Study protocol
Rationale and design of an independent randomised controlled trial evaluating the effectiveness of aripiprazole or haloperidol in combination with clozapine for treatment-resistant schizophrenia
1 Department of Medicine and Public Health, Section of Psychiatry and Clinical Psychology, University of Verona, Italy
2 Unit of Epidemiology and Medical Statistics, Department of Medicine and Public Health University of Verona, Italy
3 Dipartimento di Salute Mentale, ASL n. 3 " Genovese", Genova, Italy
4 UOP 51 Psichiatria A.O. San Paolo, Milano, Italy
5 Department of Applied Health and Behavioral Sciences, Section of Psychiatry, University of Pavia, Italy
6 Centro S. Giovanni di Dio IRCCS FBF, Brescia, Italy
7 Institute of Psychiatry, Bologna University, Italy
8 Dipartimento Salute Mentale- Servizio Psichiatrico Area sud-ULSS 22, Verona, Italy
9 Section of Psychiatry, Department of Medical Sciences of Communication and Behaviour, University of Ferrara and Department of Mental Health, Ferrara, Italy
10 DSM ASL Salerno 1, Salerno, Italy
11 Dipartimento di Neuroscienze, Universita' degli Studi di Torino, Italy
12 Dipartimento Salute Mentale, ASL Taranto, Italy
13 DSM, ASL 19, Asti, Italy
14 Unità Operativa Salute Mentale, distretto 112/113, ASL Salerno 3, Salerno, Italy
15 Dipartimento di Salute Mentale, ASL n. 3 " Genovese", Genova, Italy
16 Psychiatric Unit of Bollate, Department of Mental Health, Hospital "G. Salvini", Garbagnate Milanese, Milano, Italy
17 CSM, Azienda Sanitaria di Bolzano, Italy
18 Unità Operativa Complessa di Psichiatria, Dipartimento di Neuroscienze, Facoltà di Medicina e Chirurgia, Università degli Studi di Roma "Tor Vergata", Roma, Italy
19 UOC, SPDC, Ospedale San Filippo Neri, ASL RM E, Roma, Italy
20 Azienda Ospedaliera "Ospedale Niguarda Ca' Granda", Milano, Italy
21 Unità Operativa n42, Rho, Azienda Ospedaliera "G. Salvini", Garbagnate Milanese, Milano, Italy
22 DSM, ASL n2 "Savonese", Savona, Italy
23 ASF-Toscana (Centro Salute Mentale del MOM-SMA Q2), Firenze, Italy
24 U.O.Salute Mentale "Roseto", ASL AV2, Avellino, Italy
25 Centro di Salute Mentale di Vicenza (ULSS 6), Vicenza, Italy
26 First Psychiatric Service, ULSS 20, Ospedale Civile Maggiore, Verona, Italy
27 Centro Salute mentale ASL 5, La Spezia, Italy
28 Servizio Psichiatrico, AO Melegnano, sede Gorgonzola, Italy
29 Struttura Complessa di Psichiatria, A.S.L. CN1, Cuneo, Italy
30 Azienda Ospedaliera "Carlo Poma", Mantova, Italy
31 Clinical Psychiatry, IRCCS Ospedale Maggiore Policlinico, Milano, Italy
32 Fourth Psychiatric Service, ULSS 20, San Bonifacio, Verona, Italy
33 Second Psychiatric Service, ULSS 20, Ospedale Civile Maggiore, Verona, Italy
34 SPDC c/o Azienda Osp. Naz. Ss Antonio E Biagio-Alessandria, Italy
35 Servizio Psichiatrico di Brunico (BZ), Azienda Sanitaria di Bolzano, Italy
36 Sezione di Psichiatria, Psicologia Clinica e Riabilitazione Psichiatrica, Dipartimento di Medicina Clinica e Sperimentale, Università degli Studi di Perugia, Italy
Trials 2009, 10:31 doi:10.1186/1745-6215-10-31
Published: 15 May 2009Abstract
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.
Trial Registration
Clincaltrials.gov Identifier: NCT00395915
