Enabling Discovery, Development, and Translation of Treatments for Cognitive Dysfunction in Depression: A Workshop
February 24, 2015
National Academy of Sciences
2101 Constitution Avenue, Room 120
Washington, DC 20418
Background: It is increasingly recognized that many patients, while fulfilling traditional criteria for response or remission of depression, continue to have subjective complaints and have difficulties returning to their previous level of function (e.g., returning to work). Increasing clinical and epidemiologic evidence suggests that cognitive dysfunction is an underestimated dimension of depression. Such dysfunction could, in part, explain patients’ poor response and/or poor functional outcomes. Currently available pharmacological treatments appear to only address cognitive dysfunction in depression in a limited way, and some treatments may even worsen cognition in some patients. Moreover, there is a lack of alignment in the scientific field on the best way to assess cognitive dysfunction and whether this dimension is congruent with, or independent from, mood symptoms. There is also an opportunity in this domain to look beyond the classical definition of major depressive disorder and consider approaches involving neurocircuitry and precision medicine. The goal of the workshop is to bring together key stakeholders to explore ways of speeding improvement of the discovery, development, and regulatory path for new treatments addressing this aspect of depression.
Meeting Objectives:
- Examine opportunities to facilitate new target and validation strategies aimed at reinvigorating the development of treatments that address cognition, an undertreated aspect of depression.
- Discuss how lessons from the translational aspects of cognitive dysfunction in other disorders could apply to depression.
- Highlight gaps and limitations of current tools for assessing cognitive dysfunction in depression in clinical trials, and consider how improvements in cognition could relate to functional outcomes.
- Explore potential regulatory challenges, such as recognition of cognitive dysfunction in depression as a public health need and opportunities for treatments.
| 8:30 a.m. | Opening Remarks |
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THOMAS INSEL, Workshop Co-Chair Director National Institute of Mental Health |
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THOMAS LAUGHREN, Workshop Co-Chair Director Laughren Psychopharm Consulting, LLC |
SESSION I: BACKGROUND AND OVERVIEW
Session Objectives: Provide an overview of the unmet medical need of cognitive dysfunction in depression. Discuss lessons learned from developing treatments for cognitive dysfunction in schizophrenia. Examine opportunities to facilitate new target and validation strategies aimed at reinvigorating the development of treatments that address cognition.
| 8:40 a.m. | Opening Remarks |
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ANDREW NIERENBERG, Session Moderator Thomas P. Hackett, M.D., Endowed Chair in Psychiatry Massachusetts General Hospital |
| 8:45 a.m. | Cognitive Dysfunction in Depression: The Need for Discovery, Development, and Translation in This Domain (20 min talk + 10 min discussion) |
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BARBARA SAHAKIAN Professor of Psychiatry Cambridge University |
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| 9:15 a.m. | Experimental Design and Approaches: Opportunities to Facilitate New Target and Validation Strategies for Cognitive Dysfunction in Depression (20 min talk + 10 min discussion) |
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CATHERINE HARMER Professor of Cognitive Neuroscience University of Oxford |
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| 9:45 a.m. | Lessons Learned from Cognitive Dysfunction in Schizophrenia (20 min talk + 10 min discussion) |
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MICHAEL GREEN Professor-in-Residence Department of Psychiatry and Biobehavioral Sciences Geffen School of Medicine, University of California, Los Angeles |
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| 10:15 a.m. | BREAK |
SESSION II: STATE OF THE SCIENCE FOR TREATING COGNITIVE DYSFUNCTION IN DEPRESSION
Session Objectives: Examine the current state of the science for treating cognitive dysfunction in depression, including what aspects of this dysfunction can be treated with medications, cognitive behavioral therapy, devices, and other treatment modalities. Identify promising future directions.
| 10:30 a.m. | Opening Remarks |
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AMIT ETKIN, Session Moderator Assistant Professor of Psychiatry and Behavioral Sciences Stanford University |
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| 10:35 a.m. | Effects of Non-Pharmacological Treatments on Cognition in Depression |
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DIEGO PIZZAGALLI Professor of Psychiatry Harvard Medical School |
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| 10:50 a.m. | Effects of Pharmacological Treatments on Cognition in Depression |
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RICHARD KEEFE Professor of Psychiatry and Behavioral Sciences Duke University |
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| 11:05 a.m. | Effects of Cognitive Remediation on Cognition in Depression |
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CHRISTOPHER BOWIE (by videoconference) Clinical Psychologist and Associate Professor Queen’s University |
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| 11:20 a.m. | Discussion Among Panelists and Workshop Participants |
| 12:00 p.m. | LUNCH |
SESSION III: DESIGN AND ASSESSMENT CHALLENGES
Session Objectives: Examine opportunities and challenges in studying and assessing treatments for cognitive dysfunction in depression, including combination therapies. Highlight gaps and limitations of current tools for diagnosing and evaluating depression in clinical trials, and consider how the indexes could be expanded to include indexes of cognitive functioning.
Discuss how improved cognition can be measured in short trials and the potential role of proxy measures. Consider acute versus residual treatment.
| 12:45 p.m. | Opening Remarks |
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MADHUKAR TRIVEDI, Session Moderator Betty Jo Hay Distinguished Chair in Mental Health University of Texas Southwestern Medical Center |
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| 12:50 p.m. | Design |
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MAURIZIO FAVA Director, Clinical Research Program Massachusetts General Hospital |
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| 1:05 p.m. | Assessment |
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PHILIP HARVEY Professor of Psychiatry and Behavioral Sciences University of Miami Miller School of Medicine |
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| 1:20 p.m. | Lifespan Issues |
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PATRICIA AREÁN Professor of Psychiatry University of California, San Francisco, School of Medicine |
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| 1:35 p.m. | Discussion Among Panelists and Workshop Participants |
| 2:15 p.m. | BREAK |
SESSION IV: REGULATORY CHALLENGES AND POTENTIAL SOLUTIONS
Session Objectives: Explore potential regulatory challenges, such as recognition of cognitive dysfunction in depression as a public health need and opportunities for treatments. Examine methods for evaluating cognitive dysfunction in depression. Discuss the evidentiary base that would be needed for approval of treatments for cognitive dysfunction in depression, including combination treatments.
| 2:30 p.m. | Opening Remarks |
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THOMAS LAUGHREN, Session Moderator Director Laughren Psychopharm Consulting, LLC |
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| 2:35 p.m. | Food and Drug Administration Perspective: Drugs |
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TIFFANY FARCHIONE Acting Deputy Director Division of Psychiatry Products Food and Drug Administration |
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| 2:45 p.m. | Food and Drug Administration Perspective: Devices |
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CARLOS PEÑA Director, Division of Neurological and Physical Medicine Devices Office of Device Evaluation Center for Devices and Radiological Health Food and Drug Administration |
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| 2:55 p.m. | European Medicines Agency Perspective |
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MARIA ISAAC (by videoconference) Senior Scientific Officer European Medicines Agency |
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| 3:05 p.m. | Addressing Regulatory Challenges |
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THOMAS LAUGHREN Director Laughren Psychopharm Consulting, LLC |
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| 3:20 p.m. | Discussion Among Panelists and Workshop Participants |
| 4:00 p.m. | BREAK |
SESSION V: MOVING FORWARD
Session Objectives: A panel will synthesize and discuss key highlights from the workshop presentations and discussions, including identifying concrete next steps for action and research.
| 4:15 p.m. | Panel Discussion |
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ANDREW NIERENBERG Thomas P. Hackett, M.D., Endowed Chair in Psychiatry Massachusetts General Hospital |
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AMIT ETKIN Assistant Professor of Psychiatry and Behavioral Sciences Stanford University |
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MADHUKAR TRIVEDI Betty Jo Hay Distinguished Chair in Mental Health University of Texas Southwestern Medical Center |
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THOMAS LAUGHREN Director Laughren Psychopharm Consulting, LLC |
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| 4:40 p.m. | Discussion Among Panelists and Workshop Participants |
| 5:15 p.m. | Final Comments |
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THOMAS INSEL, Workshop Co-Chair Director National Institute of Mental Health |
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THOMAS LAUGHREN, Workshop Co-Chair Director Laughren Psychopharm Consulting, LLC |
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| 5:30 p.m. | ADJOURN WORKSHOP |
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