Criticisms of drugs in early development for the treatment of depression: what can be improved?

Abstract

Major depressive disorder (MDD) is a common and debilitating mental illness, which leads to serious functional impairment in patients, and treatment-wise, there are currently a number of different classes of antidepressants already on the market. However, emerging evidence from numerous clinical trials has confirmed that there is still an unmet need for antidepressant efficacy in terms of response and remission. Approximately only 30% of patients with MDD may remit after adequate treatment with antidepressants in clinical practice. The drawbacks of the currently available antidepressants also include inadequate overall efficacy, safety issues and the lag prior to onset of clinical improvement. The need for new agents with novel mechanisms of action has led to the development of several newer antidepressants including vilazodone, edivoxetine, ketamine, atomoxetine and vortioxetine, which have been approved for the treatment of MDD. However, the efficacy and safety of these next-generation antidepressants, in clinical trials, are still unsatisfactory. This paper provides a brief updated overview of the progress and critical limitations in the development of novel antidepressants.

Keywords:

• monoamine
• novel antidepressant
• receptor
• reuptake inhibition
• transporter

Declaration of interest

This work was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI12C0003). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.