Approaches to Gradual Dose Reduction of Chronic Off-Label Antipsychotics Used for Behavioral and Psychological Symptoms of Dementia.

Abstract

Little is known about how to best taper antipsychotics used in patients with dementia. To address this gap, we reviewed published antipsychotic discontinuation trials to summarize what is known about tapering strategies for antipsychotics used with older adults with dementia. We further developed pharmacokinetic-based gradual dose reduction (GDR) protocols based on antipsychotic half-lives. MEDLINE, EMBASE, and International Pharmaceutical Abstracts were searched up to October 2014 to identify intervention studies reporting the behavioral and psychological symptoms of dementia outcomes resulting from discontinued off-label use of antipsychotics in nursing facility populations. Recently published pharmacokinetic reviews and standard pharmacology texts were used to determine antipsychotic drug half-lives for the pharmacokinetic-based GDR protocols. For the review, studies with an intervention resulting in antipsychotic medication discontinuation or tapering were eligible, including randomized controlled trials and pre- and post-intervention studies. When available, we extracted the protocols used for antipsychotic GDR from each study included in the review. We found that clinical trials used different approaches to antipsychotic discontinuation, including abrupt discontinuation, slow tapers (more than two weeks), and mixed strategies based on drug dosage. None of the published trials described an approach based on pharmacokinetic principles. We developed a two-stage GDR protocol for tapering antipsychotic medications based on the log dose-response relationship; each stage was designed to result in a 50% dose reduction prior to discontinuation. This pharmacologically based strategy for patients chronically prescribed antipsychotics resulted in recommendations for slow tapers. Our theoretically derived GDR recommendations suggest a different approach than previously published in clinical trials. Further study is needed to evaluate the effect of this approach on patients.