Setting the Value of TRD Processing Options

Steven Levine, MD: We have identified a number of barriers, and found that there is a huge unmet need. Why not take a little deeper dive into some of the existing treatment options for people with TRD [treatment-resistant depression]? Let’s start with you, Dr. Ares-Romero. Can you talk a bit about your understanding of what a typical progression should be in terms of a pharmacological approach to treatment escalation for someone who has not responded to treatment for a major depressive disorder?

Patricia Ares-Romero, MD, FASAM: Sure. When a patient comes to see me for the first time, I make sure to teach my providers and residents that we need to optimize first. Whatever treatment they are on, we want to make sure it has been at the optimal level for the right amount of time. Two weeks of citalopram 10mg is not enough, so we optimize first. That’s what we want to do. Then we might consider changing. When we realize that the drug has not worked at an adequate time, we can replace it with another SSRI [selective serotonin reuptake inhibitor] or SNRI [serotonin–norepinephrine reuptake inhibitor]. Then we can make a combination. We can add another antidepressant or do augmentation strategies, like adding a mood stabilizer or an antipsychotic.

We always want to make sure they are in some sort of therapy, even if some patients don’t participate. Doctor [Samuel] Nordberg made a good comment about how sometimes patients don’t have the means or the desire to make it or are unable to commit to this therapy. These are some of the strategies we use as part of our algorithm for TRD in oral therapy.

Steven Levine, MD: Thank you. What if you need to go beyond these? What other options and strategies are available?

Patricia Ares-Romero, MD, FASAM: There are many others beyond oral antidepressants and antipsychotics. We have things like IV [intravenous] ketamine, which has not been approved by the FDA for treatment, but there are a few small studies and it is used for several off-label things. There’s intranasal esketamine, which is FDA-approved for major depressive disorder and TRD. There is also ECT [electroconvulsive therapy]which has existed for more than 40 years.

One of the challenges of ECT is access. In Miami-Dade County, at least, we have trouble accessing it. There is also transcranial magnetic stimulation, which patients have to enter every day for about 6 weeks. Then, of course, there are psychotherapy strategies: CBT [cognitive behavioral therapy]interpersonal psychotherapy, DBT [dialectical behavioral therapy]any of those things that can also help patients with treatment-resistant depression.

Steven Levine, MD: Thank you. Dr. Rosenzweig, we heard from Dr. Ares-Romero going through our toolkit, what’s available to us right now, ending with some therapies that we might consider alternative therapies because it’s not about drugs oral. Some of them are more tactile or require more resources. What do you think of the value of these therapies?

Martin Rosenzweig, MD: There is also an element here from the perspective of the payer. One tricky thing is that there is attention given to diagnosis. Because what we’re seeing is that a lot of people end up going through treatment, and to use Dr. Ares-Romero’s arguments, there are a lot of comorbidities. Zoloft is not going to help someone in an unhappy relationship. Part of that is making sure we’re dealing with the right thing and being able to explain where you want to go.

The other part, which is important, is also looking at the cost burden and understanding how the system works, especially from the patient’s perspective. Starting with generic drugs is an important thing to consider, especially in this phase of optimization change. You don’t want to start with brand name drugs because of the way the benefit structure is designed and the pricing structure with the drug manufacturers. You may find yourself with a patient who is reacting to a very expensive brand name drug that you will likely have to keep for months, years, or perhaps the rest of their life. You imposed a very expensive treatment on them. You probably could have done it in a much more cost-effective way and with greater uptake. The tragedy with a patient with TRD is when you make them better and they can’t afford to stay healthy. There is an element in terms of this algorithm to consider.

With certain other alternatives, including somatic treatments, transcranial magnetic stimulation and ECT, the design of benefits often requires authorization. This is very useful when you are able to extract history, whether from your own folders or elsewhere. One thing with e-prescribing is you can enter and scroll through all the prescriptions, not just the ones you give, and that’s HIPAA [Health Insurance Portability and Accountability Act] compliant. It is also very useful to review this and document the fact that you have researched the next strategy.

The other part is that we are very interested in quantifying and using care or instruments based on measurements that document improvement or lack of improvement. They are all tools, like STAR*D [Sequenced Treatment Alternatives to Relieve Depression] algorithm or other useful ones, which are out there. You also need to build the strategy around benefit coverage, because you want to advocate for that patient while driving them down those various evidence-based pathways. From an insurer’s perspective, we cover anything FDA-approved and evidence-based. Of course, I can only speak on behalf of the company I work for. This is how we make decisions, reviewing evidence and supporting documentation. There’s a partnership here on how you work within the benefit design to make sure the patient doesn’t run into those barriers.

Transcript edited for clarity

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