Clinical Trials with Memantine and Cholinesterase Inhibitors in Alzheimer's Disease and Related Disorders: A Cross Sectional Analysis

Alzheimer disease currently affects more than 35 million people worldwide. After initial enthusiasm for the acetylcholinesterase inhibitors and memantine, their symptomatic efficacy and long-term value have been questioned by public health authorities. Against this backdrop of controversy, we have used the largest clinical trial registry to analyze clinical research on these drugs. We focused on the clinical relevance of the trials and on their publication rate. We used the ClinicalTrials.gov website, which is an open registry of clinical trials. We conducted our literature search in January 2015 on clinical intervention and extracted data for the period from 2004 to 2011 inclusive, ie, 8 full years. We search publication on ClinicalTrials.gov, Medline and Google Scholar. The literature search found 54 studies published of 107 studies that met the selection criteria. About the published trials, the mean duration was 7.5 months, the mean age of participants was between 70 and 79 in 78% of the trials. In terms of results, 25 trials were positive, 25 doubtful, and 4 negative. Depending on the trial methodology, 19 of 28 placebo-controlled trials were classified as doubtful or negative. Of the 28 placebo-controlled trials, only 6 lasted one year or more, with 2 negative results and 4 doubtful results. Only half of the studies were published, and those describing a pharmacological intervention versus placebo were most often neither positive nor clinically relevant.