Antipsychotic combinations vs monotherapy in schizophrenia: a meta-analysis of randomized controlled trials.
BACKGROUND
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.


METHODS
Cochrane Schizophrenia Group register and hand searches of relevant journals/conference proceedings.


METHODS
Randomized controlled trials comparing antipsychotic monotherapy to cotreatment with a second antipsychotic.


METHODS
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.
Correll
Christoph U
CU
The Zucker Hillside Hospital, Psychiatry Research, Glen Oaks, New York, NY 11004, USA. ccorrell@lij.edu
Rummel-Kluge
Christine
C
Corves
Caroline
C
Kane
John M
JM
Leucht
Stefan
S
D000293:Adolescent; D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003024:Clozapine / Q000627:therapeutic use; D019992:Databases as Topic / Q000706:statistics & numerical data; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019338:Polypharmacy; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic / Q000706:statistics & numerical data; D012559:Schizophrenia / Q000188:drug therapy*; D012565:Schizophrenic Psychology; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D003024:Clozapine