Antipsychotic co-treatment is common in
schizophrenia, despite lacking evidence for its efficacy and safety. Areas: We conducted a systematic search of PubMed/PsycInfo/CJN/WangFan/CBM without language restrictions from database inception until 05/25/2015 for randomized trials comparing
antipsychotic monotherapy with
antipsychotic co-treatment in ≥20 adults with
schizophrenia reporting meta-analyzable adverse events (AEs) data. Meta-analyzing 67 studies (n=4,861, duration=10.3±5.2 weeks),
antipsychotic co-treatment was similar to monotherapy regarding intolerability-related discontinuation (risk ratio (RR)=0.84, 95% confidence interval (CI)=0.53-1.33, p=0.455). While incidence of ≥1 AE was lower with
antipsychotic co-treatment (RR=0.77, 95%CI=0.66-0.90, p=0.001), these results were solely driven by open-label and efficacy-focused studies. Adjunctive D2-antagonists lead to less
nausea (RR=0.220, 95%CI=0.06-0.87, p=0.030) and
insomnia (RR=0.26, 95%CI=0.08-0.86, p=0.028), but higher
prolactin (SMD=2.20, 95%CI=0.43-3.96, p=0.015). Conversely, adjunctive partial D2-agonists (
aripiprazole=100%) resulted in lower electrocardiogram abnormalities (RR=0.43, 95%CI=0.25-0.73, p=0.002),
constipation (RR=0.45, 95%CI=0.25-0.79, p=0.006),
drooling/
hypersalivation (RR=0.14, 95%CI=0.07-0.29, p<0.001),
prolactin (SMD=-1.77, 95%CI=-2.38, -1.15, p<0.001), total and
LDL-cholesterol (SMD=-0.33, 95%CI=-0.55, -0.11, p=0.003; SMD=-0.33, 95%CI=-0.54, -0.10, p=0.004).
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