Special ArticleEfficacy and Adverse Effects of Atypical Antipsychotics for Dementia: Meta-analysis of Randomized, Placebo-Controlled Trials
Section snippets
Search Strategy, Trials Selection, and Data Retrieval
The search strategy was described in detail previously.13 Briefly, MEDLINE (1966–April 2005) and the Cochrane Central Register of Controlled Trials (2005, Issue 1)15 were searched using the headings aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone (i.e., atypical antipsychotics marketed in the United States), dementia, “Alzheimer disease,” and “clinical trial.” This was supplemented by hand reviewing materials from conferences and web postings. Pharmaceutical
Search Flow
The retrieval results are detailed elsewhere13 and ultimately yielded five trials from MEDLINE and six from the Cochrane registry that included the five MEDLINE references. One placebo-controlled trial of olanzapine (N = 16 subjects)21 was not included because the only available documentation was an abstract with inadequate information; one was a review with information on an olanzapine trial not contained elsewhere.22
One recently published trial of quetiapine was included but was not
DISCUSSION
A considerable number of placebo-controlled trials of atypical antipsychotics for patients with dementia have been undertaken and not all have been published, involving over 5,000 patients treated for generally 8–12 weeks. Patients on average were advanced in age, in their 80s, most had AD, and a minority cerebrovascular dementia. After statistically combining the trials there was evidence for symptomatic efficacy of aripiprazole and risperidone. Olanzapine was not associated with efficacy
LIMITATIONS
Meta-analyses are observational studies and are subject to various biases, including the complete ascertainment of trials performed, assessing the trials' qualities, deciding on the analytic protocol, information to be abstracted, studies to be combined, statistics, and interpretation of the results. Trials varied somewhat in their inclusion criteria. Patients included may have been restricted to AD or not, or on the basis of agitation or aggression or delusions or hallucinations. There were
PRACTICE IMPLICATIONS
The modest efficacy and uncertain response rates combined with the risks detailed here suggest that antipsychotics should be used with more deliberate consideration. Medications should be prescribed and adjusted to maximize efficacy while minimizing adverse events; the adverse event evidence coupled with the efficacy evidence suggests that the use of lower doses might be prudent and effective.
Clinical improvement should be expected well within 10 or 12 weeks, the length of the trials. If
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