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First-Generation Versus Second-Generation Antipsychotics in Adults: Comparative Effectiveness

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Comparative Effectiveness of Haloperidol and SGAs for Treating Schizophrenia: General Psychopathology

Haloperidol and second-generation antipsychotics (SGAs) were compared for effectiveness in improving the general psychopathology of schizophrenia. The assessment instruments that were commonly used were the Positive and Negative Syndrome Scale (PANSS), the Hamilton Depression Scale (HAM-D), the Hamilton Anxiety Scale (HAM-A), the Montgomery-Asberg Depression Rating Score (MADRS), the Young Mania Rating Scale (YMRS), the Calgary Depression Scale for Schizophrenia (CDS-S), the Agitated Behavior Scale (ABS), and the Agitation-Calmness Evaluation Scale (ACES).

Most comparisons of haloperidol and an SGA demonstrated no statistically significant difference in a meta-analysis of pooled study data. Olanzapine demonstrated a clinically significantly greater benefit than haloperidol on the HAM-D Scale in three randomized controlled trials (RCTs; mean difference [MD] = 1.69; 95-percent confidence interval [95% CI] 1.41 to 1.96) and on the MADRS (MD = 2.46; 95% CI 1.78 to 3.14). The strength of evidence for these findings is moderate. No statistically significant differences were found on the ABS, ACES, CDS-S, or HAM-A scales, and the strength of evidence is low.

No statistically significant differences were found in comparisons of haloperidol with quetiapine on the PANSS (4 RCTS) and the CDS-S (2 RCTs); in comparisons with risperidone on the PANSS (20 RCTs), the HAM-D (2 RCTs), the CDS-S (3 RCTs), and the YMRS (2 RCTs); and in comparison with clozapine on the PANSS. The strength of evidence for these results is low.