Lucie Bartova1, Markus Dold1, Alexander Kautzky1, Chiara Fabbri2,3, Marie Spies1, Alessandro Serretti2, Daniel Souery4, Julien Mendlewicz4, Joseph Zohar5, Stuart Montgomery6, Alexandra Schosser1,7, Siegfried Kasper1. 1. Department of Psychiatry and Psychotherapy, Medical University of Vienna , Vienna , Austria. 2. Department of Biomedical and NeuroMotor Sciences, University of Bologna , Bologna , Italy. 3. Institute of Psychiatry, Psychology and Neuroscience, King's College London , London , United Kingdom. 4. Université Libre de Bruxelles , Brussels , Belgium. 5. Psychiatric Division, Chaim Sheba Medical Center , Tel Hashomer , Israel. 6. Imperial College, University of London , London , UK. 7. Zentrum für seelische Gesundheit Leopoldau, BBRZ-MED , Vienna , Austria.
Abstract
Objectives: The overview outlines two decades of research from the European Group for the Study of Resistant Depression (GSRD) that fundamentally impacted evidence-based algorithms for diagnostics and psychopharmacotherapy of treatment-resistant depression (TRD). Methods: The GSRD staging model characterising response, non-response and resistance to antidepressant (AD) treatment was applied to 2762 patients in eight European countries. Results: In case of non-response, dose escalation and switching between different AD classes did not show superiority over continuation of original AD treatment. Predictors for TRD were symptom severity, duration of the current major depressive episode (MDE), suicidality, psychotic and melancholic features, comorbid anxiety and personality disorders, add-on treatment, non-response to the first AD, adverse effects, high occupational level, recurrent disease course, previous hospitalisations, positive family history of MDD, early age of onset and novel associations of single nucleoid polymorphisms (SNPs) within the PPP3CC, ST8SIA2, CHL1, GAP43 and ITGB3 genes and gene pathways associated with neuroplasticity, intracellular signalling and chromatin silencing. A prediction model reaching accuracy of above 0.7 highlighted symptom severity, suicidality, comorbid anxiety and lifetime MDEs as the most informative predictors for TRD. Applying machine-learning algorithms, a signature of three SNPs of the BDNF, PPP3CC and HTR2A genes and lacking melancholia predicted treatment response. Conclusions: The GSRD findings offer a unique and balanced perspective on TRD representing foundation for further research elaborating on specific clinical and genetic hypotheses and treatment strategies within appropriate study-designs, especially interaction-based models and randomized controlled trials.
Objectives: The overview outlines two decades of research from the European Group for the Study of Resistant Depression (GSRD) that fundamentally impacted evidence-based algorithms for diagnostics and psychopharmacotherapy of treatment-resistant depression (TRD). Methods: The GSRD staging model characterising response, non-response and resistance to antidepressant (AD) treatment was applied to 2762 patients in eight European countries. Results: In case of non-response, dose escalation and switching between different AD classes did not show superiority over continuation of original AD treatment. Predictors for TRD were symptom severity, duration of the current major depressive episode (MDE), suicidality, psychotic and melancholic features, comorbid anxiety and personality disorders, add-on treatment, non-response to the first AD, adverse effects, high occupational level, recurrent disease course, previous hospitalisations, positive family history of MDD, early age of onset and novel associations of single nucleoid polymorphisms (SNPs) within the PPP3CC, ST8SIA2, CHL1, GAP43 and ITGB3 genes and gene pathways associated with neuroplasticity, intracellular signalling and chromatin silencing. A prediction model reaching accuracy of above 0.7 highlighted symptom severity, suicidality, comorbid anxiety and lifetime MDEs as the most informative predictors for TRD. Applying machine-learning algorithms, a signature of three SNPs of the BDNF, PPP3CC and HTR2A genes and lacking melancholia predicted treatment response. Conclusions: The GSRD findings offer a unique and balanced perspective on TRD representing foundation for further research elaborating on specific clinical and genetic hypotheses and treatment strategies within appropriate study-designs, especially interaction-based models and randomized controlled trials.
Authors: Leo R Silberbauer; Lucas Rischka; Chrysoula Vraka; Annette M Hartmann; Godber Mathis Godbersen; Cécile Philippe; Daniel Pacher; Lukas Nics; Manfred Klöbl; Jakob Unterholzner; Thomas Stimpfl; Wolfgang Wadsak; Andreas Hahn; Marcus Hacker; Dan Rujescu; Siegfried Kasper; Rupert Lanzenberger; Gregor Gryglewski Journal: Mol Psychiatry Date: 2022-09-07 Impact factor: 13.437
Authors: Gernot Fugger; Markus Dold; Lucie Bartova; Marleen M M Mitschek; Daniel Souery; Julien Mendlewicz; Alessandro Serretti; Joseph Zohar; Stuart Montgomery; Chiara Fabbri; Richard Frey; Siegfried Kasper Journal: Int J Neuropsychopharmacol Date: 2020-12-03 Impact factor: 5.176