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European Review For Medical and... Feb 2021Delirium, a common behavioral manifestation of acute brain dysfunction in Intensive Care Unit (ICU), is a significant contributor to mortality and worse long-term... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Delirium, a common behavioral manifestation of acute brain dysfunction in Intensive Care Unit (ICU), is a significant contributor to mortality and worse long-term outcome. Antipsychotics, especially haloperidol, are commonly administered for the treatment and prevention of delirium in critically ill patients while the evidence for the safety and efficacy of these drugs is still lacking. Therefore, we conducted a systematic review of the benefits of haloperidol for the prevention of delirium in ICU patients.
MATERIALS AND METHODS
We made a systematic review and meta-analysis.
RESULTS
Eight RCTs with 2806 patients were included. The prophylactic use of haloperidol did not reduce the delirium incidence (RR: 0.90, 95% CI: 0.69-1.71), the duration of delirium (MD: -0.33, 95% CI: -1.25-0.588) and the delirium/coma free days (MD: 0.08, 95% CI: -0.06-0.23). We did not find an increase of extrapyramidal effects (RR: 1.86, 95% CI: 0.30-11.39), QTc prolongation (RR: 1.11, 95% CI: 0.79-1.55) and arrhythmias (RR: 1.26, 95% CI: 0.72-2.19). The use of haloperidol did not increase the ICU (MD: 0.77, 95% CI: -0.28-1.83) and hospital length of stay (MD: -0.57, 95% CI: -1.32-0.18). Haloperidol did not increase the sedation level (RR: 1.88, 95% CI: 0.76-4.63) and mortality (RR: 0.97, 95% CI: 0.83-1.18).
CONCLUSIONS
Haloperidol did not reduce the delirium incidence, the delirium duration, the delirium/coma free-days and did not increase the incidence of extrapyramidal effects, arrhythmias, the ICU and hospital length of stays and sedation.
Topics: Antipsychotic Agents; Delirium; Haloperidol; Humans; Intensive Care Units
PubMed: 33629327
DOI: 10.26355/eurrev_202102_24868 -
The Cochrane Database of Systematic... Nov 2012Antipsychotic drugs are the mainstay treatment for schizophrenia. Long-acting depot injections of drugs such as bromperidol decanoate are extensively used as a means of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic drugs are the mainstay treatment for schizophrenia. Long-acting depot injections of drugs such as bromperidol decanoate are extensively used as a means of long-term maintenance treatment.
OBJECTIVES
To assess the effects of depot bromperidol versus placebo, oral antipsychotics and other depot antipsychotic preparations for people with schizophrenia in terms of clinical, social and economic outcomes.
SEARCH METHODS
For this 2012 update we searched the Cochrane Schizophrenia Group's Register (February 2012).
SELECTION CRITERIA
We sought all randomised trials focusing on people with schizophrenia where depot bromperidol, oral antipsychotics or other depot preparations. Primary outcomes were clinically significant change in global function, service utilisation outcomes (hospital admission, days in hospital), relapse.
DATA COLLECTION AND ANALYSIS
For the 2011 update MP independently extracted data, CEA carried out the reliability check. We calculated fixed-effect risk ratios (RR) and 95% confidence intervals (CI) for dichotomous data, and calculated weighted or standardised means for continuous data. Where possible, we calculated the number needed to treat statistic (NNT). Analysis was by intention-to-treat.For the 2012 update, data collection and analysis was not carried out as no new studies were found.
MAIN RESULTS
The 2012 search found no new studies, we have therefore included no new trials in this 2012 update. The number of included trials remain 4 RCTs, total n = 117. A single, small study of six months' duration compared bromperidol decanoate with placebo injection. Similar numbers left the study before completion (n = 20, 1 RCT, RR 0.4 CI 0.1 to 1.6) and there were no clear differences between bromperidol decanoate and placebo for a list of adverse effects (n = 20, 1 RCT, RR akathisia 2.0 CI 0.21 to 18.69, RR increased weight 3.0 CI 0.14 to 65.9, RR tremor 0.33 CI 0.04 to 2.69). When bromperidol decanoate was compared with fluphenazine depot, we found no important change on global outcome (n = 30, RR no clinical important improvement 1.50 CI 0.29 to 7.73). People allocated to fluphenazine decanoate and haloperidol decanoate had fewer relapses than those given bromperidol decanoate (n = 77, RR 3.92 Cl 1.05 to 14.60, NNH 6 CI 2 to 341). People allocated bromperidol decanoate required additional antipsychotic medication somewhat more frequently than those taking fluphenazine decanoate and haloperidol decanoate, but the results did not reach conventional levels of statistical significance (n = 77, 2 RCTs, RR 1.72 CI 0.7 to 4.2). The use of benzodiazepine drugs was very similar in both groups (n = 77, 2 RCTs, RR 1.08 CI 0.68 to 1.70). People left the bromperidol decanoate group more frequent than those taking other depot preparation due to any cause (n = 97, 3 RCTs, RR 2.17 CI 1.00 to 4.73). Anticholinergic adverse effects were equally common between bromperidol and other depots (n = 47, RR 3.13 CI 0.7 to 14.0) and additional anticholinergic medication was needed with equal frequency in both depot groups, although results did tend to favour the bromperidol decanoate group (n = 97, 3 RCTs, RR 0.80 CI 0.64 to 1.01). The incidence of movement disorders was similar in both depot groups (n = 77, 2 RCTs, RR 0.74 CI 0.47 to 1.17).
AUTHORS' CONCLUSIONS
Minimal poorly reported trial data suggests that bromperidol decanoate may be better than placebo injection but less valuable than fluphenazine or haloperidol decanoate. If bromperidol decanoate is available it may be a viable choice, especially when there are reasons not to use fluphenazine or haloperidol decanoate. Well-conducted and reported randomised trials are needed to inform practice.
Topics: Antipsychotic Agents; Delayed-Action Preparations; Haloperidol; Humans; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 23152208
DOI: 10.1002/14651858.CD001719.pub4 -
The American Journal of Psychiatry Mar 2017
Topics: Antipsychotic Agents; Anxiety Disorders; Dystonia; Female; Haloperidol; Humans; Pregnancy; Uterine Diseases
PubMed: 28245696
DOI: 10.1176/appi.ajp.2016.16070800 -
Brain Research Bulletin Jul 2023The onset of schizophrenia is associated with both genetic and environmental risks during brain development. Environmental factors during pregnancy can represent risk...
BACKGROUND
The onset of schizophrenia is associated with both genetic and environmental risks during brain development. Environmental factors during pregnancy can represent risk factors for schizophrenia, and we have previously reported that several microRNA and mRNA expression changes in fetal brains exposed to haloperidol during pregnancy may be related to the onset of this disease. This study aimed to replicate that research and focused on apoptotic-related gene expression changes.
METHODS
Haloperidol (1 mg/kg) or aripiprazole (1 mg/kg) was injected into pregnant mice. Using RNA sequencing for the hippocampus of each offspring born from pregnant mice exposed to haloperidol, we analyzed genes identified as changed in our previous report and validated two apoptosis-related genes (Cdkn1a and Apaf1) using quantitative polymerase chain reaction (qPCR) methods. Furthermore, we attempted to elucidate the direct effects of haloperidol and aripiprazole on those mRNA expressions in in vitro experiments.
RESULTS
RNA sequencing successfully replicated 16 up-regulated and 5 down-regulated genes in this study. Of those, up-regulations of Cdkn1a and Apaf1 mRNA expression were successfully validated by direct quantification. Moreover, haloperidol and aripiprazole dose-dependent upregulation of both mRNA expressions were confirmed in a Neuro2a cell line.
CONCLUSIONS
In the hippocampus of offspring, intraperitoneal injection of haloperidol to pregnant mice induced up-regulation of apoptotic genes that representing the phenotypic change without apoptosis. These findings will be useful for understanding the molecular biological mechanisms underlying the effects of antipsychotics on the fetal brain.
Topics: Mice; Animals; Haloperidol; Aripiprazole; Piperazines; Quinolones; Antipsychotic Agents; Hippocampus; RNA, Messenger
PubMed: 37150328
DOI: 10.1016/j.brainresbull.2023.110662 -
Brain and Behavior Dec 2021Anticholinergic acting drugs have been associated with delirium in older patients. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Anticholinergic acting drugs have been associated with delirium in older patients.
OBJECTIVE
To examine the association between the anticholinergic burden (ACB) and the duration and severity of delirium in older hip-surgery patients with or without haloperidol prophylaxis.
METHODS
Older patients with a postoperative delirium following hip surgery from a randomized controlled trial investigating the effects of haloperidol prophylaxis on delirium incidence were included in this study. The ACB was quantified using two different tools, the Anticholinergic Drug Scale and an Expert Panel. Using linear regression, the association between the ACB and delirium was analyzed.
RESULTS
Overall delirium duration and severity were not significantly associated with the ACB. Also, no statistically significant differences were found in delirium duration or severity between the placebo and haloperidol treatment groups for the ACB groups. The protective effect of haloperidol on delirium duration and severity however tended to be present in patients with no or a low ACB but not or to a lesser extent in patients with an intermediate to high ACB.
CONCLUSIONS
The ACB was not significantly associated with delirium duration or severity. Haloperidol prophylaxis tended to shorten delirium duration and decrease delirium severity in patients with no or a low ACB. To further explore the influence of anticholinergic acting drugs on delirium duration and severity and the effect of concomitant haloperidol use, additional research with a higher haloperidol dose, a larger study population, and ACB quantification taking drug exposure into account is warranted.
Topics: Aged; Cholinergic Antagonists; Delirium; Haloperidol; Humans
PubMed: 34758516
DOI: 10.1002/brb3.2404 -
The Cochrane Database of Systematic... Apr 2009Neuroleptic drugs with potent D-2 receptor blocking properties have been the traditional treatment for tics caused by Tourette Syndrome. Pimozide is the most studied of... (Review)
Review
BACKGROUND
Neuroleptic drugs with potent D-2 receptor blocking properties have been the traditional treatment for tics caused by Tourette Syndrome. Pimozide is the most studied of these. Use of these medications is declining because of concerns about side effects, and new atypical neuroleptics are now available. The true benefit and risks associated with pimozide compared to other drugs is not known.
OBJECTIVES
To evaluate the efficacy and harms of pimozide in comparison to placebo or other medications in the treatment of tics in Tourette Syndrome.
SEARCH STRATEGY
We cross-referenced pimozide and its proprietary names with Tourette Syndrome and its derivations, as MeSH headings and as text words, and searched the Cochrane Movement Disorders Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2007, Issue 4), MEDLINE (1950-April 2007), and EMBASE (1980-April 2007). Reference lists of relevant articles were reviewed for additional trials.
SELECTION CRITERIA
All randomized, controlled, double blind studies comparing pimozide to placebo or other medications for the treatment of tics in Tourette Syndrome were considered for inclusion in this review. Both parallel group and crossover studies of children or adults, at any dose and for any duration, were included.
DATA COLLECTION AND ANALYSIS
Data was abstracted independently by two authors onto standardized forms and disagreements were resolved by discussion.
MAIN RESULTS
Six randomized controlled trials were included (total 162 participants, age range 7 to 53 years). Pimozide was compared with: placebo and haloperidol (two trials), placebo (one trial), haloperidol (one trial), and risperidone (two trials). Methodological quality was rated 'fair' for all studies. Studies used different outcome measurement scales for assessing tic severity and adverse effects. Significant clinical heterogeneity made meta-analysis inappropriate. Pimozide was superior to placebo in three studies, though it caused more side effects than placebo in one of these. Pimozide was inferior to haloperidol in one of three studies (the other two showed no significant difference between the drugs), which also showed significantly fewer side effects associated with pimozide. No significant differences between pimozide and risperidone were detected.
AUTHORS' CONCLUSIONS
Pimozide is an effective treatment for tics in Tourette Syndrome, though the number of trials comparing its effect to placebo and other drugs is limited. Trials of longer duration (minimum six months) are needed to investigate the longer-term effects of pimozide compared to atypical neuroleptics. Future trials should use the Yale Global Tic Severity Scale to assess the main outcome measure, and quantify adverse events with the Extrapyramidal Symptoms Rating Scale.
Topics: Anti-Dyskinesia Agents; Haloperidol; Humans; Pimozide; Randomized Controlled Trials as Topic; Risperidone; Tics; Tourette Syndrome
PubMed: 19370666
DOI: 10.1002/14651858.CD006996.pub2 -
The Cochrane Database of Systematic... Jul 2014Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between antipsychotic compounds,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Antipsychotic drugs are the core treatment for schizophrenia. Treatment guidelines state that there is no difference in efficacy between antipsychotic compounds, however, low-potency antipsychotic drugs are often clinically perceived as less efficacious than high-potency compounds, and they also seem to differ in their side-effects.
OBJECTIVES
To review the effects in clinical response of haloperidol and low-potency antipsychotics for people with schizophrenia.
SEARCH METHODS
We searched the Cochrane Schizophrenia Group Trials Register (July 2010).
SELECTION CRITERIA
We included all randomised trials comparing haloperidol with first-generation low-potency antipsychotic drugs for people with schizophrenia or schizophrenia-like psychosis.
DATA COLLECTION AND ANALYSIS
We extracted data independently. For dichotomous data, we calculated risk ratios (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis based on a random-effects model. For continuous data, we calculated mean differences (MD), again based on a random-effects model.
MAIN RESULTS
The review currently includes 17 randomised trials and 877 participants. The size of the included studies was between 16 and 109 participants. All studies were short-term with a study length between two and 12 weeks. Overall, sequence generation, allocation procedures and blinding were poorly reported. We found no clear evidence that haloperidol was superior to low-potency antipsychotic drugs in terms of clinical response (haloperidol 40%, low-potency drug 36%, 14 RCTs, n = 574, RR 1.11, CI 0.86 to 1.44 lowquality evidence). There was also no clear evidence of benefit for either group in acceptability of treatment with equivocal difference in the number of participants leaving the studies early due to any reason (haloperidol 13%, low-potency antipsychotics 17%, 11 RCTs, n = 408, RR 0.82, CI 0.38 to 1.77, low quality evidence). Similar equivocal results were found between groups for experiencing at least one adverse effect (haloperidol 70%, low-potency antipsychotics 35%, 5 RCTs n = 158, RR 1.97, CI 0.69 to 5.66, very low quality evidence ). More participants from the low-potency drug group experienced sedation (haloperidol 14%, low-potency antipsychotics 41%, 2 RCTs, n = 44, RR 0.30, CI 0.11 to 0.82, moderate quality evidence), orthostasis problems (haloperidol 25%, low-potency antipsychotics 71%, 1 RCT, n = 41, RR 0.35, CI 0.16 to 0.78) and weight gain (haloperidol 5%, low-potency antipsychotics 29%, 3 RCTs, n = 88, RR 0.22, CI 0.06 to 0.81). In contrast, the outcome 'at least one movement disorder' was more frequent in the haloperidol group (haloperidol 72%, low-potency antipsychotics 41%, 5 RCTs, n = 170, RR 1.64, CI 1.22 to 2.21, low quality evidence). No data were available for death or quality of life. The results of the primary outcome were robust in several subgroup and sensitivity analyses.
AUTHORS' CONCLUSIONS
The results do not clearly show a superiority in efficacy of haloperidol compared with low-potency antipsychotics. Differences in adverse events were found for movement disorders, which were more frequent in the haloperidol group, and orthostatic problems, sedation and weight gain, which were more frequent in the low-potency antipsychotic group. The quality of studies was low, and the quality of evidence for the main outcomes of interest varied from moderate to very low, so more newer studies would be needed in order to draw a definite conclusion about whether or not haloperidol is superior or inferior to low-potency antipsychotics.
Topics: Antipsychotic Agents; Dyskinesia, Drug-Induced; Haloperidol; Humans; Patient Dropouts; Randomized Controlled Trials as Topic; Schizophrenia; Weight Gain
PubMed: 25007358
DOI: 10.1002/14651858.CD009268.pub2 -
Proceedings of the Royal Society of... 1976
Review
Topics: Adenylyl Cyclases; Animals; Antipsychotic Agents; Apomorphine; Behavior, Animal; Blepharoptosis; Brain Chemistry; Cattle; Chlorpromazine; Dogs; Drug Interactions; Emetics; Haloperidol; Homovanillic Acid; Humans; Mice; Rats; Receptors, Dopamine; Tranquilizing Agents
PubMed: 14331
DOI: No ID Found -
Intensive Care Medicine Mar 2021Haloperidol and clonidine are commonly used to treat agitation in delirious intensive care unit (ICU) patients, but it is unclear whether these agents may shorten the...
PURPOSE
Haloperidol and clonidine are commonly used to treat agitation in delirious intensive care unit (ICU) patients, but it is unclear whether these agents may shorten the duration of delirium. The objective of this study was to determine whether haloperidol, clonidine, or their combined administration to delirious ICU patients results in delirium resolution.
METHODS
This was a cohort study on a mixed ICU, excluding patients with a primary neurological disorder. The main outcome was the probability of delirium resolution, using propensity score matching and Markov multinomial logistic regression models for daily transitions. Secondary outcomes were delirium duration, number of delirium days, ventilation days, length of stay in the ICU and hospital, and ICU mortality.
RESULTS
A total of 3614 patients were included (1165 delirious [32%]; 2449 non-delirious [68%]). Delirium occurred on 4708 (18.9%) of 24,906 days. The probability of delirium resolution was lower in delirious patients who received haloperidol (OR 0.47, 95% CI 0.39-0.57), clonidine (OR 0.78, 95% CI 0.63-0.97), or both (OR 0.45, 95% CI 0.36-0.56) compared to untreated delirious patients. Delirious patients who received haloperidol, clonidine, or both had generally longer delirium duration, more delirium and ventilation days, and spent more time in the ICU and in hospital than untreated delirious patients. These agents had no effect on ICU mortality.
CONCLUSION
Haloperidol and clonidine use in delirious ICU patients may be associated with reduced probability of delirium resolution. This finding, however, merits further investigation given inherent limitations of this observational analysis.
Topics: Clonidine; Cohort Studies; Critical Illness; Delirium; Haloperidol; Humans; Intensive Care Units; Prospective Studies
PubMed: 33591422
DOI: 10.1007/s00134-021-06355-9 -
Critical Care (London, England) Aug 2023Haloperidol is frequently used in critically ill patients with delirium, but evidence for its effects has been sparse and inconclusive. By including recent trials, we... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Haloperidol is frequently used in critically ill patients with delirium, but evidence for its effects has been sparse and inconclusive. By including recent trials, we updated a systematic review assessing effects of haloperidol on mortality and serious adverse events in critically ill patients with delirium.
METHODS
This is an updated systematic review with meta-analysis and trial sequential analysis of randomised clinical trials investigating haloperidol versus placebo or any comparator in critically ill patients with delirium. We adhered to the Cochrane handbook, the PRISMA guidelines and the grading of recommendations assessment, development and evaluation statements. The primary outcomes were all-cause mortality and proportion of patients with one or more serious adverse events or reactions (SAEs/SARs). Secondary outcomes were days alive without delirium or coma, delirium severity, cognitive function and health-related quality of life.
RESULTS
We included 11 RCTs with 15 comparisons (n = 2200); five were placebo-controlled. The relative risk for mortality with haloperidol versus placebo was 0.89; 96.7% CI 0.77 to 1.03; I = 0% (moderate-certainty evidence) and for proportion of patients experiencing SAEs/SARs 0.94; 96.7% CI 0.81 to 1.10; I = 18% (low-certainty evidence). We found no difference in days alive without delirium or coma (moderate-certainty evidence). We found sparse data for other secondary outcomes and other comparators than placebo.
CONCLUSIONS
Haloperidol may reduce mortality and likely result in little to no change in the occurrence of SAEs/SARs compared with placebo in critically ill patients with delirium. However, the results were not statistically significant and more trial data are needed to provide higher certainty for the effects of haloperidol in these patients.
TRIAL REGISTRATION
CRD42017081133, date of registration 28 November 2017.
Topics: Humans; Haloperidol; Coma; Critical Illness; Quality of Life; Delirium; Randomized Controlled Trials as Topic
PubMed: 37633991
DOI: 10.1186/s13054-023-04621-4