The majority of research in critically ill patients compared haloperidol with atypical medications, such as quetiapine, in mixed populations of patients with delirium who were hypoactive, hyperactive, and mixed in nature, coming from mixed etiologies and comorbidities. Which medications may be more effective in critically ill patients with hyperactive delirium remain unclear. This comparative study compares the effectiveness of quetiapine with haloperidol as a control in treating the hyperactive form of delirium in terms of their effects on DRS-R-98 score, length of stay, and mortality. According to our findings, the study sample’s clinical response rate was 92%. The response rates for the two groups were comparable (88% for haloperidol and 96% for quetiapine, p = 0.609).

According to the study’s secondary outcomes, there were no statistically significant differences between the two groups’ mechanical ventilation needs (p > 0.99), hospital stay (p = 0.310), ICU mortality (p = 0.496), or in-hospital mortality (p = 0.321). In terms of ICU stay, there was a statistically significant difference between the haloperidol group (11.7 ± 2.6 days) and the quetiapine group (10.1 ± 2.0 days) (p = 0.018).

A single-blind RCT was undertaken by Grover et al. [10]. A total of 63 patients with delirium were enrolled, and 87% of them had the hyperactive form. Haloperidol (0.25–1.25 mg/day) was administered to 32 individuals, whereas quetiapine (12.5–75 mg/day) was given to another 31 patients. Both groups were evaluated at the beginning and 6 days later. Initially, there were no statistically significant differences between the means of the DRS-R-98 severity scores for the two groups (24.81 ± 2.19 for haloperidol, 25.48 ± 3.60 for quetiapine). Both groups showed comparable means at days 3 (p = 0.26) and 7 (p = 0.679) following the follow-up. At day 6, the response rates for the two groups were nearly identical (68.75% for haloperidol, 67.74% for quetiapine), with no statistically significant differences between them (p = 0.93) [10].

In a double-blind RCT, Maneeton et al. [11] examined 52 medically ill patients with hyperactive delirium. The most prevalent risk factors for delirium were trauma, fluid-electrolyte imbalance, and infections. Patients were given either quetiapine or haloperidol at random allocation. Baseline DRS-R-98 scores for the two groups (haloperidol, 29.7 ± 4.6 and quetiapine, 29.0 ± 4.4) were comparable (p = 0.23). After 7 days, the mean DRS-R-98 score differences between haloperidol (− 21.7 ± 6.7) and quetiapine (− 22.9 ± 6.9) were comparable but not significantly different (p = 0.59). On day 7, there were no noticeable differences in the response rates for haloperidol (78.5%) and quetiapine (79.5%) (p = 0.97) [11].

In an open label trial, 12 patients with delirium were evaluated by Sasaki et al. [5]. Patients received quetiapine (25–50 mg/day). The Japanese version of the DRS was used to evaluate patients. The mean duration of treatment until remission was 4.8 ± 3.5. The baseline mean Japanese version of the DRS score was 18.1 ± 4.2, and it was changed to 9.3 ± 1.6 after remission [5].

Omura et al. [12] evaluated 24 older patients who had been given a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, delirium diagnosis. Initial dosages of 25–50 mg/day quetiapine were given to patients, and then subsequent dosages were adjusted based on their clinical responses. Initially, the mean DRS score was 18.1 ± 3.7. The mean score was 8.9 ± 3.9 on day 7 of the quetiapine treatment, which is a statistically significant difference (p < 0.001). The clinical response at day 7 was recorded in 75% of the study population [12].

In the present trial, the median number of sleeping hours on day 1 was considerably lower in the quetiapine group than in the haloperidol group (p = 0.001). At days 3 and 7, quetiapine had significantly higher median sleeping hours than haloperidol (p = 0.038 and p = 0.001, respectively). In contrast to these findings, the Maneeton et al. [11] study found no significant differences in the mean sleeping hours between the haloperidol and quetiapine groups at day one (p = 0.26). On day 7, results showed an increase in the mean sleeping hours in both groups, with no discernible difference between them (p = 0.74) [11].

In the Sasaki et al. [5] study, the quetiapine-treated group did not exhibit severe daytime somnolence or sedation. In the Kim et al. [13] trial, quetiapine was well tolerated by all patients and had low rates of additional adverse events. There were no EPS reported. Only two patients reported experiencing more sedation [13].

To the best of our knowledge, this is the first trial to compare the effectiveness of quetiapine to the standard medication haloperidol in terms of DRS-R-98 in critically ill patients with hyperactive delirium. This study’s monocentric design might restrict how far the findings can be valid. The sample size calculation was based on the primary outcome only, and this small sample size may make it difficult to detect a mortality difference. No daily assessment for the DRS-R-98 score was planned in our protocol. The study design was liable to selection bias because of the very narrow inclusion and too wide exclusion criteria. There were no specified doses for the study drugs, it was dosing range. Doses were given once daily but at different times of the day. Additionally, most research involving critically ill patients has not been able to identify any direct antipsychotic mortality advantages. All patients in the study were undergoing active treatment, and because the study’s care providers were aware of this, it’s possible that this had an impact on some assessments, such as daily sleeping hours. Although multiple confounding factors may contribute to the duration of ICU stay, further studies should investigate the clinical significance of the decreased ICU stay addressed in this study.