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Investigating Resistance to Antidepressants in Animal Models.

Julianna E Peña1, Brian F Corbett2, Carol A Tamminga3

  • 1Department of Neurosurgery, University of Texas Southwestern Medical Center, Dallas, TX, United States; Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, United States.

Neuroscience
|May 2, 2024
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Summary

This review examines animal models for treatment-resistant depression, finding 10 strategies. Understanding these preclinical models is crucial for developing new therapies for major depressive disorder.

Keywords:
animal modelantidepressantstresstreatment resistant depressionvalidity

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Area of Science:

  • Neuroscience
  • Psychiatry
  • Pharmacology

Background:

  • Major depressive disorder (MDD) is a prevalent psychiatric condition.
  • A significant portion of patients (30-40%) do not respond adequately to existing treatments.
  • There is a critical need for novel therapeutic strategies for treatment-resistant depression (TRD).

Purpose of the Study:

  • To systematically review current preclinical approaches used in animal models to investigate treatment resistance in depression.
  • To identify and describe strategies for improving the understanding of the neurobiology underlying TRD.
  • To outline a path forward for preclinical research in TRD.

Main Methods:

  • A comprehensive literature search was conducted to identify relevant preclinical studies.
  • Studies were screened and selected based on predefined inclusion/exclusion criteria, adhering to PRISMA guidelines.
  • A total of 69 studies were included in the systematic review from an initial pool of 467.

Main Results:

  • Ten broad strategies for investigating treatment resistance in animal models were identified.
  • Stress hormone administration emerged as the most frequently employed modeling strategy.
  • The forced swim test was the most commonly utilized behavioral assessment in these studies.

Conclusions:

  • Current preclinical approaches offer valuable insights into the neurobiology of TRD but have limitations for therapeutic translation.
  • Careful consideration of the advantages and disadvantages of each animal model is essential.
  • Enhanced understanding derived from these models is vital for developing effective treatments for the substantial burden of TRD.