Treatment Options for Patients With Major Depressive Disorder (MDD), PTSD, and/or Bipolar Disorder

In Part 2 of this podcast, Steering Commitment Member Rakesh Jain, MD, MPH, answers pressing questions about rapid acting antidepressants (RADs), Zuranolone or other gamma-aminobutyric acid (GABA) urgent modulators in the treatment of PTSD, and rates of bipolar diagnoses under different treatment regimens.

Saundra Jain, MA, PsyD, LPC, Adjunct Clinical Affiliate, University of Texas at Austin School of Nursing, moderates the session.

Listen to Part 1 of this fascinating Q&A here!

Read the Transcript:

Dr Saundra Jain: Next question. What are the benefits to the patient for rapid acting antidepressants and does it make any long term impact on those patients?

Dr Rakesh Jain: I think that's a very thoughtful question because the obvious thing is less time you suffer the better it is. That is obvious. And that is obviously an advantage to RADs. It reduces the amount of time a person suffers from depression, but there are far greater advantages than just that. So let's talk about it a bit. So repeated studies, some of the studies I actually showed you during my presentation, demonstrate the following: the shorter the duration of depression, greater the chance the patient will achieve remission and lower the chance that they might have a recurrence.

So perhaps an analogy I could use or a metaphor I could use is perhaps your yard. If you've got a few weeds there, you can probably say, well, what's the big rush in taking the weeds out of my yard today. I can always take it out tomorrow. They'll still be there. Well, you're right, but just like your yard, weeds that are allowed to stay there actually spread their roots out and not only become more difficult to get rid of, they start propagating even new challenges, new weeds. That is a near perfect example of why we should be interested in RADs, not just to reduce the duration of depression though that's a very big deal, but to literally change the trajectory.

The long term course and outcome of depression in them is directly correlated to how long it took to get undepressed and how quickly were you able to move into remission status. So Saundra, I'm hoping through the sharing of this, I'm encouraging clinicians to really become really a fighter, not just for very good treatments, but good treatments that are rapid in onset because the rapidity of onset clearly seems to change the entire life course of major depression in that patient.

Dr Saundra Jain: Yeah. It seems like the other thing that comes to my mind as you're using that metaphor is strike while the iron is hot, that when we see it, do something, step in for better outcomes.

Dr Rakesh Jain: Yes. Yes. That's really well said. And outcomes are not just going to waiting around for you. The longer the depression is present in the person's mind, brain, and body just like weeds in your yard, they will be more difficult to get rid of tomorrow. So, might as well get to it as fast as you possibly can.

Dr Saundra Jain: Yeah. I love that metaphor with Rakesh because anybody who's ever managed their own yard knows exactly what you're talking about. I think that one's going to stick with all of us, so great job. Question for you regarding the treatment of PTSD. Has Zuranolone or other GABA urgent modulators also been studied for the treatment of PTSD?

Dr Rakesh Jain: Yeah. I can see why our colleague asked that question. Zuranolone, which we talked about earlier is a GABA A positive allosteric modulator. Ooh, that's a mouthful. Just saying it, you want to take a sip of water. But the key to remember is it is not a benzodiazepine. Benzodiazepines are only intra synaptic GABA A agonists, but this Zuranolone is a neuroactive steroid, NAS. Let's get to know that acronym NAS and it affects both extrasynaptic, meaning outside the synapse and intra synaptic, which means inside the synapse.

I can see why you asked that question because PTSD often comes with depression, often comes with sleep problems and anxiety problems. The answer is so far, it has not been studied, but I can absolutely see why you're intrigued about it. And one hopes that there will be studies, particularly when PTSD and major depression coexist. Just like you, I'm very intrigued by this mechanism of action medication and its potential use in PTSD.

Dr Saundra Jain: All right. Another very popular question. So this group of clinicians are asking, what is the rate of uncovering of a bipolar diagnosis using glutamate and GABA modulating RADs as compared to SSRIs and SNRIs in patients treated for a major depressive episode?

Dr Rakesh Jain: Yeah, this question's clearly coming from a clinician who just like you and I has been previously bitten by a switching on SSRIs and SNRIs. So let me first share the good news and then I'll share more good news. I don't have bad news to share with you on this. The database coming from glutamate based medications—that would be an MDA antagonist, that would be ketamine, that would be Esketamine, that would be the AXS-05 that we discussed just a little bit earlier—shows that the rate of switching is not high. It's just not. So even though those are anti-depressants for reasons not clearly elucidated so far, the switching rates are actually not high.

I would have to add the caveat in those studies. Bipolar is pretty well screened for, but still that's a good finding. In terms of the GABA medications that we talked about Saundra, the neuroactive steroid GABA medications, the same held true. The rate of switching was not significant. So it's my hope that we may be at the precipice of 2 new classes of antidepressants that in the context of a clinical trial with careful screening, the switch rates were simply not something that was of much concern at all. And one hopes that stays true for clinical practice as well. So stay very optimistic on that issue folks.

Dr Saundra Jain: I was going to say that is very good news, reassuring. Well Rakesh, you know this always happens when we run out of time. There are still many more questions, but to stay true to the clock as we kind of round out the day and get closer to the end, I want to thank our attendees. I know you'll join me in this, thanking them for some really thought provoking questions. I want to thank you as well for a robust Q&A and for a really interesting presentation this afternoon.

Dr Rakesh Jain: My pleasure, Saundra. Thank you. And I'm so glad this very important topic of rapid acting antidepressants resonates so well with our Psych  Congress family member. So that's wonderful. So thank you.

Dr Saundra Jain: Absolutely.