Aripiprazole for the Treatment of Psychosis in Patients With Alzheimer's Disease

Abstract

This study compared the efficacy, safety, and tolerability of aripiprazole, a novel antipsychotic, with placebo in patients with psychosis associated with Alzheimer's Disease (AD). This 10-week, double-blind, multicenter study randomized 208 outpatients (mean age, 81.5 years) with AD-associated psychosis to aripiprazole (n = 106) or placebo (n = 102). The initial aripiprazole dose of 2 mg/d was titrated upwards (5, 10, or 15 mg/d) according to efficacy and tolerability. Evaluations included Neuropsychiatric Inventory (NPI) Psychosis subscale and Brief Psychiatric Rating Scale (BPRS), adverse event (AE) reports, extrapyramidal symptoms (EPS) rating scales, and body weight. Overall, 172 patients (83%) completed the study. Mean aripiprazole dose at end point was 10.0 mg/d. The NPI Psychosis subscale score showed improvements in both groups (aripiprazole, -6.55; placebo, -5.52; P = 0.17 at end point). Aripiprazole-treated patients showed significantly greater improvements from baseline in BPRS Psychosis and BPRS Core subscale scores at end point compared with placebo. AEs were generally mild to moderate in severity and included (aripiprazole vs. placebo): urinary tract infection (8% vs. 12%), accidental injury (8% vs. 5%), somnolence (8% vs. 1%), and bronchitis (6% vs. 3%). Somnolence was mild and not associated with falls or accidental injury. There were no significant differences from placebo in EPS scores, or clinically significant ECG abnormalities, vital signs, or weight. In conclusion, aripiprazole showed similar improvements to placebo in psychotic symptoms as assessed by NPI Psychosis subscale scores, but significantly greater effects on BPRS Core and Psychosis assessments in community-living AD patients with psychosis. Aripiprazole was safe and well tolerated in this patient population.

Aripiprazole: A Novel Atypical Antipsychotic Drug With a Uniquely Robust Pharmacology

“…Shapiro et al (80) predicted on the basis of its 5-HT 2A /5-HT 2C profile that aripiprazole would have anorectic actions in humans. Aripiprazole is also being investigated in psychosis associated with Alzheimer's disease (24). A report from the multicenter, double-blind placebo-controlled trial involving 208 outpatients (mean age 81.5 years) indicated that aripiprazole may cause improvements in the Neuropsychiatric Inventory (NPI) Psychosis scale and in a subscale (delusions and hallucinations) of The Brief Psychiatric Rating Scale (BPRS).…”

Pharmacological recommendations for the symptomatic treatment of dementia: the Canadian Consensus Conference on the Diagnosis and Treatment of Dementia 2012

“…Th ree RCTs comparing aripiprazole with placebo in AD patients for treatment of agitation and psychosis demonstrated reasonable tolerability and benefi ts signifi cantly greater than placebo [85][86][87]. In a meta-analysis of these trials, the pooled estimate of eff ect sizes was small but statistically signifi cant and similar to benefi ts found with risperidone and olanzapine [88].…”

The management of inappropriate vocalisation in dementia: a hierarchical approach

“…Olanzapine also showed a two-fold increase in mortality in dementia patients, despite promising evidence from trials and case reports (Wathion, 2004). The newest anti-psychotic in the UK, Aripiprazole,has also been trailed with some success in patients with BPSD, but again has shown an increase in CVAE (De Deyn et al, 2003;Breder et al, 2004;Streim et al, 2004). The safety profile of other antipsychotic agents remains a topic of some uncertainty at the time of writing.…”