Steven Levine, MD: You mentioned guidelines. Dr Ares-Romero, can you talk about evidence-based guidelines that you use or that are commonly used in the approach to prescription for people with TRD [treatment-resistant depression]?

Patricia Ares-Romero, MD, FASAM: Having evidence guidelines is the most challenging part. When you look at the literature, there’s no consensus. It goes back to the definition, despite the fact that this has been around for over 40 years. Refractory depression was the name that was used before, and now it’s treatment-resistant depression. It’s been around for a long time, but we still don’t have the practice guidelines for what we should do and what the best treatment is for the patient.

In my practice, I want to make sure I collaborate with and engage my patient and have communication about where they’ve been and what their journey has been up to the point when they come and sit in front of my desk for the first time. What are their goals for treatment? How can we work together to get the best treatment for them within guidelines? It’s about engaging the patient and making sure this is going to work for the patient and that the treatment will improve their outcomes. That’s what I follow.

Of course, I do the whole optimization and all that good stuff. But once they’ve been there, most of the time they’ve seen 4 providers, maybe 1 family practitioner, and have been to the ED [emergency department] 3 times, and now they’re seeing me. What other alternatives can we try? A lot of times, they’re like, “I’m tired of this. I don’t want to take any more medication. Why do I have to keep going through this?” Or, “I’m hopeless and helpless, and I don’t know what’s going to come next.” It’s about engaging the patient, seeing where they are, and finding how we can best help them. Sometimes it’s with alternative treatments.

Steven Levine, MD: That makes a lot of sense. To layer on top of all of this, the lack of clear consensus guidelines, some of the difficulty in identifying patients with TRD, the lack of options for all patients with TRD that are guaranteed to be effective outside that level of precision. We can then layer on top something you alluded to earlier, Dr Nordberg, when you started talking about social determinants of health and the extra complexity that adds. Can you say a bit more about that?

Samuel Nordberg, PhD: I’m happy to. One challenge, with mental health in general but captured in treatment-resistant depression, is that a lot of these challenges are multimodal, meaning that the developing, supporting, and maintaining factors come from a variety of places, some of which we don’t measure, or some of which we’ve only just started to measure.

With regard to social determinants, the broad takeaway is some people are depressed because their lives are depressing and they’re not getting enough sleep, they’re not safe, or they’re constantly under threat. Maybe they have food insecurity, financial insecurity, or housing insecurity. These are some of the key social determinants that can contribute to people being depressed, because they feel defeated by life. They’ve given up hope of a better future, and all they’re doing is surviving day in and day out. Without a thorough assessment of social determinants, you can’t understand that someone’s depression may be largely maintained by the fact that their life is terrible. Therefore, you’re throwing a bunch of interventions at something that ultimately doesn’t matter if they end up back on the street.

Part of the challenge in delivering more precision interventions is understanding what you’re trying to intervene with first. At Reliant Medical Group, we’ve started collecting data about social determinants. For example, if I’m presented with a patient who has been depressed for a long time and is also homeless, we’re probably not going to throw an alternative intervention at them until we can address the homelessness. Because if you can’t create a stable environment in which to recover and benefit from something like ECT [electroconvulsive therapy], the patient isn’t going to be able to sustain their benefit anyway.

Measuring for social determinants is a perfect example of that multimodal assessment that’s required if you’re going to get a robust enough picture. It ties back to what Dr Rosenzweig was saying, which is that a critical part of intervening successfully is having a good diagnostic frame for what’s going on for this patient. What’s primary and dominant? What’s the node that we need to hit first, second, and third to have a shot at addressing these complex and often deeply entrenched problems?

If you’re not using data and assessing your patients using patient-reported outcomes, leveraging the health record to the extent that you have it, and leveraging claims and other sources of information, in many respects, you’re just increasing the chances that you’re going to make the wrong choice. Often from the payer perspective, it may seem like in the clinical world we’re just throwing 1 thing after another at a patient willy-nilly. To get away from that, we need more of a robust data collection process and a robust treatment framing and intervention design system so that we’re being very deliberate about how we target patients. All that comes back to collecting the right data.

Martin Rosenzweig, MD: If I can add 1 piece as well. There are 3 areas that commonly get overlooked or underassessed. One is trauma and its role in this, particularly adverse childhood events. The second is substance. More worrying is alcohol, because it’s very hard to detect the direct effect of alcohol, but also because it interferes with the medication at the pharmacokinetic level. The third is under-recognition of medical comorbidities that impact the rate of response. Chronic pain is a vastly underestimated factor that contributes to the lack of treatment responsiveness in this population.

Sam, in your setting in primary care, you have a better shot at this, but the problem is that a lot of psychiatrists don’t operate in those integrated settings. They don’t look or understand. The studies show that 10% to 15% of psychiatric patients have a medical condition that’s causing their presentation. It’s being attentive to those factors. If someone isn’t responding, the first step is to say, “What am I missing?” vs “What can I add?” It’s that shift in mindset that’s very important in helping this population.

Samuel Nordberg, PhD: If I may add 1 more thing about this, there’s so much potential relevant information that you can’t do this via a chart review. It’s hard to put the expectation on any 1 person to figure out that full picture. This is a place where data, data visualization, and helping the critical key components of the data rise to the surface are untapped resources that we need to be leveraging a great deal more to help reduce the amount of noise and focus on the critical important signal that tells us what kind of a patient this person is and that can spread that information across multiple providers.

Transcripts edited for clarity.