Sex difference in QTc prolongation in chronic institutionalized patients with schizophrenia on long-term treatment with typical and atypical antipsychotics

Yang, Fu De; Wang, Xiang Qun; Liu, Xiu Ping; Zhao, Ke; Fu, Wei Hong; Hao, Xue; Zhang, Xing Li; Huang, Guo Shu; Qu, Sheng Cai; Bai, Jing; Huang, Xu; Kosten, Thomas R.; Zhang, Xiang Yang

doi:10.1007/s00213-011-2188-5

Cited by 39 publications

(60 citation statements)

References 32 publications

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“…However, this decline in the whole sample was driven by the decreasing per cent of QTc prolongation in China (from 9.5% in 2004 to 0.3% in 2008/2009) and Hong Kong (from 2.4% in 2004 to 0% in 2008/2009). Our finding that 2.4% of patients had QTc prolongation is at the very low end of the range reported from other surveys, in which QTc prolongation in patients with schizophrenia ranged from 0.5% to 38% (Ramos‐Rios et al ., ; Yang et al ., ). The reason for differences between our finding and those from other studies is likely due to a number reasons, including inconsistent cutoff values for QTc prolongation ranging from 420 to 470 ms (Warner et al ., ; Reilly et al ., ), differences in patient characteristics (young versus older adults and Caucasian versus Asian patients), study settings (inpatients versus outpatients), and treatment characteristics (first‐generation antipsychotic (FGA) versus second‐generation antipsychotic (SGA) use, high versus medium/low dose, and comedications use).…”

Section: Discussioncontrasting

confidence: 76%

“…In a study conducted in China, Yang et al . () reported that the percentage of QTc prolongation in Chinese hospitalized schizophrenia patients was 4.5%, which was somewhat higher than our figure in the whole sample (2.4%) but in the range of Chinese patients between our two surveys (9.5% in 2004 and 0.3% in 2009). Interestingly, the percentage of QTc prolongation has decreased in China during the study period, which may be explained by the widespread use of SGAs and decreased use of FGAs; as compared with FGAs, SGAs have a lower risk of QTc prolongation (Jolly et al ., ; Ray et al ., ).…”

Section: Discussionmentioning

confidence: 97%

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QTc prolongation in schizophrenia patients in Asia: clinical correlates and trends between 2004 and 2008/2009

Xiang

Chiu

Ungvári

et al. 2015

Human Psychopharmacology

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Section: Discussioncontrasting

confidence: 76%

Section: Discussionmentioning

confidence: 97%

QTc prolongation in schizophrenia patients in Asia: clinical correlates and trends between 2004 and 2008/2009

Xiang

Chiu

Ungvári

et al. 2015

Human Psychopharmacology

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“…In addition to such a predisposition, cardiac electrical activity can be altered by antipsychotic use, resulting in QTc prolongation, even in younger patients, in particular in women 98,99. In adults, QTc prolongation is generally clinically relevant when QTc is >500 milliseconds or when QTc increases by ≥60 milliseconds from drug-free baseline,39 resulting in an increased risk of torsades de pointes and sudden cardiac death (SCD).…”

Section: Methodsmentioning

confidence: 99%

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

Solmi

Murru

Pacchiarotti

et al. 2017

TCRM

326

255

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Since the discovery of chlorpromazine (CPZ) in 1952, first-generation antipsychotics (FGAs) have revolutionized psychiatric care in terms of facilitating discharge from hospital and enabling large numbers of patients with severe mental illness (SMI) to be treated in the community. Second-generation antipsychotics (SGAs) ushered in a progressive shift from the paternalistic management of SMI symptoms to a patient-centered approach, which emphasized targets important to patients – psychosocial functioning, quality of life, and recovery. These drugs are no longer limited to specific Diagnostic and Statistical Manual of Mental Disorders (DSM) categories. Evidence indicates that SGAs show an improved safety and tolerability profile compared with FGAs. The incidence of treatment-emergent extrapyramidal side effects is lower, and there is less impairment of cognitive function and treatment-related negative symptoms. However, treatment with SGAs has been associated with a wide range of untoward effects, among which treatment-emergent weight gain and metabolic abnormalities are of notable concern. The present clinical review aims to summarize the safety and tolerability profile of selected FGAs and SGAs and to link treatment-related adverse effects to the pharmacodynamic profile of each drug. Evidence, predominantly derived from systematic reviews, meta-analyses, and clinical trials of the drugs amisulpride, aripiprazole, asenapine, brexpiprazole, cariprazine, clozapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, risperidone, sertindole, ziprasidone, CPZ, haloperidol, loxapine, and perphenazine, is summarized. In addition, the safety and tolerability profiles of antipsychotics are discussed in the context of the “behavioral toxicity” conceptual framework, which considers the longitudinal course and the clinical and therapeutic consequences of treatment-emergent side effects. In SMI, SGAs with safer metabolic profiles should ideally be prescribed first. However, alongside with safety, efficacy should also be considered on a patient-tailored basis.

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“…aripiprazol, clothiapine, haloperidol; data not depicted). In particular, the administration of clozapine, known to be associated with higher QT-prolongation risk than risperidone [9], had no effect on QT-length (Figure 1B). …”

Section: Case Reportmentioning

confidence: 99%

Selective acquired long QT syndrome (saLQTS) upon risperidone treatment

et al. 2012

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BackgroundNumerous structurally unrelated drugs, including antipsychotics, can prolong QT interval and trigger the acquired long QT syndrome (aLQTS). All of them are thought to act at the level of KCNH2, a subunit of the potassium channel. Although the QT-prolonging drugs are proscribed in the subjects with aLQTS, the individual response to diverse QT-prolonging drugs may vary substantially.Case presentationWe report here a case of aLQTS in response to small doses of risperidone that was confirmed at three independent drug challenges in the absence of other QT-prolonging drugs. On the other hand, the patient did not respond with QT prolongation to some other antipsychotics. In particular, the administration of clozapine, known to be associated with higher QT-prolongation risk than risperidone, had no effect on QT-length. A detailed genetic analysis revealed no mutations or polymorphisms in KCNH2, KCNE1, KCNE2, SCN5A and KCNQ1 genes.ConclusionsOur observation suggests that some patients may display a selective aLQTS to a single antipsychotic, without a potassium channel-related genetic substrate. Contrasting with the idea of a common target of the aLQTS-triggerring drugs, our data suggests existence of an alternative target protein, which unlike the KCNH2 would be drug-selective.

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Sex difference in QTc prolongation in chronic institutionalized patients with schizophrenia on long-term treatment with typical and atypical antipsychotics

Abstract: Our present findings suggest that there are sex differences in the prevalence of QTc prolongation and QTc lengthening in schizophrenia. Antipsychotic types are risk factors for QTc prolongation, and risks are substantially higher for clozapine.

Cited by 39 publications

References 32 publications

QTc prolongation in schizophrenia patients in Asia: clinical correlates and trends between 2004 and 2008/2009

QTc prolongation in schizophrenia patients in Asia: clinical correlates and trends between 2004 and 2008/2009

Safety, tolerability, and risks associated with first- and second-generation antipsychotics: a state-of-the-art clinical review

Selective acquired long QT syndrome (saLQTS) upon risperidone treatment

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