasodilatation with transient collapse, and reflex sinus tachycardia due to α₁-adrenoceptor blockade and to anticholinergic effects occur at therapeutic dosages of several psychotropic drugs. Postural hypotension was found in 77 % of patients receiving antipsychotic medication versus 15 % receiving placebo, and a correlation was found with drugs dosage.³ Furthermore, antipsychotic drug is associated with an increased risk of hip fracture with a relative risk of 2 (confidence interval [CI], 1.6 to 2.6 and accounts for a third of all falls in nursing homes.^4,5     

Electrocardiographic safety profile and monitoring guidelines in pediatric psychopharmacology

Summary. A number of medications commonly used in pediatric psychopharmacology can prolong the QTc interval of the electrocardiogram. QTc prolongation can in turn predispose to torsades de pointes, a sometimes deadly arrhythmia. These considerations are clinically relevant given documented, if still controversial, reports of sudden deaths associated with the use of the tricyclic antidepressant (TCA) desipramine in children. While most reports of QTc prolongation have involved adult patients, this adverse effect can occur in children. After discussing the QTc parameters derivation, accuracy, and limitations, this article reviews current knowledge about the propensity of the antipsychotics (both atypical and traditional), TCAs, and alpha agonists to prolong the QTc interval in young patients. Based on the literature reviewed, guidelines are provided for clinical and electrocardiographic monitoring in pediatric psychopharmacology.     

QTc prolongation by antiepileptic drugs and the risk of torsade de pointes in patients with epilepsy

Sudden unexpected death in epilepsy (SUDEP) is the most common epilepsy-related cause of death. While the precise pathophysiological mechanisms underlying SUDEP are still uncertain, impaired cardiac function including seizure-induced arrhythmias has received increased attention. In addition, the potential role of antiepileptic drugs has been suggested. While the preponderance of clinical data would suggest that use of most antiepileptic drugs does not pose excessive additional risk of QT prolongation, available data also do not provide sufficient evidence that these drugs are entirely free of risk in all patients. In particular, the potential for these medications, either alone or in combination, to prolong the QT interval should be considered. This review will discuss mechanisms for drug-induced QT prolongation and its relationship to potentially fatal arrhythmias such as torsades de pointes.This article is part of a Special Issue entitled “Translational Epilepsy Research”.     

Whole genome association study identifies polymorphisms associated with QT prolongation during iloperidone treatment of schizophrenia

Administration of certain drugs (for example, antiarrhythmics, antihistamines, antibiotics, antipsychotics) may occasionally affect myocardial repolarization and cause prolongation of the QT interval. We performed a whole genome association study of drug-induced QT prolongation after 14 days of treatment in a phase 3 clinical trial evaluating the efficacy, safety and tolerability of a novel atypical antipsychotic, iloperidone, in patients with schizophrenia. We identified DNA polymorphisms associated with QT prolongation in six loci, including the CERKL and SLCO3A1 genes. Each single nucleotide polymorphism (SNP) defined two genotype groups associated with a low mean QT change (ranging from -0.69 to 5.67 ms depending on the SNP) or a higher mean QT prolongation (ranging from 14.16 to 17.81 ms). The CERKL protein is thought to be part of the ceramide pathway, which regulates currents conducted by various potassium channels, including the hERG channel. It is well established that inhibition of the hERG channel can prolong the QT interval. SLCO3A1 is thought to play a role in the translocation of prostaglandins, which have known cardioprotective properties, including the prevention of torsades de pointes. Our findings also point to genes involved in myocardial infarction (PALLD), cardiac structure and function (BRUNOL4) and cardiac development (NRG3). Results of this pharmacogenomic study provide new insight into the clinical response to iloperidone, developed with the goal of directing therapy to those patients with the optimal benefit/risk ratio.     

Autonomic neuropathy and prolongation of QT interval in human immunodeficiency virus infection

Autonomic neuropathy has been reported in human immunodeficiency virus positive (HIV+) patients. Since alterations in cardiac innervation may determine QT interval prolongation, this interval was studied in a group of HIV+ subjects to evaluate if it is prolonged and to compare this measurement with other diagnostic tests for autonomic neuropathy. Fifty-seven HIV+ and 23 human immunodeficiency virus negative (HIV–) subjects were studied. Autonomic function was tested by noninvasive cardiovascular reflex tests, and the QT interval on the electrocardiogram was measured at rest, at maximum tachycardia during Valsalva manoeuvre, and afterwards at maximum bradycardia. QT intervals were corrected for heart rate according to Bazzett's formula (QTc). Autonomic neuropathy was found in 37 HIV+ subjects: 25 had moderate autonomic neuropathy (HIV+/mAN) and twelve had severe autonomic neuropathy (HIV+/sAN). The 23 HIV– and 20 HIV+ (HIV+/AN–) patients did not have autonomic neuropathy. QTc intervals were significantly longer in HIV+/sAN and HIV+/mAN than in HIV– at rest; in HIV+/sAN than in HIV– at maximum tachycardia; in HIV+/sAN and HIV+/mAN than in HIV+, in HIV+/sAN and HIV+/mAN than in HIV+/AN– and in HIV+/sAN than in HIV+/mAN at maximum bradycardia. QTc was 440 ms in 24 out of 37 (64.8%) patients with autonomic neuropathy and in five out of 20 (25%) HIV+/AN– patients (sensitivity 65%, specificity 75%). A significant correlation was observed between scores of autonomic involvement and QTc interval prolongation. This study confirms that the QTc measurement is a reliable parameter indicating the presence of autonomic neuropathy. Since QT prolongation may determine ventricular arrhythmias, such patients must be followed because they may be at increased risk of sudden death.     

Antipsychotic drugs and cardiovascular safety: current studies of prolonged QT interval and risk of ventricular arrhythmia

Cardiovascular mortality is higher among schizophrenic patients than in the general population, and it is possible that most unexplained sudden deaths among these patients are due to ventricular arrhythmias for which antipsychotic drugs are either the cause or a predisposing factor. Most antipsychotic agents show electrophysiological effects resembling those of class 1a antiarrhythmic agents, and may be responsible for prolonging the QT interval, potentially going on to cause torsades de pointes. Some of the antipsychotic agents carry a high risk of arrhythmias, related to their effects on the QT interval. These include thioridazine, pimozide, sultopride, droperidol, and to a lesser extent haloperidol and chlorpromazine. In the case of the new atypical antipsychotic agents, it is possible to rank the risks of different drugs, with sertindole (now withdrawn from sale) having the highest risk, and ziprasidone somewhat lower, followed by risperidone and finally by quetiapine, clozapine and olanzapine which have negligible effects on the QT interval. A number of risk factors have been demonstrated, particularly: hypokalaemia and hypomagnesaemia, bradycardia, congenital long QT syndrome, and any underlying cardiac pathology. Lastly, the risk associated with any given antipsychotic agent is increased if it is combined either with any other drug known to prolong the QT interval and provoke torsades de pointes, or with any drug capable of inhibiting the hepatic metabolism of the antipsychotic agent. A list of such drugs is provided, together with advice on the action to be taken when prescribing an antipsychotic agent to a patient with a long QT interval.     

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.     

The potential for QT prolongation by antiepileptic drugs in children

Cardiac arrhythmia may be one of the major causes of sudden unexpected death in children with epilepsy. We assessed drug-induced QT prolongation to establish whether the use of antiepileptic drugs contributes to sudden unexpected death. A total of 178 children with epilepsy (93 males and 85 females, with ages ranging from 1 month to 18.9 years; mean age 7.0 +/- 4.1 years) were involved in the study. The QT intervals were manually measured and corrected using Fridericia's formula (QTFc = QT/RR(1/3)). The mean corrected QT interval (QTc) of 152 children on antiepileptic drugs during the study period was 0.40 +/- 0.03 s, and for 26 age-matched, antiepileptic drug-free control patients it was 0.40 +/- 0.03 s. The mean QTc of the children with monotherapy was 0.40 +/- 0.03 s for the valproate group (n = 42), 0.39 +/- 0.02 s for the carbamazepine/oxcarbazepine group (n = 34), and 0.40 +/- 0.02 s for the topiramate group (n = 26), respectively. There was no statistically significant difference among the groups as assessed by analysis of variance. In addition, there was no significant difference between the monotherapy group (n = 109; 0.40 +/- 0.02 s) and the polytherapy group (n = 43; 0.39 +/- 0.03 s). Major antiepileptic drugs may not precipitate prolongation of the QT interval into sudden unexpected death in children with epilepsy, however further studies are required.     

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.     

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.     

Abnormalities of rate-corrected QT intervals in Parkinson's disease-a comparison with multiple system atrophy and progressive supranuclear palsy

A number of patients with Parkinson's disease (PD) and multiple system atrophy (MSA), in whom sudden death does occur occasionally, have QT or rate-corrected QT (QTc) interval prolongation on electrocardiogram (ECG). Although these QT or QTc interval abnormalities are likely related to autonomic dysfunction, the pathophysiology remains unknown. The aim of this study was to compare the degree of QTc interval prolongation among akinetic-rigid syndromes, namely PD and related disorders, and to evaluate the relationship between QTc prolongation and severity of autonomic dysfunction. Thirty-four patients with PD, 22 with MSA, 11 with progressive supranuclear palsy (PSP) and 30 healthy controls underwent standard autonomic function tests, and electrocardiography variables (RR, QT and QTc intervals) were measured by an ECG recorder with an automated analyzer. The relationship between QTc interval and cardiovascular reflex tests were also analyzed. Orthostatic hypotension and decreased heart rate in response to respiratory stimuli were prominent in MSA, while these were relatively mild in PD. Unlike the RR and QT intervals, the QTc interval significantly differed among all groups (p<0.01). The QTc interval was significantly prolonged in PD (409+/-17 ms; p<0.001) and MSA (404+/-14 ms; p<0.05) compared with healthy controls (394+/-19 ms). Neither autonomic dysfunction nor QTc interval prolongation was evident in PSP. QTc intervals and cardiovascular reflexes did not correlate, except for Valsalva ratio. The QTc interval was obviously prolonged in PD patients to an extent that could not be accounted for simply by autonomic dysfunction levels. MSA patients showed slightly prolonged QTc intervals in spite of marked cardiovascular autonomic dysfunction. Abnormalities of the QTc may reflect the degeneration of cardioselective sympathetic and parasympathetic neurons that cannot be fully captured by cardiovascular autonomic function tests.     

精神科住院患者猝死的相关因素分析：一项病例对照研究

目的识别精神科住院患者猝死的潜在危险因素，为探讨如何进一步预防住院精神病患者的猝死提供依据。方法选取1987年1月至2006年12月在广州市精神病医院精神科住院期间发生猝死的患者作为猝死组，选取与猝死组同性别相同或相近年龄、入院时间及在猝死者猝死当日仍住院的非死亡病例作为对照组，进行1：1匹配的病例对照研究。结果共有47例住院精神病患者发生猝死，猝死发生率1．68‰，（95％CI 1．20‰～2．16‰）。与对照组相比，猝死组合并心血管疾病、QTc间期延长及联用抗精神病药物的情况较多，差异有统计学意义（均P〈0．05）。结论对住院精神病患者的猝死危险评估和预防时要充分考虑其发生猝死的相关因素。     

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.