TY - JOUR
T1 - Relapse prevention in schizophrenia
T2 - A systematic review and meta-analysis of second-generation antipsychotics versus first-generation antipsychotics
AU - Kishimoto, T.
AU - Agarwal, V.
AU - Kishi, T.
AU - Leucht, S.
AU - Kane, J. M.
AU - Correll, C. U.
N1 - Funding Information:
Dr Kishimoto has received speaker’s honoraria from Banyu, Eli Lilly, Dainippon Sumitomo, Janssen, Otsuka and Pfizer. He has received grant support from the Byoutaitaisyakenkyukai Fellowship (Fellowship of Astellas Foundation of Research on Metabolic Disorders) and Eli Lilly Fellowship for Clinical Psychopharmacology. Dr Agarwal has nothing to disclose. Dr Kishi has received speaker’s honoraria from Astellas, Dainippon Sumitomo, Eli Lilly, Glax-oSmithKline, Janssen, Otsuka and Pfizer, and has received grant support from the Fellowship of Japan Research Foundation for Clinical Pharmacology. Dr Leucht received speaker/consultancy/advisory board honoraria from SanofiAventis, BMS, Eli Lilly, Essex Pharma, Astra-Zeneca, Alkermes, GlaxoSmithKline, Janssen/Johnson & Johnson, Lundbeck, Medavante and Pfizer, SanofiAventis and Eli Lilly supported research projects by SL. Dr Kane has been a consultant to Astra-Zeneca, Janssen, Pfizer, Eli Lilly, Bristol-Myers Squibb, Dainippon Sumitomo/Sepracor /Sunovion, Johnson & Johnson, Otsuka, Vanda, Proteus, Takeda, Targacept, IntraCellular Therapies, Merck, Lundbeck, Novartis, Roche, Rules Based Medicine and Sunovion, and has received honoraria for lectures from Otsuka, Eli Lilly, Esai, Boehringer-Ingelheim, Bristol-Myers Squibb and Janssen. He has received grant support from The National Institute of Mental Health. Dr Correll has been a consultant and/ or advisor to or has received honoraria from Actelion, Astra-Zeneca, Bristol-Myers Squibb, Cephalon, Eli Lilly, GSK, IntraCellular Therapies, Ortho-McNeill/ Janssen/J&J, Merck, Novartis, Otsuka, Pfizer and Sunovion. He has received grant support from the Feinstein Institute for Medical Research, the National Institute of Mental Health (NIMH), and the National Alliance for Research in Schizophrenia and Depression (NARSAD), BMS, Otsuka and Ortho-McNeill/ Janssen/J&J.
Funding Information:
This work was supported in part by The Zucker Hillside Hospital Advanced Center for Intervention and Services Research for the Study of Schizophrenia (MH090590) from the National Institute of Mental Health, Bethesda, MD, USA. The sponsor had no influence on the design, data acquisition, data analysis, data interpretation or writing of the report. We thank Gennady Gelman, MD, and Allyssa Brody, BS, for help with the literature search and data abstraction. We thank the following authors and pharmaceutical companies for providing additional, unpublished data on their studies relevant for this meta-analysis: Drs Benedicto Crespo-Facorro, Eduardo Pondé de Sena, Jeffrey A Lieberman, Robert Hamer, Eli Lilly (Drs Bruce Kinon and Virginia Stauffer), Janssen-Cilag Brazil (Dr de Sena) and Novartis Pharmaceuticals Corporation (Dr Marla Hochfeld).
PY - 2013/1
Y1 - 2013/1
N2 - Few controlled trials compared second-generation antipsychotics (SGAs) with first-generation antipsychotics (FGAs) regarding relapse prevention in schizophrenia. We conducted a systematic review/meta-analysis of randomized trials, lasting 6 months comparing SGAs with FGAs in schizophrenia. Primary outcome was study-defined relapse; secondary outcomes included relapse at 3, 6 and 12 months; treatment failure; hospitalization; and dropout owing to any cause, non-adherence and intolerability. Pooled relative risk (RR) (±95% confidence intervals (CIs)) was calculated using random-effects model, with numbers-needed-to-treat (NNT) calculations where appropriate. Across 23 studies (n4504, mean duration61.9±22.4 weeks), none of the individual SGAs outperformed FGAs (mainly haloperidol) regarding study-defined relapse, except for isolated, single trial-based superiority, and except for risperidone's superiority at 3 and 6 months when requiring 3 trials. Grouped together, however, SGAs prevented relapse more than FGAs (29.0 versus 37.5%, RR0.80, CI: 0.70-0.91, P0.0007, I 2 37%; NNT17, CI: 10-50, P0.003). SGAs were also superior regarding relapse at 3, 6 and 12 months (P0.04, P0.0001, P0.0001), treatment failure (P0.003) and hospitalization (P0.004). SGAs showed trend-level superiority for dropout owing to intolerability (P0.05). Superiority of SGAs regarding relapse was modest (NNT17), but confirmed in double-blind trials, first- and multi-episode patients, using preferentially or exclusively raw or estimated relapse rates, and for different haloperidol equivalent comparator doses. There was no significant heterogeneity or publication bias. The relevance of the somewhat greater efficacy of SGAs over FGAs on several key outcomes depends on whether SGAs form a meaningful group and whether mid- or low-potency FGAs differ from haloperidol. Regardless, treatment selection needs to be individualized considering patient- and medication-related factors.
AB - Few controlled trials compared second-generation antipsychotics (SGAs) with first-generation antipsychotics (FGAs) regarding relapse prevention in schizophrenia. We conducted a systematic review/meta-analysis of randomized trials, lasting 6 months comparing SGAs with FGAs in schizophrenia. Primary outcome was study-defined relapse; secondary outcomes included relapse at 3, 6 and 12 months; treatment failure; hospitalization; and dropout owing to any cause, non-adherence and intolerability. Pooled relative risk (RR) (±95% confidence intervals (CIs)) was calculated using random-effects model, with numbers-needed-to-treat (NNT) calculations where appropriate. Across 23 studies (n4504, mean duration61.9±22.4 weeks), none of the individual SGAs outperformed FGAs (mainly haloperidol) regarding study-defined relapse, except for isolated, single trial-based superiority, and except for risperidone's superiority at 3 and 6 months when requiring 3 trials. Grouped together, however, SGAs prevented relapse more than FGAs (29.0 versus 37.5%, RR0.80, CI: 0.70-0.91, P0.0007, I 2 37%; NNT17, CI: 10-50, P0.003). SGAs were also superior regarding relapse at 3, 6 and 12 months (P0.04, P0.0001, P0.0001), treatment failure (P0.003) and hospitalization (P0.004). SGAs showed trend-level superiority for dropout owing to intolerability (P0.05). Superiority of SGAs regarding relapse was modest (NNT17), but confirmed in double-blind trials, first- and multi-episode patients, using preferentially or exclusively raw or estimated relapse rates, and for different haloperidol equivalent comparator doses. There was no significant heterogeneity or publication bias. The relevance of the somewhat greater efficacy of SGAs over FGAs on several key outcomes depends on whether SGAs form a meaningful group and whether mid- or low-potency FGAs differ from haloperidol. Regardless, treatment selection needs to be individualized considering patient- and medication-related factors.
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U2 - 10.1038/mp.2011.143
DO - 10.1038/mp.2011.143
M3 - Article
C2 - 22124274
AN - SCOPUS:84871288077
VL - 18
SP - 53
EP - 66
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
IS - 1
ER -