I just became aware of this research in January, 2006, although I had seen mention of it very early in my career under the name of electro-sleep.  Although it has been available for many years, Cranial Electrotherapy Stimulation (CES) is certainly not very popular, since I have never come across a single patient in my 30 year career using it in the four different states in which I have worked.  However, the research looks acceptable and positive, although larger, higher quality studies would certainly help.  It is true that many of the review articles and some of the published research are by the manufacturer.  However, most of the depression double-blind studies appear independent of the manufacturer and the manufacturer has a sensible policy of assisting research by providing devices and a double-blinding apparatus to researchers totally independent from the manufacturer.  The device costs $495 and operating costs add another $10 per month.  I have bought five devices to try out as loaners to patients, but don't yet have any impression on patient reception.

TENS is somewhat similar to CES, although at somewhat higher levels of electricity.  Electroacupuncture is also included here, since it appears much more effective than acupuncture, is quite different from acupuncture, and appears to be very similar to CES.  In fact, the research findings on traditional acupuncture in high quality studies find that it is virtually worthless.  For more, see acupuncture.

CES has been used for aggression, anxiety, depression, closed head injury, headache, fibromyalgia, and pain.

Cranial Electrostimulation Manufacturer Information: The manufacturer says that with the Alpha-Stim stimulator one out of 506 people will experience a mild headache, and one out of 910 will have a skin reaction at the electrode site. Usually a minor self-limiting reddening of the skin. There are no other significant side effects reported in over 55 research studies, or in 24 years of clinical and home use. The Alpha-Stim 100, Alpha-Stim PPM or Alpha-Stim SCS may effect the operation of cardiac pacemakers (particularly demand type pacemakers). Do not stimulate directly on the eyes, or over the carotid sinus (on the neck beside the larynx). Federal Law (USA only) restricts these devices to sale by, or on the order of a licensed health care practitioner. The Alpha Stim cost is $895. The Alpha-Stim SCS Stress Control System is $495. It is promoted for anxiety, depression, and insomnia. http://www.alpha-stim.com/Merchant2/merchant.mv Most CES devices limit the stimulus intensity to less than 1.0 milliampere at 0.5 or 100 Hz from a 9 volt source. Over the past three decades, at least eight medical device companies have applied for and received FDA clearance to market CES devices. They use a different waveform at a much lower current level than TENS units. The current up to a comfortable or subsensory level and leaves it at that level for 20 minutes to one hour for the treatment. Longer duration may be used to make up for lower current level. A note elsewhere states that it is contraindicated in pregnancy.

Cranial Electrotherapy Stimulation: Manufacturer's Review: According to the manufacturer, there are 26 published studies of patients with depression and measured physiological and/or psychological changes after CES treatment. Twenty-one of the 26 (81%) studies reported positive results for depression. The five CES studies which reported negative or indeterminate results were from the 1970s with CES devices that are no longer commercially available. Three studies showed both actual treatment and sham treated groups to improve significantly, most likely because both groups were also taking medications (Levitt, James, & Flavell, 1975; Marshall & Izard, 1974; Passini, Watson, & Herder, 1976). One study reported no significant change on anxiety or depression scales, but subjective insomnia improved (P < .05) during active treatment (Moore, Mellor, Standage, & Strong, 1975). Only one early CES study published over 30 years ago conducted on a population of insomniacs with an average duration of symptoms of nearly 20 years did not show any significant change at all in any parameters (Frankel, Buchbinder, & Snyder, 1973). In 22 CES studies from a meta-analyzes of 1,075 patients, the treatment effect size was 57% improvement when corrected for sample size (Kirsch & Smith, 2004). The mean effectiveness of CES above that of the placebo controls in the CES studies was 63%, vs. 23% for 8 DB PC studies using anti-depressant medication. Gilula, Marshall F, Kirsch, Daniel L Cranial electrotherapy stimulation review: a safer alternative to psychopharmaceuticals in the treatment of depression. Journal of Neurotherapy, 9(2):63-77, 2005.

Adverse Effects, According to Manufacturer: Adverse effects are usually mild and self-limiting. Adverse effects seen in approximately 4,541 patients in controlled, open, uncontrolled conditions, and by physician survey and reasonably associated with the use of CES are dizziness (6 cases, 0.13%), skin irritation/electrode burns (5 cases, 0.11%), and headaches (9 cases, 0.20%). Prolonged CES treatment at higher than necessary currents may cause dizziness or nausea that can last for hours to days. Treatment immediately prior to going to sleep may cause difficulty sleeping due to increased alertness. It is recommended that CES be used at least 3 hours before going to sleep. Paradoxical reactions such as hyperexcited states, increased anxiety, and sleep disturbances may occur. If the Alpha-Stim SCS does not control your anxiety, depression and/or insomnia within 3 weeks, discontinue use. While pregnancy is not a contraindication, safety during pregnancy has not been established. 

Aggression: Cranial Electrotherapy Stimulation Might Help: Nine aggressive, retarded patients refractory to conventional care at a maximum security hospital were given a 3-month course of cranial electrotherapy stimulation, usually 45-60 minutes twice a day. Aggressive episodes declined 59% from baseline; seclusions were down 72%; restraints were down 58%; and use of prescribed-as-needed sedative medications decreased 53%. No patients discontinued cranial electrotherapy stimulation (CES) because of side effects. Cranial electrotherapy stimulation reduces aggression in a violent retarded population: a preliminary report. Childs A. North Texas State Hospital, Vernon, TX. . J Neuropsychiatry Clin NeuroSci 2005 Fall;17(4):548-51. Ed: This is a clinical, not a research report, since there were no controls, and no blinding.

Alcoholism: CES Helped Mood in Alcoholics, But Not Drinking: A recent controlled study in the treatment of opiate withdrawal has been positive. In a 4-week DB study of 64 alcoholic males, 30 minutes/day of cerebral electrical stimulation resulted in less weekend drinking and less depression and anxiety but no change in general drinking behavior when compared to a sham stimulation. Effects of cerebral electrical stimulation on alcoholism: a pilot study. Padjen AL, et al. Alcohol Research Program, Verdun, Que, Canada. Alc Clin Exp Res 1995 Aug;19(4):1004-10.

Alzheimer's: Cranial Electrostimulation No Benefit in 6 Week Study: In one study, behavioral disorders of patients with vascular dementia reacted positively to cranial electrostimulation (CES). In this DB sham controlled study of 18 probable Alzheimer's disease patients, 30 min per day, 5 days a week, for 6 weeks resulted in no improvements in cognition and (affective) behavior were found after CES. Cranial electrostimulation (CES) in patients with probable Alzheimer's disease. Scherder EJ, et al. Vrije Universiteit, Amsterdam, The Netherlands. . Behav Brain Res 2002 Jan 22;128(2):215-7.

Anxiety: Cranial Electrotherapy Stimulation: Reported to Help During Dental Procedures: In a DB PC study of 33 dental patients, the active CES treatment group was significantly less anxious than the placebo group at the conclusion of various dental procedures. CES was used starting 5 minutes before the procedure and continued during the procedure. 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.

Anxiety in Substance Abusers: Cranial Electrostimulation Reported to Helped: In a DB sham-controlled study of 40 inpatient alcohol and/or polydrug users with an additional 20 patients serving as normal hospital routine controls, CES-treated patients showed significantly greater improvement on all anxiety measures than did either control group. Cranial electrotherapy stimulation as a treatment for anxiety in chemically dependent persons. Schmitt R, et al. Alcohol Clin Exp Res 1986 Mar-Apr;10(2):158-60.

Closed Head Injury: Cranial Electrostimulation Claimed of Benefit: In an unreliable manufacter's DB sham controlled study of 15 closed-head-injured patients, cranial electrostimulation for 45 min daily, 4 days a week for 3 weeks, responded significantly on all negative mood factors of the Profile Of Mood States. While the majority of the patients were known seizure cases, no patient suffered a seizure during CES therapy. No placebo effects were found, nor were any negative effects from CES treatment seen. The use of cranial electrotherapy stimulation in the treatment of closed-head-injured patients. Smith RB, Tiberi A, Marshall J. MedTec 2000, Inc, Fort Worth, Texas. Brain Inj 1994 May-Jun;8(4):357-61. The manufacturer also separately reported that 5 multiple sclerosis patients had sent back manufacturer warranty cards reporting benefit. 

Depression: Cranial Electrostimulation May Help But Manual Acupuncture Does Not: Seven randomized comparative trials involving 509 patients were analyzed. The evidence is inconsistent on whether manual acupuncture is superior to sham, and suggests that acupuncture was not superior to waiting list. Evidence suggests that the effect of electroacupuncture may not be significantly different from antidepressant medication, weighted mean difference -0.43(95% CI -5.61 to 4.76). There is inconclusive evidence on whether acupuncture has an additive effect when given as an adjunct to antidepressant drugs. The effectiveness of acupuncture for depression--a systematic review of randomised controlled trials. Mukaino Y, et al. Peninsula Medical School, Exeter, UK. [email protected].  Acupunc Med 2005 Jun;23(2):70-6.

Depression and Fatigue: Electroacupunture and Acupuncture Reported to Help Hemodialysis Patients: In a 1-month random assignment study of 106 hemodialysis patients, acupressure 3 times per week led to significantly less fatigue, better sleep, and less depression as did Transcutaneous Electrical Acupoint Stimulation compared to controls with no difference between the two. Acupressure and Transcutaneous Electrical Acupoint Stimulation in improving fatigue, sleep quality and depression in hemodialysis patients. Tsay SL, et al. National Taipei College of Nursing, Taiwan, R.O.C. . Am J Chin Med 2004;32(3):407-16.

Depression: Electroacupuncture Did as Well as Amitriptyline and Better for Anxiety: Electroacupuncture (EA) stimulation influences brain norepinephrine metabolism in experimental animals. Preliminary clinical research found that EA treatment is as effective as amitriptyline for patients with depression. In a 6-week DB PC study of 29 depressed inpatients with three groups: EA + placebo; amitriptyline; and EA + amitriptyline and in a following DB PC multicenter study of 241 inpatients with depression comparing electroacupuncture + placebo to amitriptyline, the results from both studies showed that the therapeutic efficacy of EA was equal to that of amitriptyline for depressive disorders (P > 0.05). Electro-acupuncture had a better therapeutic effect for anxiety somatization and cognitive process disturbance of depressed patients than amitriptyline (P < 0.05). The side effects of EA were much less (P < 0.001). Clinical research on the therapeutic effect of the electro-acupuncture treatment in patients with depression. Luo H, et al. Beijing Medical University, PR China. Psychiatry Clin Neurosci 1998 Dec;52 Suppl:S338-40.

Depression Studies: Cranial Electrotherapy Stimulation: CES studies reporting a significant reductions in clinical depression: Cox, A., & Heath, R. G. (1975). Neurotone therapy: A preliminary report of its effect on electrical activity of forebrain structures. Diseases of the Nervous System, 36, 245-247; Bianco, F., Jr. (1994). The efficacy of cranial electrotherapy stimulation (CES) for the relief of anxiety and depression among polysubstance abusers in chemical dependency treatment. Unpublished doctoral dissertation, The University of Tulsa; Philip, P., Demotes-Mainard, J., Bourgeois, M., & Vincent, J. D. (1991). Efficiency of transcranial electrostimulation on anxiety and insomnia symptoms during a washout period in depressed patients: A double-blind study. Biological Psychiatry, 29, 451-456; Rosenthal, S. H. (1972). Electrosleep: A double-blind clinical study. Biological Psychiatry, 4, 179-185; Feighner, J. P., Brown, S. L.,&Olivier, J. E. (1973). Electrosleep therapy: A controlled double-blind study. Journal of Nervous and Mental Disorders, 157, 121; McKenzie, R. E., Rosenthal, S. H., & Driessner, J. S. (1976). Some psychophysiologic effects of electrical transcranial stimulation (electrosleep). In N. L. Wulfsohn & A. Sances (Eds.), The nervous system and electric currents (pp. 163-167). New York:Plenum; Matteson, M. T., & Ivancevich, J. M. (1986). An exploratory investigation of CES as an employee stress management technique. Journal of Health and Human Resource Administration, 9, 93-109; Rosenthal, S. H., & Wulfsohn, N. L. (1970a). Studies of electrosleep with active and simulated treatment. Current Therapeutic Research, 12 (3), 126-130. Rosenthal, S. H.,&Wulfsohn, N. L. (1970b). Electrosleep: A preliminary communication. Journal of Nervous and Mental Disease, 151, 146-151; Rosenthal, S. H. (1972). Electrosleep: A double-blind clinical study. Biological Psychiatry, 4, 179-185; Shealy, C. N., Cady, R. K., Wilkie, R. G., Cox, R., Liss, S., & Clossen,W. (1989). Depression: A diagnostic, neurochemical profile and therapy with cranial electrical stimulation (CES). Journal of Neurological and Orthopaedic Medicine and Surgery, 10 (4), 319-321; Smith, R. B. (1999). Cranial electrotherapy stimulation in the treatment of stress related cognitive dysfunction with an eighteen month follow-up. Journal of Cognitive Rehabilitation, 17 (6), 14-18. Smith, R. B.,&O’Neill, L. (1975). Electrosleep in the management of alcoholism. Biological Psychiatry, 10 (6), 675-680).

Depression: Electroacupuncture Equal to Maprotiline in Poorly Controlled Study: In a randomized study of 61 depressed patients, electro-acupuncture on Baihui (GV20), Yintang (EX-HN3) and the differential points was compared to maprotiline. HAMD scores decreased for both groups without significant between-group differences (P > 0.05). Side-effects were higher for the anti-depressant. Clinical study on electro-acupuncture treatment for 30 cases of mental depression. Han C, et al. Beijing University of Traditional Chinese Medicine. J Trad Chin Med 2004 Sep;24(3):172-6.

Fibromyalgia: Cranial Electrotherapy Stimulation Reported to Help: in a double-blind crossover study examining the effect of cranial electrotherapy stimulation (CES) on the pain associated with fibromyalgia. Initially, 39 patients were randomly allocated to CES and 35 patients were allocated to a sham group. Measurements taken at baseline and after three weeks included pain intensity, McGill Pain Score, tenderpoint score, profile of mood states, and Oswestry Score. Three weeks after crossover, measurements were repeated. Significant CES effects were identified, revealing an improvement in pain intensity, McGill Score, tenderpoint score, and profile of mood states (p<0.05). The Effect of Cranial Electrotherapy Stimulation (CES) on Pain Associated with Fibromyalgia. Cook RC, et al. Louisiana State Univ.  Internet J Anesthesiol 2004.

Headache: Cranial Electrostimulation Reportedly Helped Tension Headaches: In a DB sham controlled study a single 20 minute treatment of 100 patients with tension headaches with scores just before and after treatments, those using the Pain Suppressor Unit, a cranial electrotherapy stimulator using extremely low level, high frequency current applied transcranially, reported an average reduction in pain intensity of approximately 35%. Placebo patients reported a reduction of approximately 18% (p = 0.01). Both physicians and patients rated the stimulator as more effective than placebo (p = 0.004). Safety and effectiveness of cranial electrotherapy in the treatment of tension headache. Solomon S, et al. Headache 1989 Jul;29(7):445-50.

Mild Cognitive Impairment: TENS Reported Helped: Transcutaneous electrical nerve stimulation (TENS) has been applied to patients with either Alzheimer's disease (AD) or incipient dementia, resulting in an enhancement in memory and verbal fluency. Moreover, affective behavior was shown to improve. In a study of nondemented elderly with mild cognitive impairment living in a residential home, TENS resulted a mild improvement in self-efficacy and mood, while the placebo group showed a considerable reduction in self-efficacy and an increase in depression. Effects of transcutaneous electrical nerve stimulation (TENS) on self-efficacy and mood in elderly with mild cognitive impairment. Luijpen MW, et al. Vrije Universiteit, Amsterdam, the Netherlands. . Neurorehabil Neural Repair 2004 Sep;18(3):166-75.

Pain: Spinal Cord Injury Central Pain Helped: Using a very safe technique of non-invasive brain stimulation - transcranial direct current stimulation (tDCS) - on pain control in patients with central pain due to traumatic spinal cord injury, patients were randomized to receive sham or active motor tDCS (2mA, 20min for 5 consecutive days). There was a significant pain improvement after active anodal stimulation of the motor cortex, but not after sham stimulation. These results were not confounded by depression or anxiety changes. Cognitive performance was not significantly changed throughout the trial in both treatment groups. A sham-controlled, phase II trial of transcranial direct current stimulation for the treatment of central pain in traumatic spinal cord injury. Fregni F, et al. Harvard. Pain 2006 Mar 23.

Substance Abuse: Cranial Electrostimulation No Benefit: In a DB sham controlled study of 101 smokers trying to stop, cranial electrical stimulation on 5 consecutive days had no significant benefit on daily cigarettes smoked, exhaled carbon monoxide, urinary cotinine levels, treatment retention, smoking urges, or total tobacco withdrawal scores, although subjects in the CES group had less cigarette craving and anxiety during the first 2 experimental days. The ineffectiveness of CES to reduce withdrawal symptoms and facilitate smoking cessation are similar to results of other clinical studies of CES in drug dependence, although positive effects of CES in animal studies have been reported. Evaluation of cranial electrostimulation therapy on short-term smoking cessation. Pickworth WB, et al. National Institute on Drug Abuse, Addiction Research Center, Baltimore, Maryland. Biol Psychiatry 1997 Jul 15;42(2):116-21.

Schizophrenia: Electroacupuncture as an Add-On: In a DB study of 90 schizophrenia patients, electroacupuncture was added to clozapine and clozapine alone. The total effective rate was 75% with added electroacupunture and 73% with clozapine alone. However, somatic complaint was lower and compliance was higher in the EA group. Short-term curative effect of electroacupuncture as an adjunctive treatment on schizophrenia. Feng-Ju Y, et al. Second Affiliated Hospital of Xinxiang Medical College, Henan, China. . Zhongguo Zhong Xi Yi He Za Zhi 2006 Mar;26(3):253-5. Ed: Electroacupunture is very similar to Cranial Electrostimulation.  It is easy and harmless.  However, I can't tell if it had any beneficial effect in this study.  It has been found helpful by itself for depression.

OBJECTIVE: To study effects of electroacupuncture at Jiaji (EX-B2) on protracted withdrawl syndrome of the patient of heroin dependence. METHODS: One hundred and twenty cases of heroin dependence were randomly divided into 4 groups: acupuncture group I (Jianji and Shenshu acupoints), acupuncture group II (acupoints at limbs), simulation group and control group. Protracted withdrawl syndrome scale, Hamilton anxiety scale (HAMA) and self-rating depression scale (SDS) were used to observe changes of the scores before and after treatment of 4, 8, 10 weeks. RESULTS: In the treatment of 4, 8, 10 weeks, the cumulative scores for protracted withdrawl syndrome, HAMA and SDS in the acupuncture group I and II decreased significantly as compared with those in the control group (P < 0.01). CONCLUSION: Electroacupuncture can significantly improve protracted withdrawl syndrome, alleviate anxiety and depression, and electroacupuncture at Jiaji (EX-B2) being better than at the acupoints of the limbs. Clinical study on electroacupuncture at Jiaji (EX-B2) for interfering protracted withdrawal syndrome in the patient of heroin dependence. Mu JP, et al.  Yunyang Medical College, Hubei, China. . Zhongguo Zhen Jiu 2005 Sep;25(9):599-602.

Thomas E. Radecki, M.D., J.D.

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