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Query: UMLS:C0085631 (agitation)
 12,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Agitation occurs commonly in patients with dementia. Before symptomatic pharmacotherapy is undertaken, it is imperative to perform a sequence of evaluations and interventions to establish whether simpler and safer, nonpharmacologic approaches will be beneficial. When psychotropic medications are used they should be used judiciously, in the lowest effective doses and for the shortest period of time necessary. Ineffective medications should be stopped, and even effective medications should be empirically tapered in most patients to learn whether treatment is still necessary. Antipsychotics probably show the greatest benefit for agitation associated with psychotic features; they have less demonstrated efficacy for agitation not associated with psychotic features. The side effects of typical agents are legion; data are pending regarding atypical agents. The available evidence regarding nonneuroleptic medications ranges from case reports to well-designed, double-blind, placebo-controlled, randomized, parallel group studies. Literature exists describing the use of anticonvulsants, anxiolytics, serotonergic antidepressants, and other agents to manage agitation. Carbamazepine and divalproex sodium (valproate) have demonstrated efficacy in uncontrolled studies, whereas the use of carbamazepine has produced negative results in one small controlled study and positive results in two larger controlled studies. Buspirone has shown benefit in some open trials. Encouraging early findings have been reported for trazodone, including from one controlled trial. Varying results have been obtained using selective serotonin reuptake inhibitors, but with consistently encouraging anecdotes. In the aggregate, the evidence suggests but does not prove that alternatives to traditional antipsychotics exist. Again, none of these agents has yet been approved for this purpose by the FDA. As more studies become available we will have a better idea about which classes of agents are most efficacious. It is likely that there may be a role for "rational" polypharmacy in the management of this distressing complication of dementia. However, no studies that we know of address combination therapy, so the clinician must contemplate this option on a case-by-case basis. Clinical trials data are pending from studies with divalproex sodium, carbamazepine, haloperidol versus trazodone versus placebo, risperidone, olanzapine, quetiapine, donepezil, xanomeline, tacrine, buspirone, and sertraline, at the very least. These data will undoubtedly have a major impact on how we care for our patients and lead to revisions of current practice guidelines.
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PMID:Treatment of agitation in dementia. 952 May 29

The authors describe a series of 22 patients with dementia and behavioral disturbances, including agitation, aggression, delusions, and hallucinations, who were treated with risperidone. Risperidone, in low doses, was well tolerated; 50% of patients experienced significant improvement, although 50% experienced some extrapyramidal symptoms.
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PMID:Risperidone for the treatment of behavioral disturbances in dementia: a case series. 960 13

Risperidone has proven efficacy with reduced likelihood of causing extrapyramidal symptoms in the treatment of schizophrenia. Initial work suggests its utility in the management of aggression and self injury in patients with mental retardation. The use of risperidone in eight adult patients with moderate to profound mental retardation is described. Risperidone in these individuals was associated with significant reduction in aggression and self injurious behavior. Side effects were primarily those of sedation and restlessness. These cases illustrate the possible utility of risperidone in the treatment of aggression and self injury in adult patients with moderate to profound mental retardation.
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PMID:Risperidone for aggression and self-injurious behavior in adults with mental retardation. 965 34

The authors retrospectively assessed the effectiveness and side effects of risperidone used to treat behavioral disturbances in elderly outpatients with dementia. In 41 patients treated with risperidone 1.8 +/- 1.4 mg/day, there was complete suppression of the target symptom in 15%, partial response in 41%, and no response in 44%. Risperidone appeared equally effective in treating agitation and psychosis. New or worsening extrapyramidal side effects (EPS) occurred in 32%, associated with longer duration of treatment and possibly with concomitant use of serotonergic anti-depressants. Risperidone was a useful adjunct in the treatment of agitation and psychosis in outpatients with dementia but was limited by EPS in about one-third of patients.
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PMID:Risperidone treatment of behavioral disturbances in outpatients with dementia. 1044 9

Currently available research on the use of risperidone to manage agitation in patients with dementia is discussed. Dementia affects up to 70% of nursing-home patients, and more than 90% of them exhibit aggressive or agitated behavior or severe depression. Agitation includes combativeness, hyperactivity, disinhibition, wandering, and restlessness. Environmental interventions are preferred for mild symptoms; medications are the treatment of choice for severe manifestations. Traditional neuroleptics have been the mainstay of treatment for agitated behavior in persons with dementia, but these agents have limited efficacy and are associated with high rates of adverse effects, including worsening of already poor cognitive functioning. Although the literature on the use of risperidone in elderly patients with dementia consists largely of uncontrolled trials, case reports, and chart reviews, it appears that this agent is effective for managing agitation in this population and does so with a low frequency of extrapyramidal symptoms (EPS). Risperidone may also be useful for treating acute agitation in patients with a high risk of EPS and for long-term treatment of "sundowning" (agitation and confusion starting in the late afternoon and worsening at night). A low initial dosage that is gradually adjusted upward is recommended. Risperidone appears effective in controlling agitation in patients with dementia and has a relatively benign adverse-effect profile, but more clinical trials are needed to elucidate its role for this indication.
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PMID:Risperidone for control of agitation in dementia patients. 1084 May 27

The importance of behavioural and psychological symptoms in dementia (BPSD) is increasingly being recognised. Symptoms such as verbal and physical aggression, agitation, sleep disturbances and wandering are common, cause great distress to caregivers and are likely to lead to institutionalisation of patients. At present, these symptoms are also more amenable to treatment compared with the progressive intellectual decline caused by dementing illnesses. The care of individuals with BPSD involves a broad range of psychosocial treatments for the patient and his or her family. If pharmacotherapy is deemed necessary to manage BPSD, a careful balance must be struck between the benefits of symptom control and the inherent risks associated with most psychotropic agents in the elderly. Elderly patients in general, and patients with dementia in particular, are more sensitive to medication adverse effects, including anticholinergic effects, orthostatic hypotension, sedation, parkinsonism, tardive dyskinesia and cognitive impairment than younger patients with dementia or individuals without dementia. To date, treatment of symptoms of aggression and psychosis has relied on the empirical use of antidepressants, anxiolytics, typical antipsychotics (neuroleptics) and other agents. Treatment-limiting adverse effects are frequently reported with all of these agents. However, it is the typical antipsychotics and the atypical antipsychotic clozapine that are associated with the greatest risk of adverse effects in the elderly. The present review highlights the issues that limit the use of older psychotropic agents in the elderly, and presents an assessment of the available evidence concerning the efficacy, safety and tolerability of the atypical antipsychotic risperidone, in the treatment of BPSD in elderly patients with dementia. The extensive clinical development programme for risperidone has shown the drug to be effective and well tolerated in many fragile patients. As a result of its efficacy and safety profile, risperidone can be used for the treatment of behavioural and psychological symptoms in patients with dementia. Risperidone therefore represents a significant addition to the armamentarium for BPSD. While efforts continue in the development of treatment for the cognitive decline associated with dementia, treatment is now available for the noncognitive symptoms. By treating the latter, risperidone has the potential to be of substantial benefit to patients with dementia, their carers and the costs of healthcare.
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PMID:A risk-benefit assessment of risperidone for the treatment of behavioural and psychological symptoms in dementia. 1100 2

Risperidone is a potent antagonist of both dopamine (D2) and serotonin (5-HT2) receptors, demonstrating improvement of both positive and negative symptoms and a lower propensity for inducing extrapyramidal symptoms (EPS) than typical neuroleptics. Its most common side-effects, found in the Canadian multi-centre trial (Chouinard et al., 1993), were agitation, anxiety, insomnia, EPS, headache and nausea, in order of frequency. With regard to endocrine effects, risperidone causes an increase in prolactin levels similar to that of other neuroleptics (Claus et al., 1992). In open clinical trials (De Cuyper, 1991), the overall incidence of risperidone-induced endocrine side-effects was quite low: 2.9 % for amenorrhoea and 1-2% for galactorrhoea. However, it is assumed that the incidence can vary depending upon the characteristics of patients and the drug regimen, i.e. dosage and titration schedule. In our experience, hyperolactinaemia is likely to occur when prescribing risperidone to female or first-onset psychotic patients: we are reporting 5 cases of risperidone-induced hyperprolactinaemia with these characteristics.
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PMID:Hyperprolactinaemia induced by risperidone. 1128 51

Risperidone offers physicians the unique combination of extensive, published clinical experience and a good safety profile for treating patients with dementia who have symptoms of aggression, agitation, and psychosis. Numerous open-label and, more recently, placebo-controlled trials have documented the efficacy of risperidone in the management of behavioral and psychological symptoms of dementia. These trials also show that risperidone is better tolerated than conventional neuroleptic agents. Comparatively, patients treated with risperidone experience substantially fewer side effects, including extrapyramidal symptoms, cognitive toxicity, and tardive dyskinesia.
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PMID:Risperidone for the treatment of behavioral and psychological symptoms of dementia. 1158 86

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.
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PMID: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. 1592 6

The objectives of this retrospective, naturalistic study were to provide preliminary data on the effects of 6 months treatment with risperidone, olanzapine and quetiapine on behavioral disturbances, within a sample of outpatients with mild to moderate Alzheimer's disease, and on predictors of response. Between July 2005 and December 2005, data were collected from 58 consecutive outpatients with a DSM-IV-TR diagnosis of Alzheimer's disease with behavioral disturbances, who received a 6-month treatment with risperidone, olanzapine or quetiapine. Primary outcome measures were Neuropsychiatric Inventory (NPI) total score and its items forming the basic core of behavioral disturbances in Alzheimer's disease: delusions, hallucinations and agitation/aggressiveness. Secondary outcome measures were Mini-Mental State Examination (MMSE), Activities of Daily Living, Instrumental Activities of Daily Living and Clinical Insight Rating scale. Correlations between baseline MMSE score and improvements in behavioral disturbances were investigated. At 6 months mean NPI total score had fallen 43.5% in the risperidone group, 45.6% in the olanzapine group and 33.3% in the quetiapine group, with no significant between-group differences. Global cognitive function showed no significant change from baseline to end-point. Incidence of adverse events was low. A significant correlation was found between MMSE score and NPI total score and NPI item agitation decreases. Risperidone, olanzapine and quetiapine produced significant improvements in behavioral disturbances and were well tolerated. No significant differences emerged among treatments. The preliminary results also suggest that baseline cognitive function might influence treatment response.
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PMID:Risperidone, olanzapine and quetiapine in the treatment of behavioral and psychological symptoms in patients with Alzheimer's disease: preliminary findings from a naturalistic, retrospective study. 1808 22


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