Benzodiazepines for psychosis‐induced aggression or agitation
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ABSTRACT:
SUBMITTER: Zaman H
PROVIDER: S-EPMC6486117 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: Not available
| S-EPMC6483410 | 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: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:ObjectivesThe effects of masupirdine on the neuropsychiatric symptoms were explored.MethodsMasupirdine (SUVN-502) was evaluated for its effects on cognition in patients with moderate AD. The prespecified primary outcome showed no drug-placebo difference. Post hoc analyses of domains of the 12-item neuropsychiatric inventory scale were carried out.ResultsIn a subgroup of patients (placebo, n = 57; masupirdine 50 mg, n = 53; masupirdine 100 mg, n = 48) with baseline agitation/aggression symptoms ≥1, a statistically significant reduction in agitation/aggression scores was observed in masupirdine 50 mg (95% confidence interval (CI), -1.9 to -0.5, p < 0.001) and masupirdine 100 mg (95% CI, -1.7 to -0.3, p = 0.007) treated arms at Week 13 in comparison to placebo and the effect was sustained for trial duration of 26 weeks in the masupirdine 50 mg treatment arm (95% CI, -2.3 to -0.8, p < 0.001). Similar observations were noted in the subgroup of patients (placebo, n = 29; masupirdine 50 mg, n = 30; masupirdine 100 mg, n = 21) with baseline agitation/aggression symptoms ≥3. In the subgroup of patients (placebo, n = 28; masupirdine 50 mg, n = 28; masupirdine 100 mg, n = 28) who had baseline psychosis symptoms and/or symptom emergence, a significant reduction in psychosis scores was observed in the masupirdine 50 mg (Week 4: 95% CI, -2.8 to -1.4, p < 0.001; Week 13: 95% CI, -3.3 to -1.3, p < 0.001) and masupirdine 100 mg (Week 4: 95% CI, -1.4 to 0, p = 0.046; Week 13: 95% CI, -1.9 to 0.1, p = 0.073) treatment arms in comparison to placebo.ConclusionFurther research is warranted to explore the potential beneficial effects of masupirdine on NPS.
| S-EPMC9828442 | 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 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: Not available
| S-EPMC8678509 | 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:BackgroundThe purpose of this study is to identify factors that predict nursing home placement among community-dwelling Alzheimer's disease (AD) patients with psychosis and/or agitation in a randomized clinical trial (ClinicalTrials.gov number, NCT00015548).Methods418 participants with AD enrolled in the Clinical Antipsychotic Trial of Intervention Effectiveness - AD (CATIE-AD) trial of anti-psychotic medications and having no evidence of nursing home use at baseline were followed at 9 months post-random assignment using data provided by caregiver proxy. χ2 tests, t-tests and Cox proportional hazard modeling were used to examine the baseline correlates of nursing home use.ResultsOf outpatients with no prior nursing home use, 15% were placed in a nursing home in the 9 months following baseline, with the average time to placement being 122 days. Bivariate analyses indicate that those with prior outpatient mental health use at study entry were more likely to be admitted; so too were those with worse physical functioning - i.e. lower scores on the AD Cooperative Study Activities of Daily Living Scale (ADCS-ADL), lower utility scores on the Health Utility Index (HUI)-III, and worse cognition on the Mini-mental State Examination. Controlling for other factors, non-Hispanic white race (hazard ratio [HR] = 2.16) and prior mental health use (HR = 1.87) increased the likelihood of admission. Those with higher ADCS-ADL scores were less likely to be placed (HR = 0.97).ConclusionsFactors leading to nursing home entry among psychotic/agitated AD patients are similar to the general population, though high incidence of nursing home entry highlights the importance of accounting for such utilization in health economic studies of AD outcomes. It also highlights the importance of using information on ADLs and other characteristics to develop profiles identifying those at greater or lesser risk of nursing home entry and, in so doing, inform population planning associated with AD and identification of those patients and caregivers who might benefit most from interventions to prevent eventual placement.
| S-EPMC3951873 | biostudies-literature
Project description:ObjectivesExplore the relationship between behavioral and psychological symptoms of dementia (BPSD; specifically, delusions, hallucinations, and agitation/aggression) and associated caregiver distress with emergency department (ED) utilization, inpatient hospitalization, and expenditures for direct medical care.Design/setting/participantsRetrospective cross-sectional cohort of participants with dementia (N = 332) and informants from the Aging, Demographics, and Memory Study, a nationally representative survey of U.S. adults >70 years old.MeasurementsBPSD of interest and associated informant distress (trichotomized as none/low/high) were assessed using the Neuropsychiatric Inventory (NPI). Outcomes were determined from one year of Medicare claims and examined according to presence of BPSD and associated informant distress, adjusting for participant demographics, dementia severity, and comorbidity.ResultsFifty-eight (15%) participants with dementia had clinically significant delusions, hallucinations, or agitation/aggression. ED visits, inpatient admissions, and costs were not significantly higher among the group with significant BPSD. In fully adjusted models, a high level of informant distress was associated with all outcomes: ED visit incident rate ratio (IRR) 3.03 (95% CI: 1.98-4.63; p < 0.001), hospitalization IRR 2.78 (95% CI: 1.73-4.46; p < 0.001), and relative cost ratio 2.00 (95% CI: 1.12-3.59; p = 0.02).ConclusionsA high level of informant distress related to participant BPSD, rather than the symptoms themselves, was associated with increased healthcare utilization and costs. Effectively identifying, educating, and supporting distressed caregivers may help reduce excess healthcare utilization for the growing number of older adults with dementia.
| S-EPMC5600647 | biostudies-literature