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Background <p>Major depressive disorder remains a clinical challenge, with a significant number of patients failing to achieve remission with antidepressants. New evidence suggests that neuroinflammation and immune dysfunction may contribute to the pathophysiology of depression. This evidence has increased interest in immunotherapy as a potential therapeutic approach.</p> Objective <p>In this review, the authors sought to investigate if there is a relationship between depression and inflammation and evaluate if the use of anti-inflammatory drugs and immunotherapy may help treat depression.</p> Methods <p>The authors reviewed studies on Pubmed and Cochrane from 2000 to 2024 involving adults with major unipolar depression without psychotic features, based on DSM-IV/V or ICD-10/11 criteria. They also included studies on patients with secondary symptoms from immunological therapies.</p> Results <p>Several immunomodulatory agents demonstrated potential antidepressant effects. Celecoxib was associated with improved treatment outcomes when combined with standard antidepressants. Infliximab showed efficacy primarily in patients with elevated inflammatory markers. Pentoxifylline showed anti-inflammatory properties and neuroprotective effects, leading to a clinical improvement. There were mixed results concerning minocycline. Interferon alfa was associated with the worsening of depressive symptoms.</p> Conclusion <p>Immunotherapy is promising for depression treatment, particularly in patients with elevated inflammation. However, findings remain heterogeneous, and further research is needed to refine treatment selection criteria, establish optimal dosing strategies, and evaluate long-term safety and efficacy.</p>

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The Role of Immunotherapy in the Treatment of Major Depressive Disorder A Narrative Review

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月10日

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  • Francisca Ribeirinho Soares ,
  • André Buinho,
  • Teresa Oliveira,
  • Zoe Correia Sá,
  • João Paulo Rema,
  • Filipa Novais

摘要

Background

Major depressive disorder remains a clinical challenge, with a significant number of patients failing to achieve remission with antidepressants. New evidence suggests that neuroinflammation and immune dysfunction may contribute to the pathophysiology of depression. This evidence has increased interest in immunotherapy as a potential therapeutic approach.

Objective

In this review, the authors sought to investigate if there is a relationship between depression and inflammation and evaluate if the use of anti-inflammatory drugs and immunotherapy may help treat depression.

Methods

The authors reviewed studies on Pubmed and Cochrane from 2000 to 2024 involving adults with major unipolar depression without psychotic features, based on DSM-IV/V or ICD-10/11 criteria. They also included studies on patients with secondary symptoms from immunological therapies.

Results

Several immunomodulatory agents demonstrated potential antidepressant effects. Celecoxib was associated with improved treatment outcomes when combined with standard antidepressants. Infliximab showed efficacy primarily in patients with elevated inflammatory markers. Pentoxifylline showed anti-inflammatory properties and neuroprotective effects, leading to a clinical improvement. There were mixed results concerning minocycline. Interferon alfa was associated with the worsening of depressive symptoms.

Conclusion

Immunotherapy is promising for depression treatment, particularly in patients with elevated inflammation. However, findings remain heterogeneous, and further research is needed to refine treatment selection criteria, establish optimal dosing strategies, and evaluate long-term safety and efficacy.