Results of the European Group for the Study of Resistant Depression (GSRD) — basis for further research and clinical practice

Lucie Bartova; Markus Dold; Alexander Kautzky; Chiara Fabbri; Marie Spies; Alessandro Serretti; Daniel Souery; Julien Mendlewicz; Joseph Zohar; Stuart Montgomery; Alexandra Schosser; Siegfried Kasper

doi:10.1080/15622975.2019.1635270

Results of the European Group for the Study of Resistant Depression (GSRD) — basis for further research and clinical practice

Lucie Bartova, Markus Dold, Alexander Kautzky, Chiara Fabbri, Marie Spies, Alessandro Serretti, Daniel Souery, Julien Mendlewicz, Joseph Zohar, Stuart Montgomery, Alexandra Schosser, Siegfried Kasper^*

^*Corresponding author for this work

Research output: Contribution to journal › Review article › peer-review

106 Citations (Scopus)

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.

Original language	English
Pages (from-to)	427-448
Number of pages	22
Journal	World Journal of Biological Psychiatry
Volume	20
Issue number	6
DOIs	https://doi.org/10.1080/15622975.2019.1635270
Publication status	Published - 3 Jul 2019

Keywords

Depression
predictor
psychopharmacotherapy
response
treatment resistance

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10.1080/15622975.2019.1635270

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Bartova, L., Dold, M., Kautzky, A., Fabbri, C., Spies, M., Serretti, A., Souery, D., Mendlewicz, J., Zohar, J., Montgomery, S., Schosser, A., & Kasper, S. (2019). Results of the European Group for the Study of Resistant Depression (GSRD) — basis for further research and clinical practice. World Journal of Biological Psychiatry, 20(6), 427-448. https://doi.org/10.1080/15622975.2019.1635270

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title = "Results of the European Group for the Study of Resistant Depression (GSRD) — basis for further research and clinical practice",

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.",

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author = "Lucie Bartova and Markus Dold and Alexander Kautzky and Chiara Fabbri and Marie Spies and Alessandro Serretti and Daniel Souery and Julien Mendlewicz and Joseph Zohar and Stuart Montgomery and Alexandra Schosser and Siegfried Kasper",

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month = jul,

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doi = "10.1080/15622975.2019.1635270",

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Bartova, L, Dold, M, Kautzky, A, Fabbri, C, Spies, M, Serretti, A, Souery, D, Mendlewicz, J, Zohar, J, Montgomery, S, Schosser, A & Kasper, S 2019, 'Results of the European Group for the Study of Resistant Depression (GSRD) — basis for further research and clinical practice', World Journal of Biological Psychiatry, vol. 20, no. 6, pp. 427-448. https://doi.org/10.1080/15622975.2019.1635270

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T1 - Results of the European Group for the Study of Resistant Depression (GSRD) — basis for further research and clinical practice

AU - Bartova, Lucie

AU - Dold, Markus

AU - Kautzky, Alexander

AU - Fabbri, Chiara

AU - Spies, Marie

AU - Serretti, Alessandro

AU - Souery, Daniel

AU - Mendlewicz, Julien

AU - Zohar, Joseph

AU - Montgomery, Stuart

AU - Schosser, Alexandra

AU - Kasper, Siegfried

PY - 2019/7/3

Y1 - 2019/7/3

N2 - 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.

AB - 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.

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KW - predictor

KW - psychopharmacotherapy

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ER -

Results of the European Group for the Study of Resistant Depression (GSRD) — basis for further research and clinical practice

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