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.
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.
Authors: Christoph U Correll; Anil K Malhotra; Saurabh Kaushik; Marjorie McMeniman; John M Kane Journal: Am J Psychiatry Date: 2003-11 Impact factor: 18.112
Authors: Anthony F Lehman; Jeffrey A Lieberman; Lisa B Dixon; Thomas H McGlashan; Alexander L Miller; Diana O Perkins; Julie Kreyenbuhl Journal: Am J Psychiatry Date: 2004-02 Impact factor: 18.112
Authors: Delbert G Robinson; Margaret G Woerner; Marjorie McMeniman; Alan Mendelowitz; Robert M Bilder Journal: Am J Psychiatry Date: 2004-03 Impact factor: 18.112
Authors: Alexander L Miller; Catherine S Hall; Robert W Buchanan; Peter F Buckley; John A Chiles; Robert R Conley; M Lynn Crismon; Larry Ereshefsky; Susan M Essock; Molly Finnerty; Stephen R Marder; Del D Miller; Joseph P McEvoy; A John Rush; Sy A Saeed; Nina R Schooler; Steven P Shon; Scott Stroup; Bernardo Tarin-Godoy Journal: J Clin Psychiatry Date: 2004-04 Impact factor: 4.384
Authors: Juan A Gallego; Jimmi Nielsen; Marc De Hert; John M Kane; Christoph U Correll Journal: Expert Opin Drug Saf Date: 2012-05-08 Impact factor: 4.250
Authors: Masahiro Nitta; Taishiro Kishimoto; Norbert Müller; Mark Weiser; Michael Davidson; John M Kane; Christoph U Correll Journal: Schizophr Bull Date: 2013-05-29 Impact factor: 9.306
Authors: William G Honer; Ric M Procyshyn; Eric Y H Chen; G William MacEwan; Alasdair M Barr Journal: J Psychiatry Neurosci Date: 2009-11 Impact factor: 6.186