Cranial electrotherapy stimulation (CES), also known as cranial electrical stimulation, transcranial electrical stimulation, or electrical stimulation therapy, utilize devices such as Alpha-Stim to deliver weak pulses of electrical current to the earlobes, mastoid processes, or scalp. According to the manufacture, CES can be performed in either setting: the outpatient office or at-home as a durable medical device. The purpose of cranial electrotherapy stimulation is to provide an alternative treatment option or to improve upon the existing therapies, such as medical management and other conservative therapies for a variety of indications. CES has been evaluated for the following conditions: headache, pain (acute or chronic), insomnia, depression, anxiety, and functional constipation.
Headaches are common pain ailments that consist consist of painful sensations (e.g., pressure, tension) across areas of the head. The pain ranges from dull to sharp, and could be caused by underlying disease or by a number of other causes. Primary headache disorders include migraine, cluster, and tension headaches. Three trials have evaluated CES in the treatment of headache. Klawansky et al (1995) published a meta-analysis of 14 RCTs comparing CES with sham for the treatment of various psychological and physiological conditions. The literature search, conducted through 1991, identified 2 trials evaluating CES for the treatment of headache. Pooled analysis of the 2 trials (total N=102 participants) favored CES over placebo (0.68; 95% confidence interval [CI], 0.09 to 1.28). Pooled analyses found marginal benefits for a headache with CES.
A Cochrane review by Bronfort et al (2004) assessed noninvasive treatments for headaches; the reviewers conducted a literature search through November 2002. They identified one poor quality, placebo-controlled, randomized trial (N=100) of CES for a migraine or a tension type headache. Results from the trial showed greater reductions in pain intensity in the CES group compared in the placebo group (0.4; 95% CI, 0.0 to 0.8). The trial was under-powered and the evidence is limited to demonstrate efficacy. The evidence is insufficient to determine the effects of the technology on health outcomes.
For individuals who have acute or chronic pain treated by CES, the evidence includes a number of small sham-controlled randomized trials, and pooled analyses. Relevant outcomes are symptoms, morbid events, functional outcomes, and treatment related morbidity.
There are five studies that assessed chronic pain treated by CES in a review by O'Connell et al (2014). A meta-analysis of these 5 trials (n=270 participants) found no significant difference in pain scores between active and sham stimulation (-0.24; 95% CI, -0.48 to 0.01) for the treatment for chronic pain. An updated Cochrane review by O'Connell et al (2018) evaluated six low-quality studies on short-term outcomes for pain treated by CES, No individual study in this analysis demonstrated superiority of active stimulation over sham and the results of the meta-analysis do not demonstrate a clear effect (SMD -0.24, 95% CI -0.48 to 0.01, P = 0.06). The evidence is insufficient to determine the effects of the technology on health outcomes and does not support the use of CES in the treatment of pain.
PSYCHIATRIC, BEHAVIORAL, NEUROLOGIC INDICATIONS
For individuals who have psychiatric, behavioral, or neurologic conditions (eg, depression and anxiety, Parkinson disease, addiction) who receive CES, the evidence includes a number of small sham-controlled randomized trials. Relevant outcomes are symptoms, morbid events, functional outcomes, and treatment-related morbidity. Three randomized controlled trials (RCTs) evaluated CES for depression and anxiety and reported inconsistent outcomes. Comparisons between these trials cannot be made due to the heterogeneity in study populations and treatment protocols.
Barclay et al (2014) reported on a randomized, double-blind, sham-controlled trial evaluating the effectiveness of one hour of daily CES in individuals with anxiety (n=115) and comorbid depression (n=23). Analysis of covariance showed a significant advantage of active CES over sham for both anxiety (p=0.001) and depression (p=0.001) over 5 weeks of treatment. The mean decrease in the Hamilton Rating Scale for Anxiety score was 32.8% for active CES and 9.1% for sham. The mean decrease in the Hamilton Rating Scale for Depression score was 32.9% for active CES and 2.6% for sham. The trial was limited by small samples and short follow-up.
In a smaller double-blind, sham-controlled randomized trial (N=30), Mischoulon et al (2015) found no significant benefit of CES as an adjunctive therapy in individuals with treatment-resistant major depression. Both active and sham groups showed improvements in depression over the 3 weeks of the study, suggestive of a bias based on placebo effect.
A sham-controlled, double-blind randomized trial by Lyon et al (2015) found no significant benefit of CES with the Alpha-Stim device for symptoms of depression, anxiety, pain, fatigue, and sleep disturbances in women receiving chemotherapy for breast cancer. This trial randomized 167 women with early-stage breast cancer to one hour of daily CES or to sham stimulation beginning within 48 hours of the first chemotherapy session and continuing until 2 weeks after chemotherapy ended (range, 6-32 weeks). Stimulation intensity was below the level of sensation. Active and sham devices were factory preset, and neither evaluators nor participants were aware of the treatment assignment. Outcomes were measured using validated questionnaires that assessed pain, anxiety, and depression, fatigue, and sleep disturbance. There were no significant differences between the active and sham CES groups during treatment. However, the trial effectiveness might have been limited by the low symptoms levels at baseline, resulting in a floor effect, and the low level of stimulation.
Other conditions investigated with CES, include studies for Parkinson disease and smoking cessation. The results of these trials do not support the use of CES for these conditions. Shill et al (2011) found no benefit of CES with the Nexalin device for motor or psychological symptoms in a crossover study of 23 participants with early Parkinson disease. Pickworth et al (1997) reported that 5 days of CES was ineffective for reducing withdrawal symptoms or facilitating smoking cessation in a double-blind RCT of 101 cigarette smokers who wanted to stop smoking. The evidence is insufficient to determine the effects of the technology on health outcomes.
OTHER INDICATIONS FOR CES
For individuals who have functional constipation who receive CES, the evidence includes an RCT. Relevant outcomes are symptoms, morbid events, functional outcomes, and treatment related morbidity. The single RCT by Gong et al (2016) reported on a single-center, unblinded, RCT, which compared 74 participants with functional constipation. The authors report positive results for the treatment of constipation with CES. Individuals were randomized to biofeedback with CES (n=38) or biofeedback alone (n=36) and followed at 4 time points (baseline and 3 follow-up visits); however, the duration of time between each follow-up visit was not specified. In a repeated-measures analysis of variance model for change from baseline, at the second and third follow-up visits, there were significant differences between groups in: self-rating anxiety scale score (41.8 for CES group vs 46.8 for controls; p<0.001); self-rating depression scale score (43.08 for CES group vs 48.8 for controls; p<0.001) and the Wexner Constipation Score (10.0 for CES arm vs 12.6 for controls; p<0.001). Serious methodology limitations were observed in the trials and the outcomes were self-reported. The evidence does not permit firm conclusions to be drawn on the effects of this technology on health outcomes for constipation.