Non-invasive neurostimulation for enhancing peripheral brain-derived neurotrophic factor levels in major depressive disorder: A meta-analysis of randomized controlled trials
In brief
Non-invasive brain stimulation raises BDNF levels by one SD in depression
A meta-analysis of 16 randomized trials (1,271 patients) found that rTMS and tDCS together increased peripheral BDNF by roughly one standard deviation and cut depressive symptom scores by about one standard deviation. The BDNF rise was driven mainly by rTMS and was larger with treatment courses of four weeks or more, suggesting BDNF could serve as a response biomarker, though tDCS showed no effect.
- Journal
- Journal of psychiatric research (Q1)
- Published
- 6 August 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Jing Ni, Meng-Xuan Qiao, Yun-Ge Lin, Hua Yu, Tao Li
- PMID
- 42574930
- DOI
- 10.1016/j.jpsychires.2026.08.001
Why clinicians should know about it
- Picked for Biochemistry (medical) (top studies of the week, 16 August 2026): Meta‑analysis of BDNF changes after non‑invasive brain stimulation
Abstract
BACKGROUND: Brain-derived neurotrophic factor (BDNF), a critical modulator of neuroplasticity, has been strongly implicated in the pathophysiology of major depressive disorder (MDD). Non-invasive brain stimulation (NIBS), including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), shows therapeutic promise for MDD. However, their impact on peripheral BDNF levels remains inconclusive. OBJECTIVE: This meta-analysis aimed to quantify the effects of NIBS on peripheral BDNF levels in MDD patients and to evaluate BDNF as a potential biomarker of treatment response. METHODS: Following PRISMA guidelines, randomized controlled trials (RCTs) comparing NIBS with sham stimulation in MDD were identified through a systematic search of five databases. Sixteen RCTs (n = 1271) were included. Random-effects models were used to estimate pooled standardized mean differences (SMDs) for peripheral BDNF levels and depressive symptom severity. Subgroup and moderator analyses examined the effects of BDNF elevation, stimulation modality, and treatment duration. RESULTS: NIBS significantly increased peripheral BDNF levels (SMD = 1.05, 95% CI: 0.57 to 1.52, p < 0.001) and reduced depressive symptoms (SMD = -0.90, 95% CI: -1.13 to -0.67, p < 0.001). Moderator analyses demonstrated that BDNF elevation was associated with greater antidepressant effects. Subgroup analyses revealed that rTMS significantly increased BDNF levels, whereas tDCS did not. Extended rTMS protocols (≥4 weeks) were associated with greater BDNF increases than shorter durations. CONCLUSION: NIBS is associated with increased peripheral BDNF levels and improved depressive symptoms in MDD patients, suggesting the potential utility of BDNF as a biomarker for neuromodulation efficacy. PROSPERO REGISTRATION: CRD42025630845.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.