On the second day of the congress, the program featured several highly relevant sessions that focused on managing major depressive disorder (MDD) and treatment-resistant depression, the use of real-world big data to understand mental illness, and topics like neuroscience-based nomenclature.
Here are the highlights from the second day in detail:
Managing major depressive disorder and treatment-resistant depression: from neurobiology to clinical care
Functional recovery in major depressive disorder and treatment-resistant depression: focus on the patient and caregiver
Speaker: Diane McIntosh
Dr. Diane began her presentation emphasizing that while many patients may not meet TRD criteria, they still struggle with inadequate treatment responses, residual symptoms, and functional impairments. TRD is generally defined as failing to respond to two or more antidepressants, but adherence and dose optimization issues make accurate assessment challenging. The psychosocial impacts of TRD are extensive, affecting quality of life, work performance, and increasing the risk of comorbidities and suicide.
An observational study with over 340 participants revealed significant work impairment, underscoring the financial and emotional toll on both individuals and the economy. The doctor emphasizes the importance of achieving full functional recovery, which involves early and accurate diagnosis, personalized care, and continuous treatment optimization through measurement-based care. A patient’s personal story illustrated the profound impact of depression on all aspects of life and the challenges of inadequate treatment engagement.
The discussion then shifted to shared decision-making, which bridges the gap between clinical goals and patient needs. This approach is underutilized in psychiatry despite its proven benefits, including increased patient satisfaction, better adherence to treatment, and improved diagnostic accuracy. Shared decision-making involves clinicians providing scientific insights and patients sharing their values and preferences, fostering a collaborative treatment process.
Dr. Diane highlighted the importance of involving a support person in the patient’s recovery journey, which enhances communication and provides additional support. This practice can alleviate some of the burdens on healthcare providers and prevent burnout. The presentation concluded with a focus on reducing stigma within medicine and supporting caregivers, recognizing the significant impact of mental illness on both patients and their supporters. The importance of listening to patients and considering their individual experiences was one of the most important topics in this presentation. Dr. Diane reiterated that early optimized treatment and shared decision-making are crucial for managing residual symptoms and achieving full functional recovery.
Managing major depressive disorder and treatment-resistant depression: real-world evidence and clinical insights
Speaker: Giovanni Martinotti
During the session on major depression and treatment-resistant depression, Dr. Giovanni discussed the complexities of these conditions, highlighting their global burden. Patients with depression face increased risks of premature death, dementia, multimorbidity, and hospitalization, with TRD patients experiencing even higher disease hardships, including increased comorbidities, all-cause mortality, and suicide rates. The definition of TRD varies, making it a challenging topic. Current real-world clinical practice shows low response rates and marginally higher long-term remission rates.
The doctor emphasized the importance of standardized assessments in future studies and discussed recent treatment options for TRD. These include extending antidepressant trials, switching or combining antidepressants, using second-generation antipsychotics, electroconvulsive therapy (ECT), repetitive transcranial magnetic stimulation (rTMS), vagus nerve stimulation, psychotherapies, and particularly esketamine and esketamine. Esketamine has shown rapid response, increased relapse prevention, and good long-term safety in real-world studies.
Real-world data is crucial as randomized controlled trials (RCTs) often exclude patients with complex cases and comorbidities. This session presented a study conducted in Italian centers assessing the real-world effectiveness of esketamine nasal spray. The study showed significant reductions in depression scores over three months, especially in complex cases, although initial non-response rates were high. The speaker highlighted the importance of patience in these cases, as responses improved over time.
Clinical data was also shared, including patient characteristics and common comorbidities such as anxiety, substance use disorders, and personality disorders. The study found significant improvements in patients with TRD using esketamine nasal spray, including those with comorbidities and older adults. Notably, patients with alcohol use disorder responded well to esketamine. The study’s design involved baseline evaluations followed by assessments at one and three months using standard clinical scales.
The session included a detailed case study of a 48-year-old woman with a history of TRD. Despite multiple treatments, including SSRIs and SNRIs, she showed a significant improvement with esketamine nasal spray, even after a relapse during the third month. The flexibility in dosing and administration frequency was highlighted as a key benefit of esketamine treatment. The patient eventually achieved remission and improved quality of life with continued treatment.
In conclusion, Dr. Giovanni emphasized that while MDD is a significant global burden, TRD patients face even greater challenges. Esketamine nasal spray offers a promising treatment for TRD, particularly when other options have failed. However, real-world studies are essential to understanding its full potential, especially in complex cases. The session underscored the need for continued therapy and personalized treatment approaches to achieve the best outcomes for patients with TRD.
Advances in understanding major depressive disorder and treatment-resistant depression: from neurobiology to bedside
Speaker: Allan Young
During his presentation Dr. Allan highlighted the significant advances and ongoing changes in the field of psychiatry, particularly in the treatment of major depressive disorder (MDD) and treatment-resistant depression (TRD). The discussion initially focus on the complexity and heterogeneity of major depression, noting that it encompasses a wide range of symptomatology and etiologies, making it essential to understand its underlying mechanisms.
The doctor argued for a dual approach to diagnosis, combining symptom-based and brain-based methods to enhance diagnostic accuracy and treatment outcomes. He discussed the historical context of the monoamine hypothesis and its limitations, highlighting the importance of the default mode network in understanding depression. The session also covered recent studies using biotypes to classify patients based on brain circuit dysfunctions, emphasizing the need for longitudinal studies to validate these findings.
A detailed overview of the current MDD treatment pathway was provided, noting the lack of significant changes over the years and the anticipation of new treatments that will disrupt this pathway. Dr. Allan underscored the role of shared decision-making and the integration of psychotherapy and neurostimulation at various stages of treatment. He discussed the emerging treatments, particularly the use of esketamine, and its implications for clinical practice, including its effectiveness and the need for careful management of anxiety symptoms.
The session also compared different augmentation strategies, such as quetiapine versus lithium, with recent trials showing quetiapine’s superior effectiveness. He also discussed the comparative benefits of esketamine versus electroconvulsive therapy (ECT), with esketamine showing promising results in certain studies.
Neurobiological mechanisms, particularly the role of neuroplasticity, were a focal point. Dr. Allan explained how new glutamate-targeting antidepressants like esketamine promote neuroplasticity, leading to rapid and enduring symptom remission. The speaker highlighted the importance of enhancing neuroplasticity for long-term recovery and the potential of these treatments to reset brain health.
In conclusion, Dr. Allan emphasized the significance of clinical guidelines and consensus statements in guiding current practice while acknowledging the rapid changes in treatment strategies. He envisions a new era in psychiatry, driven by advances in neurobiology and innovative treatments, and called for the early use of these new treatments to potentially alter the disease course, benefiting patients, families, and society as a whole.
Using real-world big data to understand mental illness (REALMENT)
Speaker: Olav Smeland
This interactive session brings up the integration of precision medicine into psychiatry, emphasizing the importance of customize treatments to individual patients using multimodal data like genetics, biomarkers, and environmental factors. It highlighted the limitations of current psychiatric treatments, where patients often receive ineffective drugs with adverse side effects due to the lack of personalized approaches. This discussion emphasizes the need for predictive tools that utilize large-scale data, including registries and biobanks, to enhance diagnostic and treatment outcomes, particularly in early diagnosis and treatment of mental illnesses like schizophrenia, bipolar disorder, and ADHD.
Several key challenges were addressed, such as the complexity of combining genetic, cognitive, and clinical data into practical tools that clinicians can use. The group explored the concept of population screening for mental health issues but acknowledged the difficulties in applying such methods commonly, citing issues of false positives and predictive value. They also discussed the necessity of more specific diagnostic tools for early-stage mental illnesses, as well as the importance of developing tools for drug selection and managing side effects, such as weight gain from antipsychotics.
Another central theme was the role of big data and machine learning in identifying patterns and markers across large patient populations. While some participants were optimistic about the potential of digital tools, such as apps and sensors to track patient behaviors, others emphasized the need for more research to understand the psychological significance of these new data streams.
The conversation concluded by addressing the practical problem in data collection, particularly in ensuring standardization across different healthcare systems and managing privacy concerns. Solutions like derived data, network learning, and using predictive models based on large, anonymized datasets were suggested as ways to advance the field without compromising patient confidentiality.
Highlights in schizophrenia
Speaker: Armida Mucci
In her class, Dr. Arminda presented five important papers on schizophrenia, each addressing different facets of the disorder and its treatment, published in the last twelve months.
The first paper, titled “Schizophrenia: Time to Commit to Policy Change,” revisits a study initially published in 2014, with an updated version discussing unmet treatment needs and research focuses. It highlights the significant challenges faced by individuals with schizophrenia, including a reduced life expectancy by 10-20 years compared to the general population. The paper underscores the need for better management of physical comorbidities, improved access to specialized care, and the involvement of patients in treatment decisions.
The second paper, published in European Neuropsychopharmacology by Somi et al., is a sub-analysis of a meta-analysis on cardiovascular risk in patients with schizophrenia. It found that first-generation antipsychotics are associated with an increased risk of cardiovascular events, while second-generation antipsychotics and clozapine might offer some protective benefits. This paper challenges the notion that first-generation antipsychotics are better in managing cardiometabolic risks, suggesting that improved patient care could mitigate these risks even when using drugs like clozapine.
The third study focuses on distinguishing primary and secondary cognitive impairments in schizophrenia. It discusses the impact of secondary factors like depression, autistic traits, and pharmacotherapy on cognitive functions. Addressing these factors can alleviate cognitive impairments, suggesting that better management of depression, reducing anticholinergic burden, and avoiding polypharmacy can improve cognitive outcomes for patients.
The fourth paper, part of the World Psychiatry journal, details a longitudinal study on recent onset patients with first episode psychosis. The study found that 69% of the sample had favorable outcomes regarding positive symptoms, while predictors of poor clinical outcomes included higher levels of negative symptoms at baseline, neurocognitive impairment, longer duration of untreated psychosis, and substance use disorders. It highlighted the importance of early diagnosis and treatment, as well as addressing negative symptoms and cognitive impairments to improve functional outcomes.
The last study, published in Schizophrenia Bulletin Open, reviews remote assessment methods for negative symptoms in schizophrenia. It explores various modalities, such as video interviews and digital phenotyping, emphasizing the potential of these methods to reach more patients. However, it also stresses the need for validation against traditional clinical measures and the involvement of multiple stakeholders, including patients and caregivers, to ensure the accuracy and reliability of these new assessment tools.
Overall, these papers collectively emphasize the need for better management of physical and cognitive comorbidities, improved assessment methods, and innovative treatment approaches to enhance the quality of care for individuals with schizophrenia.
Neuroscience-based Nomenclature Session
Updates on Neuroscience-based Nomenclature (NbN)
Speaker: Joseph Zohar
In this presentation, Dr. Joseph provided a concise update on the neuroscience-based nomenclature system known as NBN. The discussion began by referencing Confucius’s notion that wisdom starts with accurately naming things. This is particularly relevant in psychiatry, where terms like “antidepressants” and “antipsychotics” are often misapplied, leading to confusion among patients about the nature of their treatments. The doctor pointed out that the existing nomenclature, which has been in place for 60 years, fails to reflect advancements in neuroscience.
The speaker argued for a shift from disease-based terminology to a nomenclature driven by pharmacological mechanisms, similar to how medications for hypertension are classified. The NBN initiative, which involves collaboration among four major colleges of neuropsychopharmacology, proposes using terms like “dopamine blockers” instead of “antipsychotics” and “monoamine enhancers” instead of “antidepressants.” This revised nomenclature has received recognition from significant scientific organizations and is being incorporated into prominent psychiatric textbooks.
Dr. Joseph emphasized that the NBN includes various components, such as resources for children and adolescents, and is developing a version for patients and families to help them better understand their medications. He encouraged psychiatrists to download the free app associated with NBN to access these resources and enhance their clinical practice. Overall, this presentation highlighted the importance of improving communication in psychiatry through more precise language grounded in scientific understanding.
The relevance of NbN in teaching medical students
Speaker: Sasson Zemach
Dr. Sasson presented a pilot study that examined the effectiveness of the NBN (neuroscience-based nomenclature) as a teaching tool in medical education, particularly for medical students studying psychopharmacology. Published last year in the Journal of International Clinical Psychopharmacology, the primary aim of the study was to determine whether introducing NBN terminology and principles in psychopharmacology classes would positively influence students’ perceptions of psychiatry and enhance their learning outcomes.
The study involved a cohort of 56 medical students during their psychiatry clinical clerkship, divided into two groups: an intervention group taught using NBN terminology and a control group that received standard education based on traditional disease classifications. Students completed identical questionnaires at the beginning and end of the clerkship, assessing their attitudes toward psychiatry, psychopharmacology, and their knowledge of neuroscience.
The results showed that the NBN group exhibited significant improvements in various areas, including a greater interest in pursuing residency in psychiatry and a better understanding of the mechanisms behind psychiatric medications. The data, displayed as delta scores comparing pre- and post-intervention results, indicated that the NBN group outperformed the control group on several measures.
While the study had a relatively small sample size, which the speaker acknowledged as a limitation, the findings were deemed statistically valid and promising. Dr. Sasson encouraged further research with larger samples to explore these trends more comprehensively. In summary, the introduction of NBN in medical education appeared to enhance students’ educational experiences, deepen their understanding of psychotropic medications, and foster greater interest in a career in psychiatry.
NbN and precision in dopamine blockers prescribing
Speaker: Christoph U. Correll
During this presentation, Dr. Christoph addressed the challenges and limitations of the current classification system for psychopharmacology, particularly in relation to antipsychotic medications. The discussion began with a critical examination of whether the existing system truly reflects the current understanding of brain science and medication mechanisms. It was suggested that instead of focusing solely on efficacy, the classification should consider pharmacological actions and the complexities of different medications.
The speaker highlighted a significant upcoming event, the FDA’s anticipated approval of the first muscarinic receptor enhancer, which will likely be labeled as an antipsychotic. This raises concerns about mislabeling and the potential for confusion regarding its mechanism of action, particularly regarding the associated risks such as tardive dyskinesia. The discussion emphasized the need for clarity in medication labeling, as current classifications often do not accurately represent the pharmacological nuances of these drugs.
Throughout the presentation, the doctor brings to light the importance of using precise terminology and the development of a neuroscience-based nomenclature (NBN) that can better inform both healthcare providers and patients. The NBN aims to provide a clearer understanding of drug mechanisms, thereby improving communication about treatment options.
Engaging the audience, the speaker solicited feedback on their satisfaction with current antipsychotic classifications, revealing widespread confusion among practitioners. This emphasized the need for improvement in the way medications are categorized and discussed.
Finally, the session underscored the potential of the NBN system to enhance the understanding of psychotropic medications, promote evidence-based practice, and facilitate better patient communication, all while advocating for necessary changes in how these medications are classified and reimbursed. Dr. Christoph concluded by calling for collaboration among medical professionals to push for these improvements in psychopharmacological education and practice.
Challenges and opportunities in incorporating serotonergic agonists (“psychedelics”) into NbN
Speaker: Guy Goodwin
Dr. Guy explored the integration of serotoninergic agonists and psychedelics into modern psychopharmacology, focusing on their mechanisms of action. They began by discussing their affiliation with Compass Pathways and emphasized the need to shift from traditional indication-based nomenclature to a mechanism-based approach. The central question raised was how well we understand the modes of action of these psychedelic compounds, most of which act as agonists at the 5-HT2A serotonin receptor.
The doctor highlighted that the clinical effects of these psychedelics often require high doses, and the aim is to understand whether these effects enhance psychotherapy or are merely side effects of the drugs. Various hypotheses were presented about how psychedelics might work: as facilitators of therapeutic experiences, as agents that change cognitive The processes, or as substances that alter brain function directly.
The discussion included findings from clinical trials, which measured subjective experiences like “oceanic boundlessness,” anxiety, and visual and auditory effects. Notably, the results showed dose-related changes across these dimensions, with oceanic boundlessness correlating more strongly with positive outcomes than other experiences. This specificity suggests that the mechanism of action may involve changes in brain connectivity rather than just side effects.
In conclusion, the speaker concluded that while there is compelling evidence linking serotoninergic activity to the subjective effects of psychedelics, the relationship remains complex and not fully understood. For now, these substances should be classified as serotonergic agonists at high doses, pending further research to clarify their roles and mechanisms in therapeutic settings.
MDD, antidepressants and sexual dysfunction
Speaker: Anita Clayton
This interactive session focused on sexual dysfunction, particularly in relation to depression and the use of antidepressants. Dr. Anita highlighted that about 70% of individuals with major depression experience sexual dysfunction, which impacts relationships, intimacy, and self-esteem. The discussion also covered the effects of various medications on sexual health, with SSRIs like paroxetine causing dysfunction in a high percentage of patients. Dr. Anita emphasized the importance of using tools like the Changes in Sexual Function Questionnaire to monitor these effects throughout treatment.
Medications like tricyclics and atypical antidepressants such as mirtazapine and bupropion were discussed as alternatives, as they have lower rates of sexual dysfunction. The talk also explored the role of dopamine and norepinephrine in sexual function, noting that drugs with serotonin receptor activity tend to inhibit sexual responses, while those affecting dopamine can be more stimulating.
Another significant point was the importance of assessing sexual function before starting treatment and continuing to monitor it, as well as considering patient preferences regarding side effects like sexual dysfunction or weight gain. Questions from the audience explore topics such as persistent sexual dysfunction after stopping SSRIs, with Dr. Anita acknowledging the lack of concrete data but recommending treatments that address underlying conditions like depression or anxiety.
The conversation also touched on sexual dysfunction in women, noting the differences in how dysfunction is reported and treated compared to men. Tools like the Female Sexual Distress Scale were highlighted for measuring distress related to sexual issues. Dr. Anita underscored the need for clinicians to openly discuss sexual health with patients, integrating it into routine care alongside other lifestyle factors. Cultural factors affecting the willingness to discuss sexual health were also addressed, with acknowledgment that many healthcare providers still do not regularly ask about sexual function.
References
• DUDEK, D. Managing major depressive disorder and treatment-resistant depression: from neurobiology to clinical care. In: 37th ECNP Congress, Milan, Italy.
• SMELAND, O. Using real-world big data to understand mental illness (REALMENT). In: 37th ECNP Congress, Milan, Italy.
• MUCI. A. Highlights in schizophrenia. In: 37th ECNP Congress, Milan, Italy.
• ZOHAR, J. Neuroscience-based Nomenclature Session. In: 37th ECNP Congress, Milan, Italy.
• CLAYTON, A. MDD, antidepressants and sexual dysfunction. In: 37th ECNP Congress, Milan, Italy.
Developed under the direction and sponsorship of Johnson & Johnson