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INTRODUCTION: Despite previous literature, the superiority of Second-generation Antipsychotics (SGAs) relative to First-generation Antipsychotics- especially haloperidol - on cognitive management in schizophrenia is still controversial. Thus, we aimed to compare the effects of haloperidol versus SGAs on the cognitive performance of individuals with schizophrenia or related disorders. METHODS: We conducted an updated systematic review and nine pairwise meta-analyses of double-blinded randomized controlled trials published up to October 30th, 2022, using Medline, Web of Science, and Embase. RESULTS: Twenty-eight trials were included, enrolling 1,932 individuals. Compared to SGAs, haloperidol performed worse on cognitive composite (MD -0.13; 95% CI: -0.33 to -0.03; MD = mean difference, CI = confidence interval), processing speed (MD -0.17; 95% CI: -0.28 to -0.07), attention (MD -0.14; 95% CI: -0.26 to -0.02), motor performance (MD -0.17; 95% CI: -0.31 to -0.03), memory and verbal learning (MD -0.21; 95% CI: -0.35 to -0.08), and executive function (MD -0.27; 95% CI: -0.43 to -0.11). In contrast, there were no significant differences between SGAs and haloperidol on working memory (MD 0.10; 95% CI: -0.08 to 0.27), visual learning (MD 0.08; 95% CI: -0.05 to 0.21), social cognition (MD 0.29; 95% CI: -0.30 to 0.88), and visuoconstruction (MD 0.17; 95% CI: -0.04 to 0.39). CONCLUSION: Haloperidol had poorer performance in global cognition and in some cognitive domains, but with small effect sizes. Therefore, it was not possible to conclude that haloperidol is certainly worse than SGAs in the long-term cognitive management of schizophrenia.
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OBJECTIVE: Bipolar disorder (BD) is associated with premature mortality. All-cause and specific mortality risks in this population remain unclear, and more studies are still needed to further understand this issue and guide individual and public strategies to prevent mortality in bipolar disorder Thus, a systematic review and meta-analysis of studies assessing mortality risk in people with BD versus the general population was conducted. The primary outcome was all-cause mortality, whilst secondary outcomes were mortality due to suicide, natural, unnatural, and specific-causes mortality. RESULTS: Fifty-seven studies were included (BD; n = 678,353). All-cause mortality was increased in people with BD (RR = 2.02, 95% CI: 1.89-2.16, k = 39). Specific-cause mortality was highest for suicide (RR = 11.69, 95% CI: 9.22-14.81, k = 25). Risk of death due to unnatural causes (RR = 7.29, 95% CI: 6.41-8.28, k = 17) and natural causes (RR = 1.90, 95% CI: 1.75-2.06, k = 17) were also increased. Among specific natural causes analyzed, infectious causes had the higher RR (RR = 4,38, 95%CI: 1.5-12.69, k = 3), but the analysis was limited by the inclusion of few studies. Mortality risk due to respiratory (RR = 3.18, 95% CI: 2.55-3.96, k = 6), cardiovascular (RR = 1.76, 95% CI: 1.53-2.01, k = 27), and cerebrovascular (RR = 1.57, 95% CI: 1.34-1.84, k = 13) causes were increased as well. No difference was identified in mortality by cancer (RR = 0.99, 95% CI: 0.88-1.11, k = 16). Subgroup analyses and meta-regression did not affect the findings. CONCLUSION: Results presented in this meta-analysis show that risk of premature death in BD is not only due to suicide and unnatural causes, but somatic comorbidities are also implicated. Not only the prevention of suicide, but also the promotion of physical health and the prevention of physical conditions in individuals with BD may mitigate the premature mortality in this population. Notwithstanding this is to our knowledge the largest synthesis of evidence on BD-related mortality, further well-designed studies are still warranted to inform this field.