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Clinical Question:
Do atypical antipsychotic drugs increase the risk of death for patients with
dementia?
Bottom Line:
Atypical antipsychotic drugs may be associated with a small increased risk
for death compared with placebo. This risk should be considered within the
context of medical need for the drugs, efficacy evidence, medical
comorbidity, and the efficacy and safety of alternatives. Individual patient
analyses modeling survival and causes of death are needed.
Reference:
Schneider LS, Dagerman KS, Insel P. Risk of death with atypical
antipsychotic drug treatment for dementia. Meta-analysis of randomized
placebo-controlled trials. JAMA 2005;294:1934-43.
Study Design:
Meta-analysis (randomized controlled trials)
Funding:
Government
Setting:
Various (meta-analysis)
Synopsis:
Atypical antipsychotic medications are widely used to treat delusions,
aggression, and agitation in people with Alzheimer disease and other
dementia; however, concerns have arisen about the increased risk for
cerebrovascular adverse events, rapid cognitive decline, and mortality with
their use. To assess the evidence for increased mortality from atypical
antipsychotic drug treatment for people with dementia. MEDLINE (1966 to
April 2005), the Cochrane Controlled Trials Register (2005, Issue 1),
meetings presentations (1997-2004), and information from the sponsors were
searched using the terms for atypical antipsychotic drugs (aripiprazole,
clozapine, olanzapine, quetiapine, risperidone, and ziprasidone), dementia,
Alzheimer disease, and clinical trial. Published and unpublished randomized
placebo-controlled, parallel-group clinical trials of atypical antipsychotic
drugs marketed in the United States to treat patients with Alzheimer disease
or dementia were selected by consensus of the authors. Trials, baseline
characteristics, outcomes, all-cause dropouts, and deaths were extracted by
one reviewer; treatment exposure was obtained or estimated. Data were
checked by a second reviewer. Fifteen trials (9 unpublished), generally 10
to 12 weeks in duration, including 16 contrasts of atypical antipsychotic
drugs with placebo met criteria (aripiprazole [n = 3], olanzapine [n = 5],
quetiapine [n = 3], risperidone [n = 5]). A total of 3353 patients were
randomized to study drug and 1757 were randomized to placebo. Outcomes were
assessed using standard methods (with random- or fixed-effects models) to
calculate odds ratios (ORs) and risk differences based on patients
randomized and relative risks based on total exposure to treatment. There
were no differences in dropouts. Death occurred more often among patients
randomized to drugs (118 [3.5%] vs 40 [2.3%]. The OR by meta-analysis was
1.54; 95% confidence interval [CI], 1.06-2.23; P = .02; and risk difference
was 0.01; 95% CI, 0.004-0.02; P = .01). Sensitivity analyses did not show
evidence for differential risks for individual drugs, severity, sample
selection, or diagnosis. |