Ketamine: Promising Path or False Prophecy in the Development of Novel Therapeutics for Mood Disorders?
Sanacora, G., Schatzberg, A. F.
This commentary review (2014) highlights the strength of evidence from recent proof-of-concept studies of ketamine which bear promise for the rapid treatment of depression which currently lacks efficient treatment alternatives. However, the authors disagree about the underlying mechanism mediating these effects and doubt whether there is a sufficient degree of preclinical evidence to warrant the initiation of novel treatment approaches or widespread availability of the drug in clinical settings.
Abstract
Large ‘real world’ studies demonstrating the limited effectiveness and slow onset of clinical response associated with our existing antidepressant medications has highlighted the need for the development of new therapeutic strategies for major depression and other mood disorders. Yet, despite intense research efforts, the field has had little success in developing antidepressant treatments with fundamentally novel mechanisms of action over the past six decades, leaving the field wary and skeptical about any new developments. However, a series of relatively small proof-of-concept studies conducted over the last 15 years has gradually gained great interest by providing strong evidence that a unique, rapid onset of sustained, but still temporally limited, antidepressant effects can be achieved with a single administration of ketamine. We are now left with several questions regarding the true clinical meaningfulness of the findings and the mechanisms underlying the antidepressant action. In this Circumspectives piece, Dr. Sanacora and Dr. Schatzberg share their opinions on these issues and discuss paths to move the field forward.