TY - JOUR
T1 - Antipsychotic combinations vs monotherapy in schizophrenia
T2 - A meta-analysis of randomized controlled trials
AU - Correll, Christoph U.
AU - Rummel-Kluge, Christine
AU - Corves, Caroline
AU - Kane, John M.
AU - Leucht, Stefan
PY - 2009/5
Y1 - 2009/5
N2 - Context: Despite lacking evidence for its safety and efficacy, antipsychotic cotreatment is common in schizophrenia. Objective: To evaluate therapeutic and adverse effects of antipsychotic cotreatment vs monotherapy in schizophrenia. Data Sources: Cochrane Schizophrenia Group register and hand searches of relevant journals/conference proceedings. Study Selection: Randomized controlled trials comparing antipsychotic monotherapy to cotreatment with a second antipsychotic. Data Extraction and Analysis: Two authors independently extracted data. For homogenous dichotomous data, we calculated random effects, relative risk (RR), 95% confidence intervals (CIs), and numbers needed to treat (NNT). For continuous data, weighted mean differences were calculated. Results: In 19 studies (1229 patients) with 28 monotherapy and 19 cotreatment arms, antipsychotic cotreatment was superior to monotherapy regarding 2 a priori defined coprimary outcomes: less study-specific defined inefficacy (N = 22, n = 1202, RR = 0.76, CI = 0.63-0.90, P =.002, NNT = 7, CI = 4-17, P =.0008, I 2 = 78.9%) and all-cause discontinuation (N = 20, n = 1052, RR = 0.65, CI = 0.54-0.78, P <.00001). Results were consistent using Clinical Global Impressions thresholds of less than much (P =.006) and less than minimally (P =.01) improved. Specific psychopathology and adverse event data were insufficient to yield meaningful results. In sensitivity analyses, 5 efficacy moderators emerged: concurrent polypharmacy initiation, clozapine combinations, trial duration >10 weeks, Chinese trials, and second-generation + first-generation antipsychotics. In a meta-regression, similar dose combinations, second-generation + first-generation antipsychotics and concurrent polypharmacy initiation remained significant. Conclusions: In certain clinical situations, antipsychotic cotreatment may be superior to monotherapy. However, the database is subject to possible publication bias and too heterogeneous to derive firm clinical recommendations, underscoring the need for future research.
AB - Context: Despite lacking evidence for its safety and efficacy, antipsychotic cotreatment is common in schizophrenia. Objective: To evaluate therapeutic and adverse effects of antipsychotic cotreatment vs monotherapy in schizophrenia. Data Sources: Cochrane Schizophrenia Group register and hand searches of relevant journals/conference proceedings. Study Selection: Randomized controlled trials comparing antipsychotic monotherapy to cotreatment with a second antipsychotic. Data Extraction and Analysis: Two authors independently extracted data. For homogenous dichotomous data, we calculated random effects, relative risk (RR), 95% confidence intervals (CIs), and numbers needed to treat (NNT). For continuous data, weighted mean differences were calculated. Results: In 19 studies (1229 patients) with 28 monotherapy and 19 cotreatment arms, antipsychotic cotreatment was superior to monotherapy regarding 2 a priori defined coprimary outcomes: less study-specific defined inefficacy (N = 22, n = 1202, RR = 0.76, CI = 0.63-0.90, P =.002, NNT = 7, CI = 4-17, P =.0008, I 2 = 78.9%) and all-cause discontinuation (N = 20, n = 1052, RR = 0.65, CI = 0.54-0.78, P <.00001). Results were consistent using Clinical Global Impressions thresholds of less than much (P =.006) and less than minimally (P =.01) improved. Specific psychopathology and adverse event data were insufficient to yield meaningful results. In sensitivity analyses, 5 efficacy moderators emerged: concurrent polypharmacy initiation, clozapine combinations, trial duration >10 weeks, Chinese trials, and second-generation + first-generation antipsychotics. In a meta-regression, similar dose combinations, second-generation + first-generation antipsychotics and concurrent polypharmacy initiation remained significant. Conclusions: In certain clinical situations, antipsychotic cotreatment may be superior to monotherapy. However, the database is subject to possible publication bias and too heterogeneous to derive firm clinical recommendations, underscoring the need for future research.
KW - All-cause discontinuation
KW - Antipsychotics
KW - Combination
KW - Efficacy
KW - Monotherapy
KW - Polypharmacy
KW - Schizophrenia
KW - Side effects
KW - Trial methodology
UR - http://www.scopus.com/inward/record.url?scp=65349112410&partnerID=8YFLogxK
U2 - 10.1093/schbul/sbn018
DO - 10.1093/schbul/sbn018
M3 - Article
C2 - 18417466
AN - SCOPUS:65349112410
SN - 0586-7614
VL - 35
SP - 443
EP - 457
JO - Schizophrenia Bulletin
JF - Schizophrenia Bulletin
IS - 2
ER -