Abstract Details

Title Combination of Antidepressants and Antipsychotics as Novel Treatment Options for Psychosis in Alzheimer’s Disease

Topic Aging, Dementia, and Behavioral Neurology

Presentation(s) P18 - Poster Session 18 (5:30 PM-6:30 PM)

Poster/Presentation
Number 3-004

Background As one of the most common complications of AD, psychotic symptoms are reported in roughly half of all AD patients. However, the current recommended treatments, second-generation antipsychotics, are shown to have modest efficacy in AD+P. Both genome-wide association study (GWAS) results and early clinical trials promoted the potential beneficial effects of antidepressants against AD+P which provide rationale their combination therapy.

Objective The goal of this study is to investigate the beneficial effects of antidepressants and their potentials as combination therapy with antipsychotics against AD+P (psychosis in Alzheimer’s disease or AD).

Design/Methods Latest GWAS and differentially expressed genes (DEGs) data are incorporated to construct a comprehensive protein-protein interaction (PPI) network to represent the characteristics of AD+P. The relationship between drugs and AD+P are evaluated with network analysis methods based on the topological parameters measuring associations among sub-networks. An indicator score is defined by combining the measurements on the separation between drugs and proximity between drugs and disease respectively. Higher score means bigger chance that the two drugs may have synergistic effect against AD+P.

Results

We built a comprehensive PPI network containing 77 antipsychotics targets, 63 antidepressants targets and 2013 AD+P related genes, with a total of 1703 nodes in the PPI network. A total of 638 antidepressant-antipsychotic drug pairs are listed from 29 antidepressants and 22 antipsychotics that are commonly used in clinical settings. A good separation for targets between antipsychotics and antidepressants is observed and similar proximity scores are found for antipsychotics and antidepressants. Three antidepressants, Phenelzine, Venlafaxine and Duloxetine, showed high average indicator scores suggesting they have a high potential in the combination therapies we proposed.

Conclusions

Based on our results, antipsychotics and antidepressants showed close associations with AD+P yet have different targets and distinct mechanisms with each other. A synergistic effect may be achieved if they are administrated together against AD+P.

Authors/Disclosures
Peihao Fan, MBBS (School of Pharmacy, University of Pittsburgh) PRESENTER	Mr. Fan has nothing to disclose.
	No disclosure on file
	No disclosure on file
Robert A. Sweet	Robert A. Sweet has nothing to disclose.