Antipsychotic dose mediates the association between polypharmacy and corrected QT interval

Corrado Barbui, Irene Bighelli, Giuseppe Carrà, Mariasole Castellazzi, Claudio Lucii, Giovanni Martinotti, Michela Nosè, Giovanni Ostuzzi, T. Acciavatti, A. Adamo, A. Aguglia, C. Albanese, S. Baccaglini, F. Bardicchia, R. Barone, Y. Barone, F. Bartoli, C. Bergamini, F. Bertolini, I. Bighelli & 87 others S. Bolognesi, A. Bordone, P. Bortolaso, M. Bugliani, C. Calandra, S. Calò, G. Cardamone, M. Caroleo, E. Carra, G. Carrà, D. Carretta, M. Castellazzi, L. Chiocchi, E. Cinosi, M. Clerici, M. Corbo, E. Corsi, R. Costanzo, G. Costoloni, F. D'Arienzo, S. Debolini, A. De Capua, W. A. Di Napoli, M. Dinelli, E. Facchi, F. Fargnoli, F. Fiori, A. Franchi, F. Gardellin, C. Gastaldon, E. Gazzoletti, L. Ghio, M. Giacomin, M. Gregis, N. Iovieno, D. Koukouna, A. Lax, C. Lintas, A. Luca, M. Luca, C. Lucii, M. Lussetti, M. Madrucci, N. Magnani, L. Magni, E. Manca, G. Martinotti, C. Martorelli, R. Mattafirri, M. Nosè, G. Ostuzzi, C. Paladini, D. Papola, M. Percudani, G. Perini, P. Petrosemolo, M. Pezzullo, S. Piantanida, F. Pinna, K. Prato, D. Prestia, D. Quattrone, C. Reggianini, F. Restaino, M. Ribolsi, G. Rinosi, C. Rizzo, R. Rizzo, M. Roggi, G. Rossi, S. Rossi, S. Ruberto, M. Santi, R. Santoro, G. Sepede, M. S. Signorelli, F. Soscia, F. Sozzi, P. Staffa, M. Stilo, S. Strizzolo, F. Suraniti, N. Tavian, L. Tortelli, F. Tosoni, M. Valdagno, V. Zanobini

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a crosssectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = -12.62, p < 0.001). Similarly, the mean QTc interval was significantly longer in those receiving AP polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = -2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy.

Original languageEnglish
Article number0148212
JournalPLoS One
Volume11
Issue number2
DOIs
Publication statusPublished - Feb 1 2016

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Polypharmacy
Antipsychotic Agents
dosage
antipsychotics
Confounding Factors (Epidemiology)

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Barbui, C., Bighelli, I., Carrà, G., Castellazzi, M., Lucii, C., Martinotti, G., ... Zanobini, V. (2016). Antipsychotic dose mediates the association between polypharmacy and corrected QT interval. PLoS One, 11(2), [0148212]. https://doi.org/10.1371/journal.pone.0148212

Antipsychotic dose mediates the association between polypharmacy and corrected QT interval. / Barbui, Corrado; Bighelli, Irene; Carrà, Giuseppe; Castellazzi, Mariasole; Lucii, Claudio; Martinotti, Giovanni; Nosè, Michela; Ostuzzi, Giovanni; Acciavatti, T.; Adamo, A.; Aguglia, A.; Albanese, C.; Baccaglini, S.; Bardicchia, F.; Barone, R.; Barone, Y.; Bartoli, F.; Bergamini, C.; Bertolini, F.; Bighelli, I.; Bolognesi, S.; Bordone, A.; Bortolaso, P.; Bugliani, M.; Calandra, C.; Calò, S.; Cardamone, G.; Caroleo, M.; Carra, E.; Carrà, G.; Carretta, D.; Castellazzi, M.; Chiocchi, L.; Cinosi, E.; Clerici, M.; Corbo, M.; Corsi, E.; Costanzo, R.; Costoloni, G.; D'Arienzo, F.; Debolini, S.; De Capua, A.; Di Napoli, W. A.; Dinelli, M.; Facchi, E.; Fargnoli, F.; Fiori, F.; Franchi, A.; Gardellin, F.; Gastaldon, C.; Gazzoletti, E.; Ghio, L.; Giacomin, M.; Gregis, M.; Iovieno, N.; Koukouna, D.; Lax, A.; Lintas, C.; Luca, A.; Luca, M.; Lucii, C.; Lussetti, M.; Madrucci, M.; Magnani, N.; Magni, L.; Manca, E.; Martinotti, G.; Martorelli, C.; Mattafirri, R.; Nosè, M.; Ostuzzi, G.; Paladini, C.; Papola, D.; Percudani, M.; Perini, G.; Petrosemolo, P.; Pezzullo, M.; Piantanida, S.; Pinna, F.; Prato, K.; Prestia, D.; Quattrone, D.; Reggianini, C.; Restaino, F.; Ribolsi, M.; Rinosi, G.; Rizzo, C.; Rizzo, R.; Roggi, M.; Rossi, G.; Rossi, S.; Ruberto, S.; Santi, M.; Santoro, R.; Sepede, G.; Signorelli, M. S.; Soscia, F.; Sozzi, F.; Staffa, P.; Stilo, M.; Strizzolo, S.; Suraniti, F.; Tavian, N.; Tortelli, L.; Tosoni, F.; Valdagno, M.; Zanobini, V.

In: PLoS One, Vol. 11, No. 2, 0148212, 01.02.2016.

Research output: Contribution to journalArticle

Barbui, C, Bighelli, I, Carrà, G, Castellazzi, M, Lucii, C, Martinotti, G, Nosè, M, Ostuzzi, G, Acciavatti, T, Adamo, A, Aguglia, A, Albanese, C, Baccaglini, S, Bardicchia, F, Barone, R, Barone, Y, Bartoli, F, Bergamini, C, Bertolini, F, Bighelli, I, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carrà, G, Carretta, D, Castellazzi, M, Chiocchi, L, Cinosi, E, Clerici, M, Corbo, M, Corsi, E, Costanzo, R, Costoloni, G, D'Arienzo, F, Debolini, S, De Capua, A, Di Napoli, WA, Dinelli, M, Facchi, E, Fargnoli, F, Fiori, F, Franchi, A, Gardellin, F, Gastaldon, C, Gazzoletti, E, Ghio, L, Giacomin, M, Gregis, M, Iovieno, N, Koukouna, D, Lax, A, Lintas, C, Luca, A, Luca, M, Lucii, C, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martinotti, G, Martorelli, C, Mattafirri, R, Nosè, M, Ostuzzi, G, Paladini, C, Papola, D, Percudani, M, Perini, G, Petrosemolo, P, Pezzullo, M, Piantanida, S, Pinna, F, Prato, K, Prestia, D, Quattrone, D, Reggianini, C, Restaino, F, Ribolsi, M, Rinosi, G, Rizzo, C, Rizzo, R, Roggi, M, Rossi, G, Rossi, S, Ruberto, S, Santi, M, Santoro, R, Sepede, G, Signorelli, MS, Soscia, F, Sozzi, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M & Zanobini, V 2016, 'Antipsychotic dose mediates the association between polypharmacy and corrected QT interval', PLoS One, vol. 11, no. 2, 0148212. https://doi.org/10.1371/journal.pone.0148212
Barbui C, Bighelli I, Carrà G, Castellazzi M, Lucii C, Martinotti G et al. Antipsychotic dose mediates the association between polypharmacy and corrected QT interval. PLoS One. 2016 Feb 1;11(2). 0148212. https://doi.org/10.1371/journal.pone.0148212
Barbui, Corrado ; Bighelli, Irene ; Carrà, Giuseppe ; Castellazzi, Mariasole ; Lucii, Claudio ; Martinotti, Giovanni ; Nosè, Michela ; Ostuzzi, Giovanni ; Acciavatti, T. ; Adamo, A. ; Aguglia, A. ; Albanese, C. ; Baccaglini, S. ; Bardicchia, F. ; Barone, R. ; Barone, Y. ; Bartoli, F. ; Bergamini, C. ; Bertolini, F. ; Bighelli, I. ; Bolognesi, S. ; Bordone, A. ; Bortolaso, P. ; Bugliani, M. ; Calandra, C. ; Calò, S. ; Cardamone, G. ; Caroleo, M. ; Carra, E. ; Carrà, G. ; Carretta, D. ; Castellazzi, M. ; Chiocchi, L. ; Cinosi, E. ; Clerici, M. ; Corbo, M. ; Corsi, E. ; Costanzo, R. ; Costoloni, G. ; D'Arienzo, F. ; Debolini, S. ; De Capua, A. ; Di Napoli, W. A. ; Dinelli, M. ; Facchi, E. ; Fargnoli, F. ; Fiori, F. ; Franchi, A. ; Gardellin, F. ; Gastaldon, C. ; Gazzoletti, E. ; Ghio, L. ; Giacomin, M. ; Gregis, M. ; Iovieno, N. ; Koukouna, D. ; Lax, A. ; Lintas, C. ; Luca, A. ; Luca, M. ; Lucii, C. ; Lussetti, M. ; Madrucci, M. ; Magnani, N. ; Magni, L. ; Manca, E. ; Martinotti, G. ; Martorelli, C. ; Mattafirri, R. ; Nosè, M. ; Ostuzzi, G. ; Paladini, C. ; Papola, D. ; Percudani, M. ; Perini, G. ; Petrosemolo, P. ; Pezzullo, M. ; Piantanida, S. ; Pinna, F. ; Prato, K. ; Prestia, D. ; Quattrone, D. ; Reggianini, C. ; Restaino, F. ; Ribolsi, M. ; Rinosi, G. ; Rizzo, C. ; Rizzo, R. ; Roggi, M. ; Rossi, G. ; Rossi, S. ; Ruberto, S. ; Santi, M. ; Santoro, R. ; Sepede, G. ; Signorelli, M. S. ; Soscia, F. ; Sozzi, F. ; Staffa, P. ; Stilo, M. ; Strizzolo, S. ; Suraniti, F. ; Tavian, N. ; Tortelli, L. ; Tosoni, F. ; Valdagno, M. ; Zanobini, V. / Antipsychotic dose mediates the association between polypharmacy and corrected QT interval. In: PLoS One. 2016 ; Vol. 11, No. 2.
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abstract = "Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a crosssectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26{\%}) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = -12.62, p < 0.001). Similarly, the mean QTc interval was significantly longer in those receiving AP polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = -2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy.",
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T1 - Antipsychotic dose mediates the association between polypharmacy and corrected QT interval

AU - Barbui, Corrado

AU - Bighelli, Irene

AU - Carrà, Giuseppe

AU - Castellazzi, Mariasole

AU - Lucii, Claudio

AU - Martinotti, Giovanni

AU - Nosè, Michela

AU - Ostuzzi, Giovanni

AU - Acciavatti, T.

AU - Adamo, A.

AU - Aguglia, A.

AU - Albanese, C.

AU - Baccaglini, S.

AU - Bardicchia, F.

AU - Barone, R.

AU - Barone, Y.

AU - Bartoli, F.

AU - Bergamini, C.

AU - Bertolini, F.

AU - Bighelli, I.

AU - Bolognesi, S.

AU - Bordone, A.

AU - Bortolaso, P.

AU - Bugliani, M.

AU - Calandra, C.

AU - Calò, S.

AU - Cardamone, G.

AU - Caroleo, M.

AU - Carra, E.

AU - Carrà, G.

AU - Carretta, D.

AU - Castellazzi, M.

AU - Chiocchi, L.

AU - Cinosi, E.

AU - Clerici, M.

AU - Corbo, M.

AU - Corsi, E.

AU - Costanzo, R.

AU - Costoloni, G.

AU - D'Arienzo, F.

AU - Debolini, S.

AU - De Capua, A.

AU - Di Napoli, W. A.

AU - Dinelli, M.

AU - Facchi, E.

AU - Fargnoli, F.

AU - Fiori, F.

AU - Franchi, A.

AU - Gardellin, F.

AU - Gastaldon, C.

AU - Gazzoletti, E.

AU - Ghio, L.

AU - Giacomin, M.

AU - Gregis, M.

AU - Iovieno, N.

AU - Koukouna, D.

AU - Lax, A.

AU - Lintas, C.

AU - Luca, A.

AU - Luca, M.

AU - Lucii, C.

AU - Lussetti, M.

AU - Madrucci, M.

AU - Magnani, N.

AU - Magni, L.

AU - Manca, E.

AU - Martinotti, G.

AU - Martorelli, C.

AU - Mattafirri, R.

AU - Nosè, M.

AU - Ostuzzi, G.

AU - Paladini, C.

AU - Papola, D.

AU - Percudani, M.

AU - Perini, G.

AU - Petrosemolo, P.

AU - Pezzullo, M.

AU - Piantanida, S.

AU - Pinna, F.

AU - Prato, K.

AU - Prestia, D.

AU - Quattrone, D.

AU - Reggianini, C.

AU - Restaino, F.

AU - Ribolsi, M.

AU - Rinosi, G.

AU - Rizzo, C.

AU - Rizzo, R.

AU - Roggi, M.

AU - Rossi, G.

AU - Rossi, S.

AU - Ruberto, S.

AU - Santi, M.

AU - Santoro, R.

AU - Sepede, G.

AU - Signorelli, M. S.

AU - Soscia, F.

AU - Sozzi, F.

AU - Staffa, P.

AU - Stilo, M.

AU - Strizzolo, S.

AU - Suraniti, F.

AU - Tavian, N.

AU - Tortelli, L.

AU - Tosoni, F.

AU - Valdagno, M.

AU - Zanobini, V.

PY - 2016/2/1

Y1 - 2016/2/1

N2 - Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a crosssectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = -12.62, p < 0.001). Similarly, the mean QTc interval was significantly longer in those receiving AP polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = -2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy.

AB - Antipsychotic (AP) drugs have the potential to cause prolongation of the QT interval corrected for heart rate (QTc). As this risk is dose-dependent, it may be associated with the number of AP drugs concurrently prescribed, which is known to be associated with increased cumulative equivalent AP dosage. This study analysed whether AP dose mediates the relationship between polypharmacy and QTc interval. We used data from a crosssectional survey that investigated the prevalence of QTc lengthening among people with psychiatric illnesses in Italy. AP polypharmacy was tested for evidence of association with AP dose and QTc interval using the Baron and Kenny mediational model. A total of 725 patients were included in this analysis. Of these, 186 (26%) were treated with two or more AP drugs (AP polypharmacy). The mean cumulative AP dose was significantly higher in those receiving AP polypharmacy (prescribed daily dose/defined daily dose = 2.93, standard deviation 1.31) than monotherapy (prescribed daily dose/defined daily dose = 0.82, standard deviation 0.77) (z = -12.62, p < 0.001). Similarly, the mean QTc interval was significantly longer in those receiving AP polypharmacy (mean = 420.86 milliseconds, standard deviation 27.16) than monotherapy (mean = 413.42 milliseconds, standard deviation 31.54) (z = -2.70, p = 0.006). The Baron and Kenny mediational analysis showed that, after adjustment for confounding variables, AP dose mediates the association between polypharmacy and QTc interval. The present study found that AP polypharmacy is associated with QTc interval, and this effect is mediated by AP dose. Given the high prevalence of AP polypharmacy in real-world clinical practice, clinicians should consider not only the myriad risk factors for QTc prolongation in their patients, but also that adding a second AP drug may further increase risk as compared with monotherapy.

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