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Debates and Roundtables

The Debate Conclusion

 

In this last session, our debaters have a final opportunity to change our viewers’ minds with their final arguments. They give us their closing remarks for why we should view major depressive disorder (MDD) as either a chronic or episodic condition.


Debate Transcript:

Charles Raison, MD: Hey everybody. Thank you for joining us for the closing arguments of our Great Debates in Psychiatry series, which we're going to do now. Dr Maletic, Dr Thase, now is your last chance to change our viewers' minds. Give us your closing argument for why we should view MDD as either primarily a chronic or primarily an episodic condition. Vlad, why don't you take up... I think across these three modules of the debate, talking about MDD as a continuous versus episodic condition, and again, I think the idea here is, is one position better or worse or more effective or less effective starting position, and then what are the treatment implications of that? Why don't you give us a closing argument for, again, sort of the argument for a continuous approach, not only to the sort of way of thinking about the disorder, but also to how we treat it.

Vladimir Maletic, MD: I really like what I've heard from both you and Michael, and I would continue in the same spirit by advocating chronic intervention. But this will be a very different chronic intervention. I'm speaking about chronic preventive strategies. So there's a large study, and this encompassed over 100 000 individuals. Genome Y association testing was done. GYS studies were done. And here's what they concluded. There are individuals who have low genetic loading, much like Michael is saying, the individuals who may not have huge biological burden, and the ones who did have a very substantial genetic/biological burden.

So let's look at the bottom decile and the top 10. So they had several interventions. I will make it very simple: stop smoking, keep your BMI below 30, do not drink on average more than one glass of wine or beer a day. That is it. Moderate exercise, and moderate is very generous. It's only 90 minutes of moderate exercise, walking counts as moderate exercise, 90 minutes per week. And make two dietary changes. So go away from red meats and processed meats to more fruit and vegetables. Making these very, very simple interventions in individuals who were the top 10% in their genetic risk, reduce the onset of depressive episodes fivefold. So I would say why not have other chronic interventions that are not necessarily pharmacological? And I would add why not psychotherapy in that mix? Because even in these folks who have the heaviest genetic load, it made a difference.

Charles Raison, MD: Yeah, yeah, absolutely. It's a fascinating paper. And the importance of having one person that you could confide in, one piece of social connection, which is also [inaudible 00:03:30].

Vladimir Maletic, MD: That is the British study, absolutely.

Charles Raison, MD: Yeah. And in terms of chronic medication use, comments about traditional agents against standard SSRIs, SNRIs, and maybe some of these newer agents, and how do you think about that from this sort [inaudible 00:03:45]?

Vladimir Maletic, MD: I would say with SSRIs, we're making an uneasy compromise. If the patients respond to these agents, the odds are that especially abrupt discontinuation will backfire. If combined with psychotherapy, it may be a little bit better tolerated. So with those, it's part of the initial conversation with the patient. Look, these medicines may be helpful, but this is the cost. You may have emotional blunting, you may have adverse reactions. But on the other hand, if we don't use these agents, you may develop treatment-resistant depression. You may be battling with suicidal thoughts. There are all kinds of negative consequences. So it's a very uneasy compromise. But for some patients, I agree with Michael, there's a certain threshold, some individuals are so far into it that it may be necessary evil.

As far as these new treatments, I don't think the final chapter has been written. I think the jury is still out. So I would love to see longitudinal data and see if episodic treatments may be appropriate for some individuals. Because with these newer agents, there is some evidence that they more directly modulate neuroplasticity. They may be some of them more directly suppress inflammatory signaling in CNS. So it's a different story. It's definitely a new chapter relative to monoamine-modulating antidepressants, and therefore the paradigms may change. But my opinion is right now, we don't know enough.

Charles Raison, MD: Okay. Thank you, Vlad. Okay, Michael, you want to give us your closing argument?

Michael Thase, MD: We've done the best we can with our accidentally discovered first- and second-generation antidepressant treatments. And what we learned over 20, 25 years was that the larger good could be done by continuing those who responded nicely for six to nine months, and then for those who had had many prior episodes, continuing those patients indefinitely. And that was the best that we could recommend with treatments that worked the way these monoamine-modulating treatments work. I've given some examples over these debates of treatments that that was not true for. And I think we have now the possibility of new types of treatment with different targets that may not require the same kind of continuous administration.

But who can argue with my friend Vlad's notion that taking good care of yourself and behaving in a proactive, healthy way, including, well not abstinence, what would you say? Being tempered in ingestion of alcohol and exercising and connecting with people that these are all associated with wellbeing. This is not a chronic treatment. This is wellbeing and managing a healthy lifestyle. Fundamentally, recurrent depression exists within humankind's, our social systems, our networks, the burdens we carry and suffer from. And of course, these aren't uniform illnesses. And of course, a range of treatments are necessary to help the majority of people get better. And I look forward to learning over my last 10 or 20 years in this business about what's ahead for us.

Charles Raison, MD: Great. All right. Well, I want to thank my colleagues for a lively and informative debate, an interesting lattice work of disagreements and agreements that I think really kind of help synthesize, I think, where we're at as a field. So thank you all for joining us. Be sure to tell us who you think won this debate, if you could figure that out, I would have to think about it for quite a while, by answering the poll question that you see on your screen now. And stay well, and we'll see you next time.

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