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Magnetic and Electrical Stimulation References


Magnetic Therapy References:

A)  TMS Trans-Cranial Electro-Magnetic Stimulation


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.

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.

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

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)
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.

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.

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 treatanxiety, depression, and insomnia in the general population. Whether CES is an effective treatment for patients with a DSM-IV diagnosis ofgeneralized anxiety disorder (GAD) has not previously been explored. The goal of this study was to evaluate the efficacy of CES in alleviatinganxiety 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 Federal 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.

A Single Blind, Randomized, Sham Controlled Study of Cranial Electrical Stimulation in Bipolar II Disorder SS Koppolu, G Kazariants, M Varvara, D McClure, Z Yaseen, AMR Lee, I Galynker Beth Israel Medical Center, New York, NY Poster presented at the 2012 APA
Introduction: Cranial Electrical Stimulation (CES) is a non-invasive brain stimulation technology, which has been FDA cleared for the treatment of depression, anxiety and insomnia. However, there have not been any clinical trials evaluating its efficacy in treating the depressive phase of bipolar II disorder. This single blind, randomized, sham controlled study examines the safety and efficacy in this particular group of patients. Preliminary results of the study are discussed. Methods: Eight patients diagnosed with bipolar II disorder currently experiencing depression symptoms by SCID-P were recruited from the Family Center for Bipolar in New York City. Subjects were randomly assigned to two groups in phase I: an active treatment group (n=4) and a sham to active treatment crossover group (control group) (n=4), for the first two weeks of daily 20 minute treatment sessions. Following this, both groups received an open-label active treatment for an additional two weeks in phase II. Depression symptoms were rated using the Hamilton Depression Rating Scale (HAM-D), the Beck Depression Inventory (BDI) and the quality of life was assessed using the Quality of Life Satisfaction and Enjoyment Questionnaire (Q-LES-Q). The assessments were completed at the study intake, at the end of the 2nd week (after a period of active or sham treatment) and at the end of the 4th week (after an additional two weeks of open-label active treatment for both groups). Results: Patients were 62.5% male and 62.5% white, with a mean age of 50.10. The treatment group had a 32% decrease on the HAM-D mean score (baseline M=20.25, 4thweek M=13.67), also a 32% decrease on the BDI mean score (baseline M=36.25, 4thweek M=24.50) and a minimal change on the Q-LES-Q (baseline M=30.40, 4thweek M=31.50). The control group after a period of sham treatment had 18% decrease on the HAM-D mean score (baseline M=19.50, 2ndweek M=16.00), a 7% decrease on the BDI mean score (baseline M=34.00, the 2ndweek M=31.50.) After an additional two weeks of active treatment the control group had a 33% decrease on the HAM-D (M=10.67), a 41% decrease on the BDI (M=18.67) and a 124% increase on the Q-LES-Q (M=42.00) compared with the scores at the end of the 2ndweek. Discussion: CES therapy had a positive treatment effect reducing the level of depression in the experimental group from severe to mild. In the control group the depression level decreased mildly on the clinician administered scale and the self-report scale after the period of sham treatment. After an additional two weeks of open-label active treatment the control group also had a substantial reduction in depression symptom levels and marked increase in the level of life satisfaction.

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.

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.

Cranial electrotherapy stimulation for the treatment of depression. Gunther M, Phillips KD 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.

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)

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.

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)

Pain reduction using transcranial electrostimulation: a double blind “active placebo” controlled trial.  Gabis L, Shklar B, Baruch YK, Raz R, Gabis E, Geva D. J Rehabil Med. 2009 Mar;41(4):256-61. (PubMed link)

Weinberg Child Development Center, Safra Children”s Hospital at Sheba Medical Center, Affiliated to the Tel-Aviv University Sackler School of Medicine, Tel Hashomer, Israel.

RESEARCH OBJECTIVE: To examine the efficacy of transcranial electrical stimulation a non-invasive method of reducing pain. DESIGN: A randomized, double-blind, placebo-controlled trial. SUBJECTS: A total of 119 patients with chronic pain. METHODS: Patients were treated with either transcranial electrical stimulation or an active placebo device. Short- and long-term follow-ups were evaluated for treatment efficacy with 4 ordinal scale variables: visual analogue scale (pain level), SLEEP (how often does pain disturb sleep), FREQ (frequency of pain) and MED (frequency of use of medications to relieve pain). RESULTS:Pain level decreased significantly in the transcranial electrical stimulation-treated group compared with the active-placebo group 3 weeks after the end of treatment (p = 0.0017 between groups). Other parameters did not demonstrate significant differences. Three months after the end of treatment this effect was maintained and other treatment parameters showed similar improvements. CONCLUSION: Transcranial electrical stimulation is an effective non-invasive method for pain relief. The active placebo device has a powerful effect on reported pain, which diminishes in the long-term. The involvement of possible neural mechanisms is discussed.

The treatment of fibromyalgia with cranial electrotherapy stimulation.  Lichtbroun AS, Raicer MM, Smith RB.  (PubMed link) J Clin Rheumatol. 2001 Apr;7(2):72-8; discussion 78. (PubMed link)

Robert Wood Johnson Medical School, East Brunswick, NJ 07719, USA.

In cranial electrotherapy stimulation (CES), micro-current levels of electrical stimulation are passed across the head via electrodes clipped to the ear lobes. After successful clinical use of CES with fibromyalgia patients in our clinic, it was decided to test these results with a double-blind, placebo-controlled study in which 60 randomly assigned patients were given 3 weeks of 1-hour-daily CES treatments, sham CES treatments, or were held as wait-in-line controls for any placebo effect in the sham-treated patients. Treated patients showed a 28% improvement in tender point scores, and a 27% improvement in self-rated scores of general pain level. The number of subjects rating their quality of sleep as poor dropped from 60% at the beginning of the study to 5%. In addition, there were significant gains in the self-rated feelings of well-being and quality of life, plus gains in six stress-related psychological test measures. No placebo effect was found among the sham-treated controls. A theoretical role of CES in affecting the brain”s pain message mechanisms and/or neurohormonal control systems is discussed. It is concluded that CES is as effective as the drug therapies in several trials, with no negative side effects, and deserves further consideration as an additional agent for the treatment of fibromyalgia.

Immediate influence of transcranial electrostimulation on pain and beta-endorphin blood levels: an active placebo-controlled study.  Gabis L, Shklar B, Geva D. Am J Phys Med Rehabil. 2003 Feb;82(2):81-5.  (PubMed link)

BACKGROUND: Stimulation of the antinociceptive system by noninvasive electrical current from electrodes placed on the head is a renewed method of pain relief. METHODS:We conducted a randomized, double-blind, placebo-controlled study on 20 chronic back pain patients. They were treated with eithertranscranial electrostimulation (TCES) or an active placebo device. Pain level and serum beta-endorphin levels were measured before and after treatment. RESULTS: beta-Endorphin level increased in seven of the ten patients from the treatment group and did not change in eight of ten patients from control group (P = 0.057 between groups). Pain level decreased in eight treated patients and seven control patients (significant decrease for each group, no significant difference between groups). CONCLUSIONS: Transcranial electrostimulation is a nonpharmacologic method of pain relief accompanied or mediated by beta-endorphin release. The comparable degree of the initial clinical response emphasizes the powerful placebo effect on reported pain not mediated by endorphin release. This preliminary study shows that noninvasive electrical stimulation is a safe treatment with a positive effect on beta-endorphin blood levels.

Efficacy of cranial electrotherapy stimulation for neuropathic pain following spinal cord injury: a multi-siterandomized controlled trial with a secondary 6-month open-label phase.  Tan G, Rintala DH, Jensen MP, Richards JS, Holmes SA, Parachuri R, Lashgari-Saegh S, Price LR. J Spinal Cord Med. 2011;34(3):285-96. doi: 10.1179/2045772311Y.0000000008. (PubMed link)

BACKGROUND: Chronic pain is a significant problem for many individuals following spinal cord injury (SCI). Unfortunately, SCI-related neuropathicpain has proven to be largely refractory to analgesic medications and other available treatments. Cranial electrotherapy stimulation (CES) has been effective in managing some types of pain. It involves the application of a small amount of current through the head via ear clip electrodes. OBJECTIVE: Explore the effectiveness of CES for neuropathic pain in persons with SCI and chronic pain. Study design: Multi-site, double-blind, sham-controlled study. PARTICIPANTS: Adults with SCI and chronic neuropathic pain at or below the level of injury were randomized to receive active or sham CES. INTERVENTION: Application of active CES or sham CES 1 hour daily for 21 days. Six-month open-label phase to assess ‘as-needed’ CES use. OUTCOME MEASURES: Change in pre- to post-session pain ratings as well as change in pain intensity, pain interference, pain quality, pain beliefs and coping strategies, general physical and mental health status, depressive symptomatology, perceived stress, and anxiety pre- to post-treatment. RESULTS: The active group reported a significantly greater average decrease in pain during daily treatments than the sham group (Kruskal-Wallis chi-square = 4.70, P < 0.05). During the 21-day trial, there was a significant group  time interaction for only one outcome variable; the active group showed larger pre- to post-treatment decreases in pain interference than the sham group did (F = 8.50, P < 0.01, d = 0.59). CONCLUSIONS: On average, CES appears to have provided a small but statistically significant improvement in pain intensity and pain interference with few troublesome side effects. Individual results varied from no pain relief to a great deal of relief.

The use of cranial electrotherapy stimulation in the management of chronic pain: A review.  Kirsch DL, Smith RB. NeuroRehabilitation. 2000;14(2):85-94. (PubMed link)

Cranial Electrotherapy Stimulation (CES) has a growing history of applications in rehabilitation medicine in the United States dating back to early 1970. As a recognized non-drug treatment of anxiety, depression and insomnia, CES gained its first major application in the field of addiction treatment and rehabilitation. By the mid 1980s research was showing additional important uses of CES in the treatment of closed head injured patients, and in paraplegic and quadriplegic patients. The most recent research is showing CES to be highly effective in the management of chronic pain patients. It may be elevating the pain threshold due to its stress reducing effects when anxiety and depression are reduced below clinical levels. Modern theorists of a pain neuromatrix in the cerebral cortex may provide an additional basis for understanding CES mechanisms in the control of pain related disorders.

Safety and effectiveness of cranial electrotherapy in the treatment of tension headache.  Solomon S, Elkind A, Freitag F, Gallagher RM, Moore K, Swerdlow B, Malkin S. Headache. 1989 Jul;29(7):445-50.  (PubMed link)

One hundred patients were enrolled in a multicenter double-blind study to evaluate the safety and effectiveness of the Pain Suppressor Unit, acranial electrotherapy stimulator for the symptomatic treatment of tension headaches. Treatment consisted of extremely low level, high frequency current applied transcranially. Pain scores before and after 20 minute treatments of individual headaches as well as patient and physician global evaluations were the primary efficacy variables. Following use of the active unit, patients reported an average reduction in pain intensity of approximately 35%. Placebo patients reported a reduction of approximately 18%. The difference was statistically significant (p = 0.01). The active unit was rated as moderately or highly effective in 40% by physicians, and in 36% by patients. Both physicians and patients scored the placebo unit moderately or highly effective for only 16%. The difference in ordered outcomes was statistically significant (p = 0.004). Approximately 10% of patients in each group reported at least one minor adverse experience. Cranial electrotherapy stimulation is distinct from TENS, and is safe and often effective in ameliorating the pain intensity of tension headaches. It should be considered as an alternative to the chronic usage of analgesics.

Noninvasive brain stimulation with low-intensity electrical currents: putative mechanisms of action for direct and alternating current stimulation.  Zaghi S, Acar M, Hultgren B, Boggio PS, Fregni F Neuroscientist. 2010 Jun;16(3):285-307. Epub 2009 Dec 29. (PubMed link)

Transcranial stimulation with weak direct current (DC) has been valuable in exploring the effect of cortical modulation on various neural networks. Less attention has been given, however, to cranial stimulation with low-intensity alternating current (AC). Reviewing and discussing these methods simultaneously with special attention to what is known about their mechanisms of action may provide new insights for the field of noninvasive brain stimulation. Direct current appears to modulate spontaneous neuronal activity in a polarity-dependent fashion with site-specific effects that are perpetuated throughout the brain via networks of interneuronal circuits, inducing significant effects on high-order cortical processes implicated in decision making, language, memory, sensory perception, and pain. AC stimulation has also been associated with a significant behavioral and clinical impact, but the mechanism of AC stimulation has been underinvestigated in comparison with DC stimulation. Even so, preliminary studies show that although AC stimulation has only modest effects on cortical excitability, it has been shown to induce synchronous changes in brain activity as measured by EEG activity. Thus, cranial AC stimulation may render its effects not by polarizing brain tissue, but rather via rhythmic stimulation that synchronizes and enhances the efficacy of endogenous neurophysiologic activity. Alternatively, secondary nonspecific central and peripheral effects may explain the clinical outcomes of DC or AC stimulation. Here the authors review what is known about DC and AC stimulation, and they discuss features that remain to be investigated.

The Last 50 years of Cranial Electrotherapy Research  Smith, Ray B PhD

The monograph reports five meta-analyses of Cranial Electrotherapy Stimulation (CES) covering various human clinical trials that have been published in the US scientific literature. Each meta-analysis focuses on a particular treatment indication, as follows: 1. Insomnia: 18 studies, 648 subjects, mean improvement 62% 2. Depression: 18 studies, 853 subjects, mean improvement 47% 3. Anxiety: 38 studies, 1495 subjects, mean improvement 58% 4. Drug abstinence: 15 studies, 535 subjects, mean improvement 60% 5. Cognitive dysfunction: 13 studies, 648 subjects, mean improvement 44% Most of these studies are limited by small samples, heterogeneity of symptoms, and overlap of conditions, which limits their rigorousness and generalizability to specific conditions, though these results may be more reflective of “real world” populations in which comorbidity tends to be the rule rather than the exception. CES appears to be a benign intervention with no serious adverse events.

Meta-analysis of randomized controlled trials of cranial electrostimulation. Efficacy in treating selectedpsychological and physiological conditions. Klawansky S, Yeung A, Berkey C, Shah N, Phan H, Chalmers TC. J Nerv Ment Dis. 1995 Jul;183(7):478-84.  (PubMed link)

To clarify the diverse published results of cranial electrostimulation (CES) efficacy, we conducted an extensive literature review that identified 18 of the most carefully conducted randomized controlled trials of CES versus sham treatment. For the 14 trials that had sufficient data, we used the techniques of meta-analysis to pool the published results of treating each of four conditions: anxiety (eight trials), brain dysfunction (two trials), headache (two trials), and insomnia (two trials). Because studies utilized different outcome measures, we used an effect size method to normalize measures which we then pooled across studies within each condition. The meta-analysis of anxiety showed CES to be significantly more effective than sham treatment (p < .05). Pooling did not affect results that were individually positive (headache and pain under anesthesia) or negative (brain dysfunction and insomnia). Most studies failed to report all data necessary for meta-analysis. Moreover, in all but two trials, the therapist was not blinded and knew which patients were receiving CES or sham treatment. We strongly recommend that future trials of CES report complete data and incorporate therapist blinding to avoid possible bias.

Cerebrospinal Fluid And Plasma Neurochemicals Response To Cranial Electrical Stimulation. Shealy CN, Cady RK, Wilkie RG, et al. J Neurol Orthop Med Surg 1998;18:94-97. (PubMed link)

Depression: a diagnostic neurochemical profile & therapy with cranial electrical stimulation (CES).   Shealy, C.N., Cady, R.K., Wilkie, R.G., Cox, R.H., Liss, S., Closson, W. The Journal of Neurological & Orthopaedic Medicine & Surgery. Dec 1989. 10(4):319-321. (PubMed link)

Gathering Effect   Liss, S, Liss B. Presented at the American Academy of Pain Management Conference Las Vegas, Nevada—September 1999 (PubMed link)

Physiological and Therapeutic Effects of High Frequency Electrical Pulses. Liss S, Liss B. Integr Physiol Behav Sci. 1996 Apr-Jun;31(2):88-95.(PubMed link)

Alternating low frequency stimulation of medial septal and commissural fibers induces NMDA-dependent, long-lasting potentiation of hippocampal synapses in urethane-anesthetized rats. Habib D, Dringenberg HC.  Hippocampus. 2009 Mar;19(3):299-307. doi: 10.1002/hipo.20507. (PubMed link)

Potential and current density distributions of cranial electrotherapy stimulation (CES) in a four-concentric-spheres model. Ferdjallah M, Bostick FX Jr, Barr RE. IEEE Trans Biomed Eng. 1996 Sep;43(9):939-43. (PubMed link)

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 alcoholicpatients. 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.

Treatment of drug, alcohol and nicotine addiction by neuroelectric therapy: analysis of results over 7 years.  Patterson MA, Firth J, Gardiner R. J Bioelectricity 1984; 3:193-221

NeuroElectric Therapy (NET) is a 10-day treatment with a transistorized stimulator, which rapidly reduces both acute and chronic withdrawal symptomatology of all chemical substances, without drugs and with no negative side-effects. It is hypothesized that NET acts by specific electrical frequency stimulation of endorphin production that has been decreased due to chronic substance abuse. This has been demonstrated using NET in rat models; corticosterone levels and hepatic enzyme activity were also significantly altered. Of 186 patients, 98.4% were successfully detoxified, with marked feeling of well-being and no craving (in 95%) or anxiety (in 75%). Detailed assessments of abstinence syndrome in NET are given. Of a 50% response to follow-up, 78.5% were addiction-free (80.3% of drug addicts) 1 to 8 years after NET, although average time in rehabilitation was only 16 days. Alcohol, marijuana and cigarette use were decreased in 64%. Diminished substance use was reported in 76% of recidivists.

Cranial electrotherapy stimulation treatment of cognitive brain dysfunction in chemical dependence. Schmitt R, Capo T, Frazier H, Boren D. J Clin Psychiatry. 1984 Feb;45(2):60-1, 62-3.  (PubMed link)

Several studies have shown that cranial electrotherapy stimulation (CES) is useful in treating brain dysfunction associated with alcoholism. A double-blind study replicated the latest of these findings in 60 inpatients and extended them by treating individuals with alcoholism and other chemicaldependencies. Treatment effects were assessed on three subscales of the WAIS that are clinical indicators of organic brain syndrome. No placebo effect was found. CES appears to be a valuable adjunct to rehabilitation programs for addicted persons and can effect changes in areas not addressed by other treatment modalities.

Effects of cerebral electrical stimulation on alcoholism: a pilot study. Padjen AL, Dongier M, Malec T. Alcohol Clin Exp Res. 1995 Aug;19(4):1004-10.  (PubMed link)

Cerebral electrical stimulation (CES), born from research on electroanesthesia in the seventies, consists of the application of a pulsating current of small intensity (usually less than 1 mA, and below the threshold of perception) through the skull, e.g., in daily 30-min sessions. Claims of biological effectiveness (neurochemical, hormonal and EEG changes, naloxone-reversible analgesia in rats, etc.) and of clinical effectiveness (anxiety, depression, cognitive functions in alcoholics) have often relied on poorly controlled data. A recent controlled study in the treatment of opiate withdrawal has been positive. The present double-blind controlled study compares active CES with sham stimulation in 64 alcohol-dependent males. Over 4 weeks, both treatment groups improved significantly in most aspects. In the active treatment group additional significant improvement was observed in week-end alcohol consumption, and in two psychological measures: depression and stress symptoms index, but not in general drinking behavior.

Electrosleep (electrical transcranial stimulation) in the treatment of anxiety, depression and sleep disturbance in chronic alcoholics. McKenzie, Richard E.; Costello, Raymond M.; Buck, Don C. Journal of Altered States of Consciousness, Vol 2(2), 1975-1976, 185-196.

Employed a double-blind design with treatment variables of current and suggestion, and outcome criteria of anxiety, depression, and sleep disturbance to test for effects of electrosleep (electrical transcranial stimulation) in 20 male hospitalized alcoholics (mean age, 51 yrs). Ss were randomly assigned to 1 of 4 groups; 2 groups received current and 2 did not; 1 current and 1 noncurrent group received sensation, the other 2 did not. Current was standardized at 1 mA; peak-to-peak amplitude was manipulated to control for physical sensation. Five outcome criteria were employed: 3 depression indices, 1 index of anxiety, and 1 index of quality of sleep. Results suggest that electrosleep could have both a direct effect attributable to intracranial current flow and an indirect effect attributable to the psychological influence of suggestion.

Electrostimulation: addiction treatment for the coming millennium. Patterson MA, Patterson L, Patterson SI.  J Altern Complement Med. 1996 Winter;2(4):485-91.

At a period of fundamental review of the health care system, it is timely to re-assess one of medicine’s most intractable problems–the treatment of addictions. The apparently insoluble dilemmas posed by the acute and chronic withdrawal syndromes underlie universally high drop-out and relapse rates. In a decade of HIV and AIDS infection, poly-substance addiction, potent street drugs, and ossified treatment strategies, it is urgent that policy formulators investigate seriously a flexible system of non-pharmacological transcranial electrostimulation treatment, based on its record of rapid, safe, and cost-effective detoxification in several countries, as one innovative contribution to the challenges presented by addiction in the 1990s. This is a brief report of the introduction of NeuroElectric Therapy (NET) into Germany, describing the responses of the first 22 cases. The daily progress of a heroin addict and a methadone addict are detailed: both were treated as outpatients for 8 hours daily, for 7 and 10 days respectively.

Opiate abstinent syndrome is rapidly blocked by electrostimulation. Kharchenko EP, Shesternin SL, Klimenko MN.  Dokl Biol Sci. 2001 Nov-Dec;381:516-8. (PubMed link)

A retrospective chart review of cranial electrotherapy stimulation for clients newly admitted to residential drug treatment.  David A. Deitch, Ph.D., Jennifer Butler, B.S., Charles A. Fisher, Sidney Hargrave, M.A., Norman John 2009

This pilot program was designed to determine if using CES affected retention rates among new drug rehab patients arriving at Phoenix House, the nations largest non-profit drug rehab center.  The study included 392 subjects consisting of heroin and cocaine addicts; 293 patients did not receive CES (control) and 99 patients received an average of 5 CES treatments total per patient.  A 50% increase in retention after 90 days was seen among patients who received CES versus patients who did not receive CES.  Patients who received CES also reported significant decreases in anxiety and insomnia. Phoenix House pilot program poster (link to poster, previous file in dropbox.)

The effects of cerebral electrotherapy on short-term memory impairment in alcoholic patients.  Smith, Ray B.; Day, Eleanor International Journal of the Addictions, Vol 12(4), Jun 1977, 575-582.

Two hundred twenty-seven male alcoholism patients were placed into four therapy and onc control groups. The therapy groups received cerebral electrotherapy (CET) for 40 minutes a day, Monday through Friday for 3 weeks. Groups I and II assisted the therapist in setting the current to just below sensation threshold. Group I via headbands (X = 0.40 mA) and Group II via ear stethoscopes (X = 0.21 mA). Two other groups received 0.10 and 0.20 mA respectively via ear stethoscope electrodes. It was found that CET significantly reduced brain dysfunction in all treatment groups when compared with controls as measured by the Benton Visual Retention Test.

Transcutaneous electrical stimulation with Limoge current potentiates morphine analgesia and attenuates opiateabstinence syndrome. Auriacombe M, Tignol J, Le Moal M, Stinus L.  Biol Psychiatry. 1990 Oct 15;28(8):650-6. (PubMed link)

Transcutaneous electrostimulation is a somewhat controversial technique used in the management of the opiate withdrawal syndrome. We report an animal study of a particular transcutaneous electrostimulation called transcutaneous cranial electrostimulation, based on a technique used for many years on heroin addicts for the rapid severance of their addiction, which has been validated in a clinical setting by a double-blind trial. This technique involves the application of an intermittent high-frequency current (Limoge’s current). Our experimental data show that this transcutaneous cranial electrostimulation increases morphine analgesia by threefold on the tail flick latency measure and produces a 48% attenuation of the abstinence syndrome observed after abrupt cessation of morphine administration. These results were obtained using a double-blind paradigm.

Treatment of methadone withdrawal with cerebral electrotherapy (electrosleep). Gomez E, Mikhail AR.  Br J Psychiatry. 1979 Jan;134:111-3. (PubMed link)

The use of cerebral electrotherapy (CET) in methadone detoxification was studied in 28 patients. Fourteen patients received active CET; the other 14 acted as controls and received either stimulated CET or only methadone detoxification therapy. One patient dropped out of the study. The Taylor Manifest Anxiety Scale and the Hamilton Anxiety Scale were administered before and after the study period. Nine of the patients receiving active CET were drug-free by the end of 8 to 10 days, and all experienced a marked reduction of their symptoms; the control group did not show significant changes. CET was clearly beneficial in the treatment of patients undergoing methadone withdrawal.



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