Cranial electrotherapy stimulation

Cranial Electrotherapy Stimulation (CES) is a psychiatric treatment that applies a small, pulsed electric current across a patient's head. Some researchers and doctors claim that CES has beneficial effects in conditions such as anxiety, depression, insomnia and stress. However, its effectiveness is still being studied., and is thus an experimental treatment.

History
"Electrotherapy" has been in use for at least 2000 years, as shown by the clinical literature of the early Roman physician, Scribonius Largus, who wrote in the Compositiones Medicae of 46 AD that his patients should stand on a live black torpedo fish for the relief of a variety of medical conditions, including gout and headaches. Claudius Galen (131 - 201 AD) also recommended using the shocks from the electrical fish for medical therapies.

Low intensity electrical stimulation is believed to have originated in the studies of galvanic currents in humans and animals as conducted by Giovanni Aldini, Alessandro Volta and others in the 18th century. Aldini had experimented with galvanic head current as early as 1794 (upon himself) and reported the successful treatment of patients suffering from melancholia using direct low-intensity currents in 1804.

Modern research into low intensity electrical stimulation of the brain was begun by Leduc and Rouxeau in France (1902). In 1949, the Soviet Union expanded research of CES to include the treatment of anxiety as well as sleeping disorders.

In the 1960s and 1970s, it was common for physicians and researchers to place electrodes on the eyes, thinking that any other electrode site would not be able to penetrate the cranium. It was later found that placing electrodes on the earlobes was far more convenient, and quite effective.

CES was initially studied for insomnia and called electrosleep therapy; it is also known as Cranial-Electro Stimulation  and Transcranial Electrotherapy.

In 1972, a specific form of CES was developed by Dr. Margaret Patterson,  providing small pulses of electric current across the head to ameliorate the effects of acute and chronic withdrawal from addictive substances. She named her treatment "NeuroElectric Therapy (NET)".

Effectiveness
In a 2012 review of cranial electrotherapy stimulation devices for the treatment depression, anxiety, and chronic pain, the FDA stated that: "Among studies that reported a clinical benefit of CES, few can be considered rigorous, high quality clinical studies." For example, only 12.8% (5 of 39) of the studies reported using the DSM criteria to diagnose depression, anxiety or insomnia. As a result, the FDA unanimously decided to maintain the Class III distinction for CES because "the data do not support a reasonable assurance of safety and effectiveness, the proposed special controls would be insufficient to provide such assurance, and there is an unreasonable risk of illness or injury."

In regard to depression, double-blinded studies of psychiatric patients have been inconclusive or negative. In one of these studies, four out of six clinically depressed patients dropped out of the study because of worsening of depressive symptoms, with two of them becoming suicidal again.

Soroush Zaghi et al. published an article in the journal The Neuroscientist, finding that CES increases the production of serotonin, GABA, and endorphins. These neurochemical changes explain any positive effects that might be experienced from CES.

A 1995 meta-analysis by Klawansky et al. published in Journal of Nervous & Mental Disease "showed CES to be significantly more effective than sham treatment (p < .05)", but noted that 86% of the studies included in the review were inadequately blinded and the experimenter "knew which patients were receiving CES or sham treatment." Most studies cited as evidence for the effectiveness of CES failed to report all data necessary for meta-analysis.

Computer modeling predictions using a highly detailed anatomical model show that CES induces significant currents in cortical, sub-cortical structures like thalamus,insula,and hypothalamus, and brain-stem structures.

A bibliography by Kirsch (2002) listed 126 scientific studies of CES involving human subjects and 29 animal studies. An estimated 145 human studies have been completed, encompassing over 8800 people receiving active CES.

A study published in Journal of Cognitive Rehabilitation found that 86% of the subjects tested showed improvements in their depression, 86% in state anxiety, and 90% in trait anxiety. An 18 month follow up found 18 of the original 23 subjects available to return for testing. Overall, they performed as well or better than in the original study.

A pilot study showed that CES reduced the symptom burden of generalized anxiety disorder, with a decrease in Hamilton Anxiety Rating Scale (HARS) across a 6 week study, but the study had a small sample of participants and no control group.

A systematic review which assessed 34 controlled trials involving a total of 767 CES patients and 867 control patients reported that in 77% of studies (26 of 34), CES was found to significantly reduce anxiety.

CES research has been conducted in pain management  and the reduction of anxiety in patients undergoing dental procedures.

A 3-week randomized controlled study which looked at insomnia in fibromyalgia patients found significant improvement in sleeping patterns. In a longitudinal insomnia study, subjects showed improvement of symptoms during a two-year follow-up (p<0.0008).

Several studies published in peer reviewed medical journals have found statistically significant results using CES in the treatment of depression,  and anxiety.

Regulation
In the United States, CES technology is classified by the Food and Drug Administration as Class III medical devices and must be dispensed by or on the order of a licensed healthcare practitioners, i.e. a physician, psychiatrist or nurse practitioner; psychologists, physician assistants, and occupational therapists who have an appropriate electrotherapy license may prescribe CES, dependent upon state regulations.

As a result of the 1976 Medical Device Amendments, manufacturers who prove both safety and efficacy may enter the market, with FDA clearance, utilizing the 510(k) process instead of the premarket approval process, at this time. There are currently three major manufacturers of cranial electrotherapy stimulation (CES) in the United States and one in Canada.

Proposed mechanism of action
The exact mechanism of action of CES remains unclear but it is proposed that CES reduces the stress that underpins many emotional disorders. The proposed mechanism of action for CES is that the pulses of electric current increase the ability of neural cells to produce serotonin, dopamine DHEA endorphins and other neurotransmitters stabilizing the neurohormonal system.

It has been proposed  that during CES, an electric current is focused upon the hypothalamic region; during this process, CES electrodes are placed on the ear at the mastoid, near to the face. Computer modeling suggest that current of similar magnitudes maybe induced in both cortical and sub-cortical regions. The prediction that CES induced current intensities in the sub-cortical structures are not sufficiently decreased from the cortical structures is potentially clinically meaningful.

It has been suggested that the current results in an increase of the brain's levels of serotonin, norepinephrine, and dopamine, and a decrease in its level of cortisol. After a CES treatment, users are in an "alert, yet relaxed" state, characterized by increased alpha and decreased delta brain waves as seen on EEG.