PAIN MANAGEMENT: A PRACTICAL GUIDE FOR CLINICIANS
The Official Textbook of the American Academy of Pain Management
Chapter 55 Reprint: 1998
ELECTROMEDICINE: THE OTHER SIDE OF PHYSIOLOGY

Daniel L. Kirsch, Ph.D., D.A.A.P.M.
Fred N. Lerner, Ph.D., D.A.A.P.M.

CRANIAL ELECTROTHERAPY STIMULATION

Cranial electrotherapy stimulation (CES) is the application of low-level, pulsed electrical currents (usually not exceeding one milliampere), applied to the head for medical and/or psychological purposes. It is primarily used to treat both state (situational) and trait (chronic) anxiety, but it is also indispensable for treating pain patients.
Experimentation with low intensity electrical stimulation of the brain was first reported by Drs. Leduc and Rouxeau of France in 1902. Initially, this method was called electrosleep as it was thought to be able to induce sleep. Since then, it has been referred to by many other names, the most popular being transcranial electrotherapy (TCET) and neuroelectric therapy (NET). Research on using what is now referred to as cranial electrotherapy stimulation (CES) began in the Soviet Union during the 1950's.
Cranial electrotherapy stimulation is a simple treatment that can easily be administered at any time. The current is applied by easy-to-use clip electrodes that attach on the ear lobes, or by stethoscope-type electrodes placed behind the ears. In the 1960's and early 1970's, electrodes were placed directly on the eyes because it was thought that the low level of current used in CES could not otherwise penetrate the cranium. This electrode placement has been abandoned over 20 years ago.
Anxiety reduction is usually experienced during a treatment, but may be seen hours later, or as late as one day after treatment. In some people, it may require a series of five to ten daily treatments to be effective.
Cranial electrotherapy stimulation leaves the user alert while inducing a relaxed state. Psychologists call this an alpha state. The effect differs from pharmaceutical treatment in that people usually report feeling that their bodies are more relaxed, while their minds are more alert. Most people experience a feeling that their bodies are lighter, while thinking is clearer and more creative. A mild tingling sensation at the electrode sites may also be experienced. The current should never be raised to a level that is uncomfortable. One 20 minute session is often all that is needed to effectively control anxiety for at least a day, and the effects are usually cumulative. Cranial electrotherapy stimulation may also be used as an adjunct to anxiolytic medication and/or psychotherapy, behavioral modification, and other methods of treatment. For people who have difficulty falling asleep, CES should be used at least three hours before going to bed or the increased alertness may interfere with sleep. It is difficult to adequately describe the CES experience. Only trying it or witnessing its use will do that.
After treatment, there are usually no physical limitations imposed so most people can resume normal activities immediately. Some people may experience a euphoric feeling, or a state of deep relaxation that may temporarily impair their mental and/or physical abilities for the performance of potentially hazardous tasks, such as operating a motor vehicle or heavy machinery, for up to several hours after treatment.
At present, there are over 100 research studies on CES in humans and over 20 experimental animal studies. No significant lasting side effects have ever been reported. Occasional self-limiting headache, discomfort or skin irritation under the electrodes, or lightheadedness may occur. Patients with a history of vertigo may experience dizziness for hours or days after treatment.
As in many areas of biology and therapy, the evidence of CES effectiveness is empirical. It is generally believed that the effects are primarily mediated through a direct action on the brain at the limbic system, the hypothalamus and/or reticular activating system (Brotman, 1989; Gibson, 1987; Madden, 1987). The primary role of the reticular activating system is the regulation of electrocortical activity. These are "primitive" brain stem structures. The functions of these areas and their influence on our emotional states were mapped using electrical stimulation. Electrical stimulation of the periaqueductal gray matter (PAG) has been shown to activate descending inhibitory pathways from the medial brainstem to the dorsal horn of the spinal cord, in a manner similar to Beta-endorphins (Salar, 1981; Pert, 1981; Ng, 1975). Cortical inhibition is a factor in the Melzack-Wall Gate Control theory (Melzack, 1975). Toriyama (1975) suggested it is possible that CES may produce its effects through parasympathetic autonomic nervous system dominance via stimulation of the vagus nerve (CN X). Taylor (1991) added other cranial nerves such as the trigeminal (CN V), facial (CN VII), and glossopharyngeal (CN IX). Fields (1975) showed that electrocortical activity produced by stimulation of the trigeminal nerve is implicated in the function of the limbic region of the midbrain affecting emotions. Substance P and enkephalin have been found in the trigeminal nucleus, and are postulated to be involved in limbic emotional brain factors (Hokfelt, 1977). The auditory-vertigo nerve (CN VIII) must also be effected by CES, accounting for the dizziness one experiences when the current is too high. Ideally, CES electrodes are placed on the ear lobes because that is a convenient way to direct current through the brain stem structures.
From studies of CES using monkeys, Jarzembski (1970) revealed that 42% to 46% of the total applied current enters the brain, with the highest concentration in the thalamic region. Rat studies by Krupisky (1991) showed as much as a threefold increase in Beta-endorphin concentration after just one CES treatment. Pozos (1971) conducted mongrel dog research that suggests CES releases dopamine in the basal ganglia, and that the overall physiological effects appear to be anticholinergic and catecholamine like in action. Richter (1972) found the size, location, and distribution of synaptic vesicles were all within normal limits after a serious of ten, one hour treatments in Rhesus monkeys. Several studies in humans and stump-tailed macaques revealed a temporary reduction in gastric hypersecretion (Reigel, 1970; Reigel, 1971; Wilson, 1970; Kotter, 1975).
A recent review by Kirsch (1996) of 103 human studies involving 4,848 subjects (3,404 receiving cranial electrotherapy stimulation, while the remainder served as sham-treated or controls) reveal significant changes associated with anxiolytic relaxation responses, such as lowered electromylograms (Gibson, 1987; Forster, 1963; Heffernan, 1995; Overcash, 1989; Voris, 1995), slowing on electroencephalograms (Braverman, 1990; Cox, 1975; Krupitsky, 1991; McKenzie, 1976; Singh, 1971), increased peripheral temperature (an indicator of vasodilatation) (Brotman, 1989; Heffernan, 1995), reductions in maximal acid output (Kotter, 1975), and in blood pressure, pulse, respiration, and heart rate (Heffernan, 1995; Taylor, 1991).
The efficacy of CES has also been clinically confirmed through the use of 28 different psychometric tests. The significance of CES research for treating anxiety has been reconfirmed through meta-analyses conducted at the University of Tulsa by O'Connor (1991), and by Klawansky (1995) at the Department of Health Policy and Management, Harvard School of Public Health.
Kirsch (1996) also reviewed all the aforementioned 103 CES studies for comments on side effects and safety. The most common area of complaint, reported in five studies, was transient blurring of vision lasting no more than one hour from the mechanical pressure caused by eye electrodes used in the 1960's and early 1970's. The incidence of this problem was seen equally in active CES groups and sham CES, indicating the problem was due to mechanical pressure over the orbits, and not electrically- induced. As stated previously, this problem does not apply to modern CES devices because none use eye electrodes. There was only 7 reports of headaches (0.2%), and 3 cases of skin irritation or electrode burns at the electrode sites (0.09%).
In addition, a search was conducted of United States Food and Drug Administration records through Freedom of Information Services. The search encompassed all complaints to FDA from May, 1976 through March, 1995. The search revealed only 3 entries. One was an implanted stimulator (which can hardly be considered a CES device) manufactured by Medtronic Neuro Division. The device apparently malfunctioned causing the need for it to be explanted. No death or serious injury occurred. The other two were both Pain Suppressor Model 112A malfunctions. Of these, one allegedly caused the patient to suffer extreme headache pain for about 10 hours, and lack of sleep for 48 hours. The patient discontinued use of the device, took a prescription sleeping pill and then felt better. The other was a patient who was two weeks pregnant and experienced the early signs of miscarriage. This patient was instructed not to use the device while pregnant and was referred to the instruction manual which expressly states "warning": the safety of the device during pregnancy has not been established. It should be noted that the output of the Pain Suppressor is up to 4 mA which is unusually high for a CES device.
A postmarketing survey was conducted during October, 1995 of health care practitioners using Alpha Stim products. A total of 313 individual patient report forms were received. 112 males, and 199 females were identified, ranging from 5 to 85 years old. Twenty of the forms were completed on inpatients, the balance on outpatients. 57.84% of the patients were reported to have completed CES treatment, while 42.16% were still receiving treatment at the time of the survey. Four patients discontinued treatment because it was not efficacious, 3 discontinued due to undesirable side effects, and 24 for other reasons.
Fourteen studies conducted follow-up investigations from 1 week to 2 years after treatment (Brotman, 1989; Brovar, 1984; Cartwright, 1975; Flemenbaum, 1974; Forster, 1963; Hearst, 1974; Heffernan, 1995; Koegler, 1971; Magora, 1967; Matteson, 1986; Moore, 1975; Overcash, 1995; Smith, 1993; Weiss, 1973). Thirteen of 13 (100%) reported a continued improvement after a single CES treatment, or a series of CES treatments. The other follow-up report only commented on safety (Forster, 1963). None of the 14 revealed any long term harmful effects.
When restricted to anxiety populations or studies that measured for physiological and/or psychological changes in anxiety, there are 40 scientific studies of CES, involving 1,835 patients (Kirsch, 1996). 34 of the 40 (85%) studies reported efficacious results in the treatment of anxiety. Five of the studies on CES (all using the Alpha-Stim) support the effectiveness for managing anxiety during or after a single treatment (Gibson, 1987; Heffernan, 1995; Smith, 1993; Voris, 1995; Winick, 1995).
None of the 6 of 40 (15%) anxiety studies categorized by the authors as having negative results were recent, 5 were done in the 1970's, and 1 in 1980. Three showed both actual treatment and sham groups to improve significantly, most likely because both groups were also taking medications (Levitt, 1975; Passini, 1976; Von Richtofen, 1980). One was a depression study in which the author noted that acute anxiety was not relieved and again, the study did not control for medications (Hearst, 1974). One reported no significant change on anxiety or depression scales, but subjective insomnia improved (P=.05) during active treatment (Moore, 1975). Only one study conducted on a population of insomniacs with an average duration of symptoms for almost 20 years did not show any significant change at all in any parameters (Frankel, 1973). Perhaps Frankel's study used a defective device.
Cranial electrotherapy stimulation has been well researched and clearly proven to be the most effective, and safest method of treatment for anxiety, and anxiety-related disorders. It is also highly effective for depression and insomnia, muscle tension, and headaches. As an increasing number of patients seek alternatives to the side effects and potential addiction of mood-altering pharmaceuticals and controlled substances, CES offers a viable solution. It is inexpensive to offer CES in a physician's office, clinic, or hospital, and chronically-stressed patients will find it cost-effective over time to own their own CES device.

Indications
In addition to the primary claims for anxiety, depression and insomnia, CES has been researched with significant results for many other conditions. Smith and Shiromoto (1992) showed it to be highly effective in blocking fear perception in phobic patients. Favorable results have also been reported for labor, epilepsy, glossalgia, hypertension, surgery, spinal cord injuries, chronic pain, arthritis, cerebral atherosclerosis, eczema, dental pain, asthma, ischemic heart disease, stroke, motion sickness, digestive disorders as well as various addictive disorders including cocaine, marijuana, heroin and alcohol abuse (Wharton, McCoy, Cofer, 1982; Schmitt, Capo, Frazier, Boren, 1984; Smith, 1975; Smith, 1982; Patterson, 1983; Daulouede, 1980; Gomez Mikhail, 1978; Brovar, 1984; Feighner, Brown, Olivier, 1973; Overcash Siebenthall, 1989).
Besides specific pathological disorders, there is a growing number of studies being conducted that shows increase in cognitive functions. Michael Hutchison (1986) discussed several mind enhancement techniques in his book Megabrain, with much of chapter 9 centered on CES as a tool for attaining higher levels of consciousness. Sparked by Hutchison, Madden and Kirsch (1987) completed a study that demonstrated CES to be a useful tool for improving psychomotor abilities.

Methodology
Cranial electrotherapy stimulation devices are generally similar in size and appearance to standard TENS units, but produce very different waveforms. Standard milliampere-current TENS devices must never be applied transcranially. CES electrodes can be placed bitemporally, forehead to posterior neck, bilaterally in the hollow just anterior to the mastoid processes, or through electrodes clipped to the earlobes. The latter method was developed by the authors after years of comparative clinical observations.
Most CES electrodes must first be wet with saline solution. When using ear clip electrodes, apply them to the superior aspect of the ear lobes, as close to the jaw as possible. Start with a low current and gradually increase it. If the current is too high the patient may experience a painful stinging at the electrodes, dizziness, or nausea. If any of these three symptoms arise,immediately reduce the current and the symptoms will subside in a few moments. After a minute or two, try increasing the current again, but keep it at a comfortable level. It is okay for the patient to feel the current as long as it is not uncomfortable.
The ideal treatment time is 20 to 40 minutes, but some patients may achieve the full benefits of a CES treatment within 10 minutes. Many dentists use it instead of nitrous oxide gas to help relax patients during dental procedures. Sometimes these dental procedures last for hours with the patient undergoing CES.
During the treatment, some patients will experience a subjective change in their body weight. They may feel heavier at first and then lighter, or they may feel lighter initially. The patient will feel worse during the heavy cycle and this feeling may last for days unless extra treatment time is given. Therefore it is important to continue the treatment for a few extra minutes if the patient feels heavier at the end of the allotted time, even if it has already been 20 minutes or more. Continue for at least 2 minutes after the patient feels lighter. Although quite common, not all patients will be aware of these weight-perception changes.
Although CES treatment is indicated for insomnia, because of the increased alertness some patients find it difficult to fall asleep immediately after a treatment. Accordingly, it is recommended that CES be done at least 3 hours before going to bed. Also, in most cases after daily treatments for the first week or two, treating every other day is usually more effective than every day.

Results
Immediately after a CES treatment, patients usually report feeling relaxed and sometimes inebriated for the first few minutes. This is a pleasant and very comfortable sensation. After several minutes to hours, the light-headed feelings usually disappear, the relaxed state remains and a profound sense of alertness is achieved. This relaxed/alert state will usually remain for an average of 12 to 72 hours after the first few treatments. With regular use, it is possible for a patient to habituate to this preferred state of consciousness. Some patients describe the experience as if they have a type A mind in a type B body.
Following CES, many patients relate feeling better, less distressed, and more focused on mental tasks. They generally sleep better and report improved concentration, increased learning abilities, enhanced recall, and heightened states of well-being.
These general feelings were first described by psychologists during the 1970's as an alpha state of consciousness. Such states are also produced by meditation, biofeedback training, relaxation instructions, chanting, hypnotherapy, and certain religious rituals. This is not the same as the alpha brain wave frequency of 8 to 13 Hz. Often, practitioners are confused by device representatives who claim that their particular device will output and entrain a brain to the alpha frequency. There is no evidence to support that CES devices work on an entrainment principle.

Contraindications
As mentioned earlier, there have been no significant harmful side effects reported in any of the research literature since CES was begun in the 1950's. As with all electrical devices, caution is advised during pregnancy, and with patients using a demand-type pacemaker. In addition, we recommend that patients not operate complex machinery or drive automobiles during and shortly after a CES treatment.

CES Summary
CES is an electrical transcranial therapy that employs devices which do not exceed 1.5 milliamperes, and usually work in the microampere current range. Beneficial effects have been reported for a wide variety of pain, distress, and addiction disorders.
Pain is a central nervous system event. To achieve optimal results through electromedical intervention, the brain should also be treated. Cranial electrotherapy stimulation induces a relaxed, alert state. It is a primary modality effective for controlling anxiety, depression, insomnia and generalized stress ubiquitous in pain patients. In addition, there is mounting evidence that CES can enhance various cognitive functions. Because of its safety and effectiveness, CES is highly recommended for a broad range of pain related disorders.