Antipsychotics and lengthening QT / QTc

2011 ◽  
Vol 26 (S2) ◽  
pp. 887-887
Author(s):  
L. Tarricone
Keyword(s):  
Heart Rate ◽  
Antipsychotic Medication ◽  
Qt Interval ◽  
First Generation ◽  
Second Generation ◽  
Pathophysiological Mechanism ◽  
Increased Risk ◽  
Second Generation Antipsychotics ◽  
Effective Drugs ◽  
Typical Antipsychotics

Serious arrhythmias and / or sudden deaths related to the use of first-generation or typical antipsychotics have been observed for about thirty years. It is considered that the pathophysiological mechanism that causes these events may to be block the potassium and calcium channels with abnormal ventricular repolarization. The assessment of QT, QTc corrected for heart rate, is a predictor of risk for TdP. The introduction of second generation antipsychotics raised the question if these molecules can induce prolongation of the QT interval on the increased risk of arrhythmia and / or TdP. Controlled studies also argue that second-generation antipsychotics may lead to prolongation of QT / QTc. by introducing into the routine ECG and laboratory evaluations The purpose of this study is to analyze any change in ECG QTc observed in patients admitted to the SPDC, and possible correlation with antipsychotic medication.AscoltaThe ECGs of 300 patients admitted during the period January 2009/January 2010 with QTc assessment the first day and fifteen days after the treatment with second generation antipsychotics were examined. Changes were evaluated in relation to gender, age, diagnosis, antipsychotic taken in single or co-therapy QTc value divided into three classes: 440 ≤; 441 ≥ 500 ; 501≥;). There were no significant changes in QTc in relation to medication. It is believed that second-generation antipsychotics are considered safe and effective drugs at the time and that psychiatrists should pay more attention, however, by introducing into the routine ECG and laboratory evaluations.

scholarly journals First- v. second-generation antipsychotics and risk for diabetes in schizophrenia: Systematic review and meta-analysis

2008 ◽  
Vol 192 (6) ◽  
pp. 406-411 ◽  
Author(s):  
M. Smith ◽  
D. Hopkins ◽  
R. C. Peveler ◽  
R. I. G. Holt ◽  
M. Woodward ◽  
...  
Keyword(s):  
Systematic Review ◽  
First Generation ◽  
Second Generation ◽  
Psychotic Disorders ◽  
Controlled Trial ◽  
Meta Analysis ◽  
Antipsychotic Treatment ◽  
Cross Sectional ◽  
Increased Risk ◽  
Second Generation Antipsychotics

BackgroundThe increased prevalence of diabetes in schizophrenia is partly attributed to antipsychotic treatment, in particular second-generation antipsychotics, but the evidence has not been systematically reviewed.AimsSystematic review and meta-analysis comparing diabetes risk for different antipsychotics in people with schizophrenia.MethodWe searched MEDLINE, PsycINFO, EMBASE, International Pharmaceutical Abstracts, CINAHL and Web of Knowledge until September 2006. Studies were eligible for inclusion if the design was cross-sectional, case-control, cohort or a controlled trial in individuals with schizophrenia or related psychotic disorders, where second-generation antipsychotics (defined as clozapine, olanzapine, risperidone and quetiapine) were compared with first-generation antipsychotics and diabetes was an outcome. Data were pooled using random effects inverse variance weighted meta-analysis.ResultsOf the studies that met the inclusion criteria (n=14), 11 had sufficient data to include in the meta-analysis. Four of these were retrospective cohort studies. The relative risk of diabetes in patients with schizophrenia prescribed one of the second-generation v. first-generation antipsychotics was 1.32 (95% CI 1.15-1.51). There were insufficient data to include aripiprazole, ziprasidone and amisulpride in this analysis.ConclusionsThere is tentative evidence that the second-generation antipsychotics included in this study are associated with a small increased risk for diabetes compared with firstgeneration antipsychotics in people with schizophrenia. Methodological limitations were found in most studies, leading to heterogeneity and difficulty interpreting data. Regardless of type of antipsychotic, screening for diabetes in all people with schizophrenia should be routine.

Pharmakotherapie update

2020 ◽  
Vol 25 (1) ◽  
pp. 23-32
Author(s):  
Gerd Laux
Keyword(s):  
First Generation ◽  
Second Generation ◽  
Therapeutische Maßnahmen ◽  
Second Generation Antipsychotics

Für die Therapie schizophrener Erkrankungen sind seit fast 60 Jahren Antipsychotika/Neuroleptika aufgrund ihrer antipsychotischen Wirkung von zentraler Bedeutung. Die Einteilung kann unter verschiedenen Gesichtspunkten erfolgen (chemische Struktur, neuroleptische Potenz, Rezeptorprofil), heute werden üblicherweise unterschieden typische (traditionelle, klassische, konventionelle) Antipsychotika der ersten Generation ‒ »First Generation Antipsychotics« (FGA) ‒ und sog. atypische (»neuere«) Neuroleptika bzw. Antipsychotika der zweiten Generation ‒»Second Generation Antipsychotics« (SGA). Hierzu zählen Aripiprazol, Asenapin, Cariprazin, Clozapin, Olanzapin, Quetiapin, Risperidon, Sertindol und Ziprasidon. Hierbei handelt es sich um keine homogene Gruppe – sowohl neuropharmakologisch (Wirkmechanismus), als auch hinsichtlich klinischem Wirkprofil und dem Nebenwirkungsspektrum bestehen z. T. erhebliche Unterschiede. Neben der Akut-Medikation ist eine Langzeitmedikation bzw. Rezidivprophylaxe mit Antipsychotika für die Rehabilitation vieler schizophrener Patienten im Sinne eines »Stresspuffers« von grundlegender Bedeutung. In Placebo-kontrollierten Studien trat bei Patienten, die über ein Jahr behandelt wurden, bei etwa 30% unter Neuroleptika ein Rezidiv auf, unter Placebo bei mehr als 70%. Für die Langzeitbehandlung bietet sich der Einsatz von Depot-Neuroleptika an, neu entwickelt wurden Langzeit-Depot-Injektionen mit Intervallen von bis zu 3 Monaten. Grundsätzlich ist die niedrigstmögliche (wirksame) Dosis zu verwenden. Im Zentrum der Nebenwirkungen (UAW) standen lange Zeit extrapyramidal-motorische Bewegungsstörungen (EPMS), mit der Einführung von Clozapin und anderen atypischen Antipsychotika der zweiten Generation gewannen andere Nebenwirkungen an Bedeutung. Hierzu zählen Gewichtszunahme, Störungen metabolischer Parameter und ein erhöhtes Risiko für Mortalität und zerebrovaskuläre Ereignisse bei älteren Patienten mit Demenz. Entsprechende Kontrolluntersuchungen sind erforderlich, für Clozapin gibt es aufgrund seines Agranulozytose-Risikos Sonderbestimmungen. Immer sollte ein Gesamtbehandlungsplan orientiert an der neuen S3-Praxisleitlinie Schizophrenie der DGPPN aufgestellt werden, der psychologische und milieu-/sozial-therapeutische Maßnahmen einschließt. Standard ist heute auch eine sog. Psychoedukation, für Psychopharmaka liegen bewährte Patienten-Ratgeber vor.

Abstract 187: Electrocardiographic Heart Rate-corrected Qt Interval And Risk Of Stroke In The REasons For Geographic And Racial Differences In Stroke (REGARDS) Study

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Elsayed Z Soliman ◽  
George Howard ◽  
George Howard ◽  
Mary Cushman ◽  
Brett Kissela ◽  
...  
Keyword(s):  
Heart Rate ◽  
Racial Differences ◽  
Qt Interval ◽  
Proportional Hazards ◽  
Left Ventricular ◽  
Cox Proportional Hazards ◽  
Corrected Qt Interval ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk ◽  
Regards Study

Background: Prolongation of heart rate-corrected QT interval (QTc) is a well established predictor of cardiovascular morbidity and mortality. Little is known, however, about the relationship between this simple electrocardiographic (ECG) marker and risk of stroke. Methods: A total of 27,411 participants aged > 45 years without prior stroke from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study were included in this analysis. QTc was calculated using Framingham formula (QTcFram). Stroke cases were identified and adjudicated during an up to 7 years of follow-up (median 2.7 years). Cox proportional hazards analysis was used to estimate the hazard ratios for incident stroke associated with prolonged QTcFram interval (vs. normal) and per 1 standard deviation (SD) increase, separately, in a series of incremental models. Results: The risk of incident stroke in the study participants with baseline prolonged QTcFram was almost 3 times the risk in those with normal QTcFram [HR (95% CI): 2.88 (2.12, 3.92), p<0.0001]. After adjustment for age, race, sex, antihypertensive medication use, systolic blood pressure, current smoking, diabetes, left ventricular hypertrophy, atrial fibrillation, prior cardiovascular disease, QRS duration, warfarin use, and QT-prolonging drugs (full model), the risk of stroke remained significantly high [HR (95% CI): 1.67 (1.16, 2.41), p=0.0060)], and was consistent across several subgroups of REGARDS participants. When the risk of stroke was estimated per 1 SD increase in QTcFram, a 24% increased risk was observed [HR (95% CI): 1.24 (1.16, 1.33), p<0.0001)]. This risk remained significant in the fully adjusted model [HR (95% CI): 1.12 (1.03, 1.21), p=0.0055]. Similar results were obtained when other QTc correction formulas including Hodge’s, Bazett’s and Fridericia’s were used. Conclusions: QTc prolongation is associated with a significantly increased risk of incident stroke independently from known stroke risk factors. In light of our results, examining the risk of stroke associated with QT-prolonging drugs may be warranted.

Antipsychotic utilisation and persistence in Australia: A nationwide 5-year study

2021 ◽  
pp. 000486742110516
Author(s):  
Mark Taylor ◽  
Dante Dangelo-Kemp ◽  
Dennis Liu ◽  
Steve Kisely ◽  
Simon Graham ◽  
...  
Keyword(s):  
First Generation ◽  
Second Generation ◽  
Treatment Persistence ◽  
Persistence Time ◽  
Hazard Ratios ◽  
Second Generation Antipsychotics ◽  
Time In Treatment ◽  
Second Generation Antipsychotic ◽  
Long Acting ◽  
Subsequent Relapse

Objectives: To evaluate the utilisation and persistence of antipsychotics for the treatment of schizophrenia in Australia. Methods: A retrospective study using the Australian Pharmaceutical Benefits Scheme database of a representative 10% sample. All adults with schizophrenia who were dispensed three or more supplies of oral (including clozapine) or long-acting injectable antipsychotics between 1 June 2015 and 31 May 2020 were included. Persistence time in treatment was evaluated using survival analysis and Cox hazard ratios. Results: In all, 26,847 adults with schizophrenia were studied. Oral second-generation antipsychotics were more frequently dispensed than the other antipsychotic groups studied. Median treatment persistence times were 18.3 months for second-generation antipsychotic long-acting injectables, 10.7 months for oral second-generation antipsychotics and were significantly lower for both formulations of first-generation antipsychotics at 5.2 months (long-acting injectables) and 3.7 months (oral). The median persistence time for clozapine was significantly longer than all other antipsychotics groups. Conclusions: Oral second-generation antipsychotics and second-generation antipsychotic long-acting injectables accounted for over 75% and 13% of all antipsychotics in Australia, respectively. Concerns over medication adherence and subsequent relapse have not translated into increased long-acting injectable usage despite their significantly longer persistence. Clozapine, the single most ‘persistent’ antipsychotic, was only used in 9% of people, although up to a third of all cases are likely to be treatment-resistant. Our data suggest clinicians should give consideration to the earlier use of second-generation antipsychotic long-acting injectables and clozapine, to ameliorate prognosis in schizophrenia.

Abstract 4401: Two Independent Genetic Variants in NOS1AP are Associated with QT interval in a Multi-Ethnic Population: the Dallas Heart Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Dan E Arking ◽  
Amit Khera ◽  
Chao Xing ◽  
Wen H Kao ◽  
Aravinda Chakravarti
Keyword(s):  
Heart Rate ◽  
Genetic Variants ◽  
Qt Interval ◽  
Genetic Model ◽  
Black Population ◽  
European Ancestry ◽  
Ethnic Population ◽  
Heart Study ◽  
Increased Risk ◽  
Dallas Heart Study

Extremes of QT interval are associated with increased risk for sudden cardiac death (SCD), and thus identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous work revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We thus sought to characterize the effects of NOS1AP genetic variants in the multi-ethnic population-based Dallas Heart Study (DHS). Among 3,557 participants in DHS with available DNA, those without QT interval, heart rate, age, and/or sex information, and those with QRS >120 or undetermined ethnicity were excluded, resulting in 2,949 samples available for analysis (501 Hispanic, 1,506 Black, 942 White). Sex- and ethnicity-stratified linear regression was used to correct QT interval for heart rate and age. Eight SNPs spanning the region previously associated with QT interval were genotyped, and ethnic-specific analyses were performed under an additive genetic model. The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in the White participants (+2.6 ms, P<0.005) as well as in Blacks (+3.2 ms, P<3.6 × 10 –5), with the same direction of effect in Hispanics (+1.5 ms, P<0.17). A second SNP, rs16856785, which was uncorrelated with rs16847548 (r2 < 0.01 in Blacks) was also associated with QT interval in Blacks (+1.6 ms, P<0.01), with qualitatively similar results in Whites (+0.9 ms, P<0.33) and Hispanics (+0.6 ms, P<0.66). Adjusting for local and global ancestry using Ancestry Informative Markers did not significantly alter the results. Comparing Blacks homozygous at both SNPs for the QT lengthening allele to Blacks homozygous for the complementary alleles revealed a 13.9 ms difference in QT interval. These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends in Hispanics. Further, a second, independent site within NOS1AP has been implicated in modulating QT interval, highlighting the importance of NOS1AP genetic variants in regulating QT interval.

Disease-modifying drugs for multiple sclerosis and infection risk: a cohort study

2018 ◽  
Vol 89 (10) ◽  
pp. 1050-1056 ◽  
Author(s):  
José Maria Andreas Wijnands ◽  
Feng Zhu ◽  
Elaine Kingwell ◽  
John David Fisk ◽  
Charity Evans ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
First Generation ◽  
Second Generation ◽  
Population Based ◽  
Infection Risk ◽  
Disease Modifying Drugs ◽  
Drug Classes ◽  
Increased Risk ◽  
Disease Modifying ◽  
Status Index

ObjectiveLittle is known about disease-modifying treatments (DMTs) for multiple sclerosis (MS) and infection risk in clinical practice. We examined the association between DMTs and infection-related medical encounters.MethodsUsing population-based administrative data from British Columbia, Canada, we identified MS cases and followed them from their first demyelinating event (1996–2013) until emigration, death or study end (December 2013). Associations between DMT exposure (by DMT generation or class) and infection-related physician or hospital claims were assessed using recurrent time-to-events models, adjusted for age, sex, socioeconomic status, index year and comorbidity count. Results were reported as adjusted HRs (aHRs).ResultsOf 6793 MS cases, followed for 8.5 years (mean), 1716 (25.3%) were DMT exposed. Relative to no DMT, exposure to any first-generation DMT (beta-interferon or glatiramer acetate) was not associated with infection-related physician claims (aHR: 0.96; 95% CI 0.89 to 1.02), nor was exposure to these drug classes when assessed separately. Exposure to any second-generation DMT (oral DMT or natalizumab) was associated with an increased hazard of an infection-related physician claim (aHR: 1.47; 95% CI 1.16 to 1.85); when assessed individually, the association was significant for natalizumab (aHR: 1.59; 95% CI 1.19 to 2.11) but not the oral DMTs (aHR: 1.17; 95% CI 0.88 to 1.56). While no DMTs were associated with infection-related hospital claims, these hospitalisations were also uncommon.ConclusionExposure to first-generation DMTs was not associated with an altered infection risk. However, exposure to the second-generation DMTs was, with natalizumab associated with a 59% increased risk of an infection-related physician claim. Continued pharmacovigilance is warranted, including an investigation of the DMT-associated infection burden on patient outcomes.

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