Benefits and Harms of Cranial Electrical Stimulation for Chronic Painful Conditions, Depression, Anxiety, and Insomnia: A Systematic Review

The search strategy to locate relevant studies and the remaining review was extremely biased. For example, Lande’s short 5 day insomnia study of SM’s at Walter Reed was reviewed as having no difference between groups. There was actually significant effects on Days 1 and 4 and a trend on Day 5 (p<.079). More importantly, SM’s slept an average of 43 minutes more a night (Lande, 2013). The Annals report reviewed many studies from 40 years ago which used devices long off the market while omitting research relevant to Alpha-Stim® technology which has been included in the Federal Supply Schedule and utilized by the VA since 2005. The Federal Government’s definition of scientific evidence is less restrictive. Even FDA uses many forms of valid scientific evidence. It also appropriately considers real world evidence. See: (https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfCFR/CFRSearch.cfm?FR=860.7).
When our society is desperate for new treatment approaches it defies common sense to conduct a review that purposefully restricts the fair review and exchange of all valid scientific evidence. Alpha-Stim has a patented waveform. Drugs with different chemical makeups produce different effects. Generalities regarding outcomes should be approached with caution.

Alpha-Stim has over 100 published reports over its 37 years of distribution, most by independent researchers who have attained IRB approval without funding by EPI. Many of the studies are not listed in predominate pharmaceutical research search engines, which does not deem them unscientific. A complete data base is accessible here: http://www.alpha-stim.com/healthcare-professionals/research-and-reports/ . Also published here is A Scientific and Clinical Literature Examination which is specific to Alpha-Stim and it reviews 24 randomized placebo controlled trials, 12 open-label and case studies. It contains 3 fMRI and EEG studies, a graphical summary of the studies followed by annotated abstracts of all known Alpha-Stim studies. Additionally, it contains outcomes of peer reviewed published Service Member and Veteran Surveys. The latest study published in February, 2018 from MD Anderson Cancer Center (Yennurajalingam, 2018) reports significant improvement in pain (p=0.013), anxiety (p<0.001) depression (p=0.024), daytime dysfunction (p=0.002) and reduction in sedative medication use (p=0.006). This study would have been excluded in the limited search criteria of this review thereby possibly denying our veterans a viable treatment option.

If we are actively seeking non-addictive, safe and effective treatments for anxiety, insomnia, depression and pain then a review regarding the benefits and harms of a treatment should consider all valid scientific evidence without bias, especially when no safety issues exist. That would be a true review of the benefits and harms of CES in 2018.

Jeff Marksberry MD, CCRP, FAIS
Chief Science and Clinical Officer
Electromedical Products International, Inc.



References:

Yennurajalingam S, Kang D-H, Hwu W-J, Padhye NS, Masino C, Dibaj SS, Liu DD, Williams JL, Lu Z, Bruera E. Cranial electrotherapy stimulation for the management of depression, anxiety, sleep disturbance, and pain in patients with advanced cancer: a preliminary study. Journal of Pain and Symptom Management. 2018 Feb; 55(2): 198-204.
Lande, R. Gregory and Gragnani, Cynthia. Efficacy of cranial electric stimulation for the treatment of insomnia: A randomized pilot study. Complementary Therapies in Medicine, 21(1):8-13, 2013.

We disagree with Dr. Marksberry that our search strategy and review were extremely biased. We searched multiple electronic databases without language restrictions, clinicaltrials.gov, prior systematic reviews, the reference lists of included studies, studies cited on manufacturers’ websites, an 11 page document provided by the makers of Alpha-Stim entitled “Clinical Evaluation Report” that included numerous citations of studies using the Alpha-Stim device, and an FDA Executive Summary (prepared Feburary 10, 2012) in response to a Petition to Request Change in Classification for Cranial Electrical Stimulators. We restricted eligibility to studies measuring clinical outcomes for patients with our target conditions (chronic painful conditions, depression, anxiety, and insomnia) and that were randomized controlled trials, the least-biased study design for assessing effectiveness of interventions for chronic conditions that can have a fluctuating course and variable natural history. We doubt that including addition study designs in our review would have changed our conclusion. Of note, despite the inclusion of observational studies in the FDA review, their conclusion was similar: “FDA has consistently stated that the effectiveness of CES has not been established by adequate scientific evidence”.

With regard to the study by Dr. Lande, we note that the authors of that article state “the study’s primary outcome variables were the time to sleep onset, total time slept, and number of awakenings” and that differences between groups were not statistically significant. No result in their Table 2 (“Change in hours in sleep time”), including measurements on Days 2, 3, 4, 5, 3 days post, and 10 days post, are reported as having a statistically significant difference between the treatment group and control group.

We agree with Dr. Marksberry that there is a need for additional non-addictive, safe, and effective treatments for anxiety, insomnia, depression, and pain, and look forward to well-designed and conducted studies of CES to evaluate its effectiveness.