Acute administration of ibuprofen increases serum concentration of the neuroprotective kynurenine pathway metabolite, kynurenic acid: a pilot randomized, placebo-controlled, crossover study

Jonathan Savitz, Bart N. Ford, Rayus Kuplicki, Sahib Khalsa, T. Kent Teague, Martin P. Paulus

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Rationale: At least six different types of antidepressant treatments have been shown to either increase the neuroprotective kynurenine pathway (KP) metabolite, kynurenic acid (KynA), or decrease the neurotoxic KP metabolite, quinolinic acid (QA). Nonsteroidal anti-inflammatory drugs (NSAIDs) including ibuprofen have shown some efficacy in the treatment of depression but their effects on the KP have not been studied in humans. Objectives: To evaluate the effect of ibuprofen on circulating KP metabolites. Methods: In a randomized, placebo-controlled, crossover study, 20 healthy adults (10 women) received a single oral dose of 200-mg ibuprofen, 600-mg ibuprofen, or placebo in a counterbalanced order (NCT02507219). Serum samples were drawn in the mid-afternoon, 5 h after ibuprofen/placebo administration. KP metabolites were measured blind to visit by tandem mass spectrometry. Data were analyzed with linear mixed effect models. The primary outcome was KynA/QA and the secondary outcome was KynA. Results: After Bonferroni correction, there was a significant effect of treatment on KynA/QA. The effect was driven by an increase in KynA concentration after the 600-mg dose but not the 200-mg dose relative to placebo (Cohen’s d = 1.71). In contrast, both the 200-mg (d = 1.03) and 600-mg (d = 2.05) doses of ibuprofen decreased tryptophan concentrations relative to placebo. Conclusions: Given its KynA-elevating effects, ibuprofen could have neuroprotective effects in the context of depression as well as other neuroinflammatory disorders that are characterized by a reduction in KynA.

Original languageEnglish
Pages (from-to)3919-3927
Number of pages9
JournalPsychopharmacology
Volume239
Issue number12
DOIs
StatePublished - Dec 2022

Keywords

  • Depression
  • Ibuprofen
  • Kynurenic acid
  • Kynurenine pathway
  • Nonsteroidal anti-inflammatory drugs
  • Tryptophan

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