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Evaluation of the effect of aripiprazole supplementation in the prevention of delirium in patients admitted to the general intensive care unit
Mehranoosh Nouri1, Sohrab Salimi2, Mohsen Kosha3, Dariush Abtahi1
1 Department of Anesthesiology, School of Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
2 Department of Anesthesiology, School of Medicine, Anesthesiology Research Center, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
3 Department of Neurosurgery, School of Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| Date of Submission | 09-Oct-2021 |
| Date of Acceptance | 18-Mar-2023 |
| Date of Web Publication | 27-Jul-2023 |
Correspondence Address:
Dr. Dariush Abtahi
Department of Anesthesiology, School of Medicine, Anesthesiology Research Center, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Tehran
Iran
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/abr.abr_314_21
Background: To prove the position of aripiprazole as a preventive and safe agent in delirium in patients admitted to the intensive care unit (ICU), it is necessary to conduct randomized controlled clinical trials with appropriate design.
Materials and Methods: In this study, 80 patients were randomly divided into two groups of 40. Group A received placebo mart for one week, and group B received 15 mg aripiprazole daily (dissolved in 10 cc) daily. As a criterion for assessing delirium, the Confusion Assessment methods for the ICU (CAM-ICUs) were evaluated daily for patients. At the end of the study, the trends of CAM-ICU and CAM-ICU changes on day 7 were compared between the two groups. All statistical tests were performed in two domains with a significance level of 5% using the t-test. Statistical Package for the Social Sciences (SPSS) 21 software was used to analyze the data.
Results: The use of aripiprazole in the studied indices was not statistically significant (P > 0.05). The results related to the length of stay in the ICU, showed that although the use of aripiprazole has reduced the length of hospitalization of patients in the ICU, this rate of reduction, was not significant (P > 0.05).
Conclusion: The use of aripiprazole with the approach of reducing the risk or controlling the occurrence of delirium on patients admitted to the intensive care unit, despite creating some beneficial effects such as reducing the length of hospital stay in the ICU, cannot be clearly and significantly effective.
Keywords: Aripiprazole, delirium, intensive care
How to cite this article:
Nouri M, Salimi S, Kosha M, Abtahi D. Evaluation of the effect of aripiprazole supplementation in the prevention of delirium in patients admitted to the general intensive care unit. Adv Biomed Res 2023;12:198 |
How to cite this URL:
Nouri M, Salimi S, Kosha M, Abtahi D. Evaluation of the effect of aripiprazole supplementation in the prevention of delirium in patients admitted to the general intensive care unit. Adv Biomed Res [serial online] 2023 [cited 2023 Sep 26];12:198. Available from: https://www.advbiores.net/text.asp?2023/12/1/198/382399 |
| Introduction | |  |
Delirium is a transient general disorder that impairs cognition and attention[1] and is acutely caused by physical disorders, psychological changes, intoxication, and withdrawal syndrome. Delirium has characteristics such as impaired consciousness, attention, cognition, perception, sleep, and psychomotor activity that fluctuate throughout the day.[2],[3] Delirium will have consequences such as increased morbidity, mortality, prolonged hospital stays, and poor performance.[4] This is a common problem among hospitalized patients, especially those admitted to the intensive care unit (ICU), which is reported to occur in 70% of patients.[5]
In clinical situations, antipsychotic drugs with D2 antagonistic effects are used to correct the dopaminergic system overactivity in the treatment of delirium.[6] Typical antipsychotics used for this purpose include haloperidol, chlorpromazine, and levomepromazine, of which haloperidol is the gold standard for treating delirium.[7] Atypical antipsychotics include drugs such as risperidone, olanzapine, clozapine, quetiapine, and aripiprazole for the treatment of delirium, which have a lower risk of an extrapyramidal syndrome than typical antipsychotics.[8],[9],[10]
Meanwhile, aripiprazole has a different pharmacological effect than other antipsychotic drugs due to its partial agonist effect on the D2 receptor. Aripiprazole is also called a dopamine system stabilizer. The American Psychiatric Association guidelines rank aripiprazole high in safety.[11],[12],[13]
Recently, a review study examined the efficacy and safety of aripiprazole in delirium. This article shows that aripiprazole is an effective treatment for delirium in the elderly, which is not only as effective as other antipsychotics but also safer because it has fewer extrapyramidal side effects and less weight gain.[11]
However, the efficacy of aripiprazole as a prophylactic agent for delirium in ICU patients has not been evaluated. To prove the position of aripiprazole as a preventive and safe agent in delirium in patients admitted to the ICU, it is necessary to conduct randomized controlled clinical trials with appropriate design. Therefore, considering that no double-blind and randomized studies have been performed in this field so far, this study is the first to investigate the prophylactic effects of aripiprazole on the occurrence of delirium in patients admitted to the ICU, so this may be an effective step to reduce morbidity, mortality, length of stay in the ICU, and costs.
| Materials and Methods | | |
The present comparative, interventional, double-blind, and prospective study was performed after approval by the Ethics Committee in Biomedical Research of Shahid Beheshti University of Medical Sciences (IR.SBMU.MSP.REC.1399.111) at Imam Hussein Hospital in Tehran, Iran. For this purpose, patients admitted to the ICU at the age of 18 years or more who were hospitalized in the ICU for more than 72 hours were admitted to the study with the consent of the patients or their companions. Pregnant or lactating patients, cases with active delirium, alcohol poisoning, severe liver or kidney failure (glomerular filtration rate (GFR) >15), patients who were receiving another antipsychotic drug before entering the study, addicted, and cases who had not consent to enter the study were excluded.
Finally, 89 patients were available to enter the study, but five patients did not meet the inclusion criteria and three patients were not satisfied to participate in the study and one patient was not able to continue cooperation due to being transferred from the hospital. A total of 80 patients were included in the study. [Figure 1]. Patients were randomly divided into two groups of 40 patients. Group A received a placebo for one week, and group B received 15 mg of aripiprazole (from Actoverco, Tehran, Iran) (dissolved in 10 ccs) daily. As a criterion for assessing delirium, the Confusion Assessment methods for the ICU (CAM-ICUs) were evaluated daily for patients according to Guideline 1.[14] At the end of the study, the trends of CAM-ICU and CAM-ICU changes on day 7 were compared between the two groups.
All quantitative variables are mean and standard deviation; and qualitative variables were expressed as number (percentage). The normality of quantitative variables was evaluated by the Kolmogorov–Smirnov test and box diagrams and the probability of normality. All statistical tests were performed in two domains and at a significant level of 5% using a t-test. SPSS 21 (released 2012. IBM SPSS Statistics for Windows, Version 21.0. Armonk, NY: IBM Corp) software was used to analyze the data.
| Results | | |
The mean age of the participants was 53.95 years, while 63.75% (51) of the patients were men and 36.25% (29) were women. However, according to the results in [Table 1], the mean age of patients in group A (control) was 55.4 years and patients in group B (intervention) was 52.5 years. However, the number of male patients in group A (29 patients) was more than the number of male patients (22 patients) in group B. | Table 1: Examining the demographic conditions of patients hospitalized in the study using the t-test
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Among all patients, 18 patients (22.5%) had a history of smoking, of which 12 patients were in group A and six were in group B. Looking at the history of drug use, it can be seen that of 28 patients with such a history, 18 patients were in the intervention group (A) and 10 patients were in the control group.
The study of the reason for hospitalization of patients in the ICU shows that 25% of all patients were admitted to the ICU due to MT. Sepsis, pneumonia, and cerebrovascular accident (CVA) were the next most common causes of hospitalization in the ICU [Figure 2]. However, factors such as cancer and accidents have also been among the factors causing the ICU to be admitted. | Figure 2: Investigation and comparison of factors causing ICU hospitalization in patients participating in the study
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Based on the results in [Table 2], the mean of hemodynamic and respiratory indices of patients in the two groups did not show any significant change. However, although slight changes can be seen in the comparison of the indices of the two groups, none of these changes were statistically significant for the studied indices (P > 0.005). | Table 2: Evaluation and comparison of delirium assessment parameters in patients of the two groups
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Based on the results in [Figure 3], comparing the length of hospital stay in the ICU in two groups of A with a mean of 10.1 days and B with a mean of 9.6 days does not show a significant difference (P = 0.448). | Figure 3: Comparison of length of ICU stay in patients in the control and intervention groups
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Examination of the results of CAM-ICU as a delirium index after 7 days of monitoring of patients in both groups shows that this index in 21 cases (52.5%) of patients in the control group (A) and 18 cases (45.0%) of patients in the intervention group (B) is positive and delirium conditions are observed in them. Regarding this index, it should be said that although the number of patients in the intervention group decreased, this numerical difference was not significant (P = 0.163) [Figure 4]. | Figure 4: Evaluation and comparison of CAM-ICU as a delirium index in patients of the two groups
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| Discussion | | |
Based on the prevalence of delirium, 4% of people 18 years and older in the general population develop the disease. In people over 55, this rate increases to 1.1 percent. Also, 10 to 30% of people who are hospitalized for any reason have a chance of developing delirium, which is approximately equal to 30% of patients operated on in ICUs and 10–40% of patients with cardiovascular disease admitted to critical care unit (CCUs).[15],[16],[17]
Antipsychotic drugs with a D2 antagonistic effect are used to correct the overactivity of the dopaminergic system in the treatment of delirium.[6] Meanwhile, aripiprazole has a different pharmacological effect than other antipsychotic drugs due to its partial agonist effect on the D2 receptor. Aripiprazole is also called a dopamine system stabilizer. The American Psychiatric Association guidelines rank aripiprazole high in safety.[18],[19],[20] To the best of our knowledge, there are no reports on the use of aripiprazole in the treatment of delirium successfully. Although some researches were associated with positive results, future studies should be conducted to more approve of its utilization in delirium treatment.
Recent studies have shown that aripiprazole is among the effective treatment for delirium in the elderly, which is not only as effective as other antipsychotics but also safer because it has fewer extrapyramidal side effects and less weight gain.[21],[22]
According to the results of the present study, which investigates the effect of aripiprazole supplementation on the prevention of delirium in patients admitted to the general intensive care unit, although the use of aripiprazole caused slight changes in the comparison of the indices of the two groups, none of these changes were statistically significant for the studied indices (P > 0.05). According to the results related to the duration of hospitalization in the ICU, it can be said that the use of aripiprazole has reduced the ICU length of stay. However, this decrease was not statistically significant like other indicators (P > 0.05). These results have already been acknowledged by Kato et al. In a retrospective study, he examined 41 patients with delirium in the ICU who developed delirium after entering the ICU. One group was treated with aripiprazole, and the other group was treated with other antipsychotics. There was no difference between the two groups in terms of length of hospital stay, Memorial Delirium Assessment Score (MDAS) recovery, and treatment.[22] The results of a double-blind, randomized, placebo-controlled study showed that aripiprazole can reduce delirium incidence in the neurosurgical ICU, but it has been suggested to do further studies with larger sample size in different ICU settings and longer follow-up to confirm our results.[23]
| Conclusion | | |
Based on the results, the use of aripiprazole with the approach of reducing risks or controlling the occurrence of delirium on patients admitted to the intensive care unit, despite creating some beneficial effects such as reducing the length of stay in the ICU, cannot be clearly and significantly effective.
Limitation
The smallness of the study population can be considered one of the limitations of the present study. Therefore, using a larger statistical population, prescribing different and especially higher doses to patients can help to achieve better results and optimize treatment protocols based on the use of this drug.
Acknowledgment
The authors express their sincere thanks to the staff of Shahid Beheshti University of Medical Sciences, Tehran, Iran, for their assistance.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]
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