Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia

Michela Nosè, Simone Accordini, Paola Artioli, Francesco Barale, Corrado Barbui, Rossella Beneduce, Domenico Berardi, Gerardo Bertolazzi, Bruno Biancosino, Alfredo Bisogno, Raffaella Bivi, Filippo Bogetto, Marianna Boso, Alberto Bozzani, Piera Bucolo, Marcello Casale, Liliana Cascone, Luisa Ciammella, Alessia Cicolini, Gabriele CipressoAndrea Cipriani, Paola Colombo, Barbara Dal Santo, Michele De Francesco, Giorgio Di Lorenzo, Walter Di Munzio, Giuseppe Ducci, Arcadio Erlicher, Eleonora Esposito, Luigi Ferrannini, Farida Ferrato, Antonio Ferro, Nicoletta Fragomeno, Vincenzo Fricchione Parise, Maria Frova, Francesco Gardellin, Nicola Garzotto, Andrea Giambartolomei, Giancarlo Giupponi, Luigi Grassi, Natalia Grazian, Lorella Grecu, Gualtiero Guerrini, Francesco Laddomada, Ermanna Lazzarin, Camilla Lintas, Francesca Malchiodi, Lara Malvini, Livio Marchiaro, Alessandra Marsilio, Massimo Carlo Mauri, Antonio Mautone, Marco Menchetti, Giuseppe Migliorini, Marco Mollica, Daniele Moretti, Serena Mulè, Stylianos Nicholau, Flavio Nosè, Guglielmo Occhionero, Anna Maria Pacilli, Stefania Pecchioli, Mauro Percudani, Ennio Piantato, Carlo Piazza, Francesco Pontarollo, Roger Pycha, Roberto Quartesan, Luciana Rillosi, Francesco Risso, Raffella Rizzo, Paola Rocca, Stefania Roma, Matteo Rossattini, Giuseppe Rossi, Giovanni Rossi, Alessandra Sala, Claudio Santilli, Giuseppe Saraò, Antonio Sarnicola, Francesca Sartore, Silvio Scarone, Tiziana Sciarma, Alberto Siracusano, Stefania Strizzolo, Michele Tansella, Gino Targa, Annamarie Tasser, Rodolfo Tomasi, Rossana Travaglini, Antonio Veronese, Simona Ziero

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Abstract

Background: One third to two thirds of people with schizophrenia have persistent psychotic symptoms despite clozapine treatment. Under real-world circumstances, the need to provide effective therapeutic interventions to patients who do not have an optimal response to clozapine has been cited as the most common reason for simultaneously prescribing a second antipsychotic drug in combination treatment strategies. In a clinical area where the pressing need of providing therapeutic answers has progressively increased the occurrence of antipsychotic polypharmacy, despite the lack of robust evidence of its efficacy, we sought to implement a pre-planned protocol where two alternative therapeutic answers are systematically provided and evaluated within the context of a pragmatic, multicentre, independent randomised study. Methods/Design: The principal clinical question to be answered by the present project is the relative efficacy and tolerability of combination treatment with clozapine plus aripiprazole compared with combination treatment with clozapine plus haloperidol in patients with an incomplete response to treatment with clozapine over an appropriate period of time. This project is a prospective, multicentre, randomized, parallel-group, superiority trial that follow patients over a period of 12 months. Withdrawal from allocated treatment within 3 months is the primary outcome. Discussion: The implementation of the protocol presented here shows that it is possible to create a network of community psychiatric services that accept the idea of using their everyday clinical practice to produce randomised knowledge. The employed pragmatic attitude allowed to randomly allocate more than 100 individuals, which means that this study is the largest antipsychotic combination trial conducted so far in Western countries. We expect that the current project, by generating evidence on whether it is clinically useful to combine clozapine with aripiprazole rather than with haloperidol, provides physicians with a solid evidence base to be directly applied in the routine care of patients with schizophrenia.

Original languageEnglish
Article number31
JournalTrials
Volume10
DOIs
Publication statusPublished - May 15 2009

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ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology (medical)

Cite this

Nosè, M., Accordini, S., Artioli, P., Barale, F., Barbui, C., Beneduce, R., Berardi, D., Bertolazzi, G., Biancosino, B., Bisogno, A., Bivi, R., Bogetto, F., Boso, M., Bozzani, A., Bucolo, P., Casale, M., Cascone, L., Ciammella, L., Cicolini, A., ... Ziero, S. (2009). Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia. Trials, 10, [31]. https://doi.org/10.1186/1745-6215-10-31