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March 31, 2026Current Drug Research Reviews2 citations

Treatment-refractory Addictions: Clinical Characterization and anOperational Model for Integrated Management

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JTJúlio ToralesATAnthon Daniel Torres-RomeroMWMarcela Waisman-Campos

Key Points

  • To develop a framework for understanding treatment-resistant addictions and propose criteria for effective management.
  • Analyzed existing data on treatment-resistant addictions.
  • Developed functional criteria based on depression and schizophrenia treatment frameworks.
  • Evaluated pharmacological and psychotherapeutic approaches to treatment.
  • Proposed an integrated operational model for patient care involving diagnostics and therapies.
  • Identified key characteristics of treatment-refractory addictions, including impulsive behavior and psychiatric conditions.
  • Developed criteria distinguishing true refractoriness from pseudo-resistance.
  • Highlighted various treatment combinations including GLP-1 agonists, ketamine, and psychotherapies.
  • Emphasized the need for empirical testing to validate proposed treatment frameworks.

Abstract

The current mental health system faces an important yet not well-understood problem, which involves addictions that do not respond to treatment. The cases present with ongoing substance abuse, multiple treatment failures, psychiatric conditions, social instability, and work-related problems. The absence of standardized operational criteria creates problems with immediate patient identification, comparing research study results, and healthcare providers' efforts to create structured treatment plans. The article combines existing data about treatment-resistant addiction to create an initial framework that explains its medical characteristics, brain functions, social aspects, and treatment approaches. The research uses depression and schizophrenia treatment-resistant frameworks to develop functional criteria, which include multiple treatment failures, ongoing disability, complex medical conditions, and inadequate response to optimal treatment protocols. Healthcare providers can identify actual refractoriness using established criteria that help distinguish it from pseudo-resistance, which occurs due to incorrect medical diagnoses, insufficient medication exposure, or non-compliance with treatment instructions. The research presents typical medical signs that appear in people who do not respond to substance use treatment through their impulsive behavior, their inability to identify emotions, their background of trauma, their presence of multiple psychiatric conditions, and their exposure to poverty and prison life. The review evaluates present-day pharmacological treatments that combine GLP-1 receptor agonists with ketamine and cannabidiol, partial agonists, and neuromodulation methods (rTMS and tDCS), as well as psychotherapeutic approaches (ACT, DBT, MBRP, and CRA) to improve treatment outcomes. We propose an operational system that integrates diagnostic evaluation with medication treatment and psychotherapy services, brain function assessments, and social assistance programs. This model is focused on a team-based approach aimed at delivering personalized medical care. Patients’ non-adherence is considered as a clinical issue rather than a factor of social labeling or exclusion. Empirical testing is needed to validate the proposed evaluation criteria, as well as treatment effectiveness in real-world settings should be confirmed to approve accessible and advanced care for all patients.

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Cite This Study

Torales et al. (2026) studied this question.

synapsesocial.com/papers/69cb6526e6a8c024954b93e9https://doi.org/10.2174/0125899775434631260211074804
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