Clinical Topic: Off-Label Use of Atypical Antipsychotic Drugs

The Food and Drug Administration (FDA) sent advisory warnings in 2005 about atypical antipsychotic drug treatments and the increased risk of mortality in older patients. In response, three of AHRQ’s Effective Health Care Program components (EPC, DEcIDE, and Eisenberg Center) conducted research on this topic. This focus on a clinical topic is an example of the way that the Effective Health Care Program develops information collectively to answer questions and get the word out to stakeholders.

AHRQ commissioned the Southern California/Rand Evidence-based Practice Center to develop a Comparative Effectiveness Review on off-label uses of atypical antipsychotics. The CER report, Efficacy and Comparative Effectiveness of Off-Label Use of Atypical Antipsychotics, describes the currently available evidence and gaps in that evidence. The report included information about the use of atypical antipsychotics for treating agitation in people with dementia, which is a common reason for prescribing using these drugs in older people.

The Eisenberg Center translated the findings of the CER into a brief summary guide for clinicians and policymakers entitled Off-Label Use of Atypical Antipsychotic Drugs. The Center not only engaged clinicians and policymakers to review the guide, but it also developed a Confidence Scale for summarizing the strength of evidence for the key findings of the CER. This Confidence Scale has been adopted for use in summary guides on several other clinical topics.

The Brigham and Women’s Hospital DEcIDE Center conducted a rapid turn-around retrospective cohort study that compared mortality rates among people older than 65 who had received either atypical or typical (first generation, conventional) antipsychotic drugs. The study found no difference in mortality rates between the groups treated with each type of drug. The report is titled Comparative Safety of Conventional and Atypical Antipsychotic Medications: Risk of Death in British Columbia Seniors.
The EHC Program's research has influenced clinical policy. On June 16, 2008, the FDA issued a new alert stating that both conventional and atypical antipsychotics are associated with an increased risk of mortality in older patients treated for dementia-related psychosis. The alert cites the DEcIDE research report as part of the evidence that prompted it to issue the new warning.