Preliminary efficacy and tolerability profiles of first versus second-generation Long-Acting Injectable Antipsychotics in schizophrenia: A systematic review and meta-analysis.

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 events, and (4) treatment duration ≥12 weeks. Data was synthesized using mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes using a random-effect model. Of 1872 citations, 17 trials were included, and direct comparisons of SG vs FG-LAIAs were observed in 3 (n = 459). SG and FG-LAIAs had similar effects on PANSS scores (MD -1.35; 95% CI -8.33-5.64), tardive dyskinesia (RR 0.99; 95% CI, 0.47-2.07), all-cause discontinuation (RR 1.01; 95% CI 0.75-1.36), discontinuation due to inadequate efficacy (RR 1.13; 95% CI 0.81-1.59) or adverse events (RR 1.08; 95% CI 0.55-2.11). SG-LAIAs reduced the risk of using antiparkinsonian drugs (RR 0.54; 95% CI 0.54-0.76) but significantly increased serum prolactin, weight and BMI. For long-term management, depot preparations of paliperidone, haloperidol, risperidone and fluphenazine were equally effective at symptom control and adherence, with significant differences in their safety profiles. These results however are considerably limited due to the small number of included studies and are therefore preliminary, not generalizable. More clinical trials are required to obtain a broader perspective of SG-LAIAs compared to FG-LAIAs.