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1. Genetic and psychosocial stressors have independent effects on the level of subclinical psychosis: findings from the multinational EU-GEI study

Author

Hersenen-Medisch 1, Brain, Pignon, B, Peyre, H, Ayrolles, A, Kirkbride, J B, Jamain, S, Ferchiou, A, Richard, J R, Baudin, G, Tosato, S, Jongsma, H, de Haan, L, Tarricone, I, Bernardo, M, Velthorst, E, Braca, M, Arango, C, Arrojo, M, Bobes, J, Del-Ben, C M, Di Forti, M, Gayer-Anderson, C, Jones, P B, La Cascia, C, Lasalvia, A, Menezes, P R, Quattrone, D, Sanjuán, J, Selten, J P, Tortelli, A, Llorca, P M, van Os, J, Rutten, B P F, Murray, R M, Morgan, C, Leboyer, M, Szöke, A, Schürhoff, F, Hersenen-Medisch 1, Brain, Pignon, B, Peyre, H, Ayrolles, A, Kirkbride, J B, Jamain, S, Ferchiou, A, Richard, J R, Baudin, G, Tosato, S, Jongsma, H, de Haan, L, Tarricone, I, Bernardo, M, Velthorst, E, Braca, M, Arango, C, Arrojo, M, Bobes, J, Del-Ben, C M, Di Forti, M, Gayer-Anderson, C, Jones, P B, La Cascia, C, Lasalvia, A, Menezes, P R, Quattrone, D, Sanjuán, J, Selten, J P, Tortelli, A, Llorca, P M, van Os, J, Rutten, B P F, Murray, R M, Morgan, C, Leboyer, M, Szöke, A, and Schürhoff, F

Published
2022

2. The Independent Effects of Psychosocial Stressors on Subclinical Psychosis: Findings From the Multinational EU-GEI Study

Author

Pignon, B., Pignon, B., Lajnef, M., Kirkbride, J.B., Peyre, H., Ferchiou, A., Richard, J.R., Baudin, G., Tosato, S., Jongsma, H., de Haan, L., Tarricone, I., Bernardo, M., Velthorst, E., Braca, M., Arango, C., Arrojo, M., Bobes, J., Del-Ben, C.M., Di Forti, M., Gayer-Anderson, C., Jones, P.B., La Cascia, C., Lasalvia, A., Menezes, P.R., Quattrone, D., Sanjuan, J., Selten, J.P., Tortelli, A., Llorca, P.M., van Os, J., Rutten, B.P.F., Murray, R.M., Morgan, C., Leboyer, M., Szoke, A., Schurhoff, F., Pignon, B., Pignon, B., Lajnef, M., Kirkbride, J.B., Peyre, H., Ferchiou, A., Richard, J.R., Baudin, G., Tosato, S., Jongsma, H., de Haan, L., Tarricone, I., Bernardo, M., Velthorst, E., Braca, M., Arango, C., Arrojo, M., Bobes, J., Del-Ben, C.M., Di Forti, M., Gayer-Anderson, C., Jones, P.B., La Cascia, C., Lasalvia, A., Menezes, P.R., Quattrone, D., Sanjuan, J., Selten, J.P., Tortelli, A., Llorca, P.M., van Os, J., Rutten, B.P.F., Murray, R.M., Morgan, C., Leboyer, M., Szoke, A., and Schurhoff, F.

Abstract

The influence of psychosocial stressors on psychosis risk has usually been studied in isolation and after the onset of the disorder, potentially ignoring important confounding relationships or the fact that some stressors that may be the consequence of the disorder rather than preexisting. The study of subclinical psychosis could help to address some of these issues. In this study, we investigated whether there was (i) an association between dimensions of subclinical psychosis and several psychosocial stressors including: childhood trauma, self-reported discrimination experiences, low social capital, and stressful life experiences, and (ii) any evidence of environment-environment (ExE) interactions between these factors. Data were drawn from the EUGEI study, in which healthy controls (N = 1497) and siblings of subjects with a psychotic disorder (N = 265) were included in six countries. The association between psychosocial stressors and subclinical psychosis dimensions (positive, negative and depressive dimension as measured by the Community Assessment of Psychic Experiences (CAPE) scale) and possible ExE interactions were assessed using linear regression models. After adjusting for sex, age, ethnicity, country, and control/sibling status, childhood trauma (beta for positive dimension: 0.13, negative: 0.49, depressive: 0.26) and stressful life events (positive: 0.08, negative: 0.16, depressive: 0.17) were associated with the three dimensions. Lower social capital was associated with the negative and depression dimensions (negative: 0.26, depressive: 0.13), and self-reported discrimination experiences with the positive dimension (0.06). Our findings are in favor of independent, cumulative and non-specific influences of social adversities in subclinical psychosis in non-clinical populations, without arguments for E x E interactions.

Published
2021

3. Association of extent of cannabis use and psychotic like intoxication experiences in a multi-national sample of first episode psychosis patients and controls

Author

Sami, M., Sami, M., Quattrone, D., Ferraro, L., Tripoli, G., La Cascia, E., Gayer-Anderson, C., Selten, J.P., Arango, C., Bernardo, M., Tarricone, I., Tortelli, A., Gatto, G., del Peschio, S., Del-Ben, C.M., Rutten, B.P., Jones, P.B., van Os, J., de Haan, L., Morgan, C., Lewis, C., Bhattacharyya, S., Freeman, T.P., Lynskey, M., Murray, R.M., Di Forti, M., Sami, M., Sami, M., Quattrone, D., Ferraro, L., Tripoli, G., La Cascia, E., Gayer-Anderson, C., Selten, J.P., Arango, C., Bernardo, M., Tarricone, I., Tortelli, A., Gatto, G., del Peschio, S., Del-Ben, C.M., Rutten, B.P., Jones, P.B., van Os, J., de Haan, L., Morgan, C., Lewis, C., Bhattacharyya, S., Freeman, T.P., Lynskey, M., Murray, R.M., and Di Forti, M.

Abstract

Background First episode psychosis (FEP) patients who use cannabis experience more frequent psychotic and euphoric intoxication experiences compared to controls. It is not clear whether this is consequent to patients being more vulnerable to the effects of cannabis use or to their heavier pattern of use. We aimed to determine whether extent of use predicted psychotic-like and euphoric intoxication experiences in patients and controls and whether this differs between groups. Methods We analysed data on patients who had ever used cannabis (n = 655) and controls who had ever used cannabis (n = 654) across 15 sites from six countries in the EU-GEI study (2010-2015). We used multiple regression to model predictors of cannabis-induced experiences and to determine if there was an interaction between caseness and extent of use. Results Caseness, frequency of cannabis use and money spent on cannabis predicted psychotic-like and euphoric experiences (p <= 0.001). For psychotic-like experiences (PEs) there was a significant interaction for caseness x frequency of use (p < 0.001) and caseness x money spent on cannabis (p = 0.001) such that FEP patients had increased experiences at increased levels of use compared to controls. There was no significant interaction for euphoric experiences (p > 0.5). Conclusions FEP patients are particularly sensitive to increased psychotic-like, but not euphoric experiences, at higher levels of cannabis use compared to controls. This suggests a specific psychotomimetic response in FEP patients related to heavy cannabis use. Clinicians should enquire regarding cannabis related PEs and advise that lower levels of cannabis use are associated with less frequent PEs.

Published
2021

4. Cognitive functioning throughout adulthood and illness stages in individuals with psychotic disorders and their unaffected siblings

Author

Velthorst, E, Mollon, J, Murray, RM, de Haan, L, Germeys, IM, Glahn, DC, Arango, C, van der Ven, E, Di Forti, M, Bernardo, M, Guloksuz, S, Delespaul, P, Mezquida, G, Amoretti, S, Bobes, J, Saiz, PA, Garcia-Portilla, MP, Santos, JL, Jimenez-Lopez, E, Sanjuan, J, Aguilar, EJ, Arrojo, M, Carracedo, A, Lopez, G, Gonzalez-Penas, J, Parellada, M, Atbasoglu, C, Saka, MC, Ucok, A, Alptekin, K, Akdede, B, Binbay, T, Altinyazar, V, Ulas, H, Yalincetin, B, Gumus-Akay, G, Beyaz, BC, Soygur, H, Cankurtaran, ES, Kaymak, SU, Maric, NP, Mihaljevic, MM, Petrovic, SA, Mirjanic, T, Del-Ben, CM, Ferraro, L, Gayer-Anderson, C, Jones, PB, Jongsma, HE, Kirkbride, JB, La Cascia, C, Lasalvia, A, Tosato, S, Llorca, P-M, Menezes, PR, Morgan, C, Quattrone, D, Menchetti, M, Selten, J-P, Szoke, A, Tarricone, I, Tortelli, A, McGuire, P, Valmaggia, L, Kempton, MJ, van der Gaag, M, Riecher-Rossler, A, Bressan, RA, Barrantes-Vidal, N, Nelson, B, McGorry, P, Pantelis, C, Krebs, M-O, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, Alizadeh, BZ, van Amelsvoort, T, Bartels-Velthuis, AA, Bruggeman, R, van Beveren, NJ, Luykx, JJ, Cahn, W, Simons, CJP, Kahn, RS, Schirmbeck, F, van Winkel, R, Reichenberg, A, Velthorst, E, Mollon, J, Murray, RM, de Haan, L, Germeys, IM, Glahn, DC, Arango, C, van der Ven, E, Di Forti, M, Bernardo, M, Guloksuz, S, Delespaul, P, Mezquida, G, Amoretti, S, Bobes, J, Saiz, PA, Garcia-Portilla, MP, Santos, JL, Jimenez-Lopez, E, Sanjuan, J, Aguilar, EJ, Arrojo, M, Carracedo, A, Lopez, G, Gonzalez-Penas, J, Parellada, M, Atbasoglu, C, Saka, MC, Ucok, A, Alptekin, K, Akdede, B, Binbay, T, Altinyazar, V, Ulas, H, Yalincetin, B, Gumus-Akay, G, Beyaz, BC, Soygur, H, Cankurtaran, ES, Kaymak, SU, Maric, NP, Mihaljevic, MM, Petrovic, SA, Mirjanic, T, Del-Ben, CM, Ferraro, L, Gayer-Anderson, C, Jones, PB, Jongsma, HE, Kirkbride, JB, La Cascia, C, Lasalvia, A, Tosato, S, Llorca, P-M, Menezes, PR, Morgan, C, Quattrone, D, Menchetti, M, Selten, J-P, Szoke, A, Tarricone, I, Tortelli, A, McGuire, P, Valmaggia, L, Kempton, MJ, van der Gaag, M, Riecher-Rossler, A, Bressan, RA, Barrantes-Vidal, N, Nelson, B, McGorry, P, Pantelis, C, Krebs, M-O, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, Alizadeh, BZ, van Amelsvoort, T, Bartels-Velthuis, AA, Bruggeman, R, van Beveren, NJ, Luykx, JJ, Cahn, W, Simons, CJP, Kahn, RS, Schirmbeck, F, van Winkel, R, and Reichenberg, A

Abstract

Important questions remain about the profile of cognitive impairment in psychotic disorders across adulthood and illness stages. The age-associated profile of familial impairments also remains unclear, as well as the effect of factors, such as symptoms, functioning, and medication. Using cross-sectional data from the EU-GEI and GROUP studies, comprising 8455 participants aged 18 to 65, we examined cognitive functioning across adulthood in patients with psychotic disorders (n = 2883), and their unaffected siblings (n = 2271), compared to controls (n = 3301). An abbreviated WAIS-III measured verbal knowledge, working memory, visuospatial processing, processing speed, and IQ. Patients showed medium to large deficits across all functions (ES range = -0.45 to -0.73, p < 0.001), while siblings showed small deficits on IQ, verbal knowledge, and working memory (ES = -0.14 to -0.33, p < 0.001). Magnitude of impairment was not associated with participant age, such that the size of impairment in older and younger patients did not significantly differ. However, first-episode patients performed worse than prodromal patients (ES range = -0.88 to -0.60, p < 0.001). Adjusting for cannabis use, symptom severity, and global functioning attenuated impairments in siblings, while deficits in patients remained statistically significant, albeit reduced by half (ES range = -0.13 to -0.38, p < 0.01). Antipsychotic medication also accounted for around half of the impairment in patients (ES range = -0.21 to -0.43, p < 0.01). Deficits in verbal knowledge, and working memory may specifically index familial, i.e., shared genetic and/or shared environmental, liability for psychotic disorders. Nevertheless, potentially modifiable illness-related factors account for a significant portion of the cognitive impairment in psychotic disorders.

Published
2021

5. Pre-training inter-rater reliability of clinical instruments in an international psychosis research project

Author

Berendsen, S, Kapitein, P, Schirmbeck, F, van Tricht, MJ, McGuire, P, Morgan, C, Gayer-Anderson, C, Kempton, MJ, Valmaggia, L, Quattrone, D, di Forti, M, van der Gaag, M, Kirkbride, JB, Jongsma, HE, Jones, PB, Parellada, M, Arango, C, Arrojo, M, Bernardo, M, Sanjuan, J, Santos, JL, Szoke, A, Tortelli, A, Llorca, P-M, Tarricone, I, Tripoli, G, Ferraro, L, La Cascia, C, Lasalvia, A, Tosato, S, Menezes, PR, Del-Ben, CM, Nelson, B, Riecher-Rossler, A, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, Velthorst, E, de Haan, L, Berendsen, S, Kapitein, P, Schirmbeck, F, van Tricht, MJ, McGuire, P, Morgan, C, Gayer-Anderson, C, Kempton, MJ, Valmaggia, L, Quattrone, D, di Forti, M, van der Gaag, M, Kirkbride, JB, Jongsma, HE, Jones, PB, Parellada, M, Arango, C, Arrojo, M, Bernardo, M, Sanjuan, J, Santos, JL, Szoke, A, Tortelli, A, Llorca, P-M, Tarricone, I, Tripoli, G, Ferraro, L, La Cascia, C, Lasalvia, A, Tosato, S, Menezes, PR, Del-Ben, CM, Nelson, B, Riecher-Rossler, A, Bressan, R, Barrantes-Vidal, N, Krebs, M-O, Nordentoft, M, Ruhrmann, S, Sachs, G, Rutten, BPF, van Os, J, Velthorst, E, and de Haan, L

Published
2021

6. Association of extent of cannabis use and psychotic like intoxication experiences in a multi-national sample of first episode psychosis patients and controls

Author

Sami, M., Quattrone, D., Ferraro, L., Tripoli, G., La Cascia, E., Gayer-Anderson, C., Selten, J.P., Arango, C., Bernardo, M., Tarricone, I., Tortelli, A., Gatto, G., del Peschio, S., Del-Ben, C.M., Rutten, B.P., Jones, P.B., van Os, J., de Haan, L., Morgan, C., Lewis, C., Bhattacharyya, S., Freeman, T.P., Lynskey, M., Murray, R.M., Di Forti, M., Sami, M., Quattrone, D., Ferraro, L., Tripoli, G., La Cascia, E., Gayer-Anderson, C., Selten, J.P., Arango, C., Bernardo, M., Tarricone, I., Tortelli, A., Gatto, G., del Peschio, S., Del-Ben, C.M., Rutten, B.P., Jones, P.B., van Os, J., de Haan, L., Morgan, C., Lewis, C., Bhattacharyya, S., Freeman, T.P., Lynskey, M., Murray, R.M., and Di Forti, M.

Abstract

Background First episode psychosis (FEP) patients who use cannabis experience more frequent psychotic and euphoric intoxication experiences compared to controls. It is not clear whether this is consequent to patients being more vulnerable to the effects of cannabis use or to their heavier pattern of use. We aimed to determine whether extent of use predicted psychotic-like and euphoric intoxication experiences in patients and controls and whether this differs between groups. Methods We analysed data on patients who had ever used cannabis (n = 655) and controls who had ever used cannabis (n = 654) across 15 sites from six countries in the EU-GEI study (2010-2015). We used multiple regression to model predictors of cannabis-induced experiences and to determine if there was an interaction between caseness and extent of use. Results Caseness, frequency of cannabis use and money spent on cannabis predicted psychotic-like and euphoric experiences (p <= 0.001). For psychotic-like experiences (PEs) there was a significant interaction for caseness x frequency of use (p < 0.001) and caseness x money spent on cannabis (p = 0.001) such that FEP patients had increased experiences at increased levels of use compared to controls. There was no significant interaction for euphoric experiences (p > 0.5). Conclusions FEP patients are particularly sensitive to increased psychotic-like, but not euphoric experiences, at higher levels of cannabis use compared to controls. This suggests a specific psychotomimetic response in FEP patients related to heavy cannabis use. Clinicians should enquire regarding cannabis related PEs and advise that lower levels of cannabis use are associated with less frequent PEs.

Published
2021

7. The Independent Effects of Psychosocial Stressors on Subclinical Psychosis: Findings From the Multinational EU-GEI Study

Author

Pignon, B., Lajnef, M., Kirkbride, J.B., Peyre, H., Ferchiou, A., Richard, J.R., Baudin, G., Tosato, S., Jongsma, H., de Haan, L., Tarricone, I., Bernardo, M., Velthorst, E., Braca, M., Arango, C., Arrojo, M., Bobes, J., Del-Ben, C.M., Di Forti, M., Gayer-Anderson, C., Jones, P.B., La Cascia, C., Lasalvia, A., Menezes, P.R., Quattrone, D., Sanjuan, J., Selten, J.P., Tortelli, A., Llorca, P.M., van Os, J., Rutten, B.P.F., Murray, R.M., Morgan, C., Leboyer, M., Szoke, A., Schurhoff, F., Pignon, B., Lajnef, M., Kirkbride, J.B., Peyre, H., Ferchiou, A., Richard, J.R., Baudin, G., Tosato, S., Jongsma, H., de Haan, L., Tarricone, I., Bernardo, M., Velthorst, E., Braca, M., Arango, C., Arrojo, M., Bobes, J., Del-Ben, C.M., Di Forti, M., Gayer-Anderson, C., Jones, P.B., La Cascia, C., Lasalvia, A., Menezes, P.R., Quattrone, D., Sanjuan, J., Selten, J.P., Tortelli, A., Llorca, P.M., van Os, J., Rutten, B.P.F., Murray, R.M., Morgan, C., Leboyer, M., Szoke, A., and Schurhoff, F.

Abstract

The influence of psychosocial stressors on psychosis risk has usually been studied in isolation and after the onset of the disorder, potentially ignoring important confounding relationships or the fact that some stressors that may be the consequence of the disorder rather than preexisting. The study of subclinical psychosis could help to address some of these issues. In this study, we investigated whether there was (i) an association between dimensions of subclinical psychosis and several psychosocial stressors including: childhood trauma, self-reported discrimination experiences, low social capital, and stressful life experiences, and (ii) any evidence of environment-environment (ExE) interactions between these factors. Data were drawn from the EUGEI study, in which healthy controls (N = 1497) and siblings of subjects with a psychotic disorder (N = 265) were included in six countries. The association between psychosocial stressors and subclinical psychosis dimensions (positive, negative and depressive dimension as measured by the Community Assessment of Psychic Experiences (CAPE) scale) and possible ExE interactions were assessed using linear regression models. After adjusting for sex, age, ethnicity, country, and control/sibling status, childhood trauma (beta for positive dimension: 0.13, negative: 0.49, depressive: 0.26) and stressful life events (positive: 0.08, negative: 0.16, depressive: 0.17) were associated with the three dimensions. Lower social capital was associated with the negative and depression dimensions (negative: 0.26, depressive: 0.13), and self-reported discrimination experiences with the positive dimension (0.06). Our findings are in favor of independent, cumulative and non-specific influences of social adversities in subclinical psychosis in non-clinical populations, without arguments for E x E interactions.

Published
2021

8. Combinations of QTc-prolonging drugs: towards disentangling pharmacokinetic and pharmacodynamic effects in their potentially additive nature

Author

Meid, A, Bighelli, I, Mächler, S, Mikus, G, 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, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, 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, 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, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, 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, Soscia, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, Zanobini, V, Barbui, C, Haefeli, W, A. D. Meid, I. Bighelli, S. Mächler, G. Mikus, G. Carrà, M. Castellazzi, C. Lucii, G. Martinotti, M. Nosè, G. Ostuzzi, T. Acciavatti, A. Adamo, A. Aguglia, C. Albanese, S. Baccaglini, F. Bardicchia, R. Barone, Y. Barone, F. Bartoli, C. Bergamini, F. Bertolini, S. Bolognesi, A. Bordone, P. Bortolaso, M. Bugliani, C. Calandra, S. Calò, G. Cardamone, M. Caroleo, E. Carra, D. Carretta, 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, M. Lussetti, M. Madrucci, N. Magnani, L. Magni, E. Manca, C. Martorelli, R. Mattafirri, 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, P. Staffa, M. Stilo, S. Strizzolo, F. Suraniti, N. Tavian, L. Tortelli, F. Tosoni, M. Valdagno, V. Zanobini, C. Barbui, W. E. Haefeli, Meid, A, Bighelli, I, Mächler, S, Mikus, G, 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, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, 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, 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, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, 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, Soscia, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, Zanobini, V, Barbui, C, Haefeli, W, A. D. Meid, I. Bighelli, S. Mächler, G. Mikus, G. Carrà, M. Castellazzi, C. Lucii, G. Martinotti, M. Nosè, G. Ostuzzi, T. Acciavatti, A. Adamo, A. Aguglia, C. Albanese, S. Baccaglini, F. Bardicchia, R. Barone, Y. Barone, F. Bartoli, C. Bergamini, F. Bertolini, S. Bolognesi, A. Bordone, P. Bortolaso, M. Bugliani, C. Calandra, S. Calò, G. Cardamone, M. Caroleo, E. Carra, D. Carretta, 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, M. Lussetti, M. Madrucci, N. Magnani, L. Magni, E. Manca, C. Martorelli, R. Mattafirri, 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, P. Staffa, M. Stilo, S. Strizzolo, F. Suraniti, N. Tavian, L. Tortelli, F. Tosoni, M. Valdagno, V. Zanobini, C. Barbui, and W. E. Haefeli

Abstract

Background: Whether arrhythmia risks will increase if drugs with electrocardiographic (ECG) QT-prolonging properties are combined is generally supposed but not well studied. Based on available evidence, the Arizona Center for Education and Research on Therapeutics (AZCERT) classification defines the risk of QT prolongation for exposure to single drugs. We aimed to investigate how combining AZCERT drug categories impacts QT duration and how relative drug exposure affects the extent of pharmacodynamic drug–drug interactions. Methods: In a cohort of 2558 psychiatric inpatients and outpatients, we modeled whether AZCERT class and number of coprescribed QT-prolonging drugs correlates with observed rate-corrected QT duration (QTc) while also considering age, sex, inpatient status, and other QTc-prolonging risk factors. We concurrently considered administered drug doses and pharmacokinetic interactions modulating drug clearance to calculate individual weights of relative exposure with AZCERT drugs. Because QTc duration is concentration-dependent, we estimated individual drug exposure with these drugs and included this information as weights in weighted regression analyses. Results: Drugs attributing a ‘known’ risk for clinical consequences were associated with the largest QTc prolongations. However, the presence of at least two versus one QTc-prolonging drug yielded nonsignificant prolongations [exposure-weighted parameter estimates with 95% confidence intervals for ‘known’ risk drugs + 0.93 ms (–8.88;10.75)]. Estimates for the ‘conditional’ risk class increased upon refinement with relative drug exposure and co-administration of a ‘known’ risk drug as a further risk factor. Conclusions: These observations indicate that indiscriminate combinations of QTc-prolonging drugs do not necessarily result in additive QTc prolongation and suggest that QT prolongation caused by drug combinations strongly depends on the nature of the combination partners and individual drug exposure.

Published
2017

9. Antipsychotic dose mediates the association between polypharmacy and corrected QT interval

Author

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, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, 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, 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, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, 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, Soscia, F, Sozzi, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, Zanobini, V, 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, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, 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, 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, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, 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, Soscia, F, Sozzi, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, and Zanobini, V

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.

Published
2016

10. Antipsychotic dose mediates the association between polypharmacy and corrected QT interval

Author

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, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, 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, 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, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, 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, Soscia, F, Sozzi, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, Zanobini, V, 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, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, 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, 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, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, 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, Soscia, F, Sozzi, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, and Zanobini, V

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.

Published
2016

11. Prevalence and correlates of QTc prolongation in Italian psychiatric care: Cross-sectional multicentre study

Author

Nosè, M, Bighelli, I, Castellazzi, M, Martinotti, G, Carra', G, Lucii, C, Ostuzzi, G, Sozzi, F, Barbui, C, Acciavatti, T, Adamo, A, Aguglia, A, Albanese, C, Baccaglini, S, Bardicchia, F, Barone, R, Barone, Y, Bartoli, F, Bergamini, C, Bertolini, F, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, Chiocchi, L, Clerici, M, Corbo, M, Corsi, E, Costanzo, R, Costoloni, G, D'Arienzo, F, Debolini, S, De Capua, A, Di Napoli, W, Dinelli, M, Facchi, E, Fargnoli, F, Fiori, F, Franchi, A, Gardellin, F, Gazzoletti, E, Ghio, L, Giacomin, M, Gregis, M, Iovieno, N, Koukouna, D, Lax, A, Lintas, C, Luca, A, Luca, M, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, 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, Santoro, R, Santi, M, Signorelli, M, Soscia, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, Zanobini, V, CARRA', GIUSEPPE, Barbui, C., Di Napoli, WA, Signorelli, MS, Nosè, M, Bighelli, I, Castellazzi, M, Martinotti, G, Carra', G, Lucii, C, Ostuzzi, G, Sozzi, F, Barbui, C, Acciavatti, T, Adamo, A, Aguglia, A, Albanese, C, Baccaglini, S, Bardicchia, F, Barone, R, Barone, Y, Bartoli, F, Bergamini, C, Bertolini, F, Bolognesi, S, Bordone, A, Bortolaso, P, Bugliani, M, Calandra, C, Calò, S, Cardamone, G, Caroleo, M, Carra, E, Carretta, D, Chiocchi, L, Clerici, M, Corbo, M, Corsi, E, Costanzo, R, Costoloni, G, D'Arienzo, F, Debolini, S, De Capua, A, Di Napoli, W, Dinelli, M, Facchi, E, Fargnoli, F, Fiori, F, Franchi, A, Gardellin, F, Gazzoletti, E, Ghio, L, Giacomin, M, Gregis, M, Iovieno, N, Koukouna, D, Lax, A, Lintas, C, Luca, A, Luca, M, Lussetti, M, Madrucci, M, Magnani, N, Magni, L, Manca, E, Martorelli, C, Mattafirri, R, 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, Santoro, R, Santi, M, Signorelli, M, Soscia, F, Staffa, P, Stilo, M, Strizzolo, S, Suraniti, F, Tavian, N, Tortelli, L, Tosoni, F, Valdagno, M, Zanobini, V, CARRA', GIUSEPPE, Barbui, C., Di Napoli, WA, and Signorelli, MS

Abstract

Aims. In recent years several warnings have been issued by regulatory authorities on the risk of electrocardiogram abnormalities in individuals exposed to psychotropic drugs. As a consequence of these warnings, monitoring of the QT interval corrected for heart rate (QTc) has become increasingly common. This study was conducted to measure the frequency of QTc prolongation in unselected psychiatric patients, and to document the associated factors using a cross-sectional approach. Method. The study was carried out in 35 Italian psychiatric services that are part of the STAR (Servizi Territoriali Associati per la Ricerca) Network, a research group established to produce scientific knowledge by collecting data under ordinary circumstances. During a three-month period, a consecutive unselected series of both in- and out-patients were enrolled if they performed an ECG during the recruitment period and were receiving psychotropic drugs on the day ECG was recorded. Results. During the recruitment period a total of 2411 patients were included in the study. The prevalence of QTc prolongation ranged from 14.7% (men) and 18.6% (women) for the cut-off of 450 ms, to 1.26% (men) and 1.01% (women) for the cut-off of 500 ms. In the multivariate model conducted in the whole sample of patients exposed to psychotropic drugs, female sex, age, heart rate, alcohol and/or substance abuse, cardiovascular diseases and cardiovascular drug treatment, and drug overdose were significantly associated with QTc prolongation. In patients exposed to antipsychotic drugs, polypharmacy was positively associated with QTc prolongation, whereas use of aripiprazole decreased the risk. In patients exposed to antidepressant drugs, use of citalopram, citalopram dose and use of haloperidol in addition to antidepressant drugs, were all positively associated with QTc prolongation. Conclusions. The confirmation of a link between antipsychotic polypharmacy and QTc prolongation supports the current guidelines that re

Published
2016

12. Novel psychoactive substances in young adults with and without psychiatric comorbidities

Author

Martinotti, G, Lupi, M, Acciavatti, T, Cinosi, E, Santacroce, R, Signorelli, M, Bandini, L, Lisi, G, Quattrone, D, Ciambrone, P, Aguglia, A, Pinna, F, Calò, S, Janiri, Luigi, Di Giannantonio, M., Janiri, Luigi (ORCID:0000-0002-1633-9418), Martinotti, G, Lupi, M, Acciavatti, T, Cinosi, E, Santacroce, R, Signorelli, M, Bandini, L, Lisi, G, Quattrone, D, Ciambrone, P, Aguglia, A, Pinna, F, Calò, S, Janiri, Luigi, Di Giannantonio, M., and Janiri, Luigi (ORCID:0000-0002-1633-9418)

Abstract

Comorbidities between psychiatric diseases and consumption of traditional substances of abuse (alcohol, cannabis, opioids, and cocaine) are common. Nevertheless, there is no data regarding the use of novel psychoactive substances (NPS) in the psychiatric population. The purpose of this multicentre survey is to investigate the consumption of a wide variety of psychoactive substances in a young psychiatric sample and in a paired sample of healthy subjects.

Published
2014

13. L'impiego della ritodrina ritardo per via orale nel trattamento della minaccia del parto prematuro

Author

Quattrone, D., Accardo, F. M., Granese, D., Quattrone, D., Accardo, F. M., and Granese, D.

Abstract

È stata valutata l’efficacia della ritodrina ritardo in compresse da 30 mg su un campione di 30 donne ricoverate per minaccia di parto pre-termine. Il trattamento, protratto per 21 giorni ha dato una percentuale di successi (93,34%) concordante con sperimentazioni recenti. Non sono stati registrati fenomeni collaterali di rilievo e l’accettabilità da parte delle pazienti è stata buona.

14. L'impiego della ritodrina ritardo per via orale nel trattamento della minaccia del parto prematuro

Author

Quattrone, D., Accardo, F. M., Granese, D., Quattrone, D., Accardo, F. M., and Granese, D.

Abstract

È stata valutata l’efficacia della ritodrina ritardo in compresse da 30 mg su un campione di 30 donne ricoverate per minaccia di parto pre-termine. Il trattamento, protratto per 21 giorni ha dato una percentuale di successi (93,34%) concordante con sperimentazioni recenti. Non sono stati registrati fenomeni collaterali di rilievo e l’accettabilità da parte delle pazienti è stata buona.

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