Symposium
Plenary Hall: Lomond Auditorium
Plenary Hall: Lomond Auditorium
Sunday, June 28, 10:50 AM – 12:05 PM
Symposium 11:
Treatment Resistance in Mental Disorders – Clinical Definitions, Biological Markers and New Treatment Avenues
Treatment Resistance in Mental Disorders – Clinical Definitions, Biological Markers and New Treatment Avenues
The present symposium links the latest research on the pressing clinical topic of treatment resistance in mental disorders, bringing together leading experts in schizophrenia, depression, and anxiety disorders to highlight current consensus on clinical definitions, biological markers and mechanisms, as well as innovative therapeutic strategies.
Based on her recent work, Dr. Samara will provide an overview of definitions, current pharmacological strategies, and emerging therapies in treatment-resistant schizophrenia (TR-S) (Samara et al., 2025a). TR-S is typically defined as an inadequate response to at least two different antipsychotics, affecting approximately 30% of individuals with schizophrenia and representing a major clinical challenge (Samara et al., 2025b). Clozapine remains the only approved treatment for TR-S, but its use is often delayed or limited by side effects and monitoring requirements. Dr. Samara will discuss clozapine’s role, alternative pharmacological strategies including switching, augmentation approaches, and novel compounds currently in development (Samara et al., 2025c). The presentation will emphasize how bridging evidence-based management with innovative research can inform future directions in TR-S care.
Dr. Sforzini will address treatment resistance in major depressive disorder (TR-D) from both definitional and biological perspectives, with a particular focus on insights from immunopsychiatry. First, the challenges of defining non-response in depression and present findings will be discussed based on his recent Delphi consensus guideline proposing operational criteria for TR-D and partially responsive depression (PRD) (Sforzini et al., 2022), which are intended to improve consistency in clinical trial inclusion and facilitate more robust comparisons between studies. Dr. Sforzini will then explore the biological underpinnings of TRD and PRD, drawing on his transcriptomic work indicating immune dysregulation as a potential hallmark of specific patient subgroups informing novel therapeutic targets (Sforzini et al., 2025). Finally, innovative research initiatives will be presented that integrate biological profiling with adaptive platform trial designs, aiming to develop precision psychiatry approaches that move beyond the traditional one-size-fits-all paradigm (Amasi-Hartoonian et al., 2022).
Based on a Delphi method-based consensus, Dr. Domschke will present efforts to establish a clinically useful definition of treatment resistance in anxiety disorders (TR-AD) (Domschke et al., 2024), a field where such criteria remain underdeveloped. She will discuss her research on genetic, epigenetic, and imaging genetic markers associated with treatment response, highlighting how these biomarkers may guide individualized treatment selection (Domschke et al., 2025). In addition, she will review current state-of-the-art pharmacological and psychotherapeutic options, as well as neuromodulatory interventions, outlining their potential in cases of TR-AD (Schiele et al., in press). The presentation will also explore emerging pharmacological treatments as well as personalized treatment options to improve outcomes for patients who fail to respond to first-line interventions.
By integrating the latest findings across schizophrenia, depression, and anxiety disorders, this symposium will provide a comprehensive and clinically relevant overview of treatment resistance in mental health. The focus on precise definitions, mechanistic insights, and innovative therapeutic strategies underscores the need for a paradigm shift toward personalized and biologically informed care, with the ultimate goal of improving prognosis and quality of life for patients affected by treatment-resistant mental disorders.
Based on her recent work, Dr. Samara will provide an overview of definitions, current pharmacological strategies, and emerging therapies in treatment-resistant schizophrenia (TR-S) (Samara et al., 2025a). TR-S is typically defined as an inadequate response to at least two different antipsychotics, affecting approximately 30% of individuals with schizophrenia and representing a major clinical challenge (Samara et al., 2025b). Clozapine remains the only approved treatment for TR-S, but its use is often delayed or limited by side effects and monitoring requirements. Dr. Samara will discuss clozapine’s role, alternative pharmacological strategies including switching, augmentation approaches, and novel compounds currently in development (Samara et al., 2025c). The presentation will emphasize how bridging evidence-based management with innovative research can inform future directions in TR-S care.
Dr. Sforzini will address treatment resistance in major depressive disorder (TR-D) from both definitional and biological perspectives, with a particular focus on insights from immunopsychiatry. First, the challenges of defining non-response in depression and present findings will be discussed based on his recent Delphi consensus guideline proposing operational criteria for TR-D and partially responsive depression (PRD) (Sforzini et al., 2022), which are intended to improve consistency in clinical trial inclusion and facilitate more robust comparisons between studies. Dr. Sforzini will then explore the biological underpinnings of TRD and PRD, drawing on his transcriptomic work indicating immune dysregulation as a potential hallmark of specific patient subgroups informing novel therapeutic targets (Sforzini et al., 2025). Finally, innovative research initiatives will be presented that integrate biological profiling with adaptive platform trial designs, aiming to develop precision psychiatry approaches that move beyond the traditional one-size-fits-all paradigm (Amasi-Hartoonian et al., 2022).
Based on a Delphi method-based consensus, Dr. Domschke will present efforts to establish a clinically useful definition of treatment resistance in anxiety disorders (TR-AD) (Domschke et al., 2024), a field where such criteria remain underdeveloped. She will discuss her research on genetic, epigenetic, and imaging genetic markers associated with treatment response, highlighting how these biomarkers may guide individualized treatment selection (Domschke et al., 2025). In addition, she will review current state-of-the-art pharmacological and psychotherapeutic options, as well as neuromodulatory interventions, outlining their potential in cases of TR-AD (Schiele et al., in press). The presentation will also explore emerging pharmacological treatments as well as personalized treatment options to improve outcomes for patients who fail to respond to first-line interventions.
By integrating the latest findings across schizophrenia, depression, and anxiety disorders, this symposium will provide a comprehensive and clinically relevant overview of treatment resistance in mental health. The focus on precise definitions, mechanistic insights, and innovative therapeutic strategies underscores the need for a paradigm shift toward personalized and biologically informed care, with the ultimate goal of improving prognosis and quality of life for patients affected by treatment-resistant mental disorders.