Haloperidol versus Second-generation Antipsychotics on the cognitive performance of individuals with schizophrenia and related disorders: pairwise meta-analysis of randomized controlled trials.

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.

The effect of antipsychotics on the cognitive performance of individuals with psychotic disorders: Network meta-analyses of randomized controlled trials.

Cognitive deficits are a core aspect of psychotic disorders; however, it is not clear to which extent different pharmacological treatments could distinctly impact these outcomes. Hence, we conducted a systematic review and ten network meta-analyses of randomized controlled trials to compare the effect of antipsychotics on cognitive performance of individuals with psychotic disorders. Fifty-four trials were included in the analyses, enrolling 5866 patients. Compared to other antipsychotics, amisulpride performed better on verbal learning; quetiapine on composite score, attention and verbal learning; lurasidone on composite score; olanzapine on composite score and most cognitive domains; perphenazine on composite score, executive function, working memory, and verbal learning; risperidone on executive function and verbal learning; sertindole on processing speed; and ziprasidone on composite score, working memory, and verbal learning. Oppositely, haloperidol performed poorer on all cognitive domains, occupying the last positions in all rankings; and clozapine performed poorer on composite score, executive function, verbal learning, and visuoconstruction. We hope that these results should be taken into account when assessing and treating individuals with psychosis.