A meta-analysis of cranial electrotherapy stimulation in the treatment of depression

Depression rates have reached historic highs, with 49% of Americans reporting unabating symptoms and signs of depression, representing a 12% increase compared to the same time in 2019. With depression as a moderating factor for suicide, the need for efficacious treatments for depression has never been more pronounced. Although the armamentarium of the psychiatrist seems impressive having multiple medications and psychotherapy options, with guidelines for combination and augmentation treatments; many patients do not improve or are not suitable candidates for the usual, customary and reasonable (UCR) depression treatments. The use of various forms of brain stimulation technology as a complementary or alternative treatment for depression is growing and is expected to be part of the armamentarium of most psychiatrists by 2030. One form of brain stimulation, available in a phone sized prescription device, is cranial electrical stimulation (CES) which has been used as a treatment for depression since the 1970s. We have conducted two meta-analyses of CES research for depression separating randomized controlled trials (N = 5) from non-randomized studies on interventions (N = 12). For the double-blind RCTs 100 μA was used for 1 hour per day as 100 μA is a subsensory level of current so identical sham treatment devices could be used.

Our literature review followed Cooper's Taxonomy of Literature Reviews that is appropriate for the behavioral and physical sciences and the PRISMA reporting guidelines. The evaluation of strengths and limitations of the research studies included in this report adheres to recommended published guidelines in the Cochrane Handbook for Systematic Reviews of Interventions, and in the Handbook of Research Synthesis and Meta-Analysis. We used the Cohen's d effect size summary metric in all analyses. Homogeneity of effect sizes within the fixed and random effects models are reported. Meta-analyses were performed using the Compressive Meta-Analysis, version 3 program.

The 5 RCTs represent a combined N of 242 and the 12 NRSIs represent 16 data sets with a combined N of 1173 for total of 1415 subjects across 17 studies. There were male and female subjects, from adolescents to 60 years old. The average effect for the 5 RCTs was calculated as d = -0.69 (i.e., the mean depression level at posttest for the active group was -0.69 standard deviations lower than the mean depression level for the sham group), a medium effect. The additional 12 NRSI studies analyzed show a small effect of d = -0.43 in favor of the active treatment group.

We conclude that CES has a small to medium significant effect in symptoms of depression across moderate to severe patients in civilian, military, veterans, advanced cancer and pediatric populations.