New Tulsa-based study sheds light on why antidepressants fail for 30% of patients

A groundbreaking study based at the Laureate Institute for Brain Research in Tulsa could reshape how doctors understand and treat a condition called treatment-resistant depression, or TRD.

The study, recently published in "JAMA Psychiatry," draws on massive datasets and offers new insights into the genetic and cognitive risk factors behind TRD.

The full study, which involved analysis of data from more than 500,000 participants, is part of the National Institutes of Health's All of Us Research Program.

Dr. Chun Chien Fan, the study’s principal investigator, spoke in-depth with News On 6's Dave Davis about the research and its implications.

Q: Have you ever heard of treatment-resistant depression or TRD?

A: "It's more common than you might think, and a potential breakthrough study based in Tulsa could really change the game."

Q: Tell me about this study that was published in JAMA Psychiatry.

A: "This study will look at the gigantic data. We use the data set from the research program called All of Us. It is a large study. Have half million people across the United States and they all share their medical records of their entire life, have million kinds of genetic variants, and this funded study by the National Institute of Health, they enable us to have a bunch of data scientists at Laureate Institute for Brain Research looking at the data and begin to think about what is [the] contributing factor to treatment resistance among patients with major depressive disorder?"

Q: When people have TRD, what are their bodies resisting?

A: "They are resisting any pharmacological treatment. Somehow, because the first line of treatment for major depressive disorder is an antidepressant, like SSRI. This is more like Prozac, that kind of stuff. So somehow they, they have been trying several type of these kind of antidepressant, but somehow it doesn't work at all, they just stop treatment eventually."

Q: Is this common in people with depression, where just the pills aren’t working?

A: "Yes, so it's surprisingly quite common among people who suffer from depression. It's 30% of people who have depression will read or become treatment resistant."

Q: Tell me about the genetic risk factors found in this study.

A: "What we found is, surprisingly, it is the genetic risk factor for having a personality trait that you easily get worried and you have negative thinking, they have huge impact the risk for treatment resistant. Another thing that we found is your cognitive function, meaning that how you make decisions, you also have a huge impact in terms of developing treatment resistance when you've been diagnosed with major depressive disorder."

Q: Can your findings be broadly applied? What are the ways doctors can use this now?

A: "We do think this has an immediate impact on it because think about that, usually we think about the treatment resistance. It's about, well, you might need to find the right medication. You find the right drug. But in our case, what we found is, well, how you make a decision to receive medication and maintain the treatment is quite important, so have a kind of good discussion between doctor and patients. It's quickly rolling here, and when you find your patient has a tendency to think negatively, you probably be more vigilant. Probably need to be more proactive."

Q: What is your hope for the future and what you see down the line for people suffering from depression?

A: "Yes, I think down the road we need a personalized approach, right? Right now, it's like one size fits all, or prescribed first line use and move on to the next. If it doesn't work, let's see how things play out eventually, right? But the thing is, you need more personalized touch. You need to know what is predisposing risk factor, and doctor needs to proactively discuss with the patients how to maintain the baseline of use."