Haloperidol for psychosis-induced aggression or agitation (rapid tranquillisation).
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ABSTRACT:
SUBMITTER: Ostinelli EG
PROVIDER: S-EPMC6483410 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC6486117 | biostudies-literature
Project description:IntroductionIndividuals with psychosis may access emergency services due to aggression and agitation. When the de-escalation technique fails to achieve tranquillisation, several pharmacological options are available. However, evidence on which intervention to prefer in terms of efficacy and tolerability to achieve resolution of the acute episode (ie, rapid tranquillisation) of aggression and agitation is currently fragmentary.Methods and analysisWe will include all randomised controlled trials comparing drugs or drug combinations or placebo for aggression or agitation episodes in adult individuals with psychosis. We will include individuals with psychosis (eg, schizophrenia and related disorders, bipolar disorder with psychotic symptoms, psychotic depression) but not substance or medication-induced psychosis or psychosis due to another medical condition. Our primary outcomes are the change in aggression or agitation scores within few hours since the administration of the intervention (efficacy outcome) and the proportion of participants who dropped out due to adverse effects (tolerability outcome). We will retrieve relevant studies from the register of studies of the Cochrane Schizophrenia Group. Also, we will run additional searches on CENTRAL, Embase and PubMed to retrieve potentially eligible studies focusing on other psychiatric diagnoses than those in the schizophrenia spectrum. We will conduct a random-effects network meta-analysis (NMA) for primary and secondary outcomes. In case of rare events of dichotomous outcomes, a common-effect Mantel-Haenszel NMA will be used instead. We will use the surface under the cumulative ranking curve and the mean ranks to rank all available treatments. Local and global methods of evaluation of inconsistency will be employed. Quality of evidence contributing to network estimates of the main outcomes will also be assessed with Confidence in Network Meta-Analysis.Ethics and disseminationThis study does not require ethical approval. We will disseminate our findings by publishing results in a peer-reviewed journal.Prospero registration numberCRD42019137945.
| S-EPMC6797276 | biostudies-literature
Project description:OBJECTIVE:In patients with Alzheimer's disease (AD) with psychosis or agitation that respond to haloperidol treatment, to evaluate the risk of relapse following discontinuation. METHODS:In outpatients with AD with symptoms of psychosis or agitation, responders to 20 weeks of haloperidol (0.5-5?mg daily) were randomized to a 24-week, double-blind pilot trial of discontinuation on placebo versus continuation haloperidol. Phase A response criteria were minimum 50% reduction in three target symptoms, and improvement on the Clinical Global Impression-Change (CGI-C) score for psychosis/agitation. Phase B relapse criteria required 50% worsening in target symptoms and on the CGI-C. ??=?0.1 was the significance criterion in this pilot study. RESULTS:Of 44 patients, 22 patients responded in Phase A. The sum score of target symptoms, and Brief Psychiatric Rating Scale (BPRS) psychosis and hostile suspiciousness factor scores, decreased in Phase A (p's?<?0.001). Extrapyramidal signs increased in Phase A (p?<?0.01). Of 22 responders, 21 patients entered Phase B, and 20 had at least one follow-up visit. Four of 10 patients (40%) on continuation haloperidol relapsed compared to eight of 10 patients on placebo (80%, ?(2) ?=?3.3, p?=?0.07). In survival analyses, time to relapse was shorter on placebo than haloperidol (?(2) ?=?4.1, p?=?0.04). CONCLUSIONS:Haloperidol open treatment was efficacious, and relapse was greater on placebo than with haloperidol continuation. In patients with AD who have psychosis or agitation and respond to antipsychotic medication, the increased risk of relapse after discontinuation needs to be weighed against the side effects associated with continuing the medication.
| S-EPMC3685500 | biostudies-literature
Project description:Along with cognitive decline, 90% of patients with dementia experience behavioral and psychological symptoms of dementia, such as psychosis, aggression, agitation, and depression. Atypical antipsychotics are commonly prescribed off-label to manage certain symptoms, despite warnings from the regulatory agencies regarding the increased risk of mortality associated with their use in elderly patients. Moreover, these compounds display a limited clinical efficacy, mostly owing to the fact that they were developed to treat schizophrenia, a disease characterized by neurobiological deficits. Thus, to improve clinical efficacy, it has been suggested that patients with dementia should be treated with exclusively designed and developed drugs that interact with pharmacologically relevant targets. Within this context, numerous studies have suggested druggable targets that might achieve therapeutically acceptable pharmacological profiles. Based on this, several different drug candidates have been proposed that are being investigated in clinical trials for behavioral and psychological symptoms of dementia. We highlight the recent advances toward the development of therapeutic agents for dementia-related psychosis and agitation/aggression and discuss the relationship between the relevant biological targets and their etiology. In addition, we review the compounds that are in the early stage of development (discovery or preclinical phase) and those that are currently being investigated in clinical trials for dementia-related psychosis and agitation/aggression. We also discuss the mechanism of action of these compounds and their pharmacological utility in patients with dementia.
| S-EPMC7048860 | biostudies-literature
Project description:BACKGROUND:Although mental illness accounts for only 4% of aggressive behavior in the general population, there remains a modest association between aggressive behavior and psychotic disorders, particularly in the early stages of the illness. However, little is known about the specific factors associated to this increased risk. AIMS:The present study aims to assess the rates, characteristics and risk factors of aggressive behavior in first episode psychosis patients (FEP). METHOD:We conducted a retrospective chart review of 449 FEP patients recruited from an outpatient early psychosis clinic. Aggressive behavior and clinical information were rated based upon information gathered from the chart review of data collected at baseline and after 6?months of follow-up. RESULTS:Rates of aggressive behavior were 54.3% in FEP patients. Aggressive behavior was significantly associated with higher rates of history of birth complications, neurodevelopmental delays, learning difficulties, alcohol use disorders, and the clinical domain of poverty symptoms. In addition to aggressive behavior, 16.7% of FEP patients exhibited suicidal ideation or behaviors and 11.4% exhibited non-suicidal self-injurious behavior (NSSIB). In contrast to baseline, aggressive behaviors at 6?months follow up were almost entirely absent. CONCLUSIONS:Patients at early stages of psychosis have high rates of aggressive and suicidal behavior prior to contact with clinical services. Neurodevelopmental adversities, alcohol use disorders and poverty symptoms are associated to higher risk of aggression in early psychosis. Participation in early psychosis specialty care resulted in a dramatic reduction in aggressive behavior.
| S-EPMC7259809 | biostudies-literature
Project description:The current study examined the changes in striatal gene network structure induced by short-term selective breeding from a heterogeneous stock for haloperidol response. Brain (striatum) gene expression data were obtained using the Illumina WG 8.2 array, and the datasets from responding and non-responding selected lines were independently interrogated using a weighted gene coexpression network analysis (WGCNA). We detected several gene modules (groups of coexpressed genes) in each dataset; the membership of the modules was found to be largely concordant, and a consensus network was constructed. Further validation of the network topology showed that using approximately 35 samples is sufficient to reliably infer the transcriptome network. An in-depth analysis showed significant changes in network structure and gene connectivity associated with the selected lines; these changes were validated using a bootstrapping procedure. The most dramatic changes were associated with a gene module richly annotated with neurobehavioral traits. The changes in network connectivity were concentrated in the links between this module and the rest of the network, in addition to changes within the module; this observation is consistent with recent results in protein and metabolic networks. These results suggest that a network-based strategy will help identify the genetic factors associated with haloperidol response.
| S-EPMC4460837 | biostudies-literature
Project description:The neuroanatomy of agitation and aggression in Alzheimer's disease is not well understood.We analyzed 24 months of Alzheimer's Disease Neuroimaging Initiative data for patients with Alzheimer's disease, mild cognitive impairment-stable, and mild cognitive impairment-converter (n = 462) using the Neuropsychiatric Inventory Questionnaire Agitation and Aggression subscale. Magnetic resonance imaging regions of interest that correlated with Neuropsychiatric Inventory Questionnaire Agitation and Aggression subscale raw scores were included in mixed-model, repeated-measures analyses of agitation and aggression over time with age, sex, apolipoprotein E ?4 status, education, and Mini-Mental State Examination score as covariates.Neuropsychiatric Inventory Questionnaire Agitation and Aggression subscale scores worsened in patients with Alzheimer's disease and in mild cognitive impairment-converter (P < .05; trend for mild cognitive impairment, P = .0518). Greater agitation and aggression severity was associated with greater atrophy of frontal, insular, amygdala, cingulate, and hippocampal regions of interest (P < .05). Mini-Mental State Examination score was significant in mixed-effect model repeated measures only in mild cognitive impairment-converters for posterior regions of interest. Demographics and apolipoprotein ?4 were not associated with agitation and aggression.Agitation and aggression in Alzheimer's disease and mild cognitive impairment is associated with neurodegeneration affecting the anterior salience network that may reduce capacity to process and regulate behaviors properly.
| S-EPMC3955297 | biostudies-literature
Project description:BackgroundThe safety and effectiveness of intramuscular olanzapine or haloperidol compared to midazolam as the initial pharmacological treatment for acute agitation in emergency departments (EDs) has not been evaluated.MethodsA pragmatic, randomised, double-blind, active-controlled trial was conducted from December 2014 to September 2019, in six Hong Kong EDs. Patients (aged 18-75 years) with undifferentiated acute agitation requiring parenteral sedation were randomised to 5 mg intramuscular midazolam (n = 56), olanzapine (n = 54), or haloperidol (n = 57). Primary outcomes were time to adequate sedation and proportion of patients who achieved adequate sedation at each follow-up interval. Sedation levels were measured on a 6-level validated scale (ClinicalTrials.gov Identifier: NCT02380118).FindingsOf 206 patients randomised, 167 (mean age, 42 years; 98 [58·7%] male) were analysed. Median time to sedation for IM midazolam, olanzapine, and haloperidol was 8·5 (IQR 8·0), 11·5 (IQR 30·0), and 23·0 (IQR 21·0) min, respectively. At 60 min, similar proportions of patients were adequately sedated (98%, 87%, and 97%). There were statistically significant differences for time to sedation with midazolam compared to olanzapine (p = 0·03) and haloperidol (p = 0·002). Adverse event rates were similar across the three arms. Dystonia (n = 1) and cardiac arrest (n = 1) were reported in the haloperidol group.InterpretationMidazolam resulted in faster sedation in patients with undifferentiated agitation in the emergency setting compared to olanzapine and haloperidol. Midazolam and olanzapine are preferred over haloperidol's slower time to sedation and potential for cardiovascular and extrapyramidal side effects.FundingResearch Grants Council, Hong Kong.
| S-EPMC7910711 | biostudies-literature
Project description:BackgroundAgitated behaviors are problematic in intensive care unit (ICU) patients recovering from traumatic brain injury (TBI) as they create substantial risks and challenges for healthcare providers. To date, there have been no studies evaluating their epidemiology and impact in the ICU. Prior to planning a multicenter study, assessment of recruitment, feasibility, and pilot study procedures is needed. In this pilot study, we aimed to evaluate the feasibility of conducting a large multicenter prospective cohort study.MethodsThis feasibility study recruited adult patients admitted to the ICU with TBI and an abnormal cerebral CT scan. In all patients, we documented Richmond Agitation Sedation Score (RASS) and agitated behaviors every 8-h nursing shift using a dedicated tool documenting 14 behaviors. Our feasibility objectives were to obtain consent from at least 2 patients per month; completion of screening logs for agitated behaviors by bedside nurses for more than 90% of 8-h shifts; completion of data collection in an average of 6 h or less; and obtain 6-month follow-up for surviving patients. The main clinical outcome was the incidence of agitation and individual agitated behaviors.ResultsIn total, 47 eligible patients were approached for inclusion and 30 (64% consent rate) were recruited over a 10-month period (3 patients/month). In total, 794 out of 827 (96%) possible 8-h periods of agitated behavior logs were completed by bedside nurses, with a median of 24 observations (IQR 28.0) per patient. During the ICU stay, 17 of 30 patients developed agitation (56.7%; 95% CI 0.37-0.75) defined as RASS ≥ 2 during at least one observation period and for a median of 4 days (IQR 5.5). At 6 months post-TBI, among the 24 available patients, an unfavorable score (GOS-E < 5 including death) was reported in 12 patients (50%). In the 14 patients who were alive and available at 6 months, the median QOLIBRI score was 74.5 (IQR 18.5).ConclusionsThis study demonstrates the feasibility of conducting a larger cohort study to evaluate the epidemiology and impact of agitated behaviors in critically ill TBI patients. This study also shows that agitated behaviors are frequent and are associated with adverse events.
| S-EPMC7729148 | biostudies-literature
Project description:Repeated pairings of a neutral context and the effects of haloperidol give rise to conditioned catalepsy when the context is subsequently presented in a drug-free test. In order to confirm whether this response is based on Pavlovian processes, we conducted two experiments involving two manipulations that affect conditioning intensity in classical conditioning procedures: time of joint exposure to the conditioned and the unconditioned stimulus, and the length of the inter-stimulus interval (ISI). The results revealed that both an increase in the length of context-drug pairings during conditioning and a reduced ISI between drug administration and context exposure increased conditioned catalepsy. These results are discussed in terms of the temporal peculiarities of those procedures that involve drugs as the unconditioned stimulus along with the role of Pavlovian conditioning in context-dependent catalepsy.
| S-EPMC8283013 | biostudies-literature