Transcranial Magnetic Stimulation for Depression Treatment

TMS Therapy: Is High-Frequency or Low-Frequency Stimulation the Key to Treating Depression?

Kai Mendoza in Health & Wellness December 2025 • 4 min read.

"A new meta-analysis explores the effectiveness of high-frequency versus low-frequency transcranial magnetic stimulation for major depressive disorder, offering new insights for personalized treatment."

Transcranial Magnetic Stimulation (TMS) has emerged as a promising non-invasive technique for treating major depressive disorder (MDD). Unlike medication, TMS uses magnetic pulses to stimulate nerve cells in the brain, aiming to alleviate symptoms with fewer systemic side effects. This approach has opened new avenues for individuals seeking alternative or adjunctive therapies.

The brain activity in individuals with depression often shows an imbalance between the left and right prefrontal cortex. In light of this understanding, TMS protocols have been developed to modulate this asymmetry. The conventional method involves high-frequency (HF) stimulation of the left dorsolateral prefrontal cortex (L-DLPFC) to boost activity or low-frequency (LF) stimulation of the right DLPFC (R-DLPFC) to reduce overactivity.

Despite the widespread use of these protocols, it remains unclear whether HF-TMS or LF-TMS is more effective, or if they offer comparable benefits. A new meta-analysis seeks to compare the therapeutic efficacy of the two most widely used TMS protocols for treating depression: HF-TMS over the left DLPFC and LF-TMS over the right DLPFC. By comparing response and remission rates, this study aims to provide clarity on which approach may be more beneficial for specific patients.

High-Frequency vs. Low-Frequency TMS: What the Research Shows

Transcranial Magnetic Stimulation for Depression Treatment

A comprehensive review and meta-analysis was conducted, examining studies from 1990 to August 2017. The research team scoured multiple databases, including MEDLINE, EMBASE, PsycINFO, Cochrane Central Register of Controlled Trials (CENTRAL), SCOPUS, and ProQuest Dissertations and Theses (PQDT).

The analysis focused on randomized controlled trials (RCTs) that directly compared the efficacy of HF-TMS over the left DLPFC and LF-TMS over the right DLPFC for treating MDD. Studies were included if they reported response and remission rates as primary endpoints, with or without sham-controlled conditions.

Response Rates: The meta-analysis included 12 studies with a total of 361 patients. The results showed that 44.6% of patients receiving HF-TMS and 40.9% of those receiving LF-TMS were classified as responders. The odds ratio was 1.08, with a 95% confidence interval of 0.88–1.34, indicating no significant difference between the two protocols.
Remission Rates: Data from 5 studies, including 131 patients, were analyzed. Remission rates were 21.9% for HF-TMS and 16.4% for LF-TMS. The odds ratio was 1.29, with a 95% confidence interval of 0.54–3.10, again suggesting similar efficacy between the two treatments.
Dropout Rates: Limited data from 2 RCTs showed a dropout rate of 5.5% in the HF-TMS group, with no dropouts reported in the LF-TMS group.

The findings suggest that both HF-TMS over the left DLPFC and LF-TMS over the right DLPFC demonstrate comparable therapeutic efficacy in treating patients with MDD. These results align with previous meta-analyses, reinforcing the idea that both protocols are viable options. Further research is needed to identify specific indicators that can help personalize treatment approaches and optimize outcomes for individual patients.

Personalizing TMS Treatment: The Future of Depression Therapy

While both HF-TMS and LF-TMS show promise, optimizing clinical protocols remains a challenge. Factors such as stimulation parameters and the specific location of the stimulation can significantly influence therapeutic efficacy. Emerging research is exploring new stimulation protocols, such as theta burst stimulation (TBS), and innovative coil designs to target deeper brain regions.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

Everything You Need To Know

What is Transcranial Magnetic Stimulation (TMS), and how does it work to treat depression?

Transcranial Magnetic Stimulation (TMS) is a non-invasive technique used to treat major depressive disorder (MDD). It works by using magnetic pulses to stimulate nerve cells in the brain. This process aims to alleviate the symptoms of depression without the systemic side effects often associated with medication. By targeting specific areas like the left or right dorsolateral prefrontal cortex (L-DLPFC/R-DLPFC), TMS can help modulate brain activity, potentially improving mood and cognitive function.

What are the primary differences between High-Frequency (HF) and Low-Frequency (LF) TMS protocols, and how do they target different brain regions?

HF-TMS and LF-TMS are two main protocols used in TMS treatment. HF-TMS typically involves stimulating the left dorsolateral prefrontal cortex (L-DLPFC) with high-frequency pulses to boost activity in that region, aiming to counteract the imbalances often seen in depression. Conversely, LF-TMS targets the right DLPFC (R-DLPFC) using low-frequency stimulation to reduce overactivity. The choice between HF and LF protocols depends on the specific treatment goals and the individual's brain activity patterns.

What did the meta-analysis reveal about the effectiveness of HF-TMS versus LF-TMS for treating depression?

The meta-analysis compared the therapeutic efficacy of HF-TMS over the left DLPFC and LF-TMS over the right DLPFC. The results showed that both protocols had comparable therapeutic efficacy. Response rates were similar, with 44.6% of patients responding to HF-TMS and 40.9% to LF-TMS. Remission rates also showed no significant difference. This suggests that both HF-TMS and LF-TMS are viable treatment options for major depressive disorder.

What are the implications of the meta-analysis results for patients and clinicians considering TMS treatment?

The meta-analysis suggests that both HF-TMS over the left DLPFC and LF-TMS over the right DLPFC can be considered effective treatments for major depressive disorder. For patients, this means there are multiple options for TMS treatment. For clinicians, the study emphasizes the importance of personalized treatment approaches. Factors beyond frequency, such as stimulation parameters and location, can influence the outcome. Further research is needed to identify specific indicators that can help tailor treatment.

What future developments are being explored to improve TMS treatment for depression?

Future developments in TMS treatment aim to optimize clinical protocols. Researchers are investigating new stimulation protocols, such as theta burst stimulation (TBS), and innovative coil designs to target deeper brain regions more effectively. Personalizing TMS treatment is a key area of focus, with the goal of identifying specific indicators that can guide treatment choices and enhance outcomes for individual patients. This includes refining the selection of HF-TMS versus LF-TMS protocols based on individual patient needs and brain activity patterns.