Lavender oil as a treatment for agitated behaviour in severe dementia: a placebo controlled study

OBJECTIVE: To determine whether aromatherapy with lavender oil is effective in the treatment of agitated behaviour in patients with severe dementia. DESIGN: A placebo controlled trial with blinded observer rater. SETTING: A long-stay psychogeriatric ward. PATIENTS: Fifteen patients meeting ICD-10 diagnostic criteria for severe dementia and suffering from agitated behaviour defined as a minimum score of three points on the Pittsburgh Agitation Scale (PAS). INTERVENTION: A 2% lavender oil aromatherapy stream was administered on the ward for a two hour period alternated with placebo (water) every other day for a total of ten treatment sessions. ASSESSMENTS: For each subject 10 total PAS scores were obtained. Five during treatment and five during placebo periods. RESULTS: Nine patients (60%) showed an improvement, five (33%) showed no change and one patient (7%) showed a worsening of agitated behaviour during aromatherapy compared with placebo. A comparison of the group median PAS scores during aromatherapy showed a significant improvement in agitated behaviour during aromatherapy compared with placebo (median PAS scores 3 c.f. 4; Wilcoxon Signed-Ranks test p = 0.016 (one-tailed)). CONCLUSIONS: Lavender oil administered in an aroma stream shows modest efficacy in the treatment of agitated behaviour in patients with severe dementia.     

A 3-month, randomized, placebo-controlled, neuroleptic discontinuation study in 100 people with dementia: the neuropsychiatric inventory median cutoff is a predictor of clinical outcome

BACKGROUND: Although few placebo-controlled neuroleptic discontinuation studies have been conducted in people with dementia, such studies are essential to inform key clinical decisions. METHOD: A 3-month, double-blind, placebo-controlled, neuroleptic discontinuation study (June 2000 to June 2002) was completed in 100 care-facility residents with probable or possible Alzheimer's disease (according to National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association criteria) who had no severe behavioral disturbances and had been taking neuroleptics for longer than 3 months. The Neuropsychiatric Inventory (NPI) was used to measure changes in behavioral and psychiatric symptoms. Quality of life was evaluated using Dementia Care Mapping. RESULTS: Eighty-two patients completed the 1-month assessment (36 placebo, 46 active). The number of participants withdrawing overall (N = 14 [30%] placebo, N = 14 [26%] active treatment) and because of exacerbation of behavioral symptoms (N = 6 [13%] placebo, N = 5 [9%] active treatment) was similar in the neuroleptic- and placebo-treated patients. As hypothesized, patients with baseline NPI scores at or below the median (< or = 14) had a particularly good outcome, with a significantly greater reduction of agitation in the patients receiving placebo (Mann-Whitney U test, z = 2.4, p =.018), while patients with higher baseline NPI scores were significantly more likely to develop marked behavioral problems if discontinued from neuroleptics (chi(2) = 6.8, p =.009). There was no overall difference in the change of quality of life parameters between groups. DISCUSSION: A standardized evaluation with an instrument such as the NPI may be a clinical indicator of which people with dementia are likely to benefit from discontinuation of neuroleptic treatment.     

Opioid treatment for agitation in patients with advanced dementia

BACKGROUND: Some patients with advanced dementia cannot convey the experience of pain verbally and may react to pain with aggressive and agitated behaviors. We hypothesized that unrecognized pain could contribute to agitation and that low dose opioid therapy might reduce agitation by reducing pain. We therefore attempted to determine the effect of opioids on agitation in demented patients. METHODS: We administered placebo for 4 weeks and a long-acting opioid for another 4 weeks to nursing home patients with advanced dementia and severe agitation despite treatment with psychotropic drugs. Patients and study nurses did not know if the medication administered was placebo or opioid. We measured the Cohen-Mansfield Agitation Inventory (CMAI) score at baseline and every two weeks. RESULTS: Among 47 patients who entered the study, 25 completed the two phases. The median age for the 25 patients was 85.5 years. Analyses of the data of these 25 patients and of the patients <85 years-old showed no significant differences in agitation level between the placebo and opioid phases. However, among the 13 patients who completed the study and were > or =85 years old, the agitation level at the end of the opioid phase was significantly lower than at the end of the placebo phase (mean change in CMAI score: -6.4; 95% confidence interval (CI): -10.96, -1.8). The decrease in agitation in the patients > or =85 years old persisted after adjusting for sedation. The results remained unchanged when we expanded the analyses to include four > or =85 patients who dropped out of the study after the second week of the opioid phase. CONCLUSION: Low dose, long-acting opioids can lessen agitation that is difficult to control in very old (> or =85) patients with advanced dementia.     

Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind,randomised, placebo controlled trial

OBJECTIVE: To assess the efficacy and safety of Melissa officinalis extract using a fixed dose (60 drops/day) in patients with mild to moderate Alzheimer's disease. DESIGN: A four month, parallel group, placebo controlled trial undertaken in three centres in Tehran, Iran. METHODS: Patients with mild to moderate Alzheimer's disease aged between 65 and 80 years (n = 42; 18 women, 24 men) with a score of >or= 12 on the cognitive subscale of Alzheimer's disease assessment scale (ADAS-cog) and 相似文献   

Quetiapine to treat agitation in dementia: a randomized, double-blind, placebo-controlled study

In this 10-week, double-blind, fixed-dose study, elderly institutionalized patients with dementia and agitation were randomized (3:3:2) to quetiapine 200mg/day, 100mg/day, or placebo. The primary endpoint was change in Positive and Negative Syndrome Scale (PANSS)-Excitement Component (EC) scores at endpoint, analysed using last observation carried forward (LOCF) and observed cases (OC) approaches. Other efficacy measures were the Clinical Global Impression of Change (CGI-C), and response rates (percentage with > or =40% reduction [PANSS-EC]; "much" or "very much improved" [CGI-C]), Neuropsychiatric Inventory-Nursing Home version (NPI-NH), and Cohen-Mansfield Agitation Inventory (CMAI). The key safety measure was incidence of adverse events; change in Mini-Mental State Examination (MMSE) was also assessed. Baseline characteristics of 333 participants (quetiapine 200mg/day, n=117; quetiapine 100mg/day, n=124; placebo, n=92) and completion rates (63-65%) were comparable among groups. Compared with placebo, quetiapine 200mg/day was associated with clinically greater improvements in PANSS-EC (LOCF, p=0.065; OC, p=0.014 [ANCOVA]), CGI-C (LOCF, p=0.017; OC, p=0.002 [ANOVA]), and CGI-C response rates (LOCF, p=0.002; OC, p<0.001 [Chi-square test]). Quetiapine 100mg/day did not differentiate from placebo on these measures. There were no between-group differences in NPI-NH or CMAI. Incidences of cerebrovascular adverse events, postural hypotension, and falls were similar among groups. MMSE did not change in any group. Mortality was numerically higher in the quetiapine groups; rates were not statistically different from placebo. The results of this study suggest that quetiapine 200mg/day was effective and well-tolerated for treating agitation associated with dementia. However, caution should be exercised given the concerns regarding increased mortality with atypical antipsychotics in this vulnerable patient population.     

Behavioral and psychological symptoms in patients with dementia as a target for pharmacotherapy with risperidone

OBJECTIVE: To examine the effect of risperidone on specific behavioral and psychological symptoms of dementia (BPSD). METHOD: We conducted a post hoc exploratory analysis of an integrated database from 3 randomized, controlled trials of risperidone versus placebo in treating 1150 nursing home residents with BPSD. Changes in scores were measured for items on the Cohen-Mansfield Agitation Inventory (CMAI) and Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). RESULTS: On the CMAI, risperidone was significantly more effective in treating hitting (p = .000), hurt self or other (p = .005), cursing or verbal aggression (p = .000), repetitive sentences or questions (p = .001), scratching (p = .041), general restlessness (p = .001), grabbing onto people (p = .028), constant request for attention (p = .041), pacing and aimless wandering (p = .013), and performing repetitious mannerisms (p = .045). On the BEHAVE-AD, risperidone was significantly more effective in treating physical threats and/or violence (p = .000), verbal outbursts (p = .000), other anxieties (p = .01), agitation (p = .000), tearfulness (p = .03), and nonparanoid delusions (p = .02). CONCLUSIONS: The items from the BEHAVE-AD and CMAI that were improved with risperidone included psychotic, agitated, and aggressive symptoms. These data suggest that risperidone is more effective than placebo in treating a variety of symptoms associated with dementia.     

A randomized placebo-controlled trial of risperidone for the treatment of aggression,agitation, and psychosis of dementia

BACKGROUND: This randomized, double-blind, placebo-controlled trial examined the efficacy and safety of risperidone in the treatment of aggression, agitation, and psychosis in elderly nursing-home patients with dementia. METHOD: Elderly patients with a DSM-IV diagnosis of dementia of the Alzheimer's type, vascular dementia, or a combination of the 2 (i.e., mixed dementia) and significant aggressive behaviors were randomized to receive, for a period of 12 weeks, a flexible dose of either placebo or risperidone solution up to a maximum of 2 mg/day. Outcome measures were the Cohen-Mansfield Agitation Inventory (CMAI), the Behavioral Pathology in Alzheimer's Disease (BEHAVE-AD) rating scale, and the Clinical Global Impression of Severity (CGI-S) and of Change (CGI-C) scales. RESULTS: A total of 345 patients were randomized to treatment with risperidone or placebo, and 337 patients received at least one dose of study drug. The trial was completed by 67% of patients in the placebo group and 73% of patients in the risperidone group. The mean +/- SE dose of risperidone was 0.95 +/- 0.03 mg/day. The primary endpoint of the study, the difference from baseline to endpoint in CMAI total aggression score, showed a significant reduction in aggressive behavior for risperidone versus placebo (p <.001). A similar improvement was also seen for the CMAI total non-aggression subscale (p <.002) and for the BEHAVE-AD total (p <.001) and psychotic symptoms subscale (p =.004). At endpoint, the CGI-S and the CGI-C scores indicated a significantly greater improvement with risperidone compared with placebo (p <.001). Overall, 94% and 92% of the risperidone and placebo groups, respectively, reported at least 1 adverse event. Somnolence and urinary tract infection were more common with risperidone treatment, whereas agitation was more common with placebo. There was no significant difference in the number of patients who reported extrapyramidal symptoms between the risperidone (23%) and placebo (16%) groups. CONCLUSION: Treatment with low-dose (mean = 0.95 mg/day) risperidone resulted in significant improvement in aggression, agitation, and psychosis associated with dementia.     

Prevalence and correlates of disruptive behavior in patients in Norwegian nursing homes

BACKGROUND: Although Behavioral and Psychological Symptoms of Dementia (BPSD) increase with increasing dementia severity, and institutionalization of an individual with dementia is often caused by behavioral symptoms, relatively few studies have explored the prevalence of BPSD in nursing homes. OBJECTIVE: To study the prevalence and correlates of agitation in residents with dementia, in Norwegian nursing homes. METHODS: This study has taken place in dementia wards in four Norwegian nursing homes. To measure agitation in residents with dementia we used the Cohen-Mansfield Agitation Inventory (CMAI), consisting of 29 agitation items. Dementia stage was measured by Functional Assessment Staging (FAST). RESULTS: Two hundred and eleven patients (71% female) were included in the study: mean (SD) age 85.5 (8.4), FAST 4.7 (2.1), CMAI total sumscore 39.5 (12.6). Dementia was present in 167 (79%) subjects. Among those with dementia, weekly occurrence of at least one CMAI item (i.e. a score of 3 or higher) occurred in 75.4% (95% CI 68.4-81.4). Six of the items occurred at least weekly in 20% of the residents with dementia, and 11 of the items, including physical aggression, occurred in less than 5% of the residents. Agitation was associated with more severe dementia (p = 0.001), but not with age and gender. CONCLUSION: Symptoms of agitation were common, but may nevertheless be lower compared to findings in other geographical areas. Further studies are warranted to test this hypothesis, and if confirmed, to explore possible causes for such differences.     

A pilot study on a home-based caregiver training program for improving caregiver self-efficacy and decreasing the behavioral problems of elders with dementia in Taiwan

OBJECTIVE: To investigate the effectiveness of a home-based caregiver training program for caregivers of elders with dementia and behavioral problems. METHODS: A prospective study was conducted in the communities of Northern Taiwan. Forty-eight patients with dementia and their family caregivers were included. The experimental group (n = 24) received a two-session in-home caregiver training program, and the control group (n = 24) received only written educational materials. The Chinese version of Cohen-Mansfield Agitation Inventory (CMAI), community form, was used to measure the behavioral problems of patients with dementia. The caregiver's self-efficacy, for managing the demented person's agitation, was measured by the Agitation Management Self-efficacy Scale (AMSS). The CMAI and AMSS were administered before (baseline), three weeks (1st post-test), and three months (2nd post-test) after the two-session training program. RESULTS: Except for the physically aggressive behavior subscale, the scores of physically non-aggressive behavior, verbally aggressive and non-aggressive behavior subscales as well as the overall CMAI decreased significantly and continuously in the experimental group and differed significantly from the changed scores from those in the control group (p < 0.05). Physically aggressive behaviors showed a decreasing trend for both groups. Scores of the Agitation Management Self-Efficacy Scale and its subscales increased significantly and continuously in the experimental group in comparison to those in the control group (p < 0.05). CONCLUSIONS: This home-based caregiver training program is helpful for decreasing problematic behaviors of elder people with dementia and it improves the caregiver's self-efficacy for managing problematic behaviors.     

Prevalence of neuropsychiatric symptoms in a large sample of Dutch nursing home patients with dementia

OBJECTIVE: To estimate the prevalence of neuropsychiatric symptoms of dementia patients in Dutch nursing homes. METHODS: Cross-sectional study in a large sample of 1322 demented patients living in 59 dementia special care units (SCUs) in The Netherlands. Symptoms were observed by licensed vocational nurses during regular care-giving in a 2-week observational period prior to assessment. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory- Nursing home version (NPI-NH; frequency X severity score >/= 4) and the Cohen-Mansfield Agitation Inventory (CMAI; symptoms occurring at least once a week). RESULTS: More than 80% of these patients suffered from at least one clinically significant symptom, as defined with the NPI-NH frequency X severity score >/= 4. Measured with the NPH-NH agitation/aggression, apathy and irritability were the most frequently observed behaviors, with prevalences of 30-35%. Using the CMAI, 85% of the patients showed at least one symptom of agitation, of which general restlessness was observed most frequently (44%). Other frequently observed symptoms with prevalence rates of 30% were cursing or verbal aggression, constant request for attention, negativism, repetitious sentences, mannerisms, pacing, and complaining. Physically aggressive symptoms such as hitting, kicking, biting occurred less often (less than 13%). CONCLUSIONS: Prevalence rates of neuropsychiatric symptoms in Dutch nursing home patients with dementia residing in SCUs are high, especially agitation and apathy. Insight into the prevalence rates of individual symptoms in patients with dementia has important practical consequences for the accurate planning of staff allotment and stresses the need for patient oriented care.     

Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: a multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses.

OBJECTIVE: To assess the efficacy and safety of aripiprazole for psychosis associated with Alzheimer dementia (AD). METHODS: In this double-blind, multicenter study, 487 institutionalized patients with psychosis associated with AD were randomized to placebo or aripiprazole, 2, 5 or 10 mg/day. Primary efficacy assessment was the mean change from baseline to week 10 on the Neuropsychiatric Inventory-Nursing Home (NPI-NH) version Psychosis Subscale score. Secondary measures included NPI-NH Total, Clinical Global Impression-Severity of Illness (CGI-S), Brief Psychiatric Rating Scale (BPRS) Core and Total, and the Cohen-Mansfield Agitation Inventory (CMAI) scores. RESULTS: Aripiprazole 10 mg/day showed significantly greater improvements (mean change [2 x SD]) than placebo on the NPI-NH Psychosis Subscale (-6.87 [8.6] versus -5.13 [10.0]; F = 6.29, df = 1, 422, p = 0.013 by analysis of covariance [ANCOVA]); CGI-S (-0.72 [1.8] versus -0.46 [1.6]; F = 4.68, df = 1, 419, p = 0.031 [ANCOVA]); BPRS Total (-7.12 [18.4] versus -4.17 [21.6]; F = 4.72, df = 1, 399, p = 0.030 [ANCOVA]); BPRS Core (-3.07 [6.9] versus -1.74 [7.8]; F = 7.30, df = 1, 407, p = 0.007 [ANCOVA]); CMAI (-10.96 [22.6] versus -6.64 [28.6]; F = 5.23, df = 1, 410, p = 0.023 [ANCOVA]), and NPI-NH Psychosis response rate (65 versus 50%; chi(2) = 5.52, df = 1, p = 0.019 [CMH]). Aripiprazole 5 mg/day showed significant improvements versus placebo on BPRS and CMAI scores. Aripiprazole 2 mg/day was not efficacious. Cerebrovascular adverse events were reported: aripiprazole 2 mg/day, N = 1; 5 mg/day, N = 2; 10 mg/day, N = 4; placebo, N = 0. No deaths in any group (aripiprazole 2 mg/day, 3%; 5 mg/day, 2%; 10 mg/day, 7%; placebo, 3%) were considered to be treatment-related. CONCLUSION: Aripiprazole 10 mg/day was efficacious and safe for psychosis associated with AD, significantly improving psychotic symptoms, agitation, and clinical global impression. However, clinicians should be aware of the safety considerations of atypical antipsychotic uses in this population.     

Efficacy of aromatherapy (Lavandula angustifolia) as an intervention for agitated behaviours in Chinese older persons with dementia: a cross-over randomized trial

BACKGROUND: Agitated behaviours among persons with dementia are distressing to both patients and their caregivers. As pharmacological interventions may be limited by their potentially adverse effects, the use of complementary therapies for treatment of agitation has become more popular and aromatherapy is the fastest growing one. OBJECTIVES: This study investigates the effectiveness of lavandula angustifolia (lavender) in treating agitated behaviours of demented people in Hong Kong. METHODS: It was a cross-over randomized trial. Seventy Chinese older adults with dementia were recruited; half were randomly assigned to the active group (lavender inhalation) for three weeks and then switched to control group (sunflower inhalation) for another three weeks; the other half did the opposite. Clinical response was evaluated using the Chinese versions of Cohen-Mansfield Agitation Inventory (CCMAI) and Neuropsychiatric Inventory (CNPI). RESULTS: The mean CCMAI total scores decreased from 24.68 to 17.77(t=10.79, df=69, p<0.001). The CNPI scores changed from 63.17 (SD=17.81) to 58.77 (SD=16.74) (t=14.59, df=69, p<0.001) after receiving Treatment A (Lavandula Angustifolia). There were no period and sequential effects noted. CONCLUSION: In summary, lavender is effective as an adjunctive therapy in alleviating agitated behaviours in Chinese patients with dementia. In a patient population particularly vulnerable to side effects of psychotropic medications, aromatherapy using lavender may offer an alternative option.     

Divalproex sodium in nursing home residents with possible or probable Alzheimer Disease complicated by agitation: a randomized, controlled trial.

OBJECTIVE: Three placebo-controlled clinical trials have suggested the benefit of valproate for treatment of agitation associated with dementia; one was used as the basis for this multicenter trial, conducted by the Alzheimer's Disease (AD) Cooperative Study. It addresses the efficacy, safety, and tolerability of divalproex sodium for the treatment of agitation associated with dementia. METHODS: This was a randomized, double-blind, placebo-controlled clinical trial in 153 nursing home residents with probable or possible AD complicated by agitation; 110 (72%) completed the trial. Participants were randomized to treatment with divalproex sodium at a target dose of 750 mg/day (N = 75) or placebo (N = 78) for 6 weeks. The primary outcome measure was change from baseline on the Brief Psychiatric Rating Scale (BPRS) Agitation factor. Secondary outcomes included total BPRS, Clinical Global Impression of Change, Cohen-Mansfield Agitation Inventory score, and measures of safety and tolerability. RESULTS: Compliance averaged 88%. Participants receiving divalproex achieved a mean dose of 800 mg/day. Change in mean BPRS Agitation factor scores did not differ between patients treated with divalproex and placebo, nor did secondary behavioral measures. Measures of safety and tolerability did not reveal clinically important drug/placebo differences. CONCLUSIONS: This multicenter trial showed no benefit of divalproex sodium for treatment for agitation in dementia at a mean dose of 800 mg/day over 6 weeks. The results do not support findings from previous trials indicating possible benefit.     

A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia.

OBJECTIVE: To compare effects of risperidone with placebo (efficacy and tolerability) and haloperidol (tolerability) for treating demented patients with aggression and other behavioral symptoms. METHODS: A 13-week double-blind study involving 344 patients with dementia randomly assigned to receive placebo or flexible doses (0.5 to 4 mg/d) of risperidone or haloperidol. Behavioral symptoms were assessed by the Behavior Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), the Cohen-Mansfield Agitation Inventory (CMAI), and the Clinical Global Impression (CGI) scale. Tolerability assessments included the Extrapyramidal Symptom Rating Scale, sedation levels, Functional Assessment Staging, Mini-Mental State Examination, and incidence of adverse events. RESULTS: The mean dose at endpoint was 1.1 mg/d of risperidone and 1.2 mg/d of haloperidol. Although not significant, a higher percentage of patients receiving risperidone than those receiving placebo showed clinical improvement (> or =30% reduction from baseline to endpoint in BEHAVE-AD total score) at endpoint and week 12. Reductions in the BEHAVE-AD total score were significantly greater with risperidone than with placebo at week 12. In a further analysis of aggression, the most dominant symptom in these patients, BEHAVE-AD and CMAI aggression cluster scores were significantly reduced compared with placebo at endpoint and week 12. CGI scores were also significantly reduced at endpoint and week 12. Severity of extrapyramidal symptoms with risperidone did not differ significantly from that of placebo and was less than that of haloperidol. A post hoc analysis showed significantly greater reductions in the BEHAVE-AD aggressiveness score with risperidone than haloperidol at week 12. CONCLUSION: Low-dose risperidone (mean 1.1 mg/d) was well tolerated and associated with reductions in the severity and frequency of behavioral symptoms, particularly aggression, in elderly patients with dementia.     

Actigraphic measurement of agitated behaviour in dementia

OBJECTIVES: This study examines the correlation between actigraphic measures and a validated assessment scale of agitated behaviour in dementia, the Cohen-Mansfield Agitation Inventory (CMAI). METHODS: A total of 110 patients were included. Patients either suffered from Alzheimer dementia (AD), mixed dementia (MXD), frontotemporal dementia (FTD) or diffuse Lewy body disease (DLB). All patients underwent actigraphic recordings for 48 h. CMAI was scored by professional caretakers, who were responsible for the patient during his or her actigraphic recording. RESULTS: Patients with high total CMAI scores (>or= 50) clearly had higher levels of activity during the day as measured by means of actigraphy than patients with low total CMAI scores (ANOVA, F=126.75, p<0.0001). Patients with low MMSE scores (<20) also had higher activity levels during the day than patients with higher MMSE scores (ANOVA, F= 85.74, p<0.0001). Correlations between ctigraphic data and CMAI total scores were moderate but highly significant. CONCLUSION: We conclude that actigraphy is a useful tool to examine agitated behaviour in dementia.     

A 1-year follow-up study of behavioral and psychological symptoms in dementia among people in care environments

BACKGROUND: Behavioral and psychological symptoms in dementia (BPSD) are common and distressing for patients and caregivers, but little is known about the natural history of these symptoms, particularly among patients in care facilities. This information is essential for informed clinical management. We report a 1-year follow-up study of the prevalence, incidence, and outcome of the 3 main BPSD (agitation, depression, and psychosis) in care facilities. METHOD: 136 elderly residents with dementia (29% living in social care facilities and 71% in nursing home care) were assessed longitudinally on 2 occasions a year apart using a range of standardized psychiatric schedules, including the Neuropsychiatric Inventory. RESULTS: The overall prevalence of BPSD was stable over the year (76% at baseline and 82% at follow-up). Subjects with subclinical symptoms at baseline were more likely to develop clinically significant BPSD during follow-up than those who were symptom free (83% vs. 52%; Mann-Whitney U test, z = 2.36, p = .01). Agitation was the most common individual syndrome (55%). Although overall BPSD were persistent, > or = 45% of dementia patients with any of the major syndromes experienced resolution, indicating the development of different BPSD in many residents. There was no evidence that residents taking neuroleptics were more likely to experience resolution of BPSD than neuroleptic-free residents. CONCLUSION: BPSD are highly frequent and persistent among residents of care facilities with dementia. This emphasizes the need for ongoing treatment trials. The pattern of resolution with the development of new symptoms indicates that short focused periods of treatment may be a more effective management approach. In addition, the potential value in treating patients with subclinical BPSD to prevent the development of full-blown syndromes needs to be investigated.     

Management of agitation, aggression, and psychosis associated with dementia: a pooled analysis including three randomized, placebo-controlled double-blind trials in nursing home residents treated with risperidone

This analysis used pooled data from three randomized, placebo-controlled trials that examined the efficacy and safety of risperidone for the treatment of agitation, aggression, and psychosis associated with dementia in elderly nursing home residents to assess the risk-benefit of the use of risperidone in this population.

The efficacy data (risperidone n = 722, placebo n = 428) were obtained from the Cohen-Mansfield agitation inventory (CMAI) and behavioral pathology in Alzheimer's disease (BEHAVE-AD) total and subscales. Additionally, clinical global impression (CGI) assessments were performed. Subgroup analyses were performed by type of dementia, severity of dementia, presence or absence of somnolence as an adverse event, and presence or absence of psychosis at baseline. Safety assessments included evaluation of treatment emergent adverse events, Extrapyramidal Symptom Rating Scale, ECG and vital signs, and Mini-Mental State Examination (MMSE). The mean dose of risperidone at end point was 1.0 mg/day (0.02 S.E.).

The observed mean change at end point was significantly higher for risperidone than for placebo on CMAI total score (−11.8 versus −6.4, respectively; p < 0.001), total aggression score (−5.0 versus −1.8, respectively; p < 0.001), BEHAVE-AD total score (−6.1 and −3.6, respectively; p < 0.001), and psychotic symptoms score (−2.1 and −1.3, respectively; p = 0.003). The main treatment effects of risperidone were similar in all subgroup analyses. Additionally, risperidone-treated patients scored significantly better than placebo-treated patients on the CGI scales at end point.

The incidence of treatment-emergent adverse events was comparable between risperidone (84.3%) and placebo (83.9%). More patients discontinued due to adverse events in the risperidone-treated group (17.2%) than in the placebo group (11.2%). Differences in adverse event incidences between placebo and risperidone were observed for extrapyramidal symptoms (EPS), mild somnolence and the less common cerebrovascular adverse events (CAE). Risperidone induced neither orthostatic, nor anticholinergic side effects nor falls nor cognitive decline.

Of all atypical antipsychotics, risperidone has the largest database of double-blind controlled trials to support its efficacy and safety in the treatment of agitation, aggression, and psychosis associated with dementia. At the recommended doses, risperidone displayed a favorable risk-benefit profile. Risperidone was well tolerated with respect to EPS, somnolence, and anticholinergic side effects in this elderly population. In view of the risk for CAEs, risperidone, should be targeted towards the treatment of those patients in whom psychotic and behavioral symptoms of dementia are prominent and associated with significant distress, functional impairment or danger to the patient.     

Components of behavioral pathology in dementia

OBJECTIVE: The purpose of this study was to examine the occurence of the noncognitive behavioral and psychological symptoms and signs of dementia in a geriatric chronic-care hospital and to separate agitated and affective components of behavioral pathology using factor analysis. METHODS: The frequency and severity of Alzheimer's disease, vascular dementia, mixed dementia and Lewy Body dementia was assessed in 145 consecutive residents of a chronic-care hospital. The presence of noncognitive behavioral symptoms was evaluated with the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD) and the Cohen-Mansfield Agitation Inventory (CMAI). A Factor analysis on the BEHAVE-AD subscores was performed to create symptom clusters. Analysis of covariance and post hoc tests were used to compare means of factor variables between different types of dementia. RESULTS: Statistical analysis showed a significant correlation between severity of dementia and BEHAVE-AD total score and between severity of dementia and CMAI total score. Factor analysis with Varimax rotation revealed the presence of three behavioral subsyndromes: agitation, affectivity and day/night disturbances. CONCLUSIONS: The finding of three factors of behavioral pathology in demented patients reflects the possibility that different etiological mechanisms could explain the expression of the symptoms and signs of psychosis in demented patients.     

Treatment of verbal agitation with a selective serotonin reuptake inhibitor

The objective of this study was to examine the safety and efficacy of paroxetine as an alternative to neuroleptic medications for the treatment of verbal agitation in demented patients. An open case series design was used, and the setting included two nursing homes and an outpatient geriatric clinic. Participants were eight consecutive nursing home residents and seven community-dwelling older adults diagnosed with dementia who exhibited verbal agitation in the form of repetitive questions or unwarranted request for attention. Patients received paroxetine orally in doses of 10 mg to 40 mg per day. The Cohen-Mansfield Agitation Inventory (CMAI) was used to rate the frequency of verbal agitation. A baseline score was obtained before starting paroxetine. Six scores were then obtained at 2-week intervals over a period of 3 months. All patients had reduction (2-4 points per item) in the CMAI scores at the end of the first month of treatment with paroxetine. Scores were further reduced (up to 5 points per item, 67%-71% reduction from baseline) in five patients at the end of the third month of treatment. Most patients tolerated paroxetine well. In this report, the use of paroxetine was associated with reduction in verbal agitation. This finding supports the possibility that verbal agitation in demented patients could be a manifestation of underlying depression.