expert roundtables

Promising Areas for Future Development

by Ira D. Glick, MD, Roger McIntyre, MD, Madhukar Trivedi, MD

Overview

Newer molecular entities are actively being researched as candidates for novel antidepressant therapies. Additionally, new insights on established antidepressant medications are coming to light. As the spotlight moves to functional recovery in depression, researchers ponder how cognition might be targeted more effectively in a multi-modal therapeutic approach. There is also optimism that relevant subsets of patients with major depressive disorder (MDD) will begin to be identified in the near future. Evidence of progress in this area is already starting to emerge. Finally, the improvement of measurement-based care is also widely anticipated, especially in relation to screening patients and measuring cognitive impairments in patients with MDD.

Q: Where do you think the most progress will occur in the next decade?

Ira D. Glick, MD

Professor of Psychiatry and Behavioral Sciences, Emeritus
Stanford University Medical Center
Stanford, CA

In the field, there is talk about things like ketamine, but there is still a long way to go to show efficacy, as far as I am concerned. I am sure some of your other panelists have more expertise in this area. The pipeline in psychiatry is decreasing, and there is a reason for that. It costs so much to bring a drug to market, and a lot of the companies are pulling away. There are some newer mechanisms, however, and vortioxetine has one.

Roger McIntyre, MD

Professor of Psychiatry and Pharmacology
University of Toronto
Head, Mood Disorders Psychopharmacology Unit
University Health Network
Toronto, Ontario

“I have wondered whether, by targeting cognition, we can increase the likelihood of success and have a multiplicative effect, much like CBT in combination with pharmacotherapy clearly produces superior outcomes in subpopulations.”

Roger McIntyre, MD

One interest for me has to do with the possibility of using several approaches together. Say, for instance, we were able to take an antidepressant or a psychotropic agent that has demonstrated the ability to improve cognitive function, and then we were to combine that with a behavioral intervention (eg, an aerobic exercise intervention, a sleep intervention, or a cognitive remediation intervention). I have wondered whether, by targeting cognition, we can increase the likelihood of success and have a multiplicative effect, much like cognitive behavioral therapy (CBT) in combination with pharmacotherapy clearly produces superior outcomes in subpopulations.

And if we can ever find that cognitive target within the world of depression, the question is whether in some patients there might be a greater, synergistic effect of the pharmacotherapy with the behavioral intervention or cognitive remediation, not only on the parameters that we measure, such as the digitalized cognition measures, but it would also be very interesting to see if those changes also comport with some of the changes that we see in the brain. For example, it may not be so much the white matter, but maybe there would be a more efficient reciprocity across and between circuitry in the brain – at least in these circuits that are subserving cognition. So, that would be of interest to me, among many things.

Madhukar Trivedi, MD

Professor of Psychiatry
Director, Center for Depression Research and Clinical Care
Peter O’Donnell Jr. Brain Institute
UT Southwestern Medical Center
Dallas, TX

“This indicates that we will be able to identify biomarkers that help us subgroup patients so that we can better match treatments to patients so that we can reduce the trial and error process.” 

Madhukar Trivedi, MD

I think that the next 5-10 years will not only bring the refinement that Dr McIntyre is talking about, but we are already beginning to see those results, eg, the C-reactive protein (CRP) results that I described earlier: patients with high systemic inflammation had higher remission rates on bupropion-selective serotonin reuptake inhibitor (SSRI) combination therapy.

I think that is probably where we are moving to – much more of a precision medicine. I am not talking about matching individual patients with individual treatments, but more on the level of subgroups, where we will be able to identify biomarkers that are relevant for that patient, so that we can select a treatment based on that. And I think the idea of matching cognitive deficits with cognitive remediation is an example, but there are more.

Something else that needs to occur is the measurement-based care for patients with MDD. You know, 20 years back, diabetes care did not include the wrap-around services of a dietician or a diabetes nurse, but now those services are covered. I have no doubt that, if we persist in providing the kind of publications we are all talking about, we could and should be able to argue in favor of measurements. Otherwise, it is a much more gestalt type of decision-making, and a large proportion of patients in the population will live in symptomatic and dysfunctional states.

Antidepressant therapies_Chart

References

Greer TL, Furman JL, Trivedi MH. Evaluation of the benefits of exercise on cognition in major depressive disorder. Gen Hosp Psychiatry. July 6, 2017. pii: S0163-8343(17)30102-0. [Epub ahead of print]. Review.

Jha MK, Minhajuddin A, Gadad BS, et al. Can C-reactive protein inform antidepressant medication selection in depressed outpatients? Findings from the CO-MED trial. Psychoneuroendocrinology. 2017;78:105-113.

Mavandadi S, Benson A, DiFilippo S, et al. A telephone-based program to provide symptom monitoring alone vs symptom monitoring plus care management for late-life depression and anxiety: a randomized clinical trial. JAMA Psychiatry. 2015;72(12):1211-1218.

Sanacora G, Frye MA, McDonald W. A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry. 2017;74(4):399-405.

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