Neuroendocrine Biomarkers of Herbal Medicine for Major Depressive Disorder: A Systematic Review and Meta-Analysis

Major depressive disorder (MDD) is a medical condition involving persistent sadness and loss of interest; however, conventional treatments with antidepressants and cognitive behavioral therapy have limitations. Based on the pathogenesis of MDD, treatments using herbal medicines (HM) have been identified in animal studies. We conducted a systematic review of clinical studies to identify neurobiological outcomes and evaluate the effectiveness of HM in treating MDD. A meta-analysis was performed by searching nine databases from their inception until 12 September 2022, including 31 randomized controlled trials with 3133 participants, to examine the effects of HM on MDD using neurobiological biomarkers and a depression questionnaire scale. Quality assessment was performed using a risk of bias tool. Compared to antidepressants alone, HM combined with an antidepressant significantly increased concentrations of serotonin (SMD = 1.96, 95% CI: 1.24–2.68, p < 0.00001, I(2) = 97%), brain-derived neurotrophic factor (SMD = 1.38, 95% CI: 0.92–1.83, p < 0.00001, I(2) = 91%), and nerve growth factors (SMD = 2.38, 95% CI: 0.67–4.10, p = 0.006, I(2) = 96%), and decreased cortisol concentrations (SMD = −3.78, 95% CI: −4.71 to −2.86, p < 0.00001, I(2) = 87%). Although HM or HM with an antidepressant benefits MDD treatment through improving neuroendocrine factors, these findings should be interpreted with caution because of the low methodological quality and clinical heterogeneity of the included studies.