Exploring Therapeutic Potential: A Comprehensive Review of Novel Treatment Targets in Psychotic Depression

Major depressive disorder (MDD) with psychotic features is a medical condition where patients suffer from depressed mood and psychotic symptoms, such as delusions. It is estimated that the lifetime prevalence of this condition is around 0.35%. It is associated with more severe symptomatology and a higher rate of relapse, compared to MDD without psychotic features. There are several treatments established, but not all patients respond well. Therefore, it is essential to find new treatment targets for MDD with psychotic symptoms. The purpose of this comprehensive review is to explore recent and breakthrough treatment targets in psychotic depression, by collecting, analyzing and processing scientific articles on the online databases of PubMed, GoogleScholar and ResearchGate.

The evidence suggests a role in targeting certain pathways and receptors in the brain that are linked with mood disorders and can be associated with the pathogenesis of psychotic depression. The hypothalamic–pituitary–adrenal (HPA) axis dysfunction and glucocorticoid receptors, and glutamate and NMDA receptors have been associated with psychotic depression and its targeting has shown to have improved the severity of the psychotic symptoms. Also, novel antipsychotics are partial agonists of the Dopamine D2 and D3 receptors which have been implicated in the improvement of not only psychotic symptoms but also depressive ones.

Limited data is currently available on newer, breakthrough treatment targets in psychotic depression. There are promising treatment targets such as the targeting of glucocorticoid receptors, glutamate receptors and specific dopamine receptors that need further research and trials in order to be considered as important strategic resources for the treatment of psychotic depression.