Efficacy and Tolerability of Cranial Electrotherapy Stimulation in the Treatment of Anxiety: A Systemic Review and Meta-Analysis

Pao-Yuan Ching, Tien-Wei Hsu, Guan-Wei Chen, Chih-Chuan Pan, Che-Sheng Chu, Po-Han Chou, Pao-Yuan Ching, Tien-Wei Hsu, Guan-Wei Chen, Chih-Chuan Pan, Che-Sheng Chu, Po-Han Chou

Abstract

Objective: We aimed to investigate the efficacy and tolerability of cranial electrotherapy stimulation (CES) for patients with anxiety symptoms.

Method: We searched the Pubmed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase and Medline for randomized control trials (RCTs) from the time of inception until November 15, 2021, following Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Data were pooled using a random-effects model. The primary outcomes were the mean change scores for anxiety symptoms. The secondary outcomes were the mean change scores for depressive symptoms.

Results: Eleven RCTs were eligible (n = 794, mean age: 41.4, mean population of female: 64.8%). CES significantly reduced the anxiety symptoms compared to the control group [k = 11, n = 692, Hedge's g = -0.625, 95% confidence intervals (CIs) = -0.952 to -0.298, P < 0.001] with moderate effect size. The subgroup analysis showed that CES reduced both primary and secondary anxiety (primary anxiety, k =3, n = 288, Hedges' g = -1.218, 95% CIs = -1.418 to -0.968, P = 0.007; secondary anxiety, k = 8, n = 504, Hedges' g = -0.334, 95% CIs = -0.570 to -0.098, P = 0.006). After performing between group analysis, we found CES has significant better efficacy for patients with primary anxiety than those with secondary anxiety (P < 0.001). For secondary outcome, CES significantly reduced depressive symptoms in patients with anxiety disorders (k = 8, n = 552, Hedges' g = -0.648, 95% CIs = -1.062 to -0.234, P = 0.002). No severe side effects were reported and the most commonly reported adverse events were ear discomfort and ear pain.

Conclusion: We found CES is effective in reducing anxiety symptoms with moderate effect size in patients with both primary and secondary anxiety. Furthermore, CES was well-tolerated and acceptable.Systematic Review Registration: PROSPERO, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021267916.

Keywords: anxiety; cranial electrotherapy stimulation; depression; efficacy; meta-analysis.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2022 Ching, Hsu, Chen, Pan, Chu and Chou.

Figures

Figure 1
Figure 1
PRISMA flowchart of study selection.
Figure 2
Figure 2
Forest plot of meta-analysis of (A) Primary outcome: change in scores of anxiety symptoms; (B) Secondary outcome: change in scores of depression symptoms.

References

    1. Bandelow B, Michaelis S. Epidemiology of anxiety disorders in the 21st century. Dialogues Clin Neurosci. (2015) 17:327–35. 10.31887/DCNS.2015.17.3/bbandelow
    1. Carter RM, Wittchen HU, Pfister H, Kessler RC. One-year prevalence of subthreshold and threshold DSM-IV generalized anxiety disorder in a nationally representative sample. Depress Anxiety. (2001) 13:78–88. 10.1002/da.1020
    1. Brenes GA. Anxiety, depression, and quality of life in primary care patients. Prim Care Companion J Clin Psychiatry. (2007) 9:437–43. 10.4088/PCC.v09n0606
    1. Oh CM, Kim HY, Na HK, Cho KH, Chu MK. The effect of anxiety and depression on sleep quality of individuals with high risk for insomnia: a population-based study. Front Neurol. (2019) 10:849. 10.3389/fneur.2019.00849
    1. Taylor S, Abramowitz JS, McKay D. Non-adherence and non-response in the treatment of anxiety disorders. J Anxiety Disord. (2012) 26:583–9. 10.1016/j.janxdis.2012.02.010
    1. Kirsch DL, Nichols F. Cranial electrotherapy stimulation for treatment of anxiety, depression, and insomnia. Psychiatr Clin North Am. (2013) 36:169–76. 10.1016/j.psc.2013.01.006
    1. Cui H, Jiang L, Wei Y, Li W, Li H, Zhu J, et al. . Efficacy and safety of repetitive transcranial magnetic stimulation for generalised anxiety disorder: a meta-analysis. Gen Psychiatry. (2019) 32:e100051. 10.1136/gpsych-2019-100051
    1. Stein DJ, Fernandes Medeiros L, Caumo W, Torres IL. Transcranial direct current stimulation in patients with anxiety: current perspectives. Neuropsychiatr Dis Treat. (2020) 16:161–9. 10.2147/NDT.S195840
    1. Coutinho JF, Fernandesl SV, Soares JM, Maia L, Gonçalves ÓF, Sampaio A. Default mode network dissociation in depressive and anxiety states. Brain Imaging Behav. (2016) 10:147–57. 10.1007/s11682-015-9375-7
    1. Feusner JD, Madsen S, Moody TD, Bohon C, Hembacher E, Bookheimer SY, et al. . Effects of cranial electrotherapy stimulation on resting state brain activity. Brain Behav. (2012) 2:211–20. 10.1002/brb3.45
    1. Barclay TH, Barclay RD. A clinical trial of cranial electrotherapy stimulation for anxiety and comorbid depression. J Affect Disord. (2014) 164:171–7. 10.1016/j.jad.2014.04.029
    1. Lu L, Hu J. A comparative study of anxiety disorders treatment with paroxetine associated with cranial electrotherapy stimulation therapy. Med Innov China. (2014) 11:80–2. 10.3969/j.issn.1674-4985.2014.08.035
    1. Chen YX, Yu L, Zhang JP, Li LJ, Chen TO, Chen Y. Results of cranial electrotherapy stimulation to children with mixed anxiety and depressive disorder. Shanghai Arch Psychiatry. (2007) 19:203–5.
    1. Shekelle PG, Cook IA, Miake-Lye IM, Booth MS, Beroes JM, Mak S. Benefits and harms of cranial electrical stimulation for chronic painful conditions, depression, anxiety, and insomnia: a systematic review. Ann Intern Med. (2018) 168:414–21. 10.7326/M17-1970
    1. Klawansky S, Yeung A, Berkey C, Shah N, Phan H, Chalmers TC. Meta-analysis of randomized controlled trials of cranial electrostimulation. Efficacy in treating selected psychological and physiological conditions. J Nerv Ment Dis. (1995) 183:478–84. 10.1097/00005053-199507000-00010
    1. Gibson TH, O'Hair DE. Cranial application of low level transcranial electrotherapy vs. relaxation instruction in anxious patients. Am J Electromed. (1987) 4:18–21.
    1. Scallet A, Cloninger R, Othmer E. The management of chronic hysteria: a review and double-blind trial of electrosleep and other relaxation methods. Dis Nerv Syst. (1976) 37:347–53.
    1. Moore J, Mellor C, Standage K, Strong H. A double-blind study of electrosleep for anxiety and insomnia. Biol Psychiatry. (1975) 10:59–63.
    1. Rosenthal S. Electrosleep: a double-blind clinical study. Biol Psychiatry. (1972) 4:179–85.
    1. Brunyé TT, Patterson JE, Wooten T, Hussey EK. A critical review of cranial electrotherapy stimulation for neuromodulation in clinical and non-clinical samples. Front Hum Neurosci. (2021) 15:625321. 10.3389/fnhum.2021.625321
    1. Do JK, Kwon DR. Efficacy of cranial microcurrent stimulation in patients with tension-type headache: a prospective, randomised, double-blinded, sham-controlled clinical trial. Int J Clin Pract. (2021) 75:e14437. 10.1111/ijcp.14437
    1. Gong BY, Ma HM, Zang XY, Wang SY, Zhang Y, Jiang N, et al. . Efficacy of cranial electrotherapy stimulation combined with biofeedback therapy in patients with functional constipation. J Neurogastroenterol Motil. (2016) 22:497–508. 10.5056/jnm15089
    1. Guleyupoglu B, Schestatsky P, Edwards D, Fregni F, Bikson M. Classification of methods in transcranial electrical stimulation (tES) and evolving strategy from historical approaches to contemporary innovations. J Neurosci Methods. (2013) 219:297–311. 10.1016/j.jneumeth.2013.07.016
    1. Wu WJ, Wang Y, Cai M, Chen YH, Zhou CH, Wang HN, et al. . A double-blind, randomized, sham-controlled study of cranial electrotherapy stimulation as an add-on treatment for tic disorders in children and adolescents. Asian J Psychiatr. (2020) 51:101992. 10.1016/j.ajp.2020.101992
    1. Bhardwaj M, Arumugam N, Gambhir S. Efficacy of cranial electrical stimulation and rational emotive behavior therapy in improving psychological illness among chronic stroke survivors: a pilot randomized controlled trial. Ann Indian Acad Neurol. (2018) 21:188–92. 10.4103/aian.AIAN_448_17
    1. Lyon D, Kelly D, Walter J, Bear H, Thacker L, Elswick RK. Randomized sham controlled trial of cranial microcurrent stimulation for symptoms of depression, anxiety, pain, fatigue, and sleep disturbances in women receiving chemotherapy for early-stage breast cancer. Springerplus. (2015) 4:369. 10.1186/s40064-015-1151-z
    1. Prasad V, Cifu AS. The necessity of sham controls. Am J Med. (2019) 132:e29–30. 10.1016/j.amjmed.2018.07.030
    1. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. . Updating guidance for reporting systematic reviews: development of the PRISMA 2020 statement. J Clin Epidemiol. (2021) 134:103–12. 10.1016/j.jclinepi.2021.02.003
    1. The ICD-10 Classification of Mental and Behavioural Disorders: Diagnostic Criteria for Research . World Health Organization (1993).
    1. Bell CC. DSM-IV. Diagnostic and statistical manual of mental disorders. JAMA. (1994) 272:828–9. 10.1001/jama.1994.03520100096046
    1. Frances A, First MB, Pincus HA. DSM-IV Guidebook. American Psychiatric Association (1995).
    1. First MB, France A, Pincus HA. DSM-IV-TR Guidebook. American Psychiatric Publishing, Inc. (2004).
    1. Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds DJ, Gavaghan DJ, et al. . Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. (1996) 17:1–12. 10.1016/0197-2456(95)00134-4
    1. Higgins JP, Sterne JA, Savovic J, Page MJ, Hróbjartsson A, Boutron I, et al. . A revised tool for assessing risk of bias in randomized trials. Cochrane Database Syst. Rev. (2016) 10:29–31.
    1. Hamilton M. The assessment of anxiety states by rating. Br J Med Psychol. (1959) 32:50–5. 10.1111/j.2044-8341.1959.tb00467.x
    1. Zung WW. A rating instrument for anxiety disorders. Psychosomatics. (1971) 12:371–9. 10.1016/S0033-3182(71)71479-0
    1. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand. (1983) 67:361–70. 10.1111/j.1600-0447.1983.tb09716.x
    1. Droppleman L, Lorr M, McNair D. POMS Manual: Profile of Mood States. San Diego, CA: Edits Educational and Industrial Testing Service; (1992). p. 3–16.
    1. Kim EJ, Lee SI, Jeong DU, Shin MS, Yoon IY. Standardization and reliability and validity of the Korean edition of profile of mood states (K-POMS). Sleep Med Psychophysiol. (2003) 10:39–51.
    1. Marteau TM, Bekker H. The development of a six-item short-form of the state scale of the Spielberger state-trait anxiety inventory (STAI). Br J Clin Psychol. (1992) 31:301–6. 10.1111/j.2044-8260.1992.tb00997.x
    1. Facco E, Stellini E, Bacci C, Manani G, Pavan C, Cavallin F, et al. . Validation of visual analogue scale for anxiety (VAS-A) in preanesthesia evaluation. Minerva Anestesiol. (2013) 79:1389–95.
    1. Kathryn G. Cranial Electrotherapy Stimulation in Burned Patients (CES). (2013) . Available online at: [accessed November 15, 2021].
    1. Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry. (1960) 23:56–62. 10.1136/jnnp.23.1.56
    1. Wang X. Rating Scales for Mental Health (Chinese Journal of Mental Health Supplement). Beijing: Chinese Association of Mental Health; (1993).
    1. Andresen EM, Malmgren JA, Carter WB, Patrick DL. Screening for depression in well older adults: evaluation of a short form of the CES-D (Center for Epidemiologic Studies Depression Scale). Am J Prev Med. (1994) 10:77–84. 10.1016/S0749-3797(18)30622-6
    1. Borenstein M, Hedges LV, Higgins JP, Rothstein HR. A basic introduction to fixed-effect and random-effects models for meta-analysis. Res Synth Methods. (2010) 1:97–111. 10.1002/jrsm.12
    1. Higgins JP, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. . The cochrane collaboration's tool for assessing risk of bias in randomised trials. BMJ. (2011) 343:d5928. 10.1136/bmj.d5928
    1. Higgins J, Green S. 16.1. 3.2 Imputing standard deviations for changes from baseline. In: Cochrane Handbook for Systematic Reviews of Interventions. Chichester: John Wiley & Sons Ltd. (2011).
    1. Thompson SG, Higgins JP. How should meta-regression analyses be undertaken and interpreted? Stat Med. (2002) 21:1559–73. 10.1002/sim.1187
    1. Cho SY, So WY, Roh HT. Effects of aerobic exercise training and cranial electrotherapy stimulation on the stress-related hormone, the neurotrophic factor, and mood states in obese middle-aged women: a pilot clinical trial. Salud Mental. (2016) 39:249–56. 10.17711/SM.0185-3325.2016.029
    1. Cork RC, Wood P, Ming N, Clifton S, James E, Price L. The effect of cranial electrotherapy stimulation (CES) on pain associated with fibromyalgia. Inet J Anesthesiol. (2004) 8:15. 10.5580/25a1
    1. Tan G, Rintala DH, Jensen MP, Richards JS, Holmes SA, Parachuri R, et al. . Efficacy of cranial electrotherapy stimulation for neuropathic pain following spinal cord injury: a multi-site randomized controlled trial with a secondary 6-month open-label phase. J Spinal Cord Med. (2011) 34:285–96. 10.1179/2045772311Y.0000000008
    1. Castro M, Quarantini LC, Daltro C, Pires-Caldas M, Koenen KC, Kraychete DC, et al. . Comorbid depression and anxiety symptoms in chronic pain patients and their impact on health-related quality of life. Arch Clin Psychiatry. (2011) 38:126–9. 10.1590/S0101-60832011000400002
    1. Sareen J, Jacobi F, Cox BJ, Belik SL, Clara I, Stein MB. Disability and poor quality of life associated with comorbid anxiety disorders and physical conditions. Arch Intern Med. (2006) 166:2109–16. 10.1001/archinte.166.19.2109
    1. Burke MJ, Kaptchuk TJ, Pascual-Leone A. Challenges of differential placebo effects in contemporary medicine: the example of brain stimulation. Ann Neurol. (2019) 85:12–20. 10.1002/ana.25387
    1. Walsh BT, Seidman SN, Sysko R, Gould M. Placebo response in studies of major depression: variable, substantial, and growing. JAMA. (2002) 287:1840–7. 10.1001/jama.287.14.1840

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