Risperidone in the treatment of psychosis of Alzheimer disease: Results from a prospective clinical trial
ABSTRACT The objective of this study was to evaluate efficacy and safety of low-dose risperidone for treating psychosis of Alzheimer disease (AD).
The authors conducted a randomized, eight-week, double-blind, placebo-controlled, multicenter trial involving nursing home residents diagnosed with AD and psychosis. Four hundred seventy-three patients were randomly assigned to placebo (N = 238) or 1.0 to 1.5 mg risperidone per day (N = 235). Coprimary efficacy end points were: changes in scores on the Behavioral pathology in Alzheimer's Disease (BEHAVE-AD) Psychosis subscale and Clinical Global Impression of Change (CGI-C). Protocol-specified subgroup analyses were performed by demographics and dementia severity.
Efficacy analysis included 416 patients. Both groups improved significantly on the BEHAVE-AD Psychosis subscale and CGI-C with no significant difference between groups. In the subgroups analyses, a statistically significant treatment by Mini-Mental Status Examination (MMSE) interaction on the CGI-C (F([2,381]) = 3.90, p = 0.021) was observed with patients with more severe dementia (MMSE <10) showing significant differences at end point favoring risperidone treatment (chi(2) () = 5.11, p = 0.024). Mean risperidone dose was 1.03 +/- 0.24 mg per day. All-cause discontinuation rates were 25% for both risperidone and placebo. Treatment-emergent adverse events occurred in 74% risperidone versus 64% placebo patients, with somnolence occurring significantly more frequently with risperidone (16.2% versus 4.6%). Nine (3.8%) risperidone- and six (2.5%) placebo patients died during or within 30 days after treatment.
This trial did not confirm earlier findings in this population.
- SourceAvailable from: Adam L Gordon[Show abstract] [Hide abstract]
ABSTRACT: UK care home residents are frail, dependent and multimorbid. General practitioners (GPs) provide their healthcare but there is evidence that existing provision fails to meet their needs. Comprehensive Geriatric Assessment (CGA) comprises comprehensive multidisciplinary assessment, goal setting and frequent review. This thesis considers a possible role for CGA in UK care homes through three research projects. The Care Home Literature Review (CHoLiR) was a systematic mapping review of randomized controlled trials (RCTs) in care homes. It found no evidence supporting CGA as a whole but described some CGA components supported by RCTs: advanced care planning; interventions to reduce prescribing; staff education around dementia and end-of-life; calcium/vitamin D and alendronate in preventing fractures and osteoporosis; vaccination/neuraminidase inhibitors in preventing influenza; functional incidental and bladder training for incontinence; and risperidone/olanzapine for agitation. The Care Home Outcome Study (CHOS) was a longitudinal cohort study recording dependency, cognition, behaviour, diagnoses, prescribing, nutrition and healthcare resource use in 227 residents across 11 care homes over six months. It reported high levels of dependency, cognitive impairment, malnutrition, multimorbidity and frequent behavioural disturbance. Polypharmacy and prescribing errors were common. Variability between homes and individuals was significant for most baseline and outcome measures. Staff Interviews in Care Homes (STICH) was a qualitative interview study of 32 staff working with care homes including: GPs; care home managers and nurses; NHS community nurses and specialist practitioners. It described care defined by discontinuity and lack-of-anticipation; driven by communication failure, inadequate training and expertise in frail older patients, and arbitrary boundaries between care homes and the NHS which interfered with care. Using the findings of these studies, the author proposes a model of care which is multidisciplinary, guided by comprehensive assessment, reinforced by frequent review and delivered by experts in the care of frail older patients: CGA has a role in UK care homes.02/2012, Degree: PhD, Supervisor: John RF Gladman
- [Show abstract] [Hide abstract]
ABSTRACT: A wide variety of atypical antipsychotic drugs (risperidone, olanzapine, quetiapine, aripiprazole, ziprasidone and clozapine) are widely used in the management of neuropsychiatric symptoms, which are commonly seen in dementia, but results from randomised controlled trials (RCTs) on the efficacy and safety of these agents are conflicting. We aimed to quantify the efficacy and safety of atypical antipsychotic drugs on neuropsychiatric symptoms in dementia patients. PubMed, EMBASE, the Cochrane Controlled Trials Register and the Cochrane Database of Systematic Reviews for reports published before August 2014 were searched for eligible randomized controlled trials of atypical antipsychotic drugs therapy in patients with psychotic symptoms of dementia. Two reviewers independently assessed the quality of the trials and extracted information. Overall, 23 relevant RCTs with 5,819 participants were identified. This meta-analysis demonstrated a significant efficacy of atypical antipsychotics on psychiatric symptoms and cognitive functions compared to placebo. In the meta-analysis, the weighted mean differences (WMDs) in change scores for psychiatric symptoms were in favor of aripiprazole (-4.4, 95% confidence interval (CI) - 7.04 to -1.77) and risperidone (-1.48, 95% CI -2.35 to -0.61) compared to placebo. In cognitive effects, WMDs in change scores for the Clinical Global Impression-Change (CGI-C) were in favor of aripiprazole, risperidone, olanzapine and quetiapine which ranged from a -0.30 points mean difference (95% CI:-0.59 to -0.01) in the aripiprazole trials to -0.43 (95% CI:-0.62 to -0.25) in the risperidone group. Patients receiving atypical antipsychotics showed no difference in risk for injuries or falls (P > 0.05), significantly higher risks (P < 0.05) for somnolence, urinary tract infection, edema and abnormal gait. However, there was no significant evidence for death reported. Aripiprazole and risperidone are able to improve psychiatric symptoms and slow decline in cognition function at average 12 weeks in patients with neuropsychiatric symptoms of dementia. However, high adverse events may offset the efficacy of atypical antipsychotics in dementia.Alzheimer's Research and Therapy 12/2015; 7(1). DOI:10.1186/s13195-015-0102-9 · 3.50 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The benefits and harms of antipsychotic medication (APM) use in nursing home residents need to be examined because, although commonly used, APMs are considered an off-label use by the Food and Drug Administration for residents with dementia and behavioral problems. The objective of this study was to provide a realist literature review, summarizing original research studies on the clinical effects of conventional and atypical APM use in nursing home residents. Searches of multiple databases identified 424 potentially relevant research articles, of which 25 met the inclusion criteria. Antipsychotic medication use in nursing home residents was found to have variable efficacy when used off-label with an increased risk of many adverse events, including mortality, hip fractures, thrombotic events, cardiovascular events and hospitalizations. Findings suggested certain APM dosing regimens (e.g. fixed-dose) and shorter duration of use might have fewer adverse events. Non-pharmacological interventions should still be considered the first-line treatment option for nursing home residents with dementia related behavioral disturbances, as more studies are needed to establish safer criteria for APM use in nursing homes residents. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.Health Policy 02/2015; 119(6). DOI:10.1016/j.healthpol.2015.02.014 · 1.73 Impact Factor