Transcranial Magnetic Stimulation in Depression. (LiTMS)

Effect of Low-intensity Transcranial Magnetic Stimulation (Li-TMS) 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. Therefore, it has been proposed to quantify markers of systemic inflammation and evaluate their correlation with MDD and their possible effect with Li-TMS. This was a probabilistic, two-arm, block-randomized, single-blind clinical trial. A qualified psychiatrist evaluated the patients according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to confirm the diagnosis of major depressive disorder. Two groups were formed and randomly assigned to receive treatment: transcranial magnetic stimulation or the sham group. The patients were unaware of the treatment; they did not know whether they would receive low-intensity transcranial magnetic stimulation (Li-TMS) or not.

It was a clinical trial, two arms, probabilistic, block randomized, single-blind. The experimental group received conventional drug treatment combined with Li-TMS, and the control group was administered standard drug therapy with coil placement, without exposure to Li-TMS emission. Both groups had the device coils placed on them.

Study Overview

• Status: Completed
• Conditions: Major Depressive Disorder (MDD)
• Intervention / Treatment: Other: control group B were administered standard drug therapy with coil placement, without exposure to Li-TMS emission.; Other: The experimental group(A) received conventional drug treatment combined with Li-TMS.

Detailed Description

In low- and middle-income countries, only 25% of patients diagnosed with depression receive some form of treatment, with the current options being standard drug therapy and/or psychotherapy (WHO, 2023) (1). However, only about 35% of patients achieve complete remission of symptoms, resulting in more than half of patients with treatment-resistant depression (4).

Several studies have evaluated the efficacy of bilateral high-frequency (10 Hz) (5,6) and low-frequency (1 Hz) (50) Li-TMS applied to the dorsolateral prefrontal cortex (DLPFC) in patients with depression and insomnia over a 6-week period, totaling 30 sessions. These studies showed improvement in depressive symptoms and sleep quality in adults beginning at session 10 (5) and 15, respectively, as assessed by the Pittsburgh Sleep Quality Index (PSQI) and the Patient Health Questionnaire-9 (PHQ9) (7).

The exact mechanism by which Li-TMS improves sleep quality in patients with depression remains unclear. However, evidence indicates that patients who underwent high-frequency repetitive transcranial magnetic stimulation (HF-rTMS) demonstrate improvement in sleep patterns, improvement in sleep stage, positive correlations in motor evoked potential, negative correlations with GABA and BDNF levels, as well as decreased levels of thyroid hormone, adrenocorticotropic hormone, and thyroid-stimulating hormone (5).

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Mexico
  • Guanajuato
    • León, Guanajuato, Mexico, 37328
      • 1Clinical Epidemiology Research Unit. OOAD Guanajuato. Mexican Social Security Institute, Leon, Mexico,

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Clinical diagnosis of major depressive disorder
• insomnia

Exclusion Criteria:

• Epilepsy
• Alzheimer's Disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: group of sham-treated patients; The Sham group was administered standard drug therapy with coil placement, without exposure to Li-TMS emission.	Other: control group B were administered standard drug therapy with coil placement, without exposure to Li-TMS emission.; the control group were administered standard drug therapy with coil placement, without exposure to Li-TMS emission.
Active Comparator: Group receive low-intensity transcranial magnetic stimulation (Li-TMS)	Other: The experimental group(A) received conventional drug treatment combined with Li-TMS.; 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 (L-DLPFC) which dispensed magnetic pulses at 25 Hz, (30 mT) for 45 minutes. Subjects received one Li-TMS session daily, from Monday through Friday. The experimental group received conventional drug treatment combined with Li-TMS, and the control group were administered standard drug therapy with coil placement, without exposure to Li-TMS emission. Both groups had the device coils placed on them. At the end of the study, the control group received Li-TMS treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in depressive symptoms following 20 sessions of transcranial magnetic stimulation.	The Hamilton Scale assesses the severity of depression or anxiety using scores that classify symptoms as mild, moderate, or severe, consists of 17 items that assess aspects such as mood, anxiety, insomnia, loss of interest, and somatic symptoms. Each item is scored between 0 and 2 or 0 and 4, depending on the symptom. The total score is obtained by adding the values of all items, with a typical range of 0 to 52 points. Interpretation of HAM-D Scores: 0-7 points: No depression. 8-13 points: Mild depression.14-18 points: Moderate depression 19-22 points: Severe depression >23 points: Very severe depression, with risk of suicide. The scale also allows for monitoring changes in symptoms over time, evaluating response to treatment or remission of depression. A decrease of at least 50% from the initial score indicates a response to treatment, and scores below-7 suggest remission.	From the start of treatment until 4 weeks after it ends.

Collaborators and Investigators

• Sponsor: Instituto Mexicano del Seguro Social
• Investigators: Principal Investigator: Blanca Olivia Murillo Ortiz, PhD, Mexican Social Security Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 6, 2025
• Primary Completion (Actual): July 25, 2025
• Study Completion (Actual): May 18, 2026

Study Registration Dates

• First Submitted: May 18, 2026
• First Submitted That Met QC Criteria: June 4, 2026
• First Posted (Actual): June 10, 2026

Study Record Updates

• Last Update Posted (Actual): June 10, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Major Depressive Disorder; low-intensity transcranial magnetic stimulation
• Additional Relevant MeSH Terms: Mental Disorders; Mood Disorders; Depressive Disorder; Depressive Disorder, Major
• Other Study ID Numbers: IMSS1; R-2024-785-075 (Registry Identifier: National Scientific Research Commission)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data will be accessible in a properly anonymized form, as the confidential information is protected and cannot be used to identify participants. However, the results are available upon formal request.
• IPD Sharing Time Frame: June 2026 to June 2028
• IPD Sharing Access Criteria: The dataset may be shared upon request by researchers interested in the research project, via the corresponding author's email address.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No