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:
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 We thank the following authors and pharmaceutical companies for providing additional, unpublished data on their studies relevant for this meta-analysis: Drs Benedicto Crespo-Facorro, Eduardo Pondé de Sena, Jeffrey A Lieberman, Robert Hamer, Eli Lilly (Drs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.
KW - antipsychotics
KW - long-term treatment
KW - maintenance
KW - meta-analysis
KW - relapse prevention
KW - schizophrenia
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U2 - 10.1038/mp.2011.143
DO - 10.1038/mp.2011.143
M3 - Article
C2 - 22124274
AN - SCOPUS:84871288077
SN - 1359-4184
VL - 18
SP - 53
EP - 66
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 1
ER -
