treatment-resistant depression

Hi, Julie and team.

I've been struggling with the treatment-resistant depression for some time.

Is it in my best interest to pursue ketamine treatment? Love from Michigan.

Okay, so Mary, before you do any kind of treatment, I want you to look up Chris Palmer, Dr. Chris Palmer.

Today, we're talking about what happens when the traits that we call personality, perfectionism, people-pleasing, achievement, anxiety, even I'm fine, may actually be roles we learned to perform in order to survive.

After childhood trauma, addiction, eating disorders, anxiety, OCD, panic disorder, complex PTSD, and chronic illness, as well as years of treatment for r- uh, treatment-resistant depression, she reached a point where she believed she had exhausted every option available to her.

After years of that roller coaster, medications, therapies, treatment programs, and hospital admissions, she ultimately underwent electroconvulsive therapy, or ECT, and began asking a better question, and we are all about the better questions in this place.

So she stopped asking, "What's wrong with me?" and asked, "What did these parts of me learn in order to survive?" So today, she writes and speaks about trauma, grief, recovery, leadership, psychological safety, and what it means to move from just enduring your life to really living it.

So yeah, my friends, what she's saying is it doesn't just magically disappear because you have new language for it and you are in recovery.

It takes hard work, um, good work, worth it work, but daily practice for sure.

Well, I wanna talk about something that you have lived through, and that is treatment-resistant depression, and what you finally found, what modality you finally found helped with that.

So for those of us who don't know, or some of our listeners who don't know, how did, how did treatment-resistant depression kind of manifest in, in your life? What were some modalities you tried before, and how did the ECT kinda change and revolutionize things for you?

This is an eight-point delta on the moderate between drug and placebo in Chase's study, and that complements the equivalent effect size in the Lancet Psychiatry PAX-D study, which translated from their outcome measure to Madras is a bit over seven point delta and that also complements the Lund study which looked at anhedonia as the outcome as opposed to traditional depressive symptoms that also showed a large effect.

We're talking 0.6, 0.8, 0.9, even as much as 1.1 Cohen's D effect sizes, which would be the equivalent of like three or four times the typical antidepressant effect in TRD patients.

So really, really exciting basis for this program now being brought into a drug development late stage framework.

Yeah, let's talk about that.

And what they did was they took treatment-resistant patients, the kind that you'd see, for example, in esketamine studies, and then added Pramopexil on top.

And so that adjunctive context is what we then are doing for the phase 2B and this first phase 3.

So TRD patients, they stay on their baseline medication.

You add Alto 207 on top, which is titrated very quickly to a higher target in terms of milligrams of Premipexol than Pax-D, so trying to really capture that efficacy while mitigating side effects and getting there quickly, two and a half times faster than the Premipexol label, and then following them for eight weeks total treatment.

Should you move to lithium? Another atypical antipsychotic? What about thyroid supplementation or ketamine? And you wonder, might there be any other options? Well, that's the question we're dealing with in today's episode.

Treatment-resistant depression, or TRDA, is defined by inadequate response to at least two different adequate antidepressant trials, and it affects more than a third of patients who seek treatment for depression.

Ketamine and esketamine can offer fast relief for many patients, but concerns about administration logistics, side effects, durability of response, and misuse potential are limiting.

Lithium, thyroid supplementation, and antipsychotic augmentation similarly can be very helpful for depression but require regular laboratory monitoring.

And now let's take a listen to Dr. Verne.

This is Derek Vergne with the Psychopharmacology Institute's Quick Takes.

Today, I'm going to be discussing a paper from a group in China titled, Neutroceutical Eicosapentaenoic Acid EPA in Treatment-Resistant Depression, Clinical and Psychoneuroimmunity Implications.

Treatment-resistant depression remains a significant challenge in psychiatric practice.

No, absolutely not.

It still has incredibly strong meta-analytic support for pulling patients out of entrenched, treatment-resistant depression.

It shouldn't be forgotten just because newer drugs exist.

So what's at the very end of the line in the depression chamber? The heavy artillery.

Since the episode first aired, multiple studies published in Nature Medicine and other medical journals have supported the potential of psychedelic treatments in reconfiguring neural circuitry as a means of treatment.

In the episode, we discuss the challenges of designing clinical trials involving psychedelic therapies and their potential applications across a range of psychiatric disorders, including treatment-resistant depression.

This field is evolving rapidly, and I hope you learn as much from this conversation as I did.

There's evidence that humans have experimented with psychedelics for thousands of years.

Studies that examine the therapeutic applications of psychedelics are gaining momentum and showing promise.

And the need now is greater than ever, given the worsening mental health epidemic and because many of today's standard forms of treatment don't work for everyone.

A fairly sizable percent of people who have mood disorders like major depression either don't respond fully or don't respond at all to conventional drugs that we have.

Psychedelic compounds might provide relief for these patients, but there are still a lot of unanswered questions about how to responsibly study them and eventually use them to treat patients with a range of mental disorders.