Dr Michael Thase Outlines Developments in the Pathophysiology of Major Depressive Disorder

There is a subset of patients who don't respond to monoamine modulating antidepressants, so there has been a focus on looking for other potential pathways for treatment, said Michael Thase, MD, professor of psychiatry and director of the Mood and Anxiety Program at the University of Pennsylvania.

Transcript

What are some recent developments in the pathophysiology of major depressive disorder?

You know, there’s this old aphorism about looking for your keys under the lamp because the street lamp is the easiest place to find them if they’re there. But what if you lost them somewhere else? The whole first 30 years centered around the discoveries of the monoamines and their importance in the regulation of basic functions like sleep and appetite and the pursuit of reward and in dampening down response to stress.

We got to the point in the past 10 or 15 years where we had the best possible monoamine modulating antidepressants that could be made, yet there was this large subset of patients who just weren’t responsive to those treatments. So, what’s happened in the past 20 or 30 years has been looking at other stress response systems and other systems that are involved in adaptation to look for other potential pathways for treatment and the accidental discovery of the anesthetic ketamine having antidepressant effects is one example of this.

But, you know, our first antidepressants were discovered accidentally, too. So, it’s not uncommon for serendipitous discoveries to lead to breakthroughs. Now, how ketamine works, the mechanisms through which is works for depression has led to pursuit of other, less problematic potential medications. The investigational antidepressant rohypnol is an example of that.

Likewise, human beings have taken opiates as long as the poppy’s been cultivated as a way of dampening down their misery, but of course the horror of opiate dependence and the current public health problems with opiates keep the use of unmodified opiates as a way of relieving bad mood just completely off the table. But now there’s investigational strategies looking at modified opiate modulators that can provide the mood benefits of the opiate without the properties that make them intoxicating or habit forming.