
Psychiatric News July 1, 2005
Volume 40 Number 13
© 2005 American Psychiatric Association
p. 25
Med Check
Jim Rosack
This is the first of a Med Check series featuring new research
presented at APA's 158th Annual Meeting, held May 21 to 26 in Atlanta. New
research presentations are generally preliminary in nature and involve
research that has yet to be peer reviewed for publication. Reports may involve
the use of medications for purposes that the Food and Drug Administration has
not approved and are largely funded by product manufacturers.
This Med Check features new research reports on the use of medications
to treat Alzheimer's disease. New research reports on pharmacotherapy
targeting attention-deficit/hyperactivity disorder, bipolar disorder,
depression/anxiety, psychotic disorders, and substance use disorders will be
presented in subsequent columns.
- 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.
APA 2005: NR 741; Funding: Forest Labs
- 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
ImpressionChange scale at week 26. Adverse events reported included
those already known to be associated with rivastigmine, including nausea,
vomiting, anorexia, weight loss, and dizziness.
APA 2005: NR 887; Funding: Novartis
- 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.
APA 2005: NR 268 and NR 742; Funding: BMS/Otsuka
- 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.
APA 2005: NR 738; Funding: Janssen
- 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
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