Drug repurposing may generate novel approaches to treating depression

OBJECTIVES: The breakthrough advancements in scientific medical research have greatly improved our understanding of the pathogenesis of depression, encouraging drug discoverers to take a shorter path than ever through drug repurposing to generate new antidepressant medications. In addition to reduced noradrenergic and serotonergic neurotransmission in the brain, other coincidence features such as glutamate neurotoxicity, inflammation and/or cerebrovascular insufficiency are implicated in the pathogenesis of major depressive disorder and late-life depression. This short review discusses the progress made in repurposing drugs for antidepressant actions. KEY FINDINGS: Drugs being repurposed as antidepressants act on novel drug targets, thereby treating resistant depression and improving remission rate. Drugs such as ketamine, dextromethorphan/quinidine and scopolamine are rapidly acting antidepressants targeting glutamate receptors. Nimodipine and quetiapine are efficient add-on therapy for late-life depression. Anti-inflammatory drugs, statins, insulin sensitizers, minocycline could remarkably contribute to treating refractory depression. SUMMARY: Drug repurposing represents an alternative approach to cope with major obstacles, including financial insufficiency and unavoidable long lag evaluation time, undermining the classical pathway of developing new hit compounds into clinically approved antidepressants.