Medication development for agitation and aggression in Alzheimer disease: Review and discussion of recent randomized clinical trial design

Maria Soto, Sandrine Andrieu, Fati Nourhashemi, Pierre Jean Ousset, Clive Ballard, Philippe Robert, Bruno Vellas, Constantine G. Lyketsos, Paul B. Rosenberg

Research output: Contribution to journalReview articlepeer-review

Abstract

Background: The management of disruptive neuropsychiatric symptom (NPS) such as agitation and aggression (A/A) is a major priority in caring for people with Alzheimer's disease (AD). Few effective pharmacological or non-pharmacological options are available. Results of randomized clinical trials (RCTs) of drugs for A/A have been disappointing. This may result from the absence of biological efficacy for medications tested in treating A/A. It may also be related to methodological issues such as the choice of outcomes. The aim of this review was to highlight key methodological issues pertaining to RCTs of current and emerging medications for the treatment of A/A in AD. Methods: We searched PubMed/Medline, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for RCTs comparing medications with either placebo or other drugs in the treatment of A/A in AD, between January 2008 and December 2013. Results: We identified a total of 18 RCTs; of these, 11 were completed and 7 ongoing. Of the ongoing RCTs, only one is in Phase III. Seven of 10 completed RCTs with reported results did not report greater benefit from drug than placebo. Each of the completed RCTs used a different definition of clinically significant A/A. There was considerable heterogeneity in study design. The primary endpoints were largely proxy-based but a variety of scales were used. The definition of caregiver and scales used to assess caregiver outcomes were similarly heterogeneous. Placebo response was notable in all trials. Conclusions: This review highlights a great heterogeneity in RCTs design of drugs for A/A in AD and some key methodological issues such as definition of A/A, choice of outcome measures and caregiver participation that could be addressed by an expert consensus to optimize future trials design.

Original languageEnglish (US)
Pages (from-to)181-197
Number of pages17
JournalInternational psychogeriatrics
Volume27
Issue number2
DOIs
StatePublished - Jul 3 2015

Keywords

  • Alzheimer's
  • aggression
  • agitation
  • behavior
  • clinical trial
  • measurement
  • therapeutics

ASJC Scopus subject areas

  • Clinical Psychology
  • Gerontology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Fingerprint

Dive into the research topics of 'Medication development for agitation and aggression in Alzheimer disease: Review and discussion of recent randomized clinical trial design'. Together they form a unique fingerprint.

Cite this