A Randomized, Double-Blind, Placebo-Controlled Tolerability Study of Intramuscular Aripiprazole in Acutely Agitated Patients With Alzheimer's, Vascular, or Mixed Dementia
ABSTRACT To evaluate the tolerability of intramuscular (IM) aripiprazole in patients with agitation associated with dementia.
A 24-hour, double-blind, placebo-controlled, randomized study.
Sixteen healthcare facilities in the United States.
A total of 129 patients with acute agitation associated with Alzheimer's, vascular or mixed dementia in healthcare facilities.
Patients were randomized to IM aripiprazole (5 mg, 10 mg, or 15 mg) or IM placebo administered in divided doses 2 hours apart.
Safety assessments included adverse event (AE) reporting, vital signs, and electrocardiograms. Preliminary efficacy analyses used the Positive and Negative Syndrome Scale-Excited Component (PEC) scores and Agitation-Calmness Evaluation Scale (ACES).
There was greater incidence of AEs with IM aripiprazole (50% to 60%) than IM placebo (32.0%), but over 90% were mild or moderate in severity. The incidence of oversedation was low. PEC scores showed greater improvements in agitation with IM aripiprazole 10 mg and 15 mg compared with IM placebo.
A total of 10 mg or 15 mg of IM aripiprazole administered in divided doses was safe and well tolerated for treatment of agitation associated with Alzheimer's, vascular, or mixed dementia in long-term care. Preliminary analysis showed greater efficacy compared with IM placebo.
SourceAvailable from: Gang Zhu[Show abstract] [Hide abstract]
ABSTRACT: Background: The application of atypical antipsychotics (SGAs) for treatment of psychiatric and behavioral symptoms of dementia is controversial since their efficacy might be offset by their adverse events (AEs). Objective: To assess the efficacy, safety, and tolerability of SGAs for treatment of psychological and behavioral symptoms of dementia. Methods: Two researchers searched MEDLINE, PsychINFO, and the Cochrane Central Register of Controlled Trials independently for double-blind, placebo-controlled, randomized controlled trials (DB-PC-RCTs) as of June 2013, written in English. Efficacy was measured using the Brief Psychiatric Rating Scale (BPRS), Cohen-Mansfield Agitation Inventory (CMAI), Neuropsychiatric Inventory (NPI), Clinical Global Impression of Change (CGI-C), and (or) Clinical Global Impression of Severity (CGI-S). Safety and tolerability were measured by frequencies of drop-outs, adverse events (AEs), and death. In total, 19 treatment comparisons drawn from 16 DB-PC-RCTs were included, and 3,343 patients randomized to the antipsychotic group and 1,707 to the placebo group were assessed. Results: This meta-analysis demonstrated a significant efficacy of atypical antipsychotics on BPRS (MD = -1.58, 95% CI = -2.52 - -0.65), CMAI (-1.84, -3.01 - -0.61), NPI (-2.81, -4.35 - -1.28), CGI-C (-0.32, -0.44 - -0.20), and CGI-S (-0.19, -0.30 - -0.09), compared to placebo (p < 0.01 for all). Patients receiving atypical antipsychotics showed no difference in risk for discontinuation (p > 0.05), significantly higher risks (p < 0.05 for all) for somnolence (OR = 2.95), extrapyramidal symptoms (1.74), cerebrovascular AEs (2.50), urinary tract infection (1.35), edema (1.80), gait abnormality (3.35), and death (1.52), and a lower risk for agitation (OR = 0.80, p = 0.03). Conclusions: The higher risks for AEs and mortality may offset the efficacy of atypical antipsychotics for treatment of dementia. Efficacy, safety, and tolerability thus should be carefully considered against clinical need.Journal of Alzheimer's disease: JAD 07/2014; 42(3). DOI:10.3233/JAD-140579 · 3.61 Impact Factor
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ABSTRACT: Dementia is a clinical syndrome with features of neurocognitive decline. Subtypes of dementia include Alzheimer's, frontotemporal, Parkinson's, Lewy body disease, and vascular type. Dementia is associated with a variety of neuropsychiatric symptoms that may include agitation, psychosis, depression, and apathy. These symptoms can lead to dangerousness to self or others and are the main source for caregiver burnout. Treatment of these symptoms consists of nonpharmacological and pharmacological interventions. However, there are no Food and Drug Administration-approved medications for the treatment of behavioral and psychological symptoms of dementia. Pharmacological interventions are used off-label. This article reviews the current evidence supporting or negating the use of psychotropic medications along with safety concerns, monitoring, regulations, and recommendations.12/2014; 4(4):72-9. DOI:10.5498/wjp.v4.i4.72
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ABSTRACT: ABSTRACT Background: The management of disruptive neuropsychiatric symptom (NPS) such as agitation and aggression (A/A) is a major priority in caring for people with Alzheimer's disease (AD). Few effective pharmacological or non-pharmacological options are available. Results of randomized clinical trials (RCTs) of drugs for A/A have been disappointing. This may result from the absence of biological efficacy for medications tested in treating A/A. It may also be related to methodological issues such as the choice of outcomes. The aim of this review was to highlight key methodological issues pertaining to RCTs of current and emerging medications for the treatment of A/A in AD. Methods: We searched PubMed/Medline, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for RCTs comparing medications with either placebo or other drugs in the treatment of A/A in AD, between January 2008 and December 2013. Results: We identified a total of 18 RCTs; of these, 11 were completed and 7 ongoing. Of the ongoing RCTs, only one is in Phase III. Seven of 10 completed RCTs with reported results did not report greater benefit from drug than placebo. Each of the completed RCTs used a different definition of "clinically significant A/A." There was considerable heterogeneity in study design. The primary endpoints were largely proxy-based but a variety of scales were used. The definition of caregiver and scales used to assess caregiver outcomes were similarly heterogeneous. Placebo response was notable in all trials. Conclusions: This review highlights a great heterogeneity in RCTs design of drugs for A/A in AD and some key methodological issues such as definition of A/A, choice of outcome measures and caregiver participation that could be addressed by an expert consensus to optimize future trials design.International Psychogeriatrics 09/2014; DOI:10.1017/S1041610214001720 · 1.89 Impact Factor