Antioxidant uric acid in treated and untreated subjects with major depressive disorder: a meta-analysis and meta-regression

  • Francesco Bartoli
  • Giulia Trotta
  • Cristina Crocamo
  • Maria Rosaria Malerba
  • Massimo Clerici
  • Giuseppe Carrà
Original Paper


Pathophysiological mechanisms of major depressive disorder (MDD) seem to be associated with oxidative stress pathways and altered purinergic metabolism. We conducted a systematic review and meta-analysis to estimate if subjects with MDD might have reduced levels of antioxidant uric acid, considering also potential influence of antidepressant treatment. We searched the main Electronic Databases, identifying 14 studies that met our inclusion criteria. Meta-analyses were carried out generating pooled Hedges’ g and mean differences (MDs), using random-effects models. Heterogeneity across studies and risk of publication bias were estimated using standard methods. Relevant sensitivity and meta-regression analyses were conducted. Subjects with MDD had levels of uric acid lower than healthy controls (Hedges’ g = −0.30; p = 0.003). Overall between-study heterogeneity was high (I 2 = 76.3%). The effect was significant among studies including drug naïve/free MDD individuals (Hedges’ g = −0.55; p = 0.023), but not among those involving treated subjects (Hedges’ g = −0.15; p = 0.062). Relevant quality- and heterogeneity-based sensitivity analyses, as well as meta-regressions, confirmed these findings. In addition, uric acid levels significantly, though inconsistently (I 2 = 79.2%), increased after treatment (MD = +0.71 mg/dL; p < 0.001), regardless of follow-up duration (p = 0.518). Our meta-analysis shows that subjects with MDD have lower levels of uric acid. Since antidepressant treatment seems to influence this association, our findings support the hypothesis that uric acid levels may represent a state marker of MDD. Nevertheless, the potential role of additional factors that might clarify the nature of this association deserves further research.


Major depressive disorder Uric acid Antidepressive agents Meta-analysis 



We wish to express our great appreciation to all the authors of studies included in the current meta-analysis. A special thanks to Fatih Canan (Department of Psychiatry, Akdeniz University School of Medicine, Antalya, Turkey), Gabriele Ghisleni (Department of Life and Health Sciences, Universidade Catolica de Pelotas, Pelotas, Rio Grande do Sul, Brazil), and Davor Lasic (Department of Psychiatry, University Hospital Centre Split, Split, Croatia), who provided additional, unpublished data.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Medicine and SurgeryUniversity of Milano BicoccaMonzaItaly
  2. 2.Division of PsychiatryUniversity College LondonLondonUK

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