Use of aripiprazole for psychosis and agitation in dementia

We report the case of an elderly woman with Alzheimer's disease, risk factors for vascular dementia, and atrium-ventricular blockade, who presented with severe agitation and psychosis. She was treated with aripiprazole and assessed with the Neuropsychiatric Inventory (NPI) over the course of 14 weeks. NPI scores showed a marked decrease in psychosis and agitation at week 4, and complete recovery at week 14, except for depression.     

Ziprasidone for dementia in elderly patients: case review

Treatment of elderly patients with dementia-related behavioral disturbances and depression-related psychosis poses a significant problem, considering patients' frailty and use of polypharmacy for comorbid medical disorders. This case series describes the use of ziprasidone, a novel atypical antipsychotic, in three frail, elderly patients admitted to the hospital for behavioral disturbances secondary to dementia-related illness after their current treatment failed to improve symptoms or produced intolerable side effects. At admission, none of the patients were taking medications contraindicated for use with ziprasidone. In each case, ziprasidone resolved symptoms of agitation, psychosis, depression, and cognitive impairment sufficiently to permit discharge on maintenance therapy to assisted-living facilities or nursing homes. No patient suffered syncope or postural hypotension during treatment with ziprasidone. Electrocardiograms taken on admission and after institution of ziprasidone disclosed minimal increases in the QTc interval or no change from baseline, and no patient had a QTc interval > 500 ms. No drug-drug interactions occurred. Similar results were observed in an additional 53 of 62 elderly patients (aged 64-92 years) admitted to our institution. This experience suggests that ziprasidone is a safe and effective treatment option in elderly individuals who require antipsychotic medication.     

Management of aggression, agitation, and psychosis in dementia: focus on atypical antipsychotics

The behavioral and psychological symptoms of dementia (BPSD), such as psychosis, agitation, or aggression have a considerable negative impact on the quality of life of both patients and their caregivers. Multiple studies have demonstrated that atypical antipsychotics are efficacious in the treatment of the aggressive and psychotic symptom clusters, and here we review their use in this indication. Because of the safety concerns associated with the use of atypical antipsychotics in this population, these drugs must be used judiciously. For patients with severe BPSD such as psychosis, agitation, or aggression, for whom there are few options, atypical antipsychotics, particularly risperidone and olanzapine, should be considered.     

Clozapine for treatment-resistant agitation in dementia

Few studies have examined the potential role of clozapine in treatment of agitation in dementia patients who have previously failed to respond to standard pharmacotherapy. We conducted a systematic chart review of all elderly patients admitted to our inpatient unit between 2001 and 2004. Of them, 16 dementia patients were treated with clozapine for treatment-resistant agitation, and their charts were blindly rated by 3 clinicians on the Clinical Global Impression (CGI) Scale, Brief Agitation Rating Scale (BARS), and the Cohen-Mansfield Agitation Inventory-Short Form (CMAI-SF). Overall, clozapine therapy seemed beneficial in treatment-resistant agitation in dementia patients.     

齐拉西酮注射液治疗儿童精神分裂症急性激越症状35例

目的探讨齐拉西酮注射液治疗儿童精神分裂症患者急性激越症状的临床效果及安全性。方法采用随机数字表法将符合《国际疾病分类(第10版)》(ICD-10)精神分裂症诊断标准的有急性激越症状的70例儿童患者分为实验组和对照组各35例,实验组给予齐拉西酮注射液,对照组给予氟哌啶醇注射液,疗程3天。于治疗前、治疗后2、12、24、48、72h分别采用阳性和阴性症状量表(PANSS)减分率、临床疗效总评量表(CGI)评定疗效,治疗结束时采用副反应量表(TESS)评定安全性。结果疗程结束时实验组和对照组PANSS评分减分率分别为46.92%、49.46%,临床好转率分别为77.14%、80.00%,两组疗效比较差异均无统计学意义(P0.05);实验组和对照组不良反应发生率分别为20.00%、37.14%,差异有统计学意义(P0.05)。结论齐拉西酮注射液对有急性激越症状的儿童精神分裂症患者的疗效与氟哌啶醇相当,不良反应发生率较低。     

Risperidone and falls in ambulatory nursing home residents with dementia and psychosis or agitation: secondary analysis of a double-blind, placebo-controlled trial.

OBJECTIVE: Authors evaluated the association between use/dosage of risperidone (RIS) and falls in a residential-care dementia population. METHODS: Authors performed secondary analysis of data from ambulatory patients in a randomized, double-blind, placebo-controlled, 12-week trial of three RIS dosages (0.5 mg/day, 1 mg/day, 2 mg/day). Outcomes included number of fallers, rate of falls, and time until the first fall after randomization. Additional analyses evaluated wandering as a potential moderating or mediating variable. RESULTS: The ambulatory sample included 537 subjects. Of those, 22.3% on placebo, 18.0% on RIS 0.5 mg/day, 12.7% on 1 mg/day, and 27.3% on 2 mg/day, respectively, fell during the trial. The difference between the RIS 1 mg/day group and placebo was significant, with a significantly lower hazard ratio in the RIS 1-mg/day group than placebo. Wandering was associated with an increased risk of falls. Among 205 patients with the highest levels of wandering at baseline, RIS 1 mg/day was associated with approximately a 70% reduction in risk for falls versus placebo condition. However, in those with the lowest levels of wandering at baseline, RIS 2 mg/day may have increased the risk of falls. CONCLUSIONS: Evaluating the benefits versus risks of risperidone in patients with dementia is complex and must consider multiple outcomes as a function of dose. At 1 mg/day, RIS was associated with decreased falls, especially in patients who exhibit wandering. However, at 2 mg/day, it may increase the risk of falls in ambulatory individuals with low levels of wandering.     

Citalopram for verbal agitation in patients with dementia

Various behaviors can be associated with dementing disorders. Management of these behaviors is often challenging to caregivers and clinicians. Verbal agitation such as talking constantly, screaming, and repeating phrases and noises is one of the most frequently encountered behaviors in the long-term care setting. We report two cases in which verbal agitation favorably responded to citalopram, a selective serotonin reuptake inhibitor. We also discuss some other factors possibly associated with this response. Nonetheless, citalopram appears to be an added option in the treatment of verbal agitation in demented patients.     

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.     

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.     

Nonpharmacological intervention for agitation in dementia: A systematic review and meta-analysis

Objective: The purpose of this study was to systematically review the literature regarding the effectiveness of nonpharmacological interventions for agitation in older adults with dementia.

Methods: Seven electronic databases (to 2004) were searched, and randomized clinical trials employing nonpharmacologic interventions for agitation in dementia published in English or Korean were selected. In addition, the reference lists from relevant review articles and all eligible studies were searched to identify other trials. Interventions were categorized into seven types: sensory intervention, social contact, activities, environmental modification, caregiver training, combination therapy, and behavioral therapy. Studies were abstracted, and data were pooled by intervention category.

Results: Fourteen studies (n = 586) were included. Sensory interventions were statistically significantly effective in reducing agitation (standardized mean difference: SMD ?1.07; 95% confidence interval (CI) ?1.76 to ?0.38, p = 0.002), while social contact (SMD ?0.19; CI ?0.71 to 0.33), activities (SMD ?0.20; CI ?0.71 to 0.31), environmental modification (weighted mean difference: WMD 1.90; CI ?2.82 to 6.62), caregiver training (SMD 0.21; CI ?0.15 to 0.57), combination therapy (WMD 1.85; CI ?1.78 to 5.48), and behavioral therapy interventions (SMD ?0.27; CI ?0.72 to 0.19) were not significantly effective in reducing agitation. These results were consistent among higher quality studies.

Conclusion: This systematic review indicated that among the seven types of nonpharmacological interventions available for agitation in older adults with dementia, only sensory interventions had efficacy in reducing agitation. More trials are needed to confirm this finding and future research should use more rigorous methods.     

Temporal patterns of agitation in dementia.

OBJECTIVE: This study investigated the temporal pattern of agitated behaviors in nursing home residents with dementia and compared it with temporal patterns of pleasure, interest in the environment, and sleep. METHODS: Trained research assistants recorded direct observations of agitation and affect by the Agitation Behavior Mapping Instrument and the Lawton's Modified Behavior Stream for 174 participants from 12 nursing homes. RESULTS: The temporal pattern found for total agitation showed a gradual increase from the morning until approximately 4 pm with a decrease thereafter. Only 26% of the sample showed a clear increase of their agitation in the later hours in comparison to the morning hours based on our criterion. Pleasure did not show a consistent pattern, whereas levels of interest peaked during lunch and dinner times. CONCLUSIONS: The results fit with a hypothesis of fatigue of daytime nursing staff members and disruption during shift change and may also be partially accounted for by resident fatigue. Although the literature supports the notion that there is a peak in overall agitation around 4 pm, the term "sundowning" is not supported and should be replaced. The phenomenon of increased levels of agitation during later hours characterizes only a minority of agitated nursing home residents, albeit the most highly agitated.     

A transcultural study of agitation in dementia

Agitation is one of the most troublesome behaviors in demented patients. It is etiologically heterogeneous and has varied associated behaviors. To explore the transcultural differences in the manifestation of agitation, we evaluated 50 consecutive Alzheimer's disease (AD) patients in three countries (Taiwan, Italy, and the United States) using the Neuropsychiatric Inventory (NPI) and the Mini-Mental State Examination (MMSE). In a focused analysis, only patients with composite NPI scores > 2 for agitation were selected, with similar levels of disease severity as measured by the MMSE, from the three groups (n = 15 per group) to evaluate culturally specific correlates of agitation. Agitated Taiwanese had significantly more hallucinations than either Italian or American patients. Agitated Italian patients had significantly more apathy than both Taiwanese and American patients. Cultural factors may influence the manifestation of agitation more than a common underlying neuropathology. Management strategies targeting unique behavioral instigators of agitation may be specific for different ethnic groups.