The news about antidepressant medications over the past several years has been mixed. The bad news from large multicenter studies such as STAR*D is that current antidepressant medications are effective, but not as effective as one might hope. Thus, there is a significant need for new treatment mechanisms for depression. On that front, there has been mixed news as well.
One of the most exciting new drugs to reach human clinical trials, one that blocks the corticotrophin releasing factor-1 (CRF1) receptor, did not work in a large clinical trial sponsored by Pfizer Pharmaceuticals. Is it time to abandon CRF1 antagonists as antidepressants or should we revisit these agents from a new perspective? It is in this context that a new paper by Alexandre Surget and colleagues, scheduled for publication in the August 15th issue of Biological Psychiatry, is particularly interesting.
Through prior work, it has been shown that the ability to reverse the stress-related disruption of hippocampal neurogenesis, the ability of the brain to make new nerve cells in adulthood, was important to the actions of our available antidepressant medications. In this new study, the researchers affirm the prior findings, but suggest that two experimental approaches to the treatment of depression, blockade of the CRF1 receptor or the vasopressin-1B (V1B) receptor, retain their efficacy in reversing the impact of stress on behavior even when neurogenesis is disrupted. Catherine Belzung, Ph.D., corresponding author on this article, further explains that "we now report evidence that restoration of the functioning of the stress axis may be the key to how these new antidepressant approaches might work."