Risperidone in the Treatment of Psychosis of Alzheimer Disease: Results From a Prospective Clinical Trial

ArticleinAmerican Journal of Geriatric Psychiatry 14(3):280-91 · April 2006with59 Reads
DOI: 10.1097/01.JGP.0000194643.63245.8c · Source: PubMed
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) ([1]) = 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.
    • "Thirteen studies measured and reported the mean change in CGI-C from baseline to end point for intervention compared with placebo: one study on aripiprazole [15], three studies on olanzapine [17,19,21], five studies on quetiapine [19,22232425 and four studies on risperidone [17,19,27282930. CGI-C scores were all significant for these trials by meta-analysis in the available data. "
    [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.
    Full-text · Article · Dec 2015
    Lin TanLin TanLan TanLan TanHui-Fu WangHui-Fu Wang+1more author...[...]
    • "The median trial duration was 56 days (range = 1–90 days). A variety of outcome measures were reported in studies including composite measures of NPS (Barnes et al., 1982; Cantillon et al., 1996; Tariot et al., 1998; 2001; 2005; 2006; De Deyn et al., 1999; 2004; Katz et al., 1999; Street et al., 2000; Porsteinsson et al., 2001; Fontaine et al., 2003; Peskind et al., 2005; Gehrman et al., 2009; Sommer et al., 2009; Wang et al., 2009), agitation (Gaber et al., 2001; Ballard et al., 2005; Verhey et al., 2006; Holmes et al., 2007; Zhong et al., 2007; Rappaport et al., 2009,), aggression (Kyomen et al., 1999; Brodaty et al., 2003; Hall et al., 2005; Huertas et al., 2007), or psychosis (Mintzer et al., 2006; 2007; Streim et al., 2008). "
    [Show abstract] [Hide abstract] ABSTRACT: Background: Medications are frequently prescribed for neuropsychiatric symptoms (NPS) associated with dementia, although information on the efficacy and safety of medications for NPS specifically in long-term care (LTC) settings is limited. The objective of this study was to provide a current review of the efficacy and safety of pharmacological treatments for NPS in LTC. Methods: We searched MEDLINE, EMBASE, PsychINFO, and the Cochrane Library for randomized controlled trials comparing medications with either placebo or other interventions in LTC. Study quality was described using the Cochrane collaboration risk of bias tool. The efficacy of medications was evaluated using NPS symptom rating scales. Safety was evaluated through rates of trial withdrawals, trial withdrawals due to adverse events, and mortality. Results: A total of 29 studies met inclusion criteria. The most common medications evaluated in studies were atypical antipsychotics (N = 15), typical antipsychotics (N = 7), anticonvulsants (N = 4), and cholinesterase inhibitors (N = 3). Statistically significant improvements in NPS were noted in some studies evaluating risperidone, olanzapine, and single studies of aripiprazole, carbamazepine, estrogen, cyproterone, propranolol, and prazosin. Study quality was difficult to rate in many cases due to incomplete reporting of details. Some studies reported higher rates of trial withdrawals, adverse events, and mortality associated with medications. Conclusions: We conclude that there is limited evidence to support the use of some atypical antipsychotics and other medications for NPS in LTC populations. However, the generally modest efficacy and risks of adverse events highlight the need for the development of safe and effective pharmacological and non-pharmacological interventions for this population.
    Full-text · Article · Oct 2012
    • "The median age of the publications was 6 years. Key methodological attributes of the studies are outlined inTable 1. 36 primary targets for interventions were identified, as summarised inTable 2. For interventions targeting resident behaviour, most pharmacological studies evaluated risperidone2223242526 or olanzapine [18,19]. Two studies evaluated interventions aimed at withdrawal of antipsychotic medications [27,28]. "
    [Show abstract] [Hide abstract] ABSTRACT: Background A thorough understanding of the literature generated from research in care homes is required to support evidence-based commissioning and delivery of healthcare. So far this research has not been compiled or described. We set out to describe the extent of the evidence base derived from randomized controlled trials conducted in care homes. Methods A systematic mapping review was conducted of the randomized controlled trials (RCTs) conducted in care homes. Medline was searched for “Nursing Home”, “Residential Facilities” and “Homes for the Aged”; CINAHL for “nursing homes”, “residential facilities” and “skilled nursing facilities”; AMED for “Nursing homes”, “Long term care”, “Residential facilities” and “Randomized controlled trial”; and BNI for “Nursing Homes”, “Residential Care” and “Long-term care”. Articles were classified against a keywording strategy describing: year and country of publication; randomization, stratification and blinding methodology; target of intervention; intervention and control treatments; number of subjects and/or clusters; outcome measures; and results. Results 3226 abstracts were identified and 291 articles reviewed in full. Most were recent (median age 6 years) and from the United States. A wide range of targets and interventions were identified. Studies were mostly functional (44 behaviour, 20 prescribing and 20 malnutrition studies) rather than disease-based. Over a quarter focussed on mental health. Conclusions This study is the first to collate data from all RCTs conducted in care homes and represents an important resource for those providing and commissioning healthcare for this sector. The evidence-base is rapidly developing. Several areas - influenza, falls, mobility, fractures, osteoporosis – are appropriate for systematic review. For other topics, researchers need to focus on outcome measures that can be compared and collated.
    Full-text · Article · Jun 2012
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