The current Review article provides a narrative review about the neurobiological
underpinnings and treatment of treatment resistant late-life depression (TRLLD). The manuscript
focuses on therapeutic targets of late-life depression, which include pharmacological, psychological,
biophysical and exercise treatment approaches. Therefore, we summarize available evidences on that
kind of therapies for patients suffering from late-life depression. The search for evidences of therapeutic
options of late-life depression were done using searching websites as “pubmed”, and using the searching
terms “depression”, “late-life depression”, “treatment”, “biophysical therapy”, “exercise therapy”, “pharmacological therapy”
and “psychological therapy”. To the end, we summarize and discuss current data, providing some directions for further
Treatment recommendations for elderly depressive patients favour a multimodal approach, containing psychological,
pharmacological and secondary biophysical therapeutic options. Particularly, a combination of psychotherapy and
antidepressant medication reflects the best therapeutic option. However, mostly accepted and used is the pharmacological
treatment although evidence suggests that the drug therapy is not as effective as it is in younger depressive patients.
Further studies employing larger samples and longer follow-up periods are necessary and may focus on comparability of
study designs and involve novel approaches to establish the validity and reliability of multimodal treatment programs.