Adjunctive N-acetylcysteine in depression: exploration of interleukin-6, C-reactive protein and brain-derived neurotrophic factor

Acta Neuropsychiatr. 2017 Dec;29(6):337-346. doi: 10.1017/neu.2017.2. Epub 2017 Mar 20.


Objective: This study aimed to explore effects of adjunctive N-acetylcysteine (NAC) treatment on inflammatory and neurogenesis markers in unipolar depression.

Methods: We embarked on a 12-week clinical trial of NAC (2000 mg/day compared with placebo) as an adjunctive treatment for unipolar depression. A follow-up visit was conducted 4 weeks following the completion of treatment. We collected serum samples at baseline and the end of the treatment phase (week 12) to determine changes in interleukin-6 (IL6), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) following NAC treatment.

Results: NAC treatment significantly improved depressive symptoms on the Montgomery-Asberg Depression Rating Scale (MADRS) over 16 weeks of the trial. Serum levels of IL6 were associated with reductions of MADRS scores independent of treatment response. However, we found no significant changes in IL6, CRP and BDNF levels following NAC treatment.

Conclusion: Overall, this suggests that our results failed to support the hypothesis that IL6, CRP and BDNF are directly involved in the therapeutic mechanism of NAC in depression. IL6 may be a useful marker for future exploration of treatment response.

Keywords: N-acetylcysteine; clinical trial; depression; inflammation; neurotrophic factor.

Publication types

  • Clinical Trial

MeSH terms

  • Acetylcysteine / therapeutic use*
  • Adult
  • Aged
  • Antidepressive Agents / therapeutic use*
  • Biomarkers / blood
  • Brain-Derived Neurotrophic Factor / blood*
  • C-Reactive Protein / analysis*
  • Depressive Disorder / blood
  • Depressive Disorder / drug therapy*
  • Female
  • Humans
  • Interleukin-6 / blood*
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales
  • Treatment Outcome
  • Young Adult


  • Antidepressive Agents
  • Biomarkers
  • Brain-Derived Neurotrophic Factor
  • Interleukin-6
  • BDNF protein, human
  • C-Reactive Protein
  • Acetylcysteine