A Summary Look at CES Studies of Depression

By Ray B. Smith, Ph.D.

Click here to view the PDF version of this article.

Executive Summary

Eighteen studies were analyzed, in which a total of 853 patients were treated with cranial electrotherapy stimulation (CES) for depression. The patients had presented with various clinical syndromes, of which depression played a major part. The treatment outcome depression scores were combined statistically in order to get a more confident look at the effectiveness of CES for treating this condition. While many of the studies were of the classic double blind protocol, others used either the single blind, the cross over design or were open clinical trials. The result of the analysis showed that the overall effectiveness of CES was 47% improvement. The results indicated that various types of depression, which accompany a wide range of clinical syndromes can be expected to respond, sometimes dramatically to CES treatment.

Introduction

Meta-analysis is a way of combining the results of many separate studies to see the effectiveness of a treatment when different types of patients are studied, under different study conditions, with different study protocols, and who came to the various studies with differing symptoms accompanying their depression problem.

The goal of clinical studies is always to first test the effectiveness of a potential treatment and secondly to discover which patients the treatment may be most effective in treating. Meta-analysis has the effect of allowing us to essentially study a larger number of patients than can usually be assembled for a single study, and the larger the combined study sample, the greater is the confidence that can be placed in the study outcome: that the study findings are true and accurate. Also, the more diverse the study group is in the combined sample, the more confident one can be in generalizing the study outcome to larger groups of patients outside the study. That is, it increases the range of potential types of depression patients that we can predict will be effectively treated with CES.

In the table below is a summary of 18 studies that were combined into the meta-analysis reported on here.

CES Depression Studies Completed Over the Past 36 Years


Study Design

Zr Scorea

Presenting
Group

No. Subjects

Measure Usedb

Reference

Double Blind

1.099

Substance Abuse

29

Clinical Rating Scale

1

Double Blind

.283

Substance Abuse

20

Self Rating Scale

2

Double Blind

.255

Psychiatric Inpatients

11

Clinical Rating Scale

3

Double Blind

.310

Closed Head Injured

21

Self Rating Scale

4

Double Blind

.321

Fibromyalgia

60

Self Rating Scale

5

Double Blind

.511

Psychiatric Outpatients

18

Clinician’s Rating

6

Double Blind

.900

Insomnia, Anxiety

17

Clinician’s Rating

7

Totals

3.679

 

176

 

 

Average

.526

 

 

 

 

Effect Sizec

r = .48

 

 

 

 

Single Blind

.486

Psychiatric Outpatients

22

Clinical Rating Scales

8

Single Blind

.881

Substance Abuse

72

Self Rating Scale

9

Totals

1.367

 

94

 

 

Average

.684

 

 

 

 

Effect Size

r =.60

 

 

 

 

Crossover

.219

Psychiatric Inpatients

23

Clinician’s Rating

10

Crossover

.929

Insomnia, Depression

28

Self Rating Scale

11

Totals

1.148

 

51

 

 

Average

.574

 

 

 

 

Effect Size

r =.52

 

 

 

 

Open Clinical

.354

Graduate Students

54

Self Rating Scale

12

Open Clinical

.365

Fibromyalgia

20

Self Rating Scale

13

Open Clinical

.266

Fibromyalgia

60

Self Rating Scale

14

Open Clinical

.662

Pain, Depression

318

Self Rating

15

Open Clinical

.350

Psychiatric Outpatients

9

Clinical Rating Scale

16

Open Clinical

.549

Chronic Pain, Depression

48

Serum Analysis

17

Open Clinical

.332

ADHD

23

Self Rating Scale

18

Totals

2.878

 

532

 

 

Average

.411

 

 

 

 

Effect Size

r =.39

 

 

 

 

SUMMARY, ALL DEPRESSION STUDIES REPORTED ABOVE

Grand Total

9.072

 

853

 

 

Average

.504

 

 

 

 

Total Effect Size

r =.47

 

 

 

 

a r correlation scores, representing percent improvement, are obtained mathematically from the study outcomes presented by the authors. Scores such as percent change scores, the statistical probability scores reported, Fscores, t scores, and the like, are changed to r correlation scores and then into Zr scores. That is because percent improvement scores can not legally be averaged. The Zr scores are then averaged and converted back to percent improvement (effect size.)

b Most of the rating scales, both by the patients and the clinicians were of published reliability and validity. In many of the studies, more than one measure of depression was used. In those cases, the average of the results was calculated and reported as the overall result of the study.

c Effect size, here, is a statistician’s basic estimate of the overall percentage improvement by the patients as a result of the treatment.

Discussion

In many of the studies, depression was but one symptom within a larger presenting syndrome. For example in many of the patients, fibromyalgia was the presenting symptom, while in another large group of studies substance abuse (drug abstinence syndrome) was the presenting diagnosis. The presenting syndrome or type of patient is given in column three of the table. In all of the studies, however, depression was a major diagnosis within the presenting syndrome or group.

A word about the study types. In the open clinical study, the patients know they are being actively treated for their depression, the clinicians know who is being treated, and the statistician who summarizes the study data also knows, since there is only one group of patients.

In the single blind study, the patients do not know which are getting treated and which are getting sham treatment, but the clinician providing the treatment knows which are the treated patients. In the single blind study, the clinician doing the post study evaluation of the patients is often blinded to treatment conditions when he completes his evaluation. The statistician is usually blinded also, so that he is given two sets of scores to compare, and doesn’t know which group received the treatment. This study design was used earlier on before treatment blinding devices came on stream. In such studies, the treatment was administered sub sensation threshold, in which the clinician turned up the current intensity until the patient just felt it, then turned it back down until the patient said he could no longer feel the stimulation. At that point, the clinician either left the current at that level or turned the unit off (down to, but not including the final click). Because both the patients and the statistician are both blind to the study conditions, some authors have unwittingly published this design as a double blind experiment. But that term is generally reserved for the true double blind experimental design as described next.

The double blind study, the gold standard of science, is usually confined to studies in which neither the patient nor the clinician knows who is being studied. Those designs became available when a double blinding box could be inserted between the patient and the CES device. The double blinding box often had three, four or more settings in addition to a “0” setting in which current flowed freely between the CES unit and the patient. Among the other settings available, some passed current to the patient and some blocked it entirely. The clinician would begin the double blind treatment session by setting all double blinding boxes to the “0” position, would connect the patient to the CES electrodes, turn the current up slowly until the patient signaled he could just feel it, then reduce the stimulus level until the patient signaled that he could no longer feel it. At that point, the clinician set the double blinding box to one of the other settings available and left the patient on the device for 30 minutes to an hour, not knowing who was getting active treatment..

Interestingly, in a good double blind experimental design, such as was the case in the majority of those reported in the table, the persons who were responsible for measuring or rating patient improvement were also blind as to whom was treated, as was the statistician who was given anonymous groups of data to analyze. Note that, in effect, that makes such studies quadruple blind, but that term is not used in science.

In the crossover design, half the patients get treated the first week or two of the study, while the other half receive sham treatment. In the second half of the study, the formerly treated patients now receive sham treatment while the formerly sham treated patients now receive treatment. If the crossover does not involve a sham treatment condition, then the crossover study is treated as an open clinical trial where all patients and staff know who is being treated at each cross of the study. That design is often referred to as a study with “wait in line” controls, in that the patients waiting to begin treatment are tested before and at the end of the waiting period before going into treatment. That is thought to control for environmental factors such as unusual stressors on the 10 O’clock news, any local dramatic weather changes, and so forth.

Interestingly we learned early on in CES work to stay clear of the cross over design in CES studies, after we discovered that the improvement begun by a week or so of CES treatment often continued after the end of treatment. That is, the patients continue to get better as time goes on following treatment. One can imagine what that does to the statistical analysis when at the end of the study, both groups have improved significantly, but the patients treated first are no longer behaving as good controls should, but are getting even better than the final treatment group is showing. Many otherwise good studies were lost early on due to that effect. The two crossover studies reported in the table above obviously avoided this difficulty, perhaps due to shorter term treatment before the crossover.

Safety

It is interesting to note that not one problem from negative side effects has ever been reported in any published CES depression study. None of the patients has threatened or attempted suicide during or following treatment. None has complained of grogginess the next day. None has complained of headaches or a foggy feeling at the end of the treatment period. When asked, CES patients have reported instead feeling more rested, more alert, and less tired following treatment.

One interesting clinical detail we learned early on is that patients who have not been sleeping well when they enter a study sometimes make up for lost REM sleep during CES treatment and have the most vivid, most colorful dreams they have ever had. We learned to warn study participants of this in advance, since some earlier patients associated this with incipient schizophrenia or some other serious mental condition. Once alerted to the possibility they have always looked forward to the effect with real anticipation.

References

1.         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. Ph.D. Dissertation, The University of Tulsa.

2.         Krupitsky, E.M., A.M. Burakov, G.F. Karandashova, J. Katsnelson, V.P. Lebedev, A.J. Grinenko, and J.S. Borodkin (1991). The administration of transcranial electric treatment for affective disturbances therapy in alcoholic patients. Drug and Alcohol Dependence. 27:1- 6.        

3.         Levitt, E.A., N.M. James, and P. Flavell (1975) A clinical trial of electrosleep therapy with a psychiatric inpatient sample. Australian and New Zealand Journal of Psychiatry. 9(4):287- 290.

4.         Smith, R.B., A. Tiberi, and J. Marshall (1994). The use of cranial electrotherapy stimulation in the treatment of closed-head-injured patients. Brain Injury. 8(4):357-361.

5.         Lichtbroun, A.S., M.C. Raicer, and R.B. Smith (2001) The treatment of fibromyalgia with cranial electrotherapy stimulation. Journal of Clinical Rheumatology. 7(2):72-78.

6.         Rosenthal, S.H. (1972) Electrosleep: A double-blind clinical study. Biological Psychiatry. 4(2):179-185.

7.         Moore, J.A., C.S. Mellor, K.F. Standage, and H.A. Strong (1975) A double-blind study of electrosleep for anxiety and insomnia. Biological Psychiatry. 10(1):59-63.

8.         Rosenthal, S.H., and N.L. Wulfson (1970) Electrosleep: A clinical trial. American Journal of Psychiatry127(4):175-176.

9.         Smith, R.B.  and  L.  O’Neill  (1975)  Electrosleep  in  the  management  of  alcoholism. Biological Psychiatry.10(6):675-680.

10.      Feighner, J.P., S.L. Brown, and J.E. Olivier (1973) Electrosleep therapy: A controlled double-blind study.Journal of Nervous and Mental Disease. 157(2):121-128.

11.      Hearst. E.D., C.R. Cloninger, E.L. Crews, and R.J. Cadoret (1974) Electrosleep therapy: a double-blind trial.Archives of General Psychiatry. 30(4):463-466.

12.      Matteson, M.T., and J.M. Ivancevich (1986) An exploratory investigation of CES as an employee stress management technique. Journal of Health and Human Resource Administration. 9:93-109.

13.      Tyers. S., and R.B. Smith (2001) A comparison of cranial electrotherapy stimulation alone or with chiropractic therapies in the treatment of fibromyalgia. The American Chiropractor. 23(2):39-41.

14.      Tyers, S. and R.B. Smith (2001) Treatment of fibromyalgia with cranial electrotherapy stimulation. The Original Internist 8(3):15-17.

15.      Smith, R.B. (2001) Is microcurrent stimulation effective in pain management? An additional perspective.American Journal of Pain Management. 11(2):62-66.

16.      Rosenthal, S.H., and N.L. Wulfson (1970) Electrosleep: A clinical trial. American Journal of Psychiatry127(4):175-176.

17.      Shealy, C.N., R.K. Cady, R.G. Wilkie, R. Cox, S. Liss, and W. Clossen (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.

18.      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.

Click here to return to the main Research page.