Effect of low-intensity transcranial magnetic stimulation on sleep disorders, inflammation levels, and brain-derived neurotrophic factor in patients with depression

Major depressive disorder (MDD) has increased in recent years, affecting 16.1% of the adult population nationwide. Currently, there are pharmacological and psychological treatments that have a 67% remission rate for depressive symptoms and insomnia after up to four trials of antidepressant treatments. Recently, low-intensity transcranial magnetic stimulation (Li-TMS) has been used to activate and generate structural and neural functioning changes in specific cortical regions such as the left dorsolateral prefrontal cortex, as its activity is altered in MDD. Furthermore, an increase in circulating levels of granulocytes, monocytes, and inflammatory cytokines has been observed in patients with MDD, suggesting an association between inflammation and neurotoxicity with the development of depression and decreased BDNF, mainly affecting the prefrontal cortex and hippocampus.

The randomized trial, parallel-group was conducted to compare effect of low-intensity transcranial magnetic stimulation (Li-TMS), it has been proposed to quantify markers of systemic inflammation and evaluate their correlation with MDD and their possible effect with Li-TMS. It was a clinical trial, randomized, single-blind. Subjects were evaluated based on the DSM-5. Each group consisted of 20 patients. Participants aged 18 to 60 years of both genders, a diagnosis of major depressive disorder previously established by the treating psychiatrist, and the presence of insomnia as assessed by the PSQI. Clinically evaluated using the HAMD-17, and the Patient Health Questionnaire-9 both prior to the first session and following the 20th Li-TMS session. Adverse events were collected. All participants provided 3 mL of venous blood for the determination of BDNF and metabolic markers.

Participants received 20 sessions of Li-TMS with the medical device Nibbot Pro Series. Each Li-TMS session consisted in positioning an eight-shaped coil over the left dorsolateral prefrontal cortex which dispensed magnetic pulses at 25 Hz, (30 mT) for 45 minutes. Subjects received one Li-TMS session daily. The experimental group received conventional drug treatment combined with Li-TMS. Both groups had the device coils placed on them. At the end of the study, the control group received Li-TMS treatment. 39 patients were included. Findings from this study suggest that (Li-TMS) produces a significant reduction in depressive symptoms, as demonstrated by the difference between baseline and post-treatment scores, HAMD-17 (14.30vs.7.38, p=0.001). The PSQ1 health perception questionnaire (14.52vs.6.90, p=0.001). The Pittsburgh PHQ9 (17vs.3, p=0.001). In the stimulation group, post-treatment analysis revealed significant alterations in triglycerides, VLDL, cortisol, and CRP concentrations.

The limitations of the study include the small sample size (n=39) and the lack of objective sleep measurements such as polysomnography. However, the consistency between the clinical and biochemical results of our study strengthens the validity of the observations.

In conclusion, Li-TMS proved to be a safe, well-tolerated intervention with relevant clinical effects and a favorable safety profile for improving sleep quality and depressive symptoms with an adequate metabolic and inflammatory response. Future controlled studies with larger samples and longitudinal follow-up are necessary to confirm these effects and establish their long-term therapeutic relationship.

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