Prof. Eric Ruhé

Talk	Why is Depression so difficult to treat and how to proceed?
Date	Friday, April 17, 2026
Time	09:05 - 09:50
Round Table	#2. Depression and Affective Disorders: From Classic Views to the Cutting Edge

Prof. Ruhe has a background in clinical psychiatry, epidemiology and brain neuroimaging (molecular and functional MRI), with extensive expertise in affective disorders. He specifically focusses on psychopharmacology and treatment of DTD. Prof. Ruhe (co-) authored more than 200 peer reviewed publications, 20 chapters in books and 4 books. With his work he was given the Ramaer-medal of the Dutch Association for Psychiatry. He was the co-chair of the Dutch Multidisciplinary Guideline for MDD (2024), chair of the ECNP Abstract and Poster Committee and currently is member of the ISAD Executive Board.

To better understand pathophysiology behind highly prevalent and burdensome affective disorders and in particular difficult to treat depression (DTD; including recurrent major depressive disorder (MDD)), Ruhe’s research includes neuroimaging methods, neuropsychological assessments and smartphone-applied cognitive training and measurements. In addition, his group performs systematic reviews and (network-)meta-analyses to obtain high-quality summarizing evidence to improve implementation of evidence-based treatments for depression in the broadest sense, including guideline development. Moreover, Ruhe is a principal investigator in a study to investigate how to discontinue antidepressants. Prof. Ruhe has a vast experience in doing randomized clinical trials, recruit drug-free subjects and perform long-term follow-up. Together with >30 hospitals in the Netherlands he formed the Esketamine Nasal-spray Consortium Netherlands (ENC-NL), whereof he is the coordinator. ENC-NL currently obtains data from ≥95% of all patients treated with esketamine nasal-spray in the Netherlands. This will improve outcomes and patient stratification for this expensive treatment. Currently, with his group, Ruhe is exploring whole brain computational dynamic functional and effective connectivity models to unravel brain disfunction in MDD/DTD. With these models he aims to develop a model-based approach to computationally assess which brain regions are causally involved in depressive symptomatology and therefore can be targets for interventions. The ultimate aims of Prof. Ruhe and his group are to apply non-invasive fMRI/molecular imaging and neuropsychological phenotyping in clinical psychiatry to: 1. Improve diagnostic work-up of heterogeneous disorders like major depressive disorder (MDD); 2. Tailor interventions to underlying mechanistic dysfunctions to eventually personalize treatments; 3. Thereby improve long term recovery of MDD/DTD and 4. Disseminate successful approaches to everyday clinical care and treatment guidelines.

In my presentation I will address several aspects why the understanding of major Depressive Disorder (MDD) has only slightly been improved in the last decades and why treatments do not develop rapidly, ultimately making depression often Treatment Resistant, which is better addressed by ‘Difficult to Treat Depression’.

First, I will address upcoming solutions for the understanding and tackling of heterogeneity in MDD. Second, I will address the clinical dilemma of many treatment possibilities, combinations: this is a big arsenal of treatments, but also a kind of misty environment to choose in. For this, I will suggest how to proceed, based on the existing evidence from clinical trials by properly using Network Meta Analyses, real world evidence, expert opinions and clinical guidelines. Third, I will elaborate on the caveat between understanding that treatments are efficacious versus understanding their mechanisms of change leading to improvement of symptoms/dimensions or functioning. Finally, I will address how we -in my group- aim to address this caveat by the use of innovative analyses based on (multi-modal) neuro-imaging. With dynamic whole-brain computational models, we aim to improve understanding of both DTD and the treatments with different pharmacological or neuromodulatory targets.

With my talk I want to summarize where we stand in the field of DTD and how to improve our approach to understand and target DTD, in order to better help our patients.

• Ruhé, H. G., et al. (2012). Staging methods for treatment resistant depression. A systematic review. Journal of Affective Disorders, 137(1–3), 35–45. doi: 10.1016/j.jad.2011.02.020.
• McAllister-Williams, R. H., et al. (2020). The identification, assessment and management of difficult-to-treat depression: An international consensus statement. Journal of Affective Disorders, 267, 264–282. doi: 10.1016/j.jad.2020.02.023.
• Hetrick, S. E., et al. (2008). Early identification and intervention in depressive disorders: Towards a clinical staging model. Psychotherapy and Psychosomatics, 77(5), 263–270. doi: 10.1159/000140085.
• McIntyre, R. S., Alsuwaidan, M., Baune, B. T., et al. (2023). Treatment-resistant depression: Definition, prevalence, detection, management, and investigational interventions. World Psychiatry, 22(3), 394–412. doi: 10.1002/wps.21120.
• Muit, J. J., van Eijndhoven, P. F. P., <...> & Ruhe, H. G. (2022). Efficacy and acceptability of next step treatment strategies in adults with treatment-resistant major depressive disorder: Protocol for systematic review and network meta-analysis. BMJ Open, 12, e056777. doi: 10.1136/bmjopen-2021-056777.