The Concept of Treatment-refractory Addiction: Drawing on Psychiatric Insights to Improve Addiction Research.

The concept of treatment-refractory addiction (TRA), while relatively new to the addiction field, is a well-established concept in other areas of medicine and psychiatry. Recent commentaries have highlighted the need for clearer conceptualization and definition of TRA. This commentary argues that conceptual frameworks established in other psychiatric domains (eg, depression, schizophrenia, obsessive-compulsive disorder) can and should inform the development of criteria and strategies for identifying and addressing TRA in substance use disorders (SUDs). Central to this effort is the recognition that treatment response variability is the norm rather than the exception in SUD care. Conceptualizations and definitions of TRA should seek to distinguish true refractoriness from suboptimal or incomplete treatment exposure, which can arise from inadequate treatment exposure or adherence, and consider whether nonresponse is present from the start (primary refractoriness) or emerges over time (secondary refractoriness). Advanced analytic methods, including unsupervised clustering, offer opportunities to characterize heterogeneity in treatment outcomes in aggregate or over time, identify patient subgroups that do not benefit from standard therapies, and explore underlying mechanisms of nonresponse. By integrating lessons learned from other psychiatric disorders, addiction scientists can develop more precise definitions of TRA, which will ultimately inform the development of diagnostic/prognostic frameworks, and targeted interventions.