UNASSIGNED: An estimated 57.4 million people live with dementia worldwide, with the social burden of the disease steadily growing. Despite the approval of lecanemab and ongoing trials, there is still a lack of effective and safe treatments for behavioral and psychological symptoms of dementia (BPSD), which affect 99% of patients. Agitation is one of the most disabling BPSD, with a cross-sectional prevalence of ≥50% in nursing homes, and refers to help-seeking behavior in response to various sources of discomfort, among which pain is a crucial component.
UNASSIGNED: This pilot phase of the BRAINAID (NCT04321889) trial aimed to assess the effectiveness of the patented nanotechnological device NanoBEO in older (≥65 years) people with severe dementia. This randomized placebo-controlled trial, with quadruple masking that involved all operators and participants, followed the SPIRIT and CONSORT statements. A total of 29 patients completed the trial. The patients were randomly allocated in a 1:1 ratio to the NanoBEO or placebo group, and the corresponding product was applied on both arms once daily for 4 weeks, with a 4-week follow-up period. The primary endpoint was efficacy against agitation. The secondary endpoints were efficacy against agitation at follow-up and efficacy against pain. Any adverse events were reported, and biochemical analyses were performed.
UNASSIGNED: The NanoBEO intervention reduced the frequency (28%) and level of disruptiveness of agitated behaviors. The effect on frequency was statistically significant after 2 weeks of treatment. The efficacy of NanoBEO on agitated behaviors lasted for the entire 4-week treatment period. No additional psychotropic drugs were prescribed throughout the study duration. The results after 1 week of treatment demonstrated that NanoBEO had statistically significant analgesic efficacy (45.46% improvement in pain intensity). The treatment was well tolerated.
UNASSIGNED: This trial investigated the efficacy of NanoBEO therapy in managing agitation and pain in dementia. No need for rescue medications was recorded, strengthening the efficacy of NanoBEO in prolonged therapy for advanced-stage dementia and the usefulness of the intervention in the deprescription of potentially harmful drugs. This study provided a robust rationale for the application of NanoBEO in a subsequent large-scale pivotal trial to allow clinical translation of the product. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04321889.

The management of schizophrenia necessitates a comprehensive treatment paradigm that considers individual patient nuances and the efficacy of lurasidone in addressing schizophrenia symptoms, particularly at elevated dosages. Numerous randomized trials have affirmed the efficacy of lurasidone across various dimensions of schizophrenia, demonstrating marked enhancements in positive, negative and cognitive symptoms compared to a placebo. In addition, lurasidone exhibits potential in ameliorating agitation amongst acutely ill patients, showcasing greater efficacy at higher doses. However, despite the favourable outcomes observed with higher lurasidone doses, routine clinical practice often opts for lower doses, potentially limiting its maximal therapeutic impact. Furthermore, lurasidone also shows efficacy in reducing post-psychotic depression in dual psychosis. Moreover, practical insights into lurasidone usage encompass swift dose escalation within a 1-5-day span and recommended combination strategies with other medications such as benzodiazepines for insomnia or agitation, beta-blockers for akathisia, and antihistamines or antimuscarinic drugs for patients transitioning rapidly from antipsychotics with substantial antihistamine and/or anticholinergic effects. Finally, a series of clinical cases is presented, highlighting benefits of lurasidone in terms of cognitive function, functional recovery and other therapeutic aspects for the management of schizophrenia.

BACKGROUND: Agitation significantly impacts Arab elders with dementia. Multisensory stimulation, such as Snoezelen, shows promise but lacks exploration in Arab contexts.
OBJECTIVE: Evaluate a culturally adapted multisensory intervention-combining Snoezelen, aromatherapy, and personal items-on agitation in Arab elders with dementia.
METHODS: A quasi-experimental design assessed 31 patients receiving the intervention against 31 controls. Agitation, quality of life, and neuropsychiatric symptoms were measured using the Cohen-Mansfield Agitation Inventory (CMAI) and the Neuropsychiatric Inventory (NPI).
RESULTS: The intervention group exhibited notable reductions in CMAI scores for aggression and agitation behaviors (p < 0.001) and improvements in quality of life and NPI scores for agitation/aggression and depression/dysphoria (p < 0.001).
CONCLUSIONS: This culturally tailored multisensory approach effectively reduced agitation and improved well-being in Arab dementia patients. The findings advocate for further research and suggest such interventions can be beneficial in culturally diverse dementia care settings.
BACKGROUND: ClinicalTrials.gov, ID NCT06216275.

UNASSIGNED: The Cohen-Mansfield Agitation Inventory (CMAI) quantifies the frequency of agitation behaviors in elderly persons. This post hoc analysis of data from the brexpiprazole clinical program aimed to determine a meaningful within-patient change (MWPC) threshold for CMAI Total score among patients with agitation associated with dementia due to Alzheimer\'s disease.
UNASSIGNED: Data were included from three 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm trials of brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer\'s disease (ClinicalTrials.gov identifiers: NCT01862640, NCT01922258, NCT03548584). Change in CMAI Total score (range 29-203; higher scores indicate higher frequency of agitation behaviors) from baseline to Week 12 was the primary endpoint in each trial. MWPC thresholds were estimated from anchor-based mean change analyses and receiver operating characteristic (ROC) curves. The Clinical Global Impression-Severity of illness (CGI-S) and Clinical Global Impression-Improvement (CGI-I) scales, both as related to agitation, were used as anchors. Empirical cumulative distribution functions (eCDFs) and probability density functions (PDFs) were plotted as supportive evidence. Distribution-based methods were also employed.
UNASSIGNED: Data from 898 patients were analyzed (mean age, 73.7 years; mean baseline CMAI Total score, 73.8). The mean CMAI Total score change corresponding to a difference of small improvement vs. stable (CGI-S one-point decrease vs. no change), or minimally improved vs. no change (CGI-I rating of 3 vs. 4), ranged from -10.6 to -13.5 points. The mean CMAI Total score change corresponding to a difference of moderate improvement vs. stable (CGI-S two-point decrease vs. no change), or much improved vs. no change (CGI-I rating of 2 vs. 4), ranged from -20.2 to -25.7 points. ROC curve analyses generally produced smaller estimates of meaningful change. eCDFs and PDFs showed good distribution and separation of CMAI Total score change between CGI-S/CGI-I categories. In distribution-based analyses, the minimal detectable change for CMAI Total score (10.5-11.8 points) was generally lower than anchor-suggested thresholds.
UNASSIGNED: Triangulation of evidence from anchor- and distribution-based analyses supports an MWPC threshold for CMAI Total score of -20 points, with a threshold range of -15 to -25 points, in patients with agitation associated with dementia due to Alzheimer\'s disease.

UNASSIGNED: There is no consensus on the optimal antipsychotic for acute agitation. Whereas haloperidol is frequently used and has proven efficacy, second generation antipsychotics show similar efficacy and improved safety and tolerability. This study aimed to determine the effectiveness of short-acting intramuscular (IM) haloperidol versus other IM antipsychotics for acute agitation in adults admitted to an inpatient psychiatry unit.
UNASSIGNED: This was a retrospective medical record review of patients who received 1 or more doses of a short-acting IM antipsychotic, including chlorpromazine, haloperidol, olanzapine, or ziprasidone. The primary endpoint was the need for subsequent IM antipsychotic(s) or physical restraint within 2 hours of the initial IM antipsychotic. Secondary endpoints assessed outcomes at 24 hours and adverse events.
UNASSIGNED: One hundred six patients were included. Four patients in the haloperidol group and 0 patients in the other antipsychotic group received an additional IM antipsychotic or required physical restraints within 2 hours (5.3% versus 0%, p = .319). More patients in the other antipsychotic group required an additional dose of IM antipsychotic within 24 hours compared with the haloperidol group (p = .0096). More adverse events were seen in patients who received haloperidol.
UNASSIGNED: Haloperidol was used more frequently than other short-acting IM antipsychotics. Whereas the effectiveness at 2 hours was not significantly different between groups, patients who received haloperidol were more likely to experience adverse events and were more often subjected to polypharmacy with benzodiazepines and/or diphenhydramine. This study further supports the use of olanzapine and ziprasidone for acute agitation in patients hospitalized in inpatient psychiatry.

BACKGROUND: Severe psychomotor agitation and aggression often require immediate pharmacological intervention, but clear evidence-based recommendations for choosing among the multiple options are lacking. To address this gap, we plan a systematic review and individual-participant-data network meta-analysis to investigate their comparative effectiveness in real-world emergency settings with increased precision.
METHODS: We will include randomized controlled trials investigating intramuscular or intravenous pharmacological interventions, as monotherapy or in combination, in adults with severe psychomotor agitation irrespective of the underlying diagnosis and requiring rapid tranquilization in general or psychiatric emergency settings. We will exclude studies before 2002, those focusing on specific reasons for agitation and placebo-controlled trials to avoid concerns related to the transitivity assumption and potential selection biases. We will search for eligible studies in BIOSIS, CENTRAL, CINAHL Plus, Embase, LILACS, MEDLINE via Ovid, PubMed, ProQuest, PsycINFO, ClinicalTrials.gov, and WHO-ICTRP. Individual-participant data will be requested from the study authors and harmonized into a uniform format, and aggregated data will also be extracted from the studies. At least two independent reviewers will conduct the study selection, data extraction, risk-of-bias assessment using RoB 2, and applicability evaluation using the RITES tool. The primary outcome will be the number of patients achieving adequate sedation within 30 min after treatment, with secondary outcomes including the need for additional interventions and adverse events, using odds ratios as the effect size. If enough individual-participant data will be collected, we will synthesize them in a network meta-regression model within a Bayesian framework, incorporating study- and participant-level characteristics to explore potential sources of heterogeneity. In cases where individual-participant data are unavailable, potential data availability bias will be explored, and models allowing for the inclusion of studies reporting only aggregated data will be considered. We will assess the confidence in the evidence using the Confidence in Network Meta-Analysis (CINeMA) approach.
CONCLUSIONS: This individual-participant-data network meta-analysis aims to provide a fine-tuned synthesis of the evidence on the comparative effectiveness of pharmacological interventions for severe psychomotor agitation in real-world emergency settings. The findings from this study can greatly be provided clearer evidence-based guidance on the most effective treatments.
BACKGROUND: PROSPERO CRD42023402365.

UNASSIGNED: Aggression, a common symptom of Alzheimer\'s disease (AD), can impose a significant burden on caregivers, necessitating early institutionalization.
UNASSIGNED: The current study examined the neural basis of aggression and its expression mechanism, to advance the development of effective treatment strategies for aggression in patients with AD.
UNASSIGNED: The study sample included 257 patients; 180 were diagnosed with AD and 77 with amnestic mild cognitive impairment (aMCI). Factor analysis of the neuropsychiatric inventory (NPI) aggression scores was performed, and the correlation between each factor and cerebral blood flow (CBF) was examined via diagnosis of AD or aMCI using statistical parametric mapping.
UNASSIGNED: Refusal of care was correlated with reduced CBF in the right hippocampus of patients with AD while no specific related regions could be identified in patients with aMCI. Violent behavior was associated with decreased CBF in the right temporal pole and medial frontal lobe of patients with AD and aMCI.
UNASSIGNED: These findings suggest that aggression, measured using NPI includes two distinct symptoms, refusal of care and violent behavior, having different underlying neural bases.

Physical restraint is usually used when trying to control and terminate a violent episode. Many causes are possible behind aggressive, agitated, and violent behavior. Some of these are such factors that can either be detected in forensic autopsies or can be evident from the person\'s medical records. Various causes for deaths during physical restraint have been suggested. In this study, we wanted to review all incidents in which physical restraint was employed, ending in death of the restrained person, whether the restraint was applied by police officers, security guards, police custody personnel, health care personnel or ordinary civilians. The main aim was to see if this new kind of study design would increase our knowledge in circumstances and causes leading to death in restraint situations. Data was collected retrospectively from all forensic autopsies performed in the Southern Finland area during 2010-2015. We went through 21,036 forensic autopsy cases and found 12 cases (0.06 %) in which a physical restraint was employed before death. Police officers were involved in the physical restraint in 7/12 of the cases: in two of these cases, police alone; in three cases, police and guards; and in two cases, police and health care personnel. Civilians carried out the restraint in 5/12 cases. With civilians responsible for the restraint, the cause of death was more likely considered to be a result of the restraint itself than in cases where police and other authorities were responsible for the restraint. This could be because civilians aren\'t educated about safe restraint methods, and they might themselves be intoxicated. Alcohol was the most common psychoactive substance found in this study and could be a risk factor for not only aggressive behavior but also death, since alcohol use can provoke cardiac arrhythmias and even sudden death. Based on this study, and previously published studies, we see restraint deaths as a varying spectrum of deaths, in which the death is often possibly a result of many factors, including the effects of agitation and restraint, intoxication, and cardiac and other illnesses.

UNASSIGNED: This review explores delirium in critically ill patients in the inpatient setting, focusing on its prevention and management. It evaluates the efficacy of both current pharmacological and non-pharmacological interventions, aiming to provide a comprehensive overview.
UNASSIGNED: A systematic literature search was conducted to identify relevant studies investigating the prevention and management of delirium resulting in a final sample of 26 articles for analysis.
UNASSIGNED: Of the 26 articles analyzed for this review (N = 8,831 participants) of controlled trials, 16 studies examined the prevention of delirium, 9 explored the treatment of delirium, and 1 investigated both prevention and treatment of delirium.
UNASSIGNED: Among the reviewed studies, there is evidence that non-pharmacologic methods are effective in the prevention of delirium. Evidence regarding pharmacological interventions for delirium prevention is varied and inconclusive, with some indication that atypical antipsychotics like aripiprazole and quetiapine may reduce the incidence of delirium. Regarding the treatment of delirium, there is limited evidence supporting the use of pharmacological agents. Additional double-blinded, randomized, placebo-controlled clinical trials are needed to investigate the efficacy of pharmacologic agents for diverse hospitalized populations.

UNASSIGNED: Agitation is a common symptom in patients with Alzheimer\'s dementia. But agitation can be a heterogeneous symptom, encompassing a diverse array of behaviors exhibited by patients. The Cohen-Mansfield Agitation Inventory (CMAI) is a 29-item scale that is used to systematically assess the frequency and severity of agitation in older adults as rated by a primary caregiver. The CMAI was originally designed for use by professional care givers in institutional care settings. Alzheimer\'s dementia, however, is associated with a significant burden on family members, who provide the majority of care, and other informal care partners.
UNASSIGNED: Our qualitative study aimed to assess the accuracy and applicability of the CMAI according to the needs and perceptions of non-professional care partners. Specifically, we wanted to determine if the behaviors included in the instrument reflect: (a) the care partner\'s experience with agitation in Alzheimer\'s dementia patients, (b) how the behaviors and their frequency are related to the perception of agitation severity, and (c) what changes in agitation behaviors are meaningful to care partners. We interviewed 30 care partners for patients with Alzheimer\'s dementia in the United States.
UNASSIGNED: The care partners confirmed all behaviors listed in the CMAI as relevant. The behaviors reflect a spectrum of severity, with aggressive behaviors considered more severe than non-aggressive behaviors and physical behaviors generally considered more severe than verbal behaviors. Any reduction or increase in the frequency of a behavior was meaningful to care partners. Generally, a change from physical to verbal behaviors and aggressive to non-aggressive was considered a meaningful improvement while a change from verbal to physical and non-aggressive to aggressive was considered a meaningful worsening.
UNASSIGNED: The CMAI appropriately captures relevant behaviors of agitation in Alzheimer\'s dementia and provides insight into the relative improvement or worsening of agitation symptoms.