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; · 3.61 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Violent behavior associated with mental disorders is a common reason for admission to a psychiatric inpatient unit. Once hospitalized, patients may continue to be intermittently agitated and have persistent aggressive behaviors, preventing their discharge back into the community. Managing agitation quickly with effective pharmacological agents can avoid further escalation to aggression and violence. In the acute setting, this usually involves the parenteral use of antipsychotics, with or without benzodiazepines. Within the past decade, short-acting intramuscular formulations of second-generation antipsychotics have become available and provide a means to induce calm with a substantially lower risk of acute dystonia or akathisia compared with haloperidol. New alternative formulations that avoid injections include inhalation and sublingual administration. Longer-term management of persistent aggressive behavior by reducing the frequency and intensity of future episodes of agitation is more complex. In contrast to agitation associated with schizophrenia or bipolar mania, no agents have yet been approved by regulatory agencies for the treatment of persistent aggressive behavior. The strongest evidence supports the use of clozapine as an antihostility agent, followed by olanzapine. Adjunctive strategies with anticonvulsants and beta-adrenergic agents may also be worthwhile to consider.CNS spectrums 02/2014; · 1.30 Impact Factor
- [Show abstract] [Hide abstract]
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.World journal of psychiatry. 12/2014; 4(4):72-9.