An Experimental Therapeutic Approach to Psychosocial Interventions
In my first few messages, I wrote about my priorities for the NIMH. In doing so, I made a decision to focus first on the perspectives I bring to the job—the opportunities and challenges I see in suicide prevention, neural circuits, and computational and theoretical approaches. I did this partially so you might have the chance to learn something about me. But I also did this because while you were learning about me, I spent most of my time learning from you about the issues facing our field. Well, six months in, I think it only fair that I start telling you something about what I’ve learned.
Of the many issues we face, one of the most important is the relative dearth of emerging, novel therapies. The oft-berated pharmaceutical industry, we hear, has de-emphasized mental illness research, with many companies leaving it altogether. And who can blame them, given that the recent history of psychiatric drug development is littered with expensive, failed trials. While we can be optimistic about the possibility of transformative treatments in the future—with increasing knowledge of genetics and neuroscience to lead the way—in the near term, we need to look elsewhere for more modest but crucial gains to help the patients of today.
A crucial toolset with the potential for near-term impact comprises psychosocial interventions. Indeed, for some conditions (e.g., eating disorders, borderline personality disorder, conduct disorders among youth), behavioral, cognitive, interpersonal, and other psychosocial treatments have proven to be the best supported, or in some cases, the only evidence-based approaches. I know this first hand—through a couple of random assignments in my residency, I somehow became skilled at Habit Reversal Therapy,1 an evidence-based, manualized treatment for trichotillomania and related disorders. I tried it in a patient after several (not very evidence-based) pharmacological treatments failed, and it worked remarkably well—for that patient, and for the handful of patients I’ve treated with it since. Still, even for the best interventions, some fraction of individuals do not respond, and for others, response is incomplete or not sustained. Indeed, a couple of my patients would return for “refresher courses” every year or two. From my perspective, and from the perspectives of those I’ve talked to in the field over these past few months, it is pretty clear that we need to develop and test new psychosocial approaches, and to refine and optimally deploy existing strategies. But how do we do so in a principled manner, avoiding simply rehashing old discoveries and focusing our efforts on approaches that can actually advance the field and improve standards of care?
One possible way forward is written into the NIMH Strategic Plan for Research, which emphasizes an experimental therapeutics approach to translating the growing understanding of the factors that cause and sustain mental illnesses into new or improved approaches to prevention and treatment. Discoveries in neuroscience and behavioral science can suggest malleable targets (and potential mediators) for novel intervention strategies. Evaluating the relationship between changes in these targets or mediators and changes in symptoms allows us to fine-tune our understanding of mental illness, and helps us prioritize the most promising interventions for further investment. Consideration of these factors enables research aimed at refining therapies to increase potency and efficiency, and personalizing interventions to ensure that they are optimally matched to individual needs.
Some have said that the experimental therapeutics approach is an impediment to psychosocial intervention research. I think this is an unfortunate misunderstanding. The experimental therapeutics approach is fundamentally consistent with the clinical psychological science field’s longstanding commitment to advancing understanding of therapeutic change mechanisms. This empirically-grounded, mechanism-based approach to the development of behavioral and psychosocial interventions identifies potentially mutable factors based on psychopathology research findings that are substantially associated with the etiology, maintenance, severity, and/or course of disorders. Intervention strategies that map onto these targets are designed and tested to see if manipulation of the putative targets leads to clinical improvement. The focus, then, is not only on testing whether interventions work, but also on understanding whether interventions work through the presumed mechanisms.
To counter the viewpoint that the experimental therapeutics approach impedes psychosocial intervention research, and to facilitate psychosocial intervention-based clinical trial applications, we have developed a new set of clinical trial funding announcements that specifically address these issues. These new and revised announcements support the development and testing of a wide range of prevention and intervention modalities: cognitive, behavioral, and other psychosocial approaches (including technology-assisted approaches to facilitate the uptake and delivery of behavioral/psychosocial approaches); psychopharmacological interventions; and interventions utilizing direct brain modulation/stimulation. They also specifically support interventions across the lifespan, and the revised language attempts to more faithfully align with the concepts and language conventionally used for different intervention modalities. We also continue to encourage research to test the effectiveness of therapeutic, preventive, and services interventions in community practice settings through specific clinical trials funding announcements.2 This funding can support projects that seek to optimize the potency and efficiency of preventive and therapeutic interventions and test strategies for promoting uptake and fidelity in the delivery of evidence-based psychosocial approaches.
These announcements underscore our continued support of the development and testing of psychosocial interventions, in the greater context of an approach that will all the while enhance our understanding of the mechanisms underlying psychiatric illness and recovery. It is still my firm belief that the breakthrough treatments of tomorrow are crucially dependent upon such an understanding, to which we remain resolutely committed. But in the meantime, we need to make sure we do all that we can for those who suffer now.