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We performed a systematic review and meta-analysis of the efficacy and safety of second generation (SG) long-acting antipsychotics (LAIAs) versus first generation (FG) LAIAs in schizophrenia. We conducted a comprehensive search in PubMed, MEDLINE, EMBASE and PsycINFO until May 2019. Inclusion criteria for randomized trials included (1) patients ≥18 years with schizophrenia, (2) efficacy evaluated through the Positive and Negative Syndrome Scale (PANSS), (3) safety assessment through clinimetry, laboratory analysis, somatometry or adverse ev