A Pilot Study of Safety and Efficacy of Cranial Electrotherapy Stimulation in Treatment of Bipolar II Depression.

Deimante McClure, BA, Samantha C. Greenman, BA, Siva Sundeep Koppolu, MBBS, Maria Varvara, MD, Zimri S. Yaseen, MD, and Igor I. Galynker, MD, PhD

J Nerv Ment Dis. 2015 Nov;203(11):827-35. doi: 10.1097/NMD.0000000000000378. (PubMed link)

This double-blind, sham-controlled study sought to investigate the effectiveness of cranial electrotherapy stimulation (CES) for the treatment of bipolar II depression (BD II). After randomization, the active group participants (n = 7) received 2 mA CES treatment for 20 minutes five days a week for 2 weeks, whereas the sham group (n = 9) had the CES device turned on and off. Symptom non-remitters from both groups received an additional 2 weeks of open-label active treatment. Active CES treatment but not sham treatment was associated with a significant decrease in the Beck Depression Inventory (BDI) scores from baseline to the second week (p = 0.003) maintaining significance until week 4 (p = 0.002). There was no difference between the groups in side effects frequency. The results of this small study indicate that CES may be a safe and effective treatment for BD II suggesting that further studies on safety and efficacy of CES may be warranted.

A clinical trial of cranial electrotherapy stimulation for anxiety and comorbid depression.

Barclay TH, Barclay RD

J Affect Disord. 2014 Aug;164:171-7. doi: 10.1016/j.jad.2014.04.029. Epub 2014 Apr 21. (PubMed link)

Anxiety disorders are among the most prevalent mental disorders and are usually treated with medication and/or psychotherapy. When anxiety disorders are accompanied with comorbid depression, this further complicates the treatment process. Medication compliance is a common problem due to adverse side effects and new and effective treatments that have minimal side effects are needed for the treatment of anxiety and depression. This study used a randomized, double-blind, sham controlled design to examine the effectiveness of CES as a treatment for anxiety disorders and comorbid depression in a primary care setting. The study was registered at clinicaltrials.gov, NCT01533415.

METHODS:

One hundred and fifteen participants, age 18 years and over, with a primary diagnosis of an anxiety disorder were enrolled from February 2012 to December 2012 The Hamilton Rating Scale for Anxiety (HAM-A) and the Hamilton Depression Rating Scale17 (HAM-D17) were used for baseline and outcome measures at weeks one, three, and five. Response to treatment was defined as a reduction of ≥50% or more on these measures.

RESULTS:

Analysis of covariance revealed a significant difference between the active CES group and the sham CES group on anxiety (p=0.001, d=0.94) and on depression (p=0.001, d=0.78) from baseline to endpoint of study in favor of the active CES group.

CONCLUSIONS:

CES significantly decreases anxiety and comorbid depression. Subjects reported no adverse events during the study.

A pilot study of cranial electrotherapy stimulation for generalized anxiety disorder.

Bystritsky A, Kerwin L, Feusner J. J Clin Psychiatry. 2008 Mar;69(3):412-7. (PubMed link)

BACKGROUND: Cranial electrotherapy stimulation (CES) is a noninvasive procedure that has been used for decades in the United States to treat anxiety, depression, and insomnia in the general population. Whether CES is an effective treatment for patients with a DSM-IV diagnosis of generalized anxiety disorder (GAD) has not previously been explored. The goal of this study was to evaluate the efficacy of CES in alleviating anxiety in patients with DSM-IV-diagnosed GAD. METHOD:Twelve patients from 29 to 58 years of age with a DSM-IV diagnosis of GAD were enrolled from August 2005 to March 2006 through the University of California, Los Angeles (UCLA) Anxiety Disorders Program. Cranial electrotherapy stimulation treatment was administered for 6 weeks using the Alpha-Stim Stress Control System at 0.5-Hz frequency and 300-muA intensity. The primary efficacy measures were the Hamilton Rating Scale for Anxiety (HAM-A) and the Clinical Global Impressions-Improvement (CGI-I) scale. Response to treatment was defined as a reduction of 50% or more on the HAM-A and a CGI-I score of 1 or 2 ("much improved" or "very much improved," respectively). RESULTS: Cranial electrotherapy stimulation was associated with a significant decrease in HAM-A scores (t = 3.083, p = .01). At endpoint, 6 patients (50% of the intent-to-treat sample and 67% of completers) had a 50% decrease in HAM-A score and a CGI-I score of 1 or 2. One additional patient significantly improved in anxiety scores but did not meet criteria for response. Adverse events were generally mild in severity, mostly consisting of headache and nausea. CONCLUSION: This preliminary study suggests that CES may reduce symptoms of anxiety in GAD. We hope that these preliminary results will encourage further research to explore the use of CES in clinical settings.

Cranial Electrotherapy Stimulation Review: A Safer Alternative to Psychopharmaceuticals in the Treatment of Depression.

Kirsch, D, Gilula, M. Journal of Neurotherapy, Vol. 9(2) 2005

The use of Cranial Electrotherapy Stimulation (CES) to treat depression and anxiety is reviewed. The data submitted to the Food and Drug Administration (FDA) for approval of medication in the treatment of depression are compared with CES data. Proposed method of action, side effects, safety factors, and treatment efficacy are discussed. The results suggest there is sufficient data to show that CES technology has equal or greater efficacy for the treatment of depression compared to antidepressant medications, with fewer side effects. A prospective research study should be undertaken to directly compare CES with antidepressant medications and to compare the different CES technologies with each other.

Cranial electrotherapy stimulation for the treatment of depression.

J Psychosoc Nurs Ment Health Serv. 2010 Nov;48(11):37-42. doi: 10.3928/02793695-20100701-01. Epub 2010 Jul 22. (PubMed link)

More prevalent in women than men, clinical depression affects approximately 15 million American adults in a given year. Psychopharmaceuticaltherapy accompanied by psychotherapy and wellness interventions (e.g., nutrition, exercise, counseling) is effective in 80% of diagnosed cases. A lesser known adjunctive therapy is that of cranial electrotherapy stimulation (CES). The major hypothesis for the use of CES in depression is that it may reset the brain to pre-stress homeostasis levels. It is conjectured that the pulsed electrical currents emitted by cranial electrical stimulators affect changes in the limbic system, the reticular activating system, and/or the hypothalamus that result in neurotransmitter secretion and downstream hormone production. While evidence is good for applied research, basic research about the mechanisms of action for CES remains in its infancy. A review of the literature provides an overview of current research findings and implications for clinical mental health practice.

Cranial electrotherapy stimulation (CES): a safe and effective low cost means of anxiety control in a dental practice.

Winick RL. Gen Dent. 1999 Jan-Feb;47(1):50-5. (PubMed link)

A double-blind placebo-controlled study was performed on 33 randomly selected dental patients to evaluate whether cranial electrotherapy stimulation (CES) is a viable procedure for reducing anxiety during routine dental procedures. The active CES treatment group was significantly less anxious than the placebo group at the conclusion of various dental procedures.

Cranial Electrotherapy Stimulation in Patients Suffering from Acute Anxiety Disorders.

Overcash, Stephen J. American Journal of Electromedicine, 16(1):49-51, 1999

Stress-induced anxiety causes the cells of the human body to produce waveforms in different frequencies than normal. Cranial electrotherapy stimulation (CES) involves the use of bioelectric therapy to reestablish the normal electrical flow in the human body by producing waveforms similar to the body's own in a relaxed state. The authors discuss the outcome of a study which tested the usefulness of CES in regard to relief of anxiety.

The administration of transcranial electric treatment for affective disturbances therapy in alcoholic patients.

Krupitsky EM, Burakov AM, Karandashova GF, Katsnelson JaS, Lebedev VP, Grinenko AJa, Borodkin JuS.
Drug Alcohol Depend. 1991 Jan;27(1):1-6. (PubMed link)

In a double blind placebo-controlled investigation it was shown that transcranial electric treatment (TET), comprising the combination of a constant current with a pulse current of square impulses of 70-80 Hz is an effective method to correct affective disturbances (anxiety, depression) in alcoholic patients. The medical effects of TET are accompanied by changes in the metabolism of GABA and monoamines, but not of beta-endorphin, and also by a decrease in the latency of alpha-rhythm appearance after closing of the eyes.

Cranial electrotherapy stimulation as a treatment for anxiety in chemically dependent persons.

Schmitt R, Capo T, Boyd E. Alcohol Clin Exp Res. 1986 Mar-Apr;10(2):158-60. (PubMed link)

Cranial electrotherapy stimulation (CES) is reported to be an effective treatment for anxiety, a major presenting symptom among chemically dependent patients. In this study, 40 inpatient alcohol and/or polydrug users were given CES or sham CES in a double blind design. An additional 20 patients served as normal hospital routine controls. Dependent measures of anxiety were the Profile of Mood States, the Institute for Personality and Ability Testing Anxiety Scale, and the State/Trait Anxiety Index. CES-treated patients showed significantly greater improvement on all anxiety measures than did either control group. There were no differences in response between older and younger patients, or between the primarily drug or alcohol abusers. No placebo effect was found on any of our measures. It is concluded that CES is a clinically significant addition to the treatment regimen for this patient population.

Efficiency of transcranial electrostimulation on anxiety and insomnia symptoms during a washout period in depressed patients. A double-blind study.

Philip P, Demotes-Mainard J, Bourgeois M, Vincent JD. Biol Psychiatry. 1991 Mar 1;29(5):451-6. (PubMed link)

In order to test the efficacy of cerebral electrostimulation (electrosleep) as an alternative to drug therapy for the treatment of anxiety and insomnia, we conducted a double-blind study in a sample of 21 depressed inpatients submitted to a 5-day period of drug washout on admission to the psychiatric department. During this withdrawal period, anxiety and insomnia were exacerbated in the placebo group, whereas anxiety decreased and sleep duration improved in the active treatment group, with a divergent evolution during the 5-day washout period. The depressive criteria did not respond differentially to treatment, however. Thus, the effects of this drug washout period are markedly attenuated by cerebral electrostimulation, which is of possible interest in the management of psychotropic drug withdrawal.

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Electrosleep: a double-blind clinical study.

Rosenthal SH. Biol Psychiatry. 1972 Apr;4(2):179-85. (PubMed link)

A double-blind clinical study evaluating the Russian electrosleep technique is presented. Twenty-two patients, mostly outpatients, with neurotic anxiety and depression were each given a course of five half-hour treatments which were either active or simulated electrosleep. In the simulated electrosleep the electrode leads were not connected to the machine. Under these double-blind conditions patients receiving active treatment showed marked clinical improvement that was significantly greater than that showed by patients receiving placebo treatment. Of the 1I patients receiving active treatment 8 made a marked improvement, 2 made a partial improvement, and 1 showed no improvement. Of the 11 receiving inactive treatment, 1 showed marked improvement, 2 showed partial improvement, and 8 showed no improvement. Average "total clinical ratings" on anxiety, sleep disturbance, and depression fell from 11.3 before treatment to 3.2 following treatment. For the patients receiving inactive treatment, average "total clinical ratings" fell from 12.2 to 9.5. Patients receiving active treatment following inactive treatment responded better than patients receiving inactive treatment but did not respond as well as those who received active treatment first. The explanation for this is not clear, but it may reflect a negative expectation following inactive treatment. Patients may have an expectation of failure and a negative placebo effect when the active treatment follows a week of ineffective treatment.

Cranial Electrotherapy Stimulation (CES) in the treatment of anxiety and other stress-related disorders: a review of controlled clinical trials.

Felice, E. Stress Medicine, VOL. 13: 31-42 (1997)

This CES review covers published and to be published clinical trials in the English language and reported to be controlled in some fashion and completed from January 1963 to January 1996. Cranial electrotherapy stimulation (CES) is defined as the application of low-level pulsed electrical current through skin surface electrodes on the head for the treatment of anxiety and other stress-related disorders. A total of 34 controlled clinical trials concerning the efficacy of CES in the treatment of anxiety and other stress-related disorders were evaluated. Overall the results suggest that CES may be capable of producing significant (p < 0.05) benefit in the short-term symptomatic relief of anxiety and other stress-related disorders. CES may be effective alone and as an adjunct to other conservative measures of treatment. The primary mechanism of action of CES appears to be a direct effect on the brain followed by secondary responses. While adverse effects were reported to occur in less than 3 per cent of patients, it is believed they are substantially underreported. The short- and long-term efficacy, adverse effects, safety and mechanism of action of CES remain to be established in rigorous, well-controlled clinical trials. Results reported in this review suggest that CES warrants further study.

Effects of transcrerebral electrotherapy (electrosleep) on state anxiety according to suggestibility levels.

Ryan JJ, Souheaver GT. Biol Psychiatry. 1976 Apr;11(2):233-7. (PubMed link)

Electrosleep therapy: a controlled study of its effects in anxiety neurosis.

Von Richthofen CL, Mellor CS.Can J Psychiatry. 1980 Apr;25(3):213-9. (PubMed link)

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Efficacy of cranial electric stimulation for the treatment of insomnia: a randomized pilot study.

Lande RG, Gragnani C.
Complement Ther Med. 2013 Feb;21(1):8-13. doi: 10.1016/j.ctim.2012.11.007. Epub 2012 Dec 21. (PubMed link)

OBJECTIVES: This pilot study examined the potential efficacy of cranial electric stimulation for the treatment of insomnia.

DESIGN: The researchers tested the hypothesis through a randomized, double-blind, and placebo controlled clinical trial. The researchers approached eligible subjects who scored 21 or above on the Pittsburgh Insomnia Rating Scale. The researchers then randomly assigned the subjects to receive either an active or sham device. Each study subject received 60min of active or sham treatment for five days. Following each intervention the subjects completed a sleep log, as well as three and ten days later.

SETTING:The researchers conducted the study among active duty service members receiving mental health care on the Psychiatry Continuity Service (PCS), Walter Reed National Military Medical Center in Bethesda, MD.

MAIN OUTCOME MEASURES:The study's primary outcome variables were the time to sleep onset, total time slept, and number of awakenings as reported by the subjects in the serial sleep logs. The researchers identified a nearly significant increase in total time slept after three cranial electricstimulation treatments among all study subjects. A closer examination of this group revealed an interesting gender bias, with men reporting a robust increase in total time slept after one treatment, decay in effect over the next two interventions, and then an increase in total time slept after the fourth treatment. The researchers speculate that the up and down effect on total time slept could be the result of an insufficient dose of cranialelectric stimulation.

Efficiency of transcranial electrostimulation on anxiety and insomnia symptoms during a washout period in depressed patients a double-blind study.

Philip P, Demotes-Mainard J, Bourgeois M, Vincent JD.
Biol Psychiatry. 1991 Mar 1;29(5):451-6. (PubMed link)

In order to test the effectiveness of cerebral electrostimulation (electrosleep) as an alternative to drug therapy for the treatment of anxiety and insomnia, we conducted a double-blind study in a sample of 21 depressed inpatients submitted to a 5-day period of drug washout on admission to the psychiatric department. During this withdrawal period, anxiety and insomnia were exacerbated in the placebo group, whereas anxiety decreased and sleep duration improved in the active treatment group, with a divergent evolution during the 5-day washout period. The depressive criteria did not respond differentially to treatment, however. Thus, the effects of this drug washout period are markedly attenuated by cerebral electrostimulation, which is of possible interest in the management of psychotropic drug withdrawal.

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The treatment of insomnia through the use of electrosleep: an EEG study.

Weiss MF.
J Nerv Ment Dis. 1973 Aug;157(2):108-20. (PubMed link)

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Electrosleep therapy: a double-blind trial.

Hearst ED, Cloninger CR, Crews EL, Cadoret RJ.
Arch Gen Psychiatry. 1974 Apr;30(4):463-6. (PubMed link)

Twenty-eight patients participated in a controlled double-blind study to determine the effectiveness of electrosleep as a treatment modality. To our knowledge this is the first study in the English literature in which the peripheral rhythmic electrical stimulation has been eliminated, thereby allowing the results of the current effect on the brain to be independently evaluated. Both global ratings by patients and physicians on the fifth day of treatment and on two-week follow-up indicate that current effect is not associated with significant improvement, although patient global ratings on day 5 indicate a trend in this direction. Self-rating scales by patients indicate no significant improvement for anxiety, insomnia, or somatic complaints. Depressive self-rating scales do show a significant improvement on day 5 of treatment, but no carry over effect to the two-week follow-up.

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Electrosleep - A clinical trial.

Rosenthal SH, Wulfsohn NL.
Am J Psychiatry. 1970 Oct;127(4):533-4. (PubMed link)

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Is Transcranial Electrical Stimulation (TCES) a safe intervention for children with Cerebral Palsy?

Alon, G, Syron S, Smith G
Neurorehabil Neural Repair June 1998 vol. 12 no. 2 65-71

We tested the safety of transcranial electrical stimulation (TCES) applied to seven children (age range 2.5 to 7.5 years) with a confirmed diagnosis of cerebral palsy (CP). Adverse responses were assessed by negative changes in the gross motor function measure test (GMFM), the popliteal angle, and the occurrence of any undesired systemic responses such as seizure, nausea, vomiting, or sleep disruption. The tests first were given before the commencement of a physical therapy exercise (PTE) program combined with a home program of TCES. The tests were repeated after 8 weeks of PTE + TCES and once again after an additional 8 weeks of PT + TCES. One of the 8- week periods involved placebo stimulation in a double-blind design. Stimulator amplitude was 0.5 mA of peak current, phase charge was 0.0166 C, and the averaged RMS current was 249 microamperes. This level was below threshold of sensory nerve excitation, and the child did not perceive the stimulation. Electrodes were placed over the right and left temporal areas of the skull. The stimulation was applied by the parents for 10 minutes, twice a day, 7 days each week. The total goal GMFM scores were greater after both active and placebo stimulation. The popliteal angle improved irrespective of the stimulation intervention. No adverse systemic responses were reported. These results support the hypothesis that TCES as used in this study is a safe procedure.

Cranial Electrotherapy Stimulation: A Safe Neuromedical Treatment for Anxiety, Depression, or Insomnia

Gilula, Marshall F. MD; Barach, Paul R. MD, MPH
Southern Medical Journal. 2004; Vol. 97(12).

Cognitive, mood, and electroencephalographic effects of noninvasive cortical stimulation with weak electrical currents.

Tadini L, El-Nazer R, Brunoni AR, Williams J, Carvas M, Boggio P, Priori A, Pascual-Leone A, Fregni F.
J ECT. 2011 Jun;27(2):134-40. doi: 10.1097/YCT.0b013e3181e631a8. (PubMed link)

OBJECTIVES:The use of noninvasive cortical electrical stimulation with weak currents has significantly increased in basic and clinical human studies. Initial, preliminary studies with this technique have shown encouraging results; however, the safety and tolerability of this method of brain stimulation have not been sufficiently explored yet. The purpose of our study was to assess the effects of direct current (DC) and alternating current (AC) stimulation at different intensities in order to measure their effects on cognition, mood, and electroencephalogram.
METHODS:Eighty-two healthy, right-handed subjects received active and sham stimulation in a randomized order. We conducted 164 ninety-minute sessions of electrical stimulation in 4 different protocols to assess safety of (1) anodal DC of the dorsolateral prefrontal cortex (DLPFC); (2) cathodal DC of the DLPFC; (3) intermittent anodal DC of the DLPFC and; (4) AC on the zygomatic process. We used weak currents of 1 to 2 mA (for DC experiments) or 0.1 to 0.2 mA (for AC experiment).
RESULTS: We found no significant changes in electroencephalogram, cognition, mood, and pain between groups and a low prevalence of mild adverse effects (0.11% and 0.08% in the active and sham stimulation groups, respectively), mainly, sleepiness and mild headache that were equally distributed between groups.
CONCLUSIONS: Here, we show no neurophysiological or behavioral signs that transcranial DC stimulation or AC stimulation with weak currents induce deleterious changes when comparing active and sham groups. This study provides therefore additional information for researchers and ethics committees, adding important results to the safety pool of studies assessing the effects of cortical stimulation using weak electrical currents. Further studies in patients with neuropsychiatric disorders are warranted.