Safety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP)

Thomas, Simon H.L.; Drici, Milou Daniel; Hall, Gillian; Crocq, Marc‐Antoine; Everitt, Barry J.; Lader, Malcolm; Jeunne, Claire Le; Naber, Dieter; Priori, Silvia; Sturkenboom, Miriam; Thibaut, Florence; Peuskens, Joseph; Mittoux, Aurélia; Tanghøj, Per; Toumi, Mondher; Moore, Nicholas; Mann, Ronald D.

doi:10.1111/j.1600-0447.2010.01563.x

Cited by 61 publications

(33 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In another study, 52 no difference in frequency of sudden death was seen between ziprasidone (the third worst drug in our analysis) and olanzapine (n518154). 51 We emphasise that amisulpride was regarded as benign in some guidelines, 13 but our findings show that it might not be-a result that is consistent with an analysis of amisulpride overdoses. 50 This result has the limitation that the evidence is indirectly derived from two comparisons with olanzapine, since direct comparisons with placebo were not available (appendix pp 92-96).…”

Section: Focussupporting

confidence: 91%

Comparative Efficacy and Tolerability of 15 Antipsychotic Drugs in Schizophrenia: A Multiple-Treatments Meta-Analysis

Leucht

Cipriani

Spineli

et al. 2014

FOC

328

503

View full text Add to dashboard Cite

Background: The question of which antipsychotic drug should be preferred for the treatment of schizophrenia is controversial, and conventional pairwise meta-analyses cannot provide a hierarchy based on the randomised evidence.We aimed to integrate the available evidence to create hierarchies of the comparative efficacy, risk of all-cause discontinuation, and major side-effects of antipsychotic drugs. Methods: We did a Bayesian-framework, multipletreatments meta-analysis (which uses both direct and indirect comparisons) of randomised controlled trials to compare 15 antipsychotic drugs and placebo in the acute treatment of schizophrenia. We searched the Cochrane Schizophrenia Group's specialised register, Medline, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for reports published up to Sept 1, 2012. Search results were supplemented by reports from the US Food and Drug Administration website and by data requested from pharmaceutical companies. Blinded, randomised controlled trials of patients with schizophrenia or related disorders were eligible. We excluded trials done in patients with predominant negative symptoms, concomitant medical illness, or treatment resistance, and those done in stable patients. Data for seven outcomes were independently extracted by two reviewers. The primary outcome was efficacy, as measured by mean overall change in symptoms. We also examined all-cause discontinuation, weight gain, extrapyramidal side-effects, prolactin increase, QTc prolongation, and sedation. Findings: We identified 212 suitable trials, with data for 43 049 participants. All drugs were significantly more effective than placebo. The standardised mean differences with 95% credible intervals were: clozapine 0·88, 0·73-1·03; amisulpride 0·66, 0·53-0·78; olanzapine 0·59, 0·53-0·65; risperidone 0·56, 0·50-0·63; paliperidone 0·50, 0·39-0·60; zotepine 0·49, 0·31-0·66; haloperidol 0·45, 0·39-0·51; quetiapine 0·44, 0·35-0·52; aripiprazole 0·43, 0·34-0·52; sertindole 0·39, 0·26-0·52; ziprasidone 0·39, 0·30-0·49; chlorpromazine 0·38, 0·23-0·54; asenapine 0·38, 0·25-0·51; lurasidone 0·33, 0·21-0·45; and iloperidone 0·33, 0·22-0·43. Odds ratios compared with placebo for all-cause discontinuation ranged from 0·43 for the best drug (amisulpride) to 0·80 for the worst drug (haloperidol); for extrapyramidal side-effects 0·30 (clozapine) to 4·76 (haloperidol); and for sedation 1·42 (amisulpride) to 8·82 (clozapine). Standardised mean differences compared with placebo for weight gain varied from 20·09 for the best drug (haloperidol) to 20·74 for the worst drug (olanzapine), for prolactin increase 0·22 (aripiprazole) to 21·30 192 (paliperidone), and for QTc prolongation 0·10 (lurasidone) to 20·90 (sertindole). Efficacy outcomes did not change substantially after removal of placebo or haloperidol groups, or when dose, percentage of withdrawals, extent of blinding, pharmaceutical industry sponsorship, study duration, chronicity, and year of publication were accounted for in metaregressions and sensitivit...

show abstract

Section: Focussupporting

confidence: 91%

Comparative Efficacy and Tolerability of 15 Antipsychotic Drugs in Schizophrenia: A Multiple-Treatments Meta-Analysis

Leucht

Cipriani

Spineli

et al. 2014

FOC

328

503

View full text Add to dashboard Cite

show abstract

“…24 With regard to the issue if intake of sertindole causes an increased risk for serious arrythmatic events and sudden cardiac death, there is a difference in opinion between the Food and Drug Administration (FDA) and the manufacturer. 25,26 In Europe, the marketing authorization of sertindole was suspended from 1998 to 2005, because of concerns about the increased risk of sudden death due to QT interval prolongation. As of May 2011, it is still not approved by the Food and Drug Administration for use in the United States.…”

mentioning

confidence: 99%

Computer Simulations of Structure–Activity Relationships for hERG Channel Blockers

et al. 2011

View full text Add to dashboard Cite

T he recent progress in the determination of three-dimensional (3D) structures of biological ion channels holds great promise for obtaining a structure-based quantitative view of interactions between channels and ligands of biological and pharmacological importance. Notwithstanding the increasing number of ion channel structures that have been determined, 1À6 there are, however, still relatively few complexes with ligands, such as channel blockers, that have been described. 7,8 From a pharmaceutical viewpoint, several of the most relevant channels have also not been structurally characterized at the atomic level. In the K + channel field, a number of key structures have been obtained 1À6 that in some cases allow for relatively reliable homology modeling of related channels and their interactions with ligands. 1,3,5 Of particular interest among the human K + channels is the human ether-a-go-go-related gene (hERG) channel that is associated with both inherited and drug-induced long QT syndrome. 9,10 The latter problem, which is a side effect caused by blockade of hERG by various compounds, is a major obstacle for drug development and is presently receiving intense attention. 11 In the cardiac action potential, the hERG channel carries the rapid delayed rectifier (I Kr ) current, and its blockade leads to a prolongation of the QT interval, with severe risks for arrhythmias and sudden death. 12,13 Most compounds causing such blockade apparently become trapped in the relatively unspecific internal pore cavity of the channel, and it is therefore of major interest to investigate the binding properties of this cavity. Unfortunately, the pore-forming helices of hERG show only relatively weak homology to K + channels with known 3D structure and particularly with members of the Shaker-related family. 5,14 The short pore helix, the selectivity filter, and the innermost S6 helices lining the pore can, however, be confidently aligned on the basis of conservation of the filter region and a glycine hinge in S6. 15,16 The situation is more ambiguous for the S5 helices that pack against the S6 helices in the tetrameric structure, and several alignments of S5 against K + channels of known structure have been published. 15À18 We have recently reported an analysis of seven different alignments and 3D pore models utilizing conventional 3D structure quality validation methods as well as molecular dynamics (MD) simulations. From that work, one model (model 6 of ref 19) emerged as the most consistent, and it also provided a rationalization of the results from mutation scanning experiments. 20 Here, we investigate the performance of our best hERG pore model with respect to prediction of binding affinities for a series of sertindole analogues listed in Table 1. 21 Sertindole is an indolylpiperidine antipsychotic agent that has nanomolar affinities for dopamine D 2 , serotonin 5-HT 2 , and R 1 adrenergic ABSTRACT: The hERG potassium channel is of major pharmaceutical importance, and its blockade by various compounds, potentially causin...

show abstract

“…Bitter et al, 2008) or the limited, number of antipsychotics in the study (e.g. Thomas et al, 2010). In general, the observational (non-randomized) design limits internal validity, and thereby endangers external validity.…”

Section: Discussionmentioning

confidence: 99%

Comparative effectiveness of depot and oral second generation antipsychotic drugs in schizophrenia: A nationwide study in Hungary

Bitter

Katona²,

Zámbori³

et al. 2013

European Neuropsychopharmacology

View full text Add to dashboard Cite

We conducted a nationwide, full-population based investigation to evaluate the comparative effectiveness of all marketed second generation antipsychotic drugs (SGA) prescribed for outpatients with the diagnosis of schizophrenia in Hungary. Using the national central register, our observational follow-up study included all patients with schizophrenia or related disorder between 01/01/2006 and 30/06/2008. The study cohort comprised 9567 patients who started new SGA during the inclusion period (01/07/2007-30/06/2008). All-cause medication discontinuation of 8 SGAs (1 depot and 7 oral formulations) marketed during the inclusion period, and the time to all-cause discontinuation were the main outcomes. Statistical models included the Kaplan-Meier and the Cox proportional hazards models with propensity score adjustment. Patients treated with a depot formulation risperidone had the longest time to discontinuation with a median of 215 days (95%CI:181-242 days), which was statistically significantly different compared to patients treated with the rest of the medications: E-mail address: czobor.pal@med.semmelweis-univ.hu (P. Czobor). 1 Istvan Bitter MD, PhD and Lajos Katona MS are co-first authors contributed equally to the article. 2 At the time of beginning of the study he worked as a psychiatry expert for NHIF.European Neuropsychopharmacology (2013Neuropsychopharmacology ( ) 23, 1383Neuropsychopharmacology ( -1390 with patients who were discharged from their first hospitalization for schizophrenia (Tiihonen et al., 2006(Tiihonen et al., , 2011; namely the median times to all-cause medication discontinuation were o120 days for the majority of the oral SGA. In terms of medication differences, our data support the superior effectiveness of the depot formulation regarding all-cause discontinuation, followed by olanzapine at the efficacy rank order.

show abstract

Safety of sertindole versus risperidone in schizophrenia: principal results of the sertindole cohort prospective study (SCoP)

Abstract: Sertindole did not increase all-cause mortality, but cardiac mortality was higher and suicide attempts may be lower with sertindole.

Cited by 61 publications

References 31 publications

Comparative Efficacy and Tolerability of 15 Antipsychotic Drugs in Schizophrenia: A Multiple-Treatments Meta-Analysis

Comparative Efficacy and Tolerability of 15 Antipsychotic Drugs in Schizophrenia: A Multiple-Treatments Meta-Analysis

Computer Simulations of Structure–Activity Relationships for hERG Channel Blockers

Comparative effectiveness of depot and oral second generation antipsychotic drugs in schizophrenia: A nationwide study in Hungary

Contact Info

Product

Resources

About