Neither all anti-inflammatory drugs nor all doses are effective in accelerating the antidepressant-like effect of fluoxetine in an animal model of depression

J Affect Disord. 2018 Aug 1:235:124-128. doi: 10.1016/j.jad.2018.04.063. Epub 2018 Apr 6.

Abstract

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) have been studied as possible adjunctive therapy in the treatment of depression. However, administering NSAIDs to increase the effectiveness of antidepressant has yielded inconsistent results.

Methods: We evaluated the effect of the co-administration of fluoxetine (5 mg/kg) and flurbiprofen (5 mg/kg) or fluoxetine (5 mg/kg) and celecoxib (5 mg/kg) in the chronic escape deficit (CED) model of depression after 7 days of treatment. The co-administration of fluoxetine plus acetylsalicylic acid (ASA, 45 mg/kg i.p.) was used as a positive control. Moreover, we tested the behavioral effect of different doses (45, 22.5, and 11.25 mg/Kg i.p.) of ASA as potentiating agent of the effect of fluoxetine in the same paradigm.

Results: Our study showed that only the co-administration of ASA with fluoxetine was able to revert the stress-induced condition of escape deficit after 7 days of treatment, and that the amplitude of the antidepressant-like effect of ASA was dose dependent. In the same experimental conditions, celecoxib with fluoxetine only partially resolved the stress-induced impaired behavior while flurbiprofen/fluoxetine cotreatment was ineffective.

Limitations: Our study is still exploratory, more doses, longer treatment regimens, and different behavioral outcomes must be investigated to draw a clear conclusion.

Conclusion: Our results further stress the importance of the type and dose when NSAIDs are associated with antidepressants to ameliorate a clinical response.

Keywords: Acetylsalicylic acid; Animal model of depression; Behavior; Fluoxetine; NSAIDs.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Antidepressive Agents / administration & dosage*
  • Behavior, Animal / drug effects
  • Celecoxib / administration & dosage
  • Depression / drug therapy*
  • Disease Models, Animal
  • Drug Therapy, Combination
  • Fluoxetine / administration & dosage*
  • Flurbiprofen / administration & dosage
  • Male
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Anti-Inflammatory Agents
  • Antidepressive Agents
  • Fluoxetine
  • Flurbiprofen
  • Celecoxib