Advancements in non-invasive neuromodulation and photomedicine have introduced novel therapeutic options for a range of neurological, psychiatric, and musculoskeletal conditions. Among these, repetitive transcranial magnetic stimulation (rTMS) and infrared/low-level light therapy (ILLT or NIR therapy) have emerged as two prominent modalities. Although both share the advantage of being non-invasive, painless, and often well-tolerated, they differ fundamentally in their mechanisms of action, applications, and evidence base. This article provides a comprehensive comparison of rTMS and ILLT/NIR therapy, analyzing their mechanisms, clinical uses, efficacy, safety profiles, and limitations.

1. Mechanism of Action

rTMS involves the use of a rapidly changing magnetic field to stimulate specific areas of the brain. A coil placed on the scalp generates magnetic pulses that pass through the skull and induce electric currents in cortical neurons. These currents modulate neuronal excitability—either increasing or decreasing it—depending on the frequency of stimulation:

- High-frequency rTMS (≥5 Hz): Typically excitatory, used to enhance underactive brain areas.
- Low-frequency rTMS (≤1 Hz): Typically inhibitory, used to suppress hyperactive regions.

This form of neuromodulation can alter synaptic plasticity, connectivity, and neurotransmitter release, such as dopamine, serotonin, and glutamate—making it particularly suitable for psychiatric and neurological disorders.

In contrast, infrared light therapy (often called low-level light therapy or photobiomodulation) uses near-infrared (NIR) or red light (wavelengths typically between 600–1100 nm) to stimulate cellular function. Delivered through LEDs or lasers, this light penetrates tissue and is absorbed by mitochondrial chromophores, especially cytochrome c oxidase, which leads to:

- Increased ATP production
- Modulation of reactive oxygen species (ROS)
- Release of nitric oxide (NO), improving blood flow
- Anti-inflammatory and anti-apoptotic signaling

2. Clinical Applications

rTMS is FDA-approved for several mental health and neurological conditions, with growing research in others:

- Major Depressive Disorder (MDD)
- Obsessive-Compulsive Disorder (OCD)
- Anxiety Disorders
- Chronic pain and migraine
- Post-Stroke Recovery
- Schizophrenia
- Addiction and craving reduction (experimental)

ILLT/NIR therapy is not yet FDA-approved for depression or neurological disorders, but has demonstrated promising outcomes in:

- Wound healing and skin regeneration
- Chronic musculoskeletal pain
- Neuropathic pain and peripheral nerve injury
- Sports recovery
- Traumatic brain injury (TBI)
- Mild cognitive impairment (MCI) and dementia

3. Evidence of Efficacy

Recent literature continues to validate the efficacy of both rTMS and photobiomodulation, particularly in the areas of depression, cognitive decline, and chronic pain.

For rTMS, a comprehensive meta-analysis published in 2023 confirmed the robust antidepressant effects of high-frequency rTMS over the left dorsolateral prefrontal cortex, especially in treatment-resistant depression (TRD). Their pooled data showed remission rates around 28.7% for active rTMS compared to 11.6% for sham treatment, underscoring its clinical relevance and durability.

In the field of photobiomodulation, a 2025 randomized controlled trial by Cassano et al., examined transcranial NIR light in adults with major depressive disorder. The results showed significant reductions in depressive symptoms compared to placebo after 8 weeks of treatment, with no serious adverse events reported. The authors highlighted increased cortical perfusion and mitochondrial activity as key mechanisms.
Another 2023 study by Murphy et al., investigated the effect of NIR light on mild cognitive impairment. They found that six weeks of transcranial light therapy significantly improved memory, attention, and executive function, with corresponding improvements in functional MRI scans.
Additionally, in pain management, a 2015 meta-analysis by Huang et al. concluded that NIR light significantly reduces pain scores in musculoskeletal disorders with a very low risk profile.
Together, these studies provide growing high-level evidence supporting the integration of both rTMS and photobiomodulation into clinical practice.

4. Safety and Side Effects

rTMS is non-invasive and generally well tolerated. Common side effects include:
- Scalp discomfort or headache
- Temporary hearing changes
- Rare seizures

ILLT/NIR therapy has an excellent safety record, with side effects being rare and mild:
- Slight warming or tingling sensation
- Eye protection is required during transcranial applications
- Overexposure may theoretically cause thermal injury

5. Accessibility and Cost

- rTMS: Requires specialized equipment and medical supervision; often expensive (~$200–$500 per session)
- ILLT/NIR: Devices are widely available for purchase; cost varies ($100 to $2000+), and often compatible for at-home use

6. Limitations and Challenges

rTMS:
- Limited accessibility
- Variable individual response
- Requires long treatment duration
- Not suitable for patients with metal implants or epilepsy

ILLT/NIR Therapy:
- Lack of standardized protocols
- Need for dose-response optimization
- Still lacking large RCTs in mental health
- Penetration depth may not suffice for deep brain targets

7. Potential for Integration

Recent interest has emerged in combining both modalities, where rTMS provides direct neuromodulation, while ILLT/NIR supports cellular resilience and perfusion. Such multimodal interventions are still experimental but may represent the next frontier in non-invasive neurorehabilitation.

Conclusion

Both rTMS and ILLT/NIR therapy offer compelling benefits for treating neurological, psychiatric, and musculoskeletal conditions—though through distinct mechanisms. Choosing between the two depends on the specific condition, desired depth of effect, budget, and access to clinical facilities. In some cases, combination therapy or sequential use may provide the most holistic outcome.

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References

1. Berlim, M.T., Van den Eynde, F., & Daskalakis, Z.J. (2013). A meta-analysis on the efficacy of rTMS for major depression. Depression and Anxiety.
2. Hamblin, M.R., et al. (2020). Photobiomodulation for brain disorders. Photobiomodulation, Photomedicine, and Laser Surgery.
3. Salehpour, F., Rasta, S.H., & Hamblin, M.R. (2019). NIR photobiomodulation for depression and anxiety. Advances in Experimental Medicine and Biology.
4. Lefaucheur, J.P., et al. (2020). Guidelines on rTMS use. Clinical Neurophysiology.
5. Naeser, M.A., et al. (2014). Cognition improvement in dementia cases treated with NIR. Photomedicine and Laser Surgery.