Efficacy
Initial antipsychotic drug selection should be guided by comparative-efficacy data. The Clinical Antipsychotic Trials of Intervention Effectiveness—Alzheimer's Disease (CATIE-AD) evaluated median time to discontinuation in elderly AD subjects taking olanzapine (mean end-study dose 5.5 mg), quetiapine (56.5 mg), or risperidone (1 mg) compared with placebo. The median time to discontinuation due to lack of efficacy was 26.1 weeks for risperidone and 22 weeks for olanzapine; the median time for both quetiapine and placebo was 9 weeks (P = .002). There were no significant differences in clinical-improvement scales among the treatment groups, however. Discontinuation due to intolerability was greatest for olanzapine (24%); risperidone and quetiapine had similar discontinuation rates (18% and 16%, respectively), but placebo was favored, with a discontinuation rate of 5% (P = .009).
The AHRQ conducted a comparative-efficacy review to examine the strength of evidence of efficacy of atypical agents in treating overall BPSD, agitation, and psychosis compared with placebo. Based on results of this review, risperidone is the only agent with strong evidence of efficacy for overall BPSD, agitation, and psychosis; aripiprazole also has strong evidence of efficacy for treating overall BPSD in dementia, whereas olanzapine and quetiapine have low evidence of efficacy. Risperidone is the only agent with strong efficacy data for treatment of psychosis in dementia; for agitation, olanzapine has proven efficacy. Because of a paucity of evidence supporting its use, quetiapine is not recommended unless other agents have failed. The AHRQ noted, however, that despite strong evidence of efficacy, the magnitude of treatment effect on clinical improvement was small and did not reach statistical significance.
The efficacy of typical agents used to treat BPSD has not been studied as extensively as that of the newer agents. Of these agents, haloperidol has the most clinical data for agitation in dementia. However, its utility is diminished by reports of high mortality and risk of EPS.