Med Check

Memantine consistently benefits memory in patients with mild to severe Alzheimer's disease and improves language function in those with moderate to severe Alzheimer's, reported Elaine Peskind, M.D., of the University of Washington and colleagues in the Memantine Study Group. The group presented an exploratory analysis of the efficacy of memantine for cognitive deficits from one trial in patients with mild to moderate disease and a second trial in patients with moderate to severe disease. The two trials, involving a total of nearly 800 patients, were 24 weeks long, double blind, and placebo controlled. The mild to moderate trial compared memantine with placebo, while the moderate to severe trial involved patients who were already taking donepezil and then had either memantine or placebo added. The findings suggest that memantine's effects in patients with mild to moderate disease are less robust than in patients with more severe disease and that the drug may provide cognitive benefit through effects on both memory and language.

Switching patients on donepezil to rivastigmine may significantly improve treatment outcomes, reported Gary Figiel, M.D., of Southeastern Geriatric Healthcare Group in Snellville, Ga., and colleagues. A 26-week switch study involving 270 patients assessed the safety and efficacy of rivastigmine in patients with mild to moderate Alzheimer's who were not responding to donepezil therapy. Seventy percent of patients experienced improvement, or no further decline, in scores on the Clinical Global Impression–Change scale at week 26. Adverse events reported included those already known to be associated with rivastigmine, including nausea, vomiting, anorexia, weight loss, and dizziness.

Aripiprazole appears to be qualitatively similar in safety compared with other antipsychotics used to treat psychosis associated with Alzheimer's, reported William Carson, M.D., and colleagues at Bristol-Myers Squibb (BMS) and Otsuka America Pharmaceuticals. A company meta-analysis of three placebo-controlled trials involved pooled safety data from 938 patients. Overall, 15.8 percent of those treated with aripiprazole discontinued the study due to an adverse event, compared with 10.2 percent of those on placebo. The most frequent adverse events seen with aripiprazole were accidental injury, urinary-tract infection, somnolence, asthenia, vomiting, pain in extremities, peripheral edema, diarrhea, and urinary incontinence. Only somnolence occurred statistically significantly more often in those on aripiprazole. Similar to other second-generation antipsychotics used in this population, aripiprazole was associated with increased mortality overall (3.9 percent) compared with placebo (1.7 percent) and an increase in cerebrovascular events (1.3 percent) compared with placebo (0.6 percent).

A separate analysis, led by BMS researcher Dusan Kostic, Ph.D., pooled efficacy data from two trials in institutionalized patients with Alzheimer's-related psychosis. In this analysis, which included 246 patients, aripiprazole was particularly effective at reducing agitation, compared with placebo. Significant reductions were also seen in measures of tension, hostility, uncooperativeness, and excitement.

Risperidone is significantly superior to placebo in reducing psychotic symptoms in patients with psychosis related to Alzheimer's, reported Jacobo Mintzer, M.D., of the Medical University of South Carolina and colleagues. In a meta-analysis of four controlled trials involving 895 patients, risperidone statistically significantly reduced psychotic symptoms as early as the second week of treatment, and beneficial effects were sustained throughout the 16-week trials. The most commonly reported adverse events associated with risperidone were injury, somnolence, urinary-tract infection, rash, cough, and peripheral edema. In these trials, incidence of mortality was 3.1 percent for those on risperidone compared with 1.8 percent for those taking placebo. Cerebrovascular adverse events occurred in 1.6 percent of those taking risperidone compared with 0.8 percent of those taking placebo.

Olanzapine and quetiapine show concentration-dependent anticholinergic activity at doses commonly prescribed to elderly patients for control of psychosis associated with Alzheimer's, reported Benoit Mulsant, M.D., of the University of Pittsburgh School of Medicine and colleagues. However, aripiprazole, risperidone, and haloperidol showed no detectable anticholinergic activity at therapeutic doses. Anticholinergic activity is thought to be of concern in elderly patients due to its linear association with cognitive decline. It is particularly important in patients with dementia who already have a cholinergic deficit. Differences in assayed anticholinergic activity may be associated with some of the differences in adverse-effect profiles of the drugs studied, including decreased cognitive function, increased risk of falls, and gastrointestinal adverse effects.

APA 2005: NR 730; Funding: Janssen ▪