Rethinking Treatment-Resistant Depression: A Systematic Review of Novel Therapeutic Strategies and Precision Medicine Approaches.

Saved in:
Bibliographic Details
Title: Rethinking Treatment-Resistant Depression: A Systematic Review of Novel Therapeutic Strategies and Precision Medicine Approaches.
Authors: Tatlı, Safiye Zeynep1, Atagün, Murat İlhan2 drilhanatagun@gmail.com
Source: Actas Espanolas de Psiquiatria. 2025, Vol. 53 Issue 6, p1395-1409. 15p.
Subjects: INDIVIDUALIZED medicine, PHARMACOGENOMICS, DRUG therapy, NEUROMODULATION, BIOMARKERS, BIPOLAR disorder, THERAPEUTICS, ANTIDEPRESSANTS
Abstract: Background: Treatment-resistant depression (TRD) is a complex and heterogeneous condition affecting a considerable subset of patients who do not respond to conventional antidepressants. Given the limitations of traditional treatment strategies, there is a growing need for alternative and personalized approaches. Objective: This review explores the neurobiological underpinnings of TRD and examines the efficacy of emerging pharmacological and neuromodulatory interventions. We also highlight the potential role of the bipolar spectrum in TRD and the need for tailored treatment strategies. Methods: A systematic review of literature from 2015 to 2025 was conducted using PubMed and Scopus. Studies on TRD treatment modalities, including augmentation strategies, mood stabilizers, atypical antipsychotics, and neuromodulation techniques, were analyzed. Results: Our findings indicate that novel interventions, such as ketamine, esketamine, psychedelics, and neuromodulation therapies (e.g., repetitive transcranial magnetic stimulation, magnetic seizure therapy) show promise in addressing TRD. Additionally, biomarker-driven and pharmacogenetic approaches may enhance treatment selection and improve outcomes. Evidence suggests that a subset of patients with TRD could fall within the bipolar spectrum, requiring mood stabilizers and antipsychotics rather than standard antidepressant regimens. Conclusion: A multidisciplinary and precision-based approach is essential for optimizing TRD management. Future research should focus on biomarker-driven treatment selection, artificial intelligence-assisted decision making, and large-scale trials to refine personalized therapeutic strategies. [ABSTRACT FROM AUTHOR]
Copyright of Actas Espanolas de Psiquiatria is the property of Maria Lopez-Ibor and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: MedicLatina
FullText Links:
  – Type: pdflink
Text:
  Availability: 0
Header DbId: lth
DbLabel: MedicLatina
An: 191763545
AccessLevel: 6
PubType: Academic Journal
PubTypeId: academicJournal
PreciseRelevancyScore: 0
IllustrationInfo
Items – Name: Title
  Label: Title
  Group: Ti
  Data: Rethinking Treatment-Resistant Depression: A Systematic Review of Novel Therapeutic Strategies and Precision Medicine Approaches.
– Name: Author
  Label: Authors
  Group: Au
  Data: <searchLink fieldCode="AR" term="%22Tatlı%2C+Safiye+Zeynep%22">Tatlı, Safiye Zeynep</searchLink><relatesTo>1</relatesTo><br /><searchLink fieldCode="AR" term="%22Atagün%2C+Murat+İlhan%22">Atagün, Murat İlhan</searchLink><relatesTo>2</relatesTo><i> drilhanatagun@gmail.com</i>
– Name: TitleSource
  Label: Source
  Group: Src
  Data: <searchLink fieldCode="JN" term="%22Actas+Espanolas+de+Psiquiatria%22">Actas Espanolas de Psiquiatria</searchLink>. 2025, Vol. 53 Issue 6, p1395-1409. 15p.
– Name: Subject
  Label: Subjects
  Group: Su
  Data: <searchLink fieldCode="DE" term="%22INDIVIDUALIZED+medicine%22">INDIVIDUALIZED medicine</searchLink><br /><searchLink fieldCode="DE" term="%22PHARMACOGENOMICS%22">PHARMACOGENOMICS</searchLink><br /><searchLink fieldCode="DE" term="%22DRUG+therapy%22">DRUG therapy</searchLink><br /><searchLink fieldCode="DE" term="%22NEUROMODULATION%22">NEUROMODULATION</searchLink><br /><searchLink fieldCode="DE" term="%22BIOMARKERS%22">BIOMARKERS</searchLink><br /><searchLink fieldCode="DE" term="%22BIPOLAR+disorder%22">BIPOLAR disorder</searchLink><br /><searchLink fieldCode="DE" term="%22THERAPEUTICS%22">THERAPEUTICS</searchLink><br /><searchLink fieldCode="DE" term="%22ANTIDEPRESSANTS%22">ANTIDEPRESSANTS</searchLink>
– Name: Abstract
  Label: Abstract
  Group: Ab
  Data: Background: Treatment-resistant depression (TRD) is a complex and heterogeneous condition affecting a considerable subset of patients who do not respond to conventional antidepressants. Given the limitations of traditional treatment strategies, there is a growing need for alternative and personalized approaches. Objective: This review explores the neurobiological underpinnings of TRD and examines the efficacy of emerging pharmacological and neuromodulatory interventions. We also highlight the potential role of the bipolar spectrum in TRD and the need for tailored treatment strategies. Methods: A systematic review of literature from 2015 to 2025 was conducted using PubMed and Scopus. Studies on TRD treatment modalities, including augmentation strategies, mood stabilizers, atypical antipsychotics, and neuromodulation techniques, were analyzed. Results: Our findings indicate that novel interventions, such as ketamine, esketamine, psychedelics, and neuromodulation therapies (e.g., repetitive transcranial magnetic stimulation, magnetic seizure therapy) show promise in addressing TRD. Additionally, biomarker-driven and pharmacogenetic approaches may enhance treatment selection and improve outcomes. Evidence suggests that a subset of patients with TRD could fall within the bipolar spectrum, requiring mood stabilizers and antipsychotics rather than standard antidepressant regimens. Conclusion: A multidisciplinary and precision-based approach is essential for optimizing TRD management. Future research should focus on biomarker-driven treatment selection, artificial intelligence-assisted decision making, and large-scale trials to refine personalized therapeutic strategies. [ABSTRACT FROM AUTHOR]
– Name: AbstractSuppliedCopyright
  Label:
  Group: Ab
  Data: <i>Copyright of Actas Espanolas de Psiquiatria is the property of Maria Lopez-Ibor and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=lth&AN=191763545
RecordInfo BibRecord:
  BibEntity:
    Identifiers:
      – Type: doi
        Value: 10.62641/aep.v53i6.1946
    Languages:
      – Code: eng
        Text: English
    PhysicalDescription:
      Pagination:
        PageCount: 15
        StartPage: 1395
    Subjects:
      – SubjectFull: INDIVIDUALIZED medicine
        Type: general
      – SubjectFull: PHARMACOGENOMICS
        Type: general
      – SubjectFull: DRUG therapy
        Type: general
      – SubjectFull: NEUROMODULATION
        Type: general
      – SubjectFull: BIOMARKERS
        Type: general
      – SubjectFull: BIPOLAR disorder
        Type: general
      – SubjectFull: THERAPEUTICS
        Type: general
      – SubjectFull: ANTIDEPRESSANTS
        Type: general
    Titles:
      – TitleFull: Rethinking Treatment-Resistant Depression: A Systematic Review of Novel Therapeutic Strategies and Precision Medicine Approaches.
        Type: main
  BibRelationships:
    HasContributorRelationships:
      – PersonEntity:
          Name:
            NameFull: Tatlı, Safiye Zeynep
      – PersonEntity:
          Name:
            NameFull: Atagün, Murat İlhan
    IsPartOfRelationships:
      – BibEntity:
          Dates:
            – D: 01
              M: 11
              Text: 2025
              Type: published
              Y: 2025
          Identifiers:
            – Type: issn-print
              Value: 11399287
          Numbering:
            – Type: volume
              Value: 53
            – Type: issue
              Value: 6
          Titles:
            – TitleFull: Actas Espanolas de Psiquiatria
              Type: main
ResultId 1