Aripiprazole for the Treatment of Psychoses in Institutionalized Patients With Alzheimer Dementia: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Assessment of Three Fixed Doses

Alzheimer's Research & Clinical Programs, Medical University of South Carolina, North Charleston, SC 29406-6076, USA.
American Journal of Geriatric Psychiatry (Impact Factor: 4.24). 12/2007; 15(11):918-31. DOI: 10.1097/JGP.0b013e3181557b47
Source: PubMed


To assess the efficacy and safety of aripiprazole for psychosis associated with Alzheimer dementia (AD).
In this double-blind, multicenter study, 487 institutionalized patients with psychosis associated with AD were randomized to placebo or aripiprazole, 2, 5 or 10 mg/day. Primary efficacy assessment was the mean change from baseline to week 10 on the Neuropsychiatric Inventory-Nursing Home (NPI-NH) version Psychosis Subscale score. Secondary measures included NPI-NH Total, Clinical Global Impression-Severity of Illness (CGI-S), Brief Psychiatric Rating Scale (BPRS) Core and Total, and the Cohen-Mansfield Agitation Inventory (CMAI) scores.
Aripiprazole 10 mg/day showed significantly greater improvements (mean change [2 x SD]) than placebo on the NPI-NH Psychosis Subscale (-6.87 [8.6] versus -5.13 [10.0]; F = 6.29, df = 1, 422, p = 0.013 by analysis of covariance [ANCOVA]); CGI-S (-0.72 [1.8] versus -0.46 [1.6]; F = 4.68, df = 1, 419, p = 0.031 [ANCOVA]); BPRS Total (-7.12 [18.4] versus -4.17 [21.6]; F = 4.72, df = 1, 399, p = 0.030 [ANCOVA]); BPRS Core (-3.07 [6.9] versus -1.74 [7.8]; F = 7.30, df = 1, 407, p = 0.007 [ANCOVA]); CMAI (-10.96 [22.6] versus -6.64 [28.6]; F = 5.23, df = 1, 410, p = 0.023 [ANCOVA]), and NPI-NH Psychosis response rate (65 versus 50%; chi(2) = 5.52, df = 1, p = 0.019 [CMH]). Aripiprazole 5 mg/day showed significant improvements versus placebo on BPRS and CMAI scores. Aripiprazole 2 mg/day was not efficacious. Cerebrovascular adverse events were reported: aripiprazole 2 mg/day, N = 1; 5 mg/day, N = 2; 10 mg/day, N = 4; placebo, N = 0. No deaths in any group (aripiprazole 2 mg/day, 3%; 5 mg/day, 2%; 10 mg/day, 7%; placebo, 3%) were considered to be treatment-related.
Aripiprazole 10 mg/day was efficacious and safe for psychosis associated with AD, significantly improving psychotic symptoms, agitation, and clinical global impression. However, clinicians should be aware of the safety considerations of atypical antipsychotic uses in this population.

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    • "results on change in NPS scores compared with placebo were noted in two studies of risperidone (Katz et al., 1999; Brodaty et al., 2003), two studies of olanzapine (Street et al., 2000; De Deyn et al., 2004), and one study of aripiprazole (Mintzer et al., 2007). One study comparing risperidone and olanzapine found no "
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    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 · International Psychogeriatrics
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    • "Kostic et al (2005) analyzed the data from the two studies (Streim et al 2004; Mintzer et al 2007) to investigate further the effect of aripiprazole on agitation as measured by reduction in NPI-Agitation Item, CMAI, and Tension/Hostility/Uncooperativeness/Excitement scores of BPRS. In the Streim et al (2004) study, NPI agitation/aggression, CMAI, and BPRS Tension/Hostility/Uncooperativeness/Excitement scores were significantly reduced at study endpoint (p = 0.001, p < 0.05, p < 0.05 respectively). "
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    ABSTRACT: Psychosis of Alzheimer's disease (AD) is characterized by delusions or hallucinations and may be associated with agitation, negative symptoms or depression. There are no psychotropic medications that are approved by the US FDA for the treatment of psychosis of AD. However, atypical antipsychotics have been widely used and recommended by geriatric experts in the management of psychosis of AD in view of the modest efficacy and relative safety until FDA warnings were issued in 2005 and meta-analytic studies showed no significant difference to placebo. The FDA warnings on the cardiac, metabolic, cerebrovascular, and mortality risks have caused serious concerns for the use of atypical antipsychotic agents in elderly patients with dementia. Only a few studies have evaluated prospectively the effects of aripiprazole in psychosis associated with AD. These studies show improvement in the symptoms of psychosis associated with AD with aripiprazole. The safety and tolerability profile of aripiprazole suggests a low potential for negative impact on dementia and overall patient health. Further studies comparing the efficacy and tolerability of aripiprazole vs other atypical antipsychotics in dementia are needed.
    Preview · Article · Feb 2008 · Clinical Interventions in Aging
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    • "EPS scores were low and similar in both groups. High rates of discontinuation due to adverse events for the 5 and 10 mg/d doses (18% and 25%, respectively) were noted in another recent trial (Mintzer et al., 2007). Adverse events reported in another placebo-controlled aripiprazole trial included urinary tract infection (aripiprazole vs. placebo) (8% vs. 12%), accidental injury (8% vs. 5%), somnolence (8% vs. 1%), and bronchitis (6% vs. 3%) (De Deyn et al., 2005). "

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