(M0930-11-62) Efficacy Difference of Antipsychotics in Alzheimer's Disease and Schizophrenia: Explained with Network Efficiency and Pathway Analysis Methods

Purpose: The goal of this study 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).

Methods: Latest postsynaptic density proteome expression data is used to construct a comprehensive protein-protein interaction (PPI) network to represent the characteristics of AD+P. The relationship between drugs and AD+P can be evaluated with network analysis methods based on the topological parameters measuring associations among sub-networks. A combined score is defined by combining the measurements on the separation between drugs and proximity between drugs and disease respectively. The higher of the score, the bigger chance that the two drugs may have synergistic effect against AD+P.

Results: We built a comprehensive PPI network containing 75 antipsychotics targets, 32 antidepressants target and 461 AD+P related proteins, with a total of 543 nodes in the PPI network. A total of 357 antidepressant-antipsychotic drug pairs are listed from 17 antidepressants and 21 antipsychotics that are commonly used in clinical settings. Most drug pairs showed a combined score around 0 which indicate that synergetic effect between antipsychotics and antidepressants may not be easily achieved within the two drug categories. However, some drugs showed promising results through the panel like Aripiprazole, Sertraline and Risperidone. Eight drug combinations are nominated for potential synergetic effect.

Conclusion: The results of this study provide us a comprehensive and quantitative overview of the underlying relationship among antipsychotics, antidepressants and AD+P. Our results supported the current choice of antipsychotics and suggested the most promising antidepressants that can be added as supplementary treatment, Sertraline and Maprotiline.