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. 2015 May;60(5):215-22.
doi: 10.1177/070674371506000503.

Antipsychotic Polypharmacy and Corrected QT Interval: A Systematic Review

Hiroyoshi Takeuchi  1 , Takefumi Suzuki  2 , Gary Remington  3 , Hiroyuki Uchida  2   4
Affiliations

Antipsychotic Polypharmacy and Corrected QT Interval: A Systematic Review

Hiroyoshi Takeuchi et al. Can J Psychiatry. 2015 May.

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] Can J Psychiatry. 2015 Oct;60(10):426. Can J Psychiatry. 2015. PMID: 26720188 Free PMC article. No abstract available.

Abstract
in English, French

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.

Objectif :: Il reste à déterminer si la polypharmacie antipsychotique, une pratique clinique courante, est liée à un risque accru de temps corrigé dans l’allongement de l’intervalle entre le début de l’onde Q et la fin de l’onde T (QTc). Nous avons mené une revue systématique de la littérature pour aborder ce problème important.

Méthode :: Une recherche systématique de la littérature a été menée en octobre 2014, dans les bases de données MEDLINE, Embase et PsycINFO. Les études et les études de cas étaient incluses si elles rendaient compte d’intervalles QTc ou de changements d’intervalles QTc avant et après la polypharmacie antipsychotique ou d’intervalles QTc dans les groupes de polypharmacie antipsychotique et de monothérapie.

Résultats :: Un total de 21 articles (10 essais cliniques, 4 études par observation, et 7 études de cas) satisfaisaient aux critères d’inclusion. Les essais cliniques ont montré qu’un traitement combiné par rispéridone ou pimozide n’est pas clairement lié à une augmentation de l’intervalle QTc, alors que la ziprasidone ou le sertindole combiné à la clozapine peuvent prolonger l’intervalle QTc. Dans les 4 études par observation, la polypharmacie antipsychotique n’était pas clairement associée à l’allongement du QTc dans 3 études, toutes transversales. Par contre, une étude prospective montrait une augmentation significative de l’intervalle QTc suivant une co-administration antipsychotique. Les études de cas indiquaient un risque accru d’allongement du QTc chez au moins certains patients recevant une polypharmacie antipsychotique.

Conclusions :: Les données probantes actuellement disponibles ne confirment pas que la polypharmacie antipsychotique aggrave l’allongement du QTc en général, car les données probantes sont rares et non consistantes. Il est recommandé que les cliniciens demeurent prudents lorsqu’ils ont recours à la polypharmacie antipsychotique, étant donné qu’une combinaison de certains antipsychotiques est susceptible de prolonger davantage l’intervalle QTc, et que l’efficacité à l’appui des avantages cliniques de la polypharmacie antipsychotique est au mieux équivoque.

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Figures

Figure 1
Figure 1
PRISMA flow diagram of the literature search QTc = corrected time between start of Q wave and end of T wave
See this image and copyright information in PMC

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References

    1. Leucht S, Cipriani A, Spineli L, et al. Comparative efficacy and tolerability of 15 antipsychotic drugs in schizophrenia: a multiple-treatments meta-analysis. Lancet. 2013;382(9896):951–962. - PubMed
    1. Hasnain M, Vieweg W. QTc interval prolongation and torsade de pointes associated with second-generation antipsychotics and antidepressants: a comprehensive review. CNS Drugs. 2014;28(10):887–920. - PubMed
    1. CredibleMeds Worldwide. Oro Valley (AZ): CredibleMeds Worldwide; 2014. QTdrugs list. [cited 2014 Dec 28]. Available from: https://www.crediblemeds.org/new-drug-list.
    1. Kongsamut S, Kang J, Chen XL, et al. A comparison of the receptor binding and hERG channel affinities for a series of antipsychotic drugs. Eur J Pharmacol. 2002;450(1):37–41. - PubMed
    1. Titier K, Canal M, Déridet E, et al. Determination of myocardium to plasma concentration ratios of five antipsychotic drugs: comparison with their ability to induce arrhythmia and sudden death in clinical practice. Toxicol Appl Pharmacol. 2004;199(1):52–60. - PubMed

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