There has been slow progress in the development of interventions that prevent and/or reduce mental-health morbidity and mortality. The National Institute of Mental Health (NIMH) launched an experimental-therapeutics initiative with the goal of accelerating the development of effective interventions. The emphasis is on interventions designed to engage a target mechanism. A target mechanism is a process (e.g., behavioral, neurobiological) proposed to underlie change in a defined clinical endpoint and through change in which an intervention exerts its effect. This article is based on discussions from an NIMH workshop conducted in February 2020 and subsequent conversations among researchers using this approach. We discuss the components of an experimental-therapeutics approach such as clinical-outcome selection, target definition and measurement, intervention design and selection, and implementation of a team-science strategy. We emphasize the important contributions of different constituencies (e.g., patients, caregivers, providers) in deriving hypotheses about novel target mechanisms. We highlight strategies for target-mechanism identification using published and hypothetical examples. We consider the decision-making dilemmas that arise with different patterns of results in purported mechanisms and clinical outcomes. We end with considerations of the practical challenges of this approach and the implications for future directions of this initiative.
Keywords: experimental therapeutics; fast fail; mental health; target mechanism; treatment.