Agitation in Dementia: Real-World Impact and Burden on Patients and the Healthcare System.

BACKGROUND: At least 90%of patients with dementia experience behavioral or neuropsychiatric symptoms including agitation, psychotic symptoms, apathy, depression, and sleep disturbances. Agitation has been reported to be experienced by 60%of patients with mild cognitive impairment and 76%of patients with Alzheimer's disease. OBJECTIVE: We aimed to assess the impact of agitation in patients with dementia on healthcare resource utilization (HCRU) and healthcare costs. METHODS: This was a retrospective analysis of physician-reported patient data from a point-in-time survey. Patients included were aged≥50 years, with early cognitive impairment or dementia. Agitated and non-agitated patients were compared. Regression analyses assessed the relationship of agitation score (calculated from number/severity of agitation symptoms) with outcomes, with covariates including age and Mini-Mental State Examination score. Sensitivity analyses compared patients with 0 and≥2 agitation symptoms following propensity score matching on the base-case covariates. RESULTS: Data were included for 1,349 patients (agitated, n = 693; non-agitated, n = 656). Based on regression analyses, agitation score was correlated with proportion of patients with professional caregivers (p < 0.01), institutionalized (p < 0.01), hospitalized in a psychiatric ward (p < 0.05), and receiving an antipsychotic/antidepressant (both p < 0.001); number of consultations with a healthcare professional (HCP), psychiatrist, or psycho-geriatrician; number and cost of hospitalizations (p < 0.01); cost of HCP consultations (p < 0.001); and total direct healthcare costs (p < 0.001). Sensitivity analyses generally supported the base-case analysis. CONCLUSION: Agitation in dementia is associated with increased HCRU and healthcare costs. Effective therapies are needed to address agitation in dementia, with the potential to alleviate patient impact, HCRU, and healthcare costs.

Distress Associated with Dementia-Related Psychosis and Agitation in Relation to Healthcare Utilization and Costs.

OBJECTIVES: Explore 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/PARTICIPANTS: Retrospective 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. MEASUREMENTS: BPSD 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. RESULTS: Fifty-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). CONCLUSIONS: A 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.

Hyperactive performance monitoring as a transdiagnostic marker: Results from health anxiety in comparison to obsessive-compulsive disorder.

Hyperactive error-related brain activity has been found in individuals with obsessive-compulsive disorder (OCD), generalized and social anxiety as well as depression and has been proposed as a transdiagnostic marker. The specific phenotype to which it is related is still debated and anxious apprehension, threat sensitivity and checking have been proposed as promising candidates. To validate the idea that hyperactive performance monitoring is shared by anxiety and anxiety-related disorders and to refine our knowledge about its specificity, data from further anxiety and anxiety-related disorders are required. We examined performance monitoring in 24 participants with health anxiety and 24 healthy participants. Further, we compared results to performance monitoring data from 24 patients with OCD taken from a previously published study (Riesel et al., 2014). The three groups were matched with regard to age, gender and level of education. The error-related and correct-related negativity (ERN, CRN) derived during a flanker task served as neural indicators of performance monitoring. Participants with health anxiety showed enhanced ERN amplitudes compared to healthy controls and did not differ from OCD patients in ERN. The Health anxiety and healthy control group did not differ in CRN amplitudes, while OCD patients showed enhanced CRN amplitudes. The results suggest that health anxiety is characterized by hyperactive error-monitoring that seems to represent a common information processing dysfunction in health anxiety and OCD. This validates the idea that hyperactive error-monitoring cuts across diagnoses and seems to be a transdiagnostic trait shared by individuals that are highly sensitive to the commission of errors.

Neuropsychiatric symptoms in dementia may predict caregiver burden: a Sicilian exploratory study.

BACKGROUND: Behavioural and psychological symptoms of dementia are very common. They represent a main cause of burden and distress in caregivers and can lead to early institutionalization of patients. We aimed to find the most specific behavioural and psychological symptoms of dementia that can strongly affect the caregivers' burden. METHODS: Twenty-seven patients and their caregivers were enrolled in this study. All of the patients were affected by Alzheimer's, vascular, or frontotemporal dementia and were evaluated with the Neuropsychiatric Inventory and Mini-Mental State Examination. Caregivers were administered the Caregiver Burden Inventory. RESULTS: Apathy, depression, anxiety, and agitation were the most common symptoms and were found in up to 90% of the patients. We detected strong correlations between patient neuropsychiatric symptoms, (i.e. irritability, hallucinations, aberrant motor behavioural, depression, and agitation) and Caregiver Burden Inventory scores. Multiple regression analysis found hallucinations, irritability, and depression to be significant predictors of caregiver burden. Moreover, the Neuropsychiatric Inventory score was more closely related to caregiver burden than the Mini-Mental State Examination score. CONCLUSION: Our results revealed that demented patients' behavioural problems are related to the level of caregiver burden and distress. Further investigations are needed to differentiate the present findings among dementia subtypes and to better evaluate the effect of caregivers' personal characteristics on their own burden.

Agitation in Alzheimer Disease as a Qualifying Condition for Medical Marijuana in the United States.

OBJECTIVE: To determine the extent to which states and localities include dementia as a qualifying condition for medical marijuana and how common this indication is. METHODS: The authors reviewed authorizing legislation and medical marijuana program websites and annual reports for the states and localities where medical marijuana is legal. RESULTS: Of the 24 states and localities where medical marijuana is legal, dementia is a qualifying condition in 10 (41.7%), primarily for agitation of Alzheimer disease. In the five states where information was available regarding qualifying conditions for certification, dementia was the indication for <0.5% of medical marijuana certifications. CONCLUSION: Dementia is somewhat commonly listed as a potential qualifying condition for medical marijuana. Currently, few applicants for medical marijuana list dementia as the reason for seeking certification. However, given increasingly open attitudes toward recreational and medical marijuana use, providers should be aware that dementia is a potential indication for licensing, despite lack of evidence for its efficacy.

Analgosedation: Improving Patient Outcomes in ICU Sedation and Pain Management.

Sedation practices in the critical care unit have been trending toward lighter sedation since the start of the new millennium, but patients continue to experience inadequate pain management and excessive sedation. This paper includes a brief examination of the problem of pain management in the ICU; trends in sedation practices, including light sedation and the daily interruption of sedation; and a literature review of analgosedation. While the analgosedation literature is relatively sparse, it offers a promising, patient-centered method for managing the triad of pain, agitation, and delirium, while reducing common complications associated with long-term ventilation. This paper concludes with a recommended method for analgosedation, the nursing implications, and a discussion of limitations and recommendations.

Assessment and management of agitation in psychiatry: Expert consensus.

BACKGROUND: Psychomotor agitation is associated with different psychiatric conditions and represents an important issue in psychiatry. Current recommendations on agitation in psychiatry are not univocal. Actually, an improper assessment and management may result in unnecessary coercive or sedative treatments. A thorough and balanced review plus an expert consensus can guide assessment and treatment decisions. METHODS: An expert task force iteratively developed consensus using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new, re-worded or re-rated items. RESULTS: Out of 2175 papers assessing psychomotor agitation, 124 were included in the review. Each component was assigned a level of evidence. Integrating the evidence and the experience of the task force members, a consensus was reached on 22 statements on this topic. CONCLUSIONS: Recommendations on the assessment of agitation emphasise the importance of identifying any possible medical cause. For its management, experts agreed in considering verbal de-escalation and environmental modification techniques as first choice, considering physical restraint as a last resort strategy. Regarding pharmacological treatment, the "ideal" medication should calm without over-sedate. Generally, oral or inhaled formulations should be preferred over i.m. routes in mildly agitated patients. Intravenous treatments should be avoided.

Effect of person-centred care on antipsychotic drug use in nursing homes (EPCentCare): study protocol for a cluster-randomised controlled trial.

BACKGROUND: The majority of nursing home residents with dementia experience behavioural and psychological symptoms like apathy, agitation, and anxiety. According to analyses of prescription prevalence in Germany, antipsychotic drugs are regularly prescribed as first-line treatment of neuropsychiatric symptoms in persons with dementia, although guidelines clearly prioritise non-pharmacological interventions. Frequently, antipsychotic drugs are prescribed for inappropriate reasons and for too long without regular reviewing. The use of antipsychotics is associated with adverse events like increased risk of falling, stroke, and mortality. The aim of the study is to investigate whether a person-centred care approach, successfully evaluated in nursing homes in the United Kingdom, can be implemented in German nursing homes and, in comparison with a control group, can result in a clinically relevant reduction of the proportion of residents with antipsychotic prescriptions. METHODS/DESIGN: The study is a cluster-randomised controlled trial comparing an intervention group (two-day initial training on person-centred care and ongoing training and support programme) with a control group. Both study groups will receive, as optimised usual care, a medication review by an experienced psychiatrist/geriatrician providing feedback to the prescribing physician. Overall, 36 nursing homes in East, North, and West Germany will be randomised. The primary outcome is the proportion of residents receiving at least one antipsychotic prescription (long-term medication) after 12 months of follow-up. Secondary outcomes are residents' quality of life, agitated behaviour, as well as safety parameters like falls and fall-related medical attention. A health economic evaluation and a process evaluation will be performed alongside the study. DISCUSSION: To improve care, a reduction of the current high prescription rate of antipsychotics in nursing homes by the intervention programme is expected. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02295462.

Clinical monitoring scales in acute brain injury: assessment of coma, pain, agitation, and delirium.

Serial clinical examination represents the most fundamental and basic form of neurological monitoring, and is often the first and only form of such monitoring in patients. Even in patients subjected to physiological monitoring using a range of technologies, the clinical examination remains an essential tool to follow neurological progress. Key aspects of the clinical examination have now been systematized into scoring schemes, and address consciousness, pain, agitation, and delirium (PAD). The Glasgow Coma Scale has been the traditional tool to measure consciousness, but the full outline of unresponsiveness (FOUR) score has recently been validated in a variety of settings, and at present, both represent clinically useful tools. Assessment of PAD in neurologically compromised patients present special challenges. For pain, the Numeric Rating Scale is the preferred initial approach, with either the Behavioral Pain Scale or the Critical Care Pain Observation Tool in subjects who are not able to respond. The Nociception Coma Scale-Revised may be useful in patients with severe disorders of consciousness. Conventional sedation scoring tools for critical care, such as the Richmond Area Sedation Scale (RASS) and Sedation-Agitation Scale (SAS) may provide reasonable tools in some neurocritical care patients. The use of sedative drugs and neuromuscular blockers may invalidate the use of some clinical examination tools in others. The use of sedation interruption to assess neurological status can result in physiological derangement in unstable patients (such as those with uncontrolled intracranial hypertension), and is not recommended.

Grouping of behavioural and psychological symptoms of dementia.

OBJECTIVE: A wide range of behavioural and psychological symptoms (BPSD) are common in dementia, and it has been suggested that groups of correlated symptoms should be studied together. Here, we describe the groups of BPSD that have been identified in the literature and how they have been used to study associations, burden, treatment and underlying biology. METHODS: The literature database PubMed was searched for articles that identified clusters or factors of BPSD or used previously defined symptom groups. RESULTS: Sixty-two studies were included. Generally, the following symptom groups were suggested: affective symptoms, including depression and anxiety; psychosis, including delusions and hallucinations; hyperactivity, including irritability and aggression; and euphoria. Symptoms that did not show consistent results include apathy, eating disturbances, night-time behaviour disturbances, disinhibition and aberrant motor behaviour. Symptom groups differed in their associations, treatment and biology. CONCLUSIONS: Studies investigating symptom groups show relatively consistent results. Studying symptom groups allows similar symptoms to be studied together, which might strengthen results and may point to differences in their aetiology and treatment. However, a large amount of the individual variability of the symptoms could not be explained by the factors, and authors should carefully address their research question and hypotheses to decide if symptoms should be studied in groups or individually. Clinicians need to consider each symptom in its own right and also to be aware of the interrelations between them when assessing patients and developing strategies for treatment.

Pain, agitation, delirium, and neuromuscular blockade: a review of basic pharmacology, assessment, and monitoring.

Agitation, pain, and delirium are focal points for targeted pharmacologic therapy in the intensive care unit. Understanding how to treat these essential entities necessitates fundamental understanding of the pharmacology of sedation, analgesia, and antipsychotics. Monitoring the effectiveness of these medications is crucial to optimize therapeutic outcomes and minimize untoward effects. Agents used in the management of agitation include drugs that target γ-aminobutyric acid A such as benzodiazepines and propofol and those with other targets such as dexmedetomidine and ketamine. Analgesia in the intensive care unit is controlled primarily using intravenous opioids, which differ on the basis of their potencies and pharmacokinetics. The management of delirium involves preventing its occurrence, removing potential causes, and pharmacotherapy with antipsychotics. Finally, the introduction of paralysis with the use neuromuscular blockers is often necessary in critically ill patients in various situations. In addition to understanding pharmacologic principles associated with the treatment of agitation, pain, and delirium, familiarization with the plethora of assessment tools used to guide therapy in these critically ill patients is mandated. This review focuses on the pharmacology of therapeutic agents used for sedation, analgesia, delirium, and neuromuscular blockade. Significant focus is given to the various assessment tools often used in practice today.

Are there sensitive time periods for dementia caregivers? The occurrence of behavioral and psychological symptoms in the early stages of dementia.

BACKGROUND: The behavioral and psychological symptoms associated with dementia (BPSD) can be burdensome to informal/family caregivers, negatively affecting mental health and expediting the institutionalization of patients. Because the dementia patient-caregiver relationship extends over long periods of time, it is useful to examine how BPSD impact caregiver depressive symptoms at varied stages of illness. The goal of this study was to assess the association of BPSD that occur during early stage dementia with subsequent caregiver depressive symptoms. METHODS: Patients were followed from the early stages of dementia every six months for up to 12 years or until death (n = 160). Caregiver symptoms were assessed on average 4.5 years following patient's early dementia behaviors. A generalized estimating equation (GEE) extension of the logistic regression model was used to determine the association between informal caregiver depressive symptoms and BPSD symptoms that occurred at the earliest stages dementia, including those persistent during the first year of dementia diagnosis. RESULTS: BPSD were common in early dementia. None of the individual symptoms observed during the first year of early stage dementia significantly impacted subsequent caregiver depressive symptoms. Only patient agitation/aggression was associated with subsequent caregiver depressive symptoms (OR = 1.76; 95% CI = 1.04-2.97) after controlling for concurrent BPSD, although not in fully adjusted models. CONCLUSIONS: Persistent agitation/aggression early in dementia diagnosis may be associated with subsequent depressive symptoms in caregivers. Future longitudinal analyses of the dementia caregiving relationship should continue to examine the negative impact of persistent agitation/aggression in the diagnosis of early stage dementia on caregivers.

Treating depression with antidepressants: drug-placebo efficacy debates limit broader considerations.

The core issue regarding antidepressants for many clinicians is whether they perform significantly better than placebos. However, this article suggests eight additional concerns beyond drug efficacy alone to consider regarding antidepressants including: (1) formulating only a one-dimensional, biological view of depression; (2) defining the client's role as passive in treatment; (3) economic corruption of the research and reporting; (4) false or misleading consumer advertising; (5) conflicting data that confuse practitioners and consumers alike; (6) over- and under-prescription of medications; (7) drug side-effects; and (8) harm to the environment. The enhanced effects of psychotherapy utilizing hypnosis offer a means of avoiding most, if not all, of the problems associated with the use of antidepressants as a primary form of treatment.

[Iatrogenic agitation in elderly patient: prevalence, aetiologies and management]. / Agitation iatrogène chez le sujet âgé : prévalence, causes et prise en charge.

Iatrogenic agitation is frequently drug-induced in the elderly. The management of the iatrogenic agitation is based on: a detailed analysis of the patient's medications, stopping non-essential drugs, prescribing drugs to the lowest and effective dose possible. This management of the iatrogenic agitation is also based on: adjustment of drugs according to renal function and limitation of polypharmacy. Special attention is necessary when prescribing treatments for patients with cognitive impairment.

Psychometric properties of the Treatment-Emergent Activation and Suicidality Assessment Profile (TEASAP) in youth with OCD.

This study evaluated the psychometric properties of the treatment-emergent activation and suicidality assessment profile (TEASAP) in a clinical sample of 56 youth aged 7-17 with obsessive-compulsive disorder (OCD) who participated in a double-blind randomized controlled trial. The 38-item TEASAP demonstrated good internal consistency for its total score (α=0.93) and adequate to good performance for its five subscale scores (α=0.65-0.92). One-week test-retest stability (N=18) was adequate (Intraclass correlation coefficient [ICC]=0.68-0.80) except for Self-Injury (ICC=0.46). Construct validity was supported by total and subscale TEASAP score relationships with related constructs, including irritability, hyperactivity, externalizing behaviors, manic symptoms, and suicidal ideation, and the absence of relationships with unrelated constructs. Predictive validity was established for the Disinhibition subscale through significant associations with subsequent activation events. Furthermore, TEASAP sensitivity to change in activation scores over time was supported by longitudinal associations of TEASAP scores with clinician ratings of activation over the course of treatment. Findings indicate that the TEASAP has acceptable psychometric properties in a clinical sample of youth with OCD and merits further study in larger samples for additional refinement of its measurement approaches.

[Assessment of the psychic sequelae of traumatisation]. / Begutachtung psychisch reaktiver Traumafolgen.

This article deals with the question why experts quite frequently arrive at totally opposite judgements in clinical psychotraumatological expert opinions. This often leads to intense controversially conducted arguments resulting in lengthy proceedings. The reasons for this will be presented for two cases taken from expert opinions issued for the "Soziales Entschädigungs- und Ausländerrecht" (Laws for Social Reparations and Foreigners). A brief synopsis on the legal background will be given and solutions suggested.

Rates of 5 common antidepressant side effects among new adult and adolescent cases of depression: a retrospective US claims study.

BACKGROUND: Antidepressants are the first-line treatment for depression, yet medication-related side effects may be associated with antidepressant discontinuation before reaching a period of exposure believed to result in effectiveness. There is a gap in knowledge of the prevalence of side effects across commonly prescribed antidepressants and the effect of the type of antidepressant on the likelihood of side effects in real-world clinical practice. OBJECTIVE: The aim of this study was to estimate and compare the prevalence of headaches, nausea or vomiting, agitation, sedation, and sexual dysfunction among patients diagnosed with depression who initiated monotherapy across different classes of antidepressants and to estimate the effect of the type of antidepressant on the likelihood of each of the 5 side effects. METHODS: A retrospective cohort of patients aged ≥13 who were newly diagnosed with depression and began antidepressant monotherapy was created using LifeLink managed care claims from 1998 to 2008. Antidepressant groups included selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), bupropion, phenylpiperazine, and tetracyclic antidepressants. Prevalence of headache, nausea or vomiting, agitation, sedation, and sexual dysfunction were compared across antidepressant groups. Propensity-adjusted Cox proportional hazards regression was used to estimate the likelihood of each of the 5 side effects for each antidepressant group compared with SSRIs, adjusted for demographic, clinical, and treatment characteristics. RESULTS: The study cohort included 40,017 patients (3617 adolescents, aged 13-18 years, and 36,400 adults, aged ≥19 years; mean age = 45 years; 67% female) with a new episode of depression who were initiated on antidepressant monotherapy within 30 days of diagnosis (SSRI [66%], bupropion [14%], SNRI [12%], other [8%]). The most common side effects were headache (up to 17/1000 person-months of therapy in adults and adolescents) and nausea (up to 7.2/1000 in adults, 9.3/1000 in adolescents). Relative to adults receiving SSRIs, adults receiving SNRIs had a higher risk of nausea (hazard ratio [HR] = 1.26; 95%CI,1.05-1.51). Adults (HR = 0.78; 95% CI, 0.62-0.96) and adolescents (HR = 0.43; 95% CI, 0.21-0.87) taking bupropion were less likely to experience headaches compared with adults and adolescents, respectively, taking an SSRI. Adolescents receiving a tetracyclic were more likely to experience headaches than adolescents receiving an SSRI (HR = 3.16; 95%CI, 1.13-8.84). CONCLUSIONS: Prevalence and risk of the 5 side effects varied across types of antidepressants for both adults and adolescents. Results from this study were consistent with prior clinical trials, suggesting that variation in side effect profiles exists in a more generalized managed care population.

Agitation in the inpatient psychiatric setting: a review of clinical presentation, burden, and treatment.

Agitation among psychiatric inpatients (particularly those diagnosed with schizophrenia or bipolar disorder) is common and, unless recognized early and managed effectively, can rapidly escalate to potentially dangerous behaviors, including physical violence. Inpatient aggression and violence have substantial adverse psychological and physical consequences for both patients and providers, and they are costly to the healthcare system. In contrast to the commonly held view that inpatient violence occurs without warning or can be predicted by "static" risk factors, such as patient demographics or clinical characteristics, research indicates that violence is usually preceded by observable behaviors, especially non-violent agitation. When agitation is recognized, staff should employ nonpharmacological de-escalation strategies and, if the behavior continues, offer pharmacological treatment to calm patients rapidly. Given the poor therapeutic efficacy and potential for adverse events associated with physical restraint and seclusion, and the potential adverse sequelae of involuntary drug treatment, these interventions should be considered last resorts. Pharmacological agents used to treat agitation include benzodiazepines and first- and second-generation antipsychotic drugs. Although no currently available agent is ideal, recommendations for selecting among them are provided. There remains an unmet need for a non-invasive and rapidly acting agent that effectively calms without excessively sedating patients, addresses the patient's underlying psychiatric symptoms, and is reasonably safe and tolerable. A treatment with these characteristics could substantially reduce the clinical and economic burden of agitation in the inpatient psychiatric setting.