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Background  Although antidepressants are commonly used in patients with schizophrenia, meta-analytic guidance on the efficacy and safety of antidepressant augmentation evaluated as a single clinical strategy in patients with insufficient response to antipsychotic monotherapy is missing.    Methods  Systematic literature search of PubMed/MEDLINE/PsycINFO/Cochrane Library without language restrictions from database inception until 07/20/2015 for randomized, double-blind, efficacy-focused trials comparing adjunctive antidepressants vs placebo to antipsychotics in schizophrenia. Random effects meta-analysis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard to evaluate the efficacy and safety of antidepressant augmentation of antipsychotics in schizophrenia.    Results  In 48 studies (n=2192, duration=10.2 ± 7.6 weeks), antidepressant augmentation outperformed placebo regarding total symptom reduction (studies=28, n=1249, standardized mean difference (SMD)=-0.36, 95% confidence interval (CI)=-0.57, -0.15, p=0.001), driven by negative (studies=32; n=1384, SMD=-0.25, 95%CI=-0.44, -0.06, p=0.010), but not positive (p=0.284) or general (p=0.118) symptom reduction. Significant improvements extended to core negative symptoms avolition/apathy (SMD=-0.54, 95%CI=-0.84, -0.24, p<0.001) and anhedonia/asociality (studies=8, n=284, SMD=-0.50, 95%CI=-0.90, -0.10, p=0.013). In predefined subgroup-analyses, superiority regarding negative symptoms was confirmed in studies augmenting first-generation antipsychotics (FGAs) (studies=10, n=433, SMD=-0.42, 95%CI=-0.76, -0.08, p=0.016), but not second-generation antipsychotics (studies=13, n=452, p=0.385). Uniquely, superiority in total symptom reduction by noradrenergic-and-specific-serotonergic-antidepressants (SMD=-0.72, 95%CI=-1.24, -0.20, p=0.007) was not driven by negative (p=0.467), but by positive symptom reduction (SMD=-0.43, 95%CI=-0.78, -0.09, p=0.013). Antidepressants did not improve depressive symptoms more than placebo (studies=24, n=1111, p=0.207). Bupropion was superior to placebo regarding smoking cessation (studies=7, n=327, RR=2.75, 95%CI=1.60–4.72, p<0.001, number-needed-to-treat (NNT)=6). Except for more dry mouth (RR=1.57, 95%CI=1.04–2.36, p=0.03) and dizziness (RR=2.01, 95%CI=1.06–3.82, p=0.032), antidepressants were not associated with more adverse effects or all-cause/specific-cause discontinuation than placebo.    Discussion  For schizophrenia patients on stable antipsychotic treatment adjunctive antidepressants are effective for total and particularly negative symptom reduction, and bupropion helps smoking cessation. However, effects are small-to-medium, differ across individual antidepressants, and negative symptom improvement seems restricted to the augmentation of FGAs.

T232. EFFICACY AND SAFETY OF ANTIDEPRESSANT AUGMENTATION OF ANTIPSYCHOTICS IN SCHIZOPHRENIA