Strategies to achieve clinical effectiveness: refining existing therapies and pursuing emerging targets

Clinical effectiveness reflects a balance between efficacy and tolerability as well as patient satisfaction and overall improvement in quality of life and function. This is of particular importance when considering the long term use of antidepressant therapies for relapse prevention.

The purpose of this review is to explore methods to enhance the modest efficacy and effectiveness outcomes reported with current antidepressant strategies. Two strategies are addressed: a) Doing better with existing treatments and b) pursuing novel targets beyond the monoamine system for new antidepressant drug development.

In the first instance, it is important to consider the balance between antidepressant efficacy and tolerability for individual patients and also be aware of evidence supporting superiority of one agent over others. Both sequential and concurrent combination therapies with existing antidepressants are also reviewed. The second approach involves a review of emerging novel pharmacological treatments based on biomarker research. Unique targets where antidepressant treatments appear effective include the melatonergic, glutamatergic, neurotrophic, cytokine, and neuropeptide systems.

While agomelatine represents an example of a clinically available antidepressant that targets melatonin receptors, drugs that act on other candidate systems are still in the development phase.