Schneider et al. (Oct. 12 issue)1 conclude that the adverse effects of atypical antipsychotic drugs for the treatment of psychosis, aggression, and agitation in patients with Alzheimer's disease offset the advantages. However, they acknowledge that the doses used in the study were lower than some clinicians would have used and that patients could discontinue a study drug (a main outcome) and randomly switch to another of the study drugs. The rate of discontinuation of treatment ranged from 77 to 85% among the four study groups.
An accompanying editorial by Karlawish2 highlights the novelty of this trial's design, with a primary outcome that attempts to reflect actual clinical events — in other words, a situation in which a switch would be made to another atypical neuroleptic agent after 2 to 4 weeks if the first drug had side effects or no apparent benefit.
There will be much discussion of this study in the coming months. One possible interpretation of the findings is that nonpharmacologic interventions and non-neuroleptic drugs should be tried before atypical antipsychotic drugs. Antidepressants, antiepileptic drugs, and the N-methyl-d-aspartate (NMDA) receptor antagonist memantine could be tried in individual patients to reduce the use of antipsychotic drugs. Another study by the Clinical Antipsychotic Trials of Intervention Effectiveness–Alzheimer's Disease (CATIE-AD) study group may be required to demonstrate the effectiveness of these drugs for psychosis, aggression, and agitation in patients with Alzheimer's disease.