Brain with light networks symbolizing rTMS therapy.

Struggling with Depression? High-Frequency vs. Low-Frequency rTMS: Which One is Right for You?

Nico Varela in Health & Wellness August 2025 • 4 min read.

"A meta-analysis reveals that both high-frequency and low-frequency rTMS offer similar benefits in treating major depressive disorder, but understanding the nuances can help personalize treatment."

Transcranial magnetic stimulation (TMS) is emerging as a non-invasive beacon of hope for individuals grappling with major depressive disorder (MDD). This innovative technique employs magnetic pulses to gently stimulate nerve cells in the brain, offering a potential pathway to alleviate depressive symptoms without the systemic side effects often associated with medication.

Within the realm of TMS, two primary protocols have garnered considerable attention: high-frequency (HF) rTMS, typically applied to the left dorsolateral prefrontal cortex (L-DLPFC), and low-frequency (LF) rTMS, often directed at the right DLPFC (R-DLPFC). While HF-rTMS has been a more traditional approach, LF-rTMS is increasingly recognized for its comparable, and potentially superior, efficacy. This has sparked a vital question: Which protocol offers the most significant benefit for those battling MDD?

To shed light on this question, a comprehensive meta-analysis was conducted, meticulously comparing the effectiveness of HF-rTMS and LF-rTMS in treating MDD. By synthesizing data from multiple randomized, double-blind trials, this analysis aimed to provide clarity and evidence-based insights into optimizing rTMS therapy for individuals seeking relief from depression.

Decoding rTMS: How High-Frequency and Low-Frequency Stimulation Work

Brain with light networks symbolizing rTMS therapy.

To fully understand the implications of this meta-analysis, it’s important to grasp the fundamental differences between HF-rTMS and LF-rTMS and how they interact with brain activity. The core principle of TMS lies in its ability to induce electrical currents in specific brain regions through magnetic pulses. These currents can then either excite or inhibit neuronal activity, depending on the stimulation parameters.

Think of the brain as having two key regions involved in depression: one that's underactive (often the left DLPFC) and one that's overactive (often the right DLPFC). The goal of rTMS is to rebalance this activity:

High-Frequency rTMS (HF-rTMS): Typically involves delivering pulses at a rate of 5 Hz or higher to the left DLPFC. This is thought to stimulate activity in this area, encouraging it to become more active and engaged.
Low-Frequency rTMS (LF-rTMS): Involves delivering pulses at a rate of 1 Hz or lower to the right DLPFC. This is thought to calm down overactivity in this region.

The meta-analysis examined studies that directly compared these two approaches to see which one led to better outcomes in people with MDD. The researchers looked at response rates (how many people had a significant reduction in symptoms) and remission rates (how many people essentially became symptom-free) to determine which method was more effective.

Personalizing rTMS: The Future of Depression Treatment

While this meta-analysis offers valuable insights, it also underscores the need for personalized approaches to rTMS therapy. Factors such as individual brain connectivity, genetic predispositions, and specific symptom profiles may influence treatment response. Future research should focus on identifying biomarkers that can predict which patients are most likely to benefit from HF-rTMS, LF-rTMS, or other emerging stimulation protocols. By tailoring treatment to the individual, we can unlock the full potential of rTMS and offer more effective, targeted relief for those living with depression.

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Everything You Need To Know

What is rTMS, and how does it help with major depressive disorder (MDD)?

rTMS, or transcranial magnetic stimulation, is a non-invasive technique that uses magnetic pulses to stimulate nerve cells in the brain. For individuals with major depressive disorder (MDD), rTMS aims to alleviate depressive symptoms by targeting specific brain regions without the systemic side effects often associated with medication. The treatment focuses on rebalancing brain activity using two primary protocols: high-frequency (HF) rTMS and low-frequency (LF) rTMS.

What's the difference between high-frequency (HF-rTMS) and low-frequency (LF-rTMS) in treating depression, and where are they typically applied?

High-frequency rTMS (HF-rTMS) typically involves delivering pulses at a rate of 5 Hz or higher to the left dorsolateral prefrontal cortex (L-DLPFC) to stimulate activity in this area. Low-frequency rTMS (LF-rTMS) involves delivering pulses at a rate of 1 Hz or lower to the right DLPFC (R-DLPFC) to calm down overactivity in that region. HF-rTMS aims to encourage activity in an underactive brain region, while LF-rTMS aims to reduce overactivity in another brain region. The selection of the treatment depends on whether stimulation or calming of the brain area is required.

A meta-analysis compared HF-rTMS and LF-rTMS for MDD. What were the key findings regarding their effectiveness?

The meta-analysis aimed to compare the effectiveness of high-frequency rTMS (HF-rTMS) and low-frequency rTMS (LF-rTMS) in treating major depressive disorder (MDD) by synthesizing data from multiple randomized, double-blind trials. The analysis focused on response rates and remission rates to determine which method was more effective. The research indicated both HF-rTMS and LF-rTMS offer similar benefits in treating major depressive disorder, but understanding the nuances can help personalize treatment.

How does rTMS rebalance brain activity in people with depression, and what role do the left and right DLPFC play?

In people with depression, rTMS works by targeting key brain regions to rebalance their activity. The left dorsolateral prefrontal cortex (L-DLPFC) is often underactive, while the right DLPFC (R-DLPFC) is often overactive. High-frequency rTMS (HF-rTMS) is applied to the left DLPFC to stimulate and encourage activity, while low-frequency rTMS (LF-rTMS) is applied to the right DLPFC to calm down the overactivity. The goal is to restore a more balanced state of neuronal activity in these regions, leading to a reduction in depressive symptoms.

What are the implications of personalized approaches to rTMS therapy, and what future research is needed to optimize treatment for individuals with depression?

Personalized approaches to rTMS therapy acknowledge that factors such as individual brain connectivity, genetic predispositions, and specific symptom profiles can influence treatment response. Future research should focus on identifying biomarkers that can predict which patients are most likely to benefit from HF-rTMS, LF-rTMS, or other emerging stimulation protocols. Tailoring treatment to the individual unlocks the full potential of rTMS and offer more effective, targeted relief for those living with depression.