A systematic review on drugs for synaptic plasticity in the treatment of dementia

The aim of the present systematic review (SR) was to provide an overview of all published and unpublished clinical trials investigating the safety and efficacy of disease-modifying drugs targeting synaptic plasticity in dementia. Searches on CT.gov and EuCT identified 27 trials (4 phase-1, 1 phase-1/2, 18 phase-2, 1 phase-2/3, 1 phase-3, 1 phase-4, and 1 not reported). Twenty of them completed, and seven are currently active or enrolling. The structured bibliographic searches yielded 3585 records. A total of 12 studies were selected on Levetiracetam, Masitinib, Saracatinib, BI 40930, Bryostatin 1, PF-04447943 and Edonerpic drugs. We used RoB tool for quality analysis of randomized studies. Efficacy was assessed as a primary outcome in all studies except one and the main scale used was ADAS-Cog (7 studies), MMSE and CDR (4 studies). Safety and tolerability were reported in eleven studies. The incidence of SAEs was similar between treatment and placebo. At the moment, only one molecule reached phase-3. This could suggest that research on these drugs is still preliminary. Of all, three studies reported promising results on Levetiracetam, Bryostatin 1 and Masitinib.