: What a Critical Scientific Review Reveals and Why TMS Remains the Better-Studied Treatment for Depression){kind=link}
At Mid City TMS, we regularly speak with patients exploring non-medication treatments for Depression, anxiety, and insomnia. One option that generates interest is cranial electrotherapy stimulation (CES), a technology that delivers very low levels of electrical current through electrodes placed on the earlobes, temples, or scalp. CES devices are portable, relatively inexpensive, and can be used at home under a clinician’s supervision, which leads some patients to wonder whether CES might offer benefits similar to transcranial magnetic stimulation (TMS).
A comprehensive review by Tad T. Brunyé and colleagues, published in the Annals of the New York Academy of Sciences, offers one of the most thorough assessments of this technology to date, evaluating decades of CES research in both healthy volunteers and clinical populations. The review’s authors concluded that CES produces measurable neurophysiological effects and may offer mild benefit for anxiety and insomnia, but that the clinical evidence for Major Depressive Disorder (MDD) is considerably weaker than the evidence supporting TMS, and is undermined by a pattern of methodological problems across the field.
What Is Cranial Electrotherapy Stimulation?
CES delivers a very low-intensity alternating current, typically in the microampere to low milliampere range, through electrodes attached to the earlobes, temples, mastoids, or eyelids. The best-known prescription CES system in the United States is the Alpha-Stim, manufactured by Electromedical Products International. Researchers have hypothesized that CES may influence brain electrical rhythms, the autonomic nervous system, and neurotransmitter systems, but the review found the evidence for most of these mechanisms to be thin and inconsistent, with only one small, methodologically limited study reporting a clear neurotransmitter effect. Unlike TMS, which directly and focally stimulates specific cortical regions involved in mood regulation, CES delivers diffuse current and appears to affect the brain more indirectly.
Why CES Draws Interest
CES has real practical advantages: small, portable devices, home-based use, minimal reported side effects for most users, relatively low cost, and ease of use. These features have led to research on CES for anxiety, insomnia, Depression, chronic pain, and other conditions. A convenient treatment is not necessarily a proven one, though, and the review’s central question was whether CES produces reliable clinical benefit once the methodology is examined closely.
CES for Anxiety and Insomnia: Moderate, Mixed Evidence
The most encouraging evidence in the review involved anxiety and sleep. One relatively large, well-conducted trial of 115 participants with an anxiety disorder found roughly a 32% reduction in anxiety symptoms by week five of treatment, compared with sham stimulation. Several smaller studies reported improvements in generalized anxiety symptoms and sleep. At the same time, the review found four sham-controlled trials of CES for insomnia with inconsistent results, some showing improvement and others showing none, and noted that most anxiety studies were limited by small samples and high rates of overlapping conditions like Depression, PTSD, or insomnia in the same patients. The evidence here is real but moderate, not definitive.
CES for Depression: A Much Weaker Evidence Base
The picture for Depression is considerably less favorable. A prior systematic review cited in this analysis found that among 270 published reports on CES and Depression, not one met the Cochrane Collaboration’s quality criteria for a well-designed clinical trial. Of the two studies the reviewers considered relatively high quality, one found a benefit for active CES over sham at two weeks but included only 16 total participants, a sample too small to draw firm conclusions from. The second, a larger trial of 30 participants, found no significant difference between active and sham CES at three weeks. That second study is also worth a closer look for a different reason: the authors described placing electrodes over the dorsolateral prefrontal cortex, but the review’s authors noted that the study’s own published figures appear to show the electrodes placed closer to the temples, which raises real uncertainty about what brain region was actually being stimulated in this widely cited trial.
The FDA’s Regulatory Distinction Matters
The FDA classifies CES devices marketed for anxiety and insomnia as Class II medical devices, meaning general controls alone are not sufficient to assure safety and effectiveness, so additional safeguards are required. CES devices marketed specifically for Depression are classified as Class III, the FDA’s highest-risk category, reserved for devices where the evidence is not strong enough to rule out an unreasonable risk of harm. This distinction reflects the same conclusion the scientific review reached independently: the evidence supporting CES for anxiety and insomnia, while moderate, is meaningfully stronger than the evidence supporting CES for Depression. CES devices remain prescription-only, meaning only a licensed practitioner can authorize their use, though the review’s own authors noted they were able to obtain a CES device for research purposes without demonstrating licensure, suggesting this requirement is not always consistently enforced in practice.
A Note on Conflicts of Interest in CES Research
One of the review’s more pointed findings is worth patients knowing about directly: close to half of the published CES research the authors examined was funded by, or authored by individuals affiliated with, CES device manufacturers. The review found that some manufacturer-affiliated reviews omitted unfavorable studies or combined incompatible types of data in ways that made the evidence look stronger than it was. This does not mean every positive CES study is unreliable, but it is a meaningful reason to weigh manufacturer-funded research more cautiously.
Safety Profile of Cranial Electrical Stimulation
Reported side effects from CES are generally mild, most commonly vertigo, skin irritation at the electrode site, and headache. Estimates of how often these occur vary considerably across studies, from as low as about 1% in some device-manufacturer literature to notably higher rates in independently run trials, including one study where 25% of participants withdrew due to dizziness or headache and another where 44% of participants, including those in the sham group, reported headache. A search of the FDA’s adverse event database identified a small number of serious reports tied to specific CES devices, including burns, severe tinnitus, and, among a handful of reports associated with one manufacturer’s device, more serious events such as brain hemorrhage and death. These reports do not establish that CES caused these outcomes, and they are rare relative to how many devices have been sold, but they are part of the full safety picture patients deserve to see.
How CES Compares Mechanistically to TMS
Computational modeling cited in the review estimates that the current intensities reaching the brain during CES are roughly 1,000 times lower than those delivered during TMS. TMS directly and focally stimulates a specific, targeted brain region using a magnetic field strong enough to activate neurons, while CES delivers a much weaker, more diffuse current that current models suggest reaches the brain only at subthreshold levels. This helps explain why the mechanisms behind any therapeutic effect of CES remain unclear, while TMS’s mechanism of action has been mapped in much greater detail.
Could CES Still Be Useful?
CES may be a reasonable option for some patients with mild anxiety, insomnia, or stress-related symptoms who want a home-based intervention and understand the limits of the current evidence. For patients with moderate to severe Depression, recurrent Depression, or treatment-resistant Depression, the evidence base is not yet strong enough to support CES as a primary treatment, and TMS remains one of the most thoroughly studied non-medication options available for this population.
Why Mid City TMS Focuses on TMS
At Mid City TMS, we offer treatments supported by the strongest available scientific evidence. TMS has demonstrated significant response and remission rates in treatment-resistant Depression, durable benefits for many patients, and strong support across major psychiatric guidelines. CES remains a genuinely interesting but comparatively underdeveloped technology, particularly where Depression is concerned.
Cranial Electrical Stimulation for Depression
CES has measurable effects on brain activity and may offer mild, real benefit for anxiety and insomnia. The evidence for Depression is limited, inconsistent, and affected by conflicts of interest across a meaningful share of the published literature, which is reflected in its Class III FDA designation for that use. TMS remains the far better-studied and more strongly supported neuromodulation treatment for Depression.
If you are exploring treatment options for Depression and want to understand what the evidence actually supports, learn how Mid City TMS can help and contact us today to schedule a consultation.
Sources
- Brunyé, T. T., Patterson, J. E., Wooten, T., & Hussey, E. K. (2021). A Critical Review of Cranial Electrotherapy Stimulation for Neuromodulation in Clinical and Non-clinical Samples. Frontiers in human neuroscience, 15, 625321. https://doi.org/10.3389/fnhum.2021.625321
- Shekelle P, Cook I, Miake-Lye IM, et al. The Effectiveness and Risks of Cranial Electrical Stimulation for the Treatment of Pain, Depression, Anxiety, PTSD, and Insomnia: A Systematic Review [Internet]. Washington (DC): Department of Veterans Affairs (US); 2018 Feb. INTRODUCTION. Available from: https://www.ncbi.nlm.nih.gov/books/NBK493129/
- Barclay, Tim & Barclay, Raymond. (2014). A clinical trial of cranial electrotherapy stimulation for anxiety and comorbid depression. Journal of affective disorders. 164C. 171-177. 10.1016/j.jad.2014.04.029.