Treating Residual MDD Symptoms With Novel Mechanisms

At Psych Congress Elevate 2023 in Las Vegas, Nevada, Greg Mattingly, MD, associate clinical professor at Washington University and president of the Midwest Research Group in St. Louis, discussed the still-unmet needs in modern depression treatment following his session “Clinical Advances in Major Depressive Disorder: Strategies to Optimize Patient Care and Outcomes.” Amid recent research that shows patients are wanting more MDD therapies that improve safety and tolerability, Dr Mattingly examines the largest challenges that patients may be facing with treatment, why that is, and how novel mechanisms coming down the pipeline could help.

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Read the Transcript:

Psych Congress Network: Research has shown that there's an unmet need in MDD treatment for therapies that help improve safety and tolerability. Why do you think this is an area that is still lacking?

Greg Mattingly, MD: We know that unfortunately in the last decade, we've been losing the battle to depression. Whereas many other health conditions, cardiovascular disease, outcomes with many types of cancer, type 2 diabetes, have seen major advances. Unfortunately, in the field of depression, we've seen setbacks. We've seen that the rates of depression have more than doubled in the United States in the last 10 years. And not only rates of depression, but disability due to depression has gone up in the last 10 years.

So when we think about kind of losing the battle of depression, it makes us step back and say, what are the unmet needs? What are the unmet challenges? What are the hurdles we can overcome to provide better care for our patients? One of the unmet needs is medications with a faster onset. If you're struggling with major depression, if that's your son at university, if that's your wife taking care of your children, if that's you trying to go to your job, think about a medicine that takes 4 weeks, 6 weeks, 8 weeks to have onset, that can feel like a lifetime.

That can be a university student who's lost a semester of college. That can be a mom who's gotten overwhelmed taking care of her children. That can be a dad who's had to go on disability at work over the course of a month waiting to see if a medicine will work. So one of the unmet needs is faster onset. So we're looking at novel mechanisms that primarily go around the GABA glutamate interface that tend to trigger neuroplasticity and induce neuroplasticity in a matter of hours to days instead of weeks to months. So faster onset.

I think the second biggest unmet need is residual symptoms. Many of our patients get partially better, but not all the way well. And the analogy I use, it's just like treating an infection. If I treat your infection but leave you with a little pocket of pneumonia, over time, the pneumonia's going to come back. The same thing's true with depression. If I get you partially better, but leave residual symptoms... those residual symptoms may be anhedonia, may be insomnia, may be energy fatigue, concentration... if I leave you with any of those residual symptoms, just like any other illness, depression's going to come back.

And when it comes back, we know that depression tends to metastasize within people's life. And when I say metastasize, what do I mean? When it comes back, it becomes more complicated. It becomes more lethal, it becomes more refractory to future treatments, and it tends to spread into other types of comorbidities. So faster onset, treating residual symptoms with novel mechanisms that are on the horizon.

Greg Mattingly, MD, is a physician and principal investigator in clinical trials for Midwest Research Group. He is also a founding partner of St. Charles Psychiatric Associates where he treats children, adolescents, and adults. A St Louis native, he earned his medical degree and received a Fulbright scholarship while attending Washington University. He is an associate clinical professor at Washington University where he teaches psychopharmacology courses for third year medical students. Dr Mattingly currently serves as the President-Elect for APSARD-The American Professional Society of ADHD and Related Disorders.