Steven Levine, MD: We’ve identified a number of barriers, and we’ve identified that there’s a huge unmet need. Why don’t we transition into taking a bit of a 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 little about your understanding of what should be a typical progression in terms of a pharmacological approach to an escalation of treatment for somebody who hasn’t responded to treatment for major depressive disorder?

Patricia Ares-Romero, MD, FASAM: Sure. When a patient initially comes to me, I make sure to teach my providers and residents that we should first optimize. Whatever treatment they’re on, we want to make sure it has been at the optimal level for the adequate amount of time. Two weeks of 10 mg of citalopram isn’t adequate, so we optimize first. That’s what we want to do. Then we might consider switching. When we realize the medication hasn’t worked at adequate time dosing, we might switch them to another SSRI [selective serotonin reuptake inhibitor] or SNRI [serotonin–norepinephrine reuptake inhibitor]. Then we can do a combination. We can add another antidepressant or do augmentation strategies, such as adding a mood stabilizer or an antipsychotic.

We always want to make sure they’re doing some kind of therapy, although some patients don’t participate in it. Dr [Samuel] Nordberg made a good comment about how sometimes patients don’t have the wherewithal or desire to get there or are unable to engage in that therapy. Those are some of the strategies we use as part of our algorithm for TRD when it comes to oral therapy.

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

Patricia Ares-Romero, MD, FASAM: There are a lot of other ones beyond oral antidepressive medications and antipsychotics. We have things such as IV [intravenous] ketamine, which hasn’t been FDA approved for treatment, but there are some small studies and it’s used for multiple things off-label. There’s intranasal esketamine, which is FDA approved for major depression disorder and TRD. There’s also ECT [electroconvulsive therapy], which has been around for over 40 years.

One challenge of ECT is access. In Miami–Dade County, at least, we have difficulty accessing it. There’s transcranial magnetic stimulation as well, where patients have to go in 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’ve heard Dr Ares-Romero essentially go through our toolbox, what’s available to us right now, finishing with some therapies that we might consider alternative therapies because they’re not oral medications. Some of them are higher-touch or require higher resources. How do you think about value among those therapies?

Martin Rosenzweig, MD: There’s a piece here as well from a payer perspective. A tricky thing is there’s attention given to the diagnosis. Because what we find is a lot of people end up in treatment, and to Dr Ares-Romero’s points, there are a lot of comorbidities. Zoloft isn’t going to help someone in an unhappy relationship. Part of it is making sure that we’re treating the right thing and able to lay our rationale about where you want to go.

The other part, which is important, is also looking at the cost burden and understanding the way the system works, particularly from the patient’s point of view. Starting with generic drugs is an important thing to consider, particularly in that optimization-switching phase. You don’t want to start with branded drugs because of the way the benefit structure is designed and the pricing structure with drug manufacturers. You may end up with a patient who responds to a very expensive branded drug that you’ll probably need to keep them on for months, years, or possibly for the rest of their lives. You’ve saddled them with a very high-cost treatment. You probably could have done that in a way that is much more cost-effective and would have greater adherence. The tragedy with a patient with TRD is when you get them better and they can’t afford to stay well. There’s a piece in terms of that algorithm to consider.

With some other alternatives, particularly the somatic treatments, transcranial magnetic stimulation, and ECT, the benefit design often requires an authorization. It’s very helpful when you’re able to extract the history, whether it’s from your own records [or elsewhere]. One thing with e-prescribing is that you can go in and scroll around among all the prescriptions, not just the ones you give, and it’s HIPAA [Health Insurance Portability and Accountability Act] compliant. It’s very helpful to also look at that and document that you’ve done that sleuthing around about what the next strategy is.

The other part is that we’re very interested in quantification and the use of measurement-based care or instruments that document improvement or lack thereof. These are all tools, like STAR*D [Sequenced Treatment Alternatives to Relieve Depression] algorithm or some other helpful ones, that are out there. You have to build the strategy around the benefit coverage as well, because you want to advocate for that patient as you drive them down these various evidence-based pathways. From an insurer point of view, we cover anything that’s FDA approved and evidence based. I can obviously speak only for the company I work for. That’s how we make the decisions, looking at the evidence and literature support. There’s a partnership here around how you work within the benefit design to make sure the patient doesn’t hit those roadblocks.

Transcripts edited for clarity.