Abstract
OBJECTIVE: Agitation represents a serious and prevalent symptomatology within acute schizophrenia. This study aims to conduct a nuanced comparison of the efficacy and safety profiles of intramuscular (IM) ziprasidone versus IM haloperidol in the management of agitation among patients with acute schizophrenia. METHODS: This investigation was structured as a randomized, 3-day study, utilizing flexible dosing strategies. It included 69 patients diagnosed with schizophrenia, who were randomly allocated to receive either IM ziprasidone (n = 35, 20 to 40 mg/day) or IM haloperidol (n = 34, 5 to 10 mg/day). The primary endpoints included comparative analyses of the change in Positive and Negative Syndrome Scale (PANSS) total scores and Positive and Negative Syndrome Scale Excited Component (PANSS-EC) scores from baseline to study completion across the two groups. RESULTS: At baseline, there were no significant differences between the IM ziprasidone and haloperidol groups. Both treatments led to significant reductions in PANSS-EC total scores (haloperidol, p = 0.001; ziprasidone, p = 0.001) and PANSS total scores (haloperidol, p = 0.001; ziprasidone, p = 0.001) from baseline to study endpoint. Nevertheless, no significant difference was observed between the two groups in terms of changes in PANSS-EC scores (p = 0.312) and PANSS total scores (p = 0.159) from baseline to endpoint. The haloperidol group exhibited a higher incidence of adverse events compared with the ziprasidone group, reaching statistical significance (p = 0.027). CONCLUSIONS: Our findings indicate that both medications are equally effective in controlling agitation symptoms. However, ziprasidone exhibited superior characteristics in safety and tolerability, particularly in reducing the incidence of extrapyramidal symptoms. CLINICAL TRIAL REGISTRATION: The study was registered at https://www.chictr.org.cn/showproj.html?proj=246996, registration number: ChiCTR2500100002, date of registration: 1 April 2025.