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

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

doi:10.1186/1745-6215-10-31

Cited by 22 publications

(6 citation statements)

References 38 publications

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“…Among clinicians, resistance to treatment with clozapine is considered a reason for antipsychotic combination treatment with or without clozapine . Trials are designed to improve the evidence base for this strategy . The common use of antipsychotic combinations for the long‐term outpatient treatment of schizophrenia was recently shown for a large sample in Germany …”

Section: Discussionmentioning

confidence: 99%

Prescription patterns of patients diagnosed with schizophrenia in mental hospitals in Tashkent/Uzbekistan and in four German cities

Mundt

Aichberger

Fakhriddinov

et al. 2011

Pharmacoepidemiology and Drug

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Section: Discussionmentioning

confidence: 99%

Prescription patterns of patients diagnosed with schizophrenia in mental hospitals in Tashkent/Uzbekistan and in four German cities

Mundt

Aichberger

Fakhriddinov

et al. 2011

Pharmacoepidemiology and Drug

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“…Its rationale, design, and methods have been described previously. 9 The study was conducted within the framework of a legislation (Decreto Ministeriale, December 17, 2004) that regulates the conduct of independent pragmatic trials in Italy. According to this law, drug costs were paid by the Italian National Health System, and fees for submitting the study protocol to the local ethics committees were waived.…”

Section: Methodsmentioning

confidence: 99%

Aripiprazole Versus Haloperidol in Combination With Clozapine for Treatment-Resistant Schizophrenia in Routine Clinical Care

Barbui¹,

Accordini²,

Nosè³

et al. 2011

Journal of Clinical Psychopharmacology

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This multisite study was conducted to compare the efficacy and tolerability of combination treatment with clozapine plus aripiprazole versus combination treatment with clozapine plus haloperidol in patients with schizophrenia who do not have an optimal response to clozapine. Patients continued to take clozapine and were randomly assigned to receive daily augmentation with aripiprazole or haloperidol. Physicians prescribed the allocated treatments according to usual clinical care. Withdrawal from allocated treatment within 3 months was the primary outcome. Secondary outcomes included severity of symptoms on the Brief Psychiatric Rating Scale and antipsychotic subjective tolerability on the Liverpool University Neuroleptic Side Effect Rating Scale. A total of 106 patients with schizophrenia were randomly assigned to treatment. After 3 months, we found no difference in the proportion of patients who discontinued treatment between the aripiprazole and haloperidol groups (13.2% vs 15.1%, P = 0.780). The 3-month change of the Brief Psychiatric Rating Scale total score was similar in the aripiprazole and haloperidol groups (-5.9 vs -4.4 points, P = 0.523), whereas the 3-month decrease of the Liverpool University Neuroleptic Side Effect Rating Scale total score was significantly higher in the aripiprazole group than in the haloperidol group (-7.4 vs -2.0 points, P = 0.006). These results suggest that augmentation of clozapine with aripiprazole offers no benefit with regard to treatment withdrawal and overall symptoms in schizophrenia compared with augmentation with haloperidol. However, an advantage in the perception of adverse effects with aripiprazole treatment may be meaningful for patients.

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“…A number of meta-analyses have been carried out to determine the e icacy of clozapine combination treatment, with inconsistent results. Barbui 2009 identified 21 studies comparing clozapine combination treatment to clozapine monotherapy or placebo. They found a significant benefit of combination treatment when all studies were included, but no significant e ect when the data from the six double-blind studies were extracted and analysed separately.…”

Section: How the Intervention Might Workmentioning

confidence: 99%

“…All primary outcomes in Cipriani 2013a were prespecified in the trial protocol (Nosè 2009), and so it was rated low risk for reporting bias. However, it was noted that some secondary outcomes (mean dose of clozapine, prolactin, QTc interval) were only reported at 12 weeks.…”

Section: Selective Reportingmentioning

confidence: 99%

Clozapine combined with different antipsychotic drugs for treatment-resistant schizophrenia

Barber

Olotu

Corsi

et al. 2017

Cochrane Database of Systematic Reviews

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The reliability of results from this review is limited, evidence is of low or very low quality. Furthermore, due to the limited number of included studies, we were unable to undertake formal meta-analyses. As a consequence, any conclusions drawn from these findings are based on single, small-sized RCTs with high risk of type II error. Properly conducted and adequately powered RCTs are required. Future trialists should seek to measure patient-important outcomes such as quality of life, as well as clinical response and adverse effects.

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

Cited by 22 publications

References 38 publications

Prescription patterns of patients diagnosed with schizophrenia in mental hospitals in Tashkent/Uzbekistan and in four German cities

Prescription patterns of patients diagnosed with schizophrenia in mental hospitals in Tashkent/Uzbekistan and in four German cities

Aripiprazole Versus Haloperidol in Combination With Clozapine for Treatment-Resistant Schizophrenia in Routine Clinical Care

Clozapine combined with different antipsychotic drugs for treatment-resistant schizophrenia

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