Download Cranial Electrotherapy Stimulation

Cranial Electrotherapy Stimulation:
The New Science of Neuromodulation For
Mood Disorders, Post Traumatic Stress Disorder,
Terrorism Trauma Syndrome and Insomnia
Daniel L. Kirsch, PhD, DAAPM, FAIS
2008 Recipient of the Richard S. Weiner Pain Educator of the Year Award
Chairman, Electromedical Products International, Inc.
Former Clinical Director of the Center for Pain and Stress-Related Disorders
of Columbia-Presbyterian Medical Center at the College of Physicians and
Surgeons of Columbia University of the City of New York
Diplomate, American Academy of Pain Management
Fellow, American Institute of Stress
Certified in Homeland Security, Level III
Member, International Society for Neurotherapy and Research
Consulting Editor, Journal of Neurotherapy - Senior Editor PTSD
Electromedicine Dept. Editor, Practical Pain Management
Member, Inter-Pain (Society of German/Swiss Pain Specialists)
Member, Presidents Council, University of North Texas
Pain, Stress and PTSD Research and Practice Consultant
to the US Army and Veterans Affairs Medical Centers
© 2010 Dr. Daniel L. Kirsch, Mineral Wells, Texas, USA. Email: [email protected]
Disclosure
Daniel L. Kirsch, PhD, DAAPM, FAIS
Chairman, Electromedical Products International, Inc.
A 29 Year Old Multinational Medical Device Company
that Manufactures CES Devices
CES Devices are the Subject Matter of This Lecture
Abstract
Over the past decade the US Food and Drug Administration (FDA) has
issued black box warnings for antidepressant medications due to the now
established increase in suicidal ideation and other adverse effects.
Simultaneously, research has shown that antidepressants may not be
as effective as previously believed in people with mild depression. On top
of that America is a nation at war and there has been a surge in mood
disorders from the war effort both in our Service Members and civilian
populations. America is in turmoil over its political leaders and the
economic downturn. That, coupled with one of the highest unemployment
rates in USA history has resulted in the need for a safer and more effective
treatment for mood disorders and insomnia.
Cranial electrotherapy stimulation (CES) offers a viable solution for
these problems and is being used and studied by the US Army, US Air
Force, Veterans Affairs Medical Centers and by civilian physicians and
psychologists for a diverse number of conditions including on label claims
of anxiety, insomnia, depression, and off label claims of fibromyalgia and
other centrally mediated pain disorders, post traumatic stress disorder,
spinal cord injuries, mild traumatic brain injury and post concussion
syndrome, attentional disorders and substance abuse. Mechanistic studies
using fMRI have recently been completed at University of California at LA.
1
Objectives
This session will describe cranial electrotherapy stimulation (CES) as
a primary, FDA-cleared prescriptive anxiolytic and antidepressive
therapy, as well as a treatment for insomnia via treatment of the brain.
It will cover the 40+ year history of CES in the USA, indications,
contraindications, adverse effects and research (overview of over 144
human plus experimental animal studies and several meta-analyses)
of this safe and effective brain therapy using mild electrical current of
up to one half milliampere (500 microamperes).
1.
2.
3.
4.
The participant will gain an understanding of cranial
electrotherapy stimulation (CES) theory and 40+ years of
research for the commonly seen disorders of anxiety, insomnia
and depression in both civilian and military contexts;
To be able to use CES and prescribe CES immediately following
this lecture;
To be able to evaluate patient responses to CES;
To be able to manage patients on CES long term, including
adverse effects.
Pre Test Questions
1. Which is true regarding scientific studies of CES:
a) You can double blind CES studies just as well as drugs
b) There are less than 50 published CES studies
c) Subjects need to feel CES stimulation for it to be effective
d) Researchers have found significant adverse side effects in CES studies
Pre Test Questions
2. Which of the following outcomes would not be expected from the use of CES:
a) The patient could feel more relaxed, with a greater feeling of well being
b) The patient could develop sudden onset tinnitus following CES treatment
c) The patient’s psychoactive medications could be reduced by one third to one
half following CES treatment
d) The patient could report having the most restful sleep that he/she has had in
years
2
Pre Test Questions
3. Which of the following has not been shown to respond to CES:
a) Anxiety
b) insomnia
c) depression
d) Acute Nephritis
We are still programmed for fight or
flight but we don’t do that anymore
– we just suffer the consequences
Traditional View of Synaptic Activity
But only 2% of neuronal communication occurs at the synapse.
Pert, Candace. Molecules of Emotion: Why You Feel The Way You Feel. Scribner, New York, 1997.
3
Electrical Synapses
Electrical synapses are formed
by the direct connection of
neurons via gap junctions
(GJs) which are specialized
cell-to-cell contacts consisting
of a collection of intercellular
channels.
The Neural Network
Synaptic transmission is
communication between
neurons accomplished by
the movement of
chemicals or electrical
signals across a synapse.
Information flows between
the blue neurons through
electrical synapses.
Information flows from
yellow neuron A, through
blue neuron B, to pink
neuron C via chemical
synapses.
Electrical and
chemical
synapses
differ
fundamentally
in their
transmission
mechanisms
(A) Electrical synapses are much faster but get weaker over distances.
At electrical synapses, gap junctions between pre- and postsynaptic membranes permit current to flow
passively through intercellular channels. This current flow initiates or inhibits generation of
postsynaptic action potentials.
(B) Chemical synapses are slower but exhibit gain (strengthening signal). At chemical synapses, there
is no intercellular continuity, and thus no direct flow of current from pre- to postsynaptic cell. Current
can only flow across the postsynaptic membrane in response to the secretion of neurotransmitters
which open or close postsynaptic ion channels after binding to receptor molecules.
Purves, Dale and Augustine, George J. et al. Neuroscience, 2nd Ed. Sinauer, Sunderland, MA , 2001.
4
Models of Receptor Activation
19th & 20th
Century
The New
21st
Century
Theory:
The Current
Theory:
Physical /
Atomic
Electromagnetic
Communication
Structural
Matching;
Chemical /
Molecular
Physical
Communication
The 3D nature of the ligand matches
the receptor. Physical proximity
induces receptor conformational
changes which triggers the cascade
of events prompting cell function
(similar to
tuning a radio)
Proximity favors co-resonance specific
bioelectrical signals with frequencies that
perfectly match the resonance of the
receptor to amplify molecular
conformational changes at all steps of the
cascade including cell function, even from
long distances
Benveniste, J. A fundamental basis for the effects of EMFs in biology and medicine: The interface between matter and function.
Chapter 13 in Bioelectromagnetic Medicine. Rosch, P and Markov, M, eds. Marcel Dekker, New York, 2004.
Proposed Mechanisms of CES
CES engages the serotonergic (5-HT)
raphe nuclei of the brainstem. 5-HT
inhibits brainstem cholinergic (ACh)
and noradrenergic (NE) systems that
project supratentorially. This
suppresses thalamo-cortical activity,
arousal, agitation, alters sensory
processing and induces EEG alpha
rhythm. 5-HT can also act directly to
modulate pain sensation in the dorsal
horn of the spinal cord, alter pain
perception, cognition and emotionality
within the limbic forebrain.
Legend:
Blue arrows: inhibitory interactions
Purple arrows: excitatory interactions
X: suppressed pathways/interactions
Ach actetylcholine
LDT laterodorsal tegmental nucleus
of the brainstem
PPN pediculo-ponitne nucleus of the
brainstem
NE
norepinephrine;
LC
locus ceruleus,
5-HT serotonin
Giordano, J. Illustrating how CES works. Insert
in Kirsch, Daniel L. Cranial electrotherapy
stimulation for the treatment of anxiety,
depression, insomnia and other conditions.
Natural Medicine, 23:118-120, 2006.
Effects of CES on Cerebralspinal
Fluid and Plasma Neurochemicals
Beta-endorphins
98% in plasma
219% in CSF
Serotonin
15 - 40% in plasma
50 - 200% in CSF
Shealy, C. Norman, Cady, Roger K., Culver-Veehoff, Diane, Cox, Richard and Liss, Saul.
Cerebralspinal fluid and plasma neurochemicals: response to cranial electrical stimulation.
Journal of Neurological and Orthopaedic Medicine and Surgery. 18(2):94-97, 1998
5
The Effects of Electrostimulation
on ATP Concentrations in Rat Skins
Electrical Current
ATP Concentration
in Microamperes
in Micromols/gram
Baseline
4.2 +/- 0.8
10
10.0 +/- 1.5
50
14.2 +/- 1.2
100
16.9 +/- 1.9
500 (P<.001)
20.1 +/- 2.2
1,000 (1 mA)
5,000 (5 mA – below normal)
15.0 +/- 1.8
3.9 +/- 0.6
Cheng, Ngok, The effects of electrical current on ATP generation, protein synthesis and membrane transport
in rat skin, Clinical Orthopedics and Related Research, 171:264-271, 1982.
14 Electroencephalogram (EEG) Studies
♦ Increase in alpha activity with a simultaneous decrease in
delta activity
♦ P300 amplitude ♦ positive shifts in alpha, beta, theta, and delta
spectra in patients who were abnormal
♦ more alert on EEG
♦ in FFT spectral smoothing
♦ 10x in RMS amplitude
♦ of 5-10 Hz during reaction time measurements
♦ in fast alpha and beta activity
♦ latency of alpha, beta, theta, and delta
♦ slower frequencies with quality and quantity of alpha
and amplitude in occipital-parietal leads
♦ normal restoration of sleep rhythm
♦ EEG confirmation of sleep induction
♦ alpha index which culminated in spindle and slow sleep
♦ in latency of sleep onset, in % of bed time awake,
in total sleep time in stage 4 and total delta sleep
References next slide
14 Electroencephalogram (EEG) Studies
Kennerly R. QEEG analysis of cranial electrotherapy: a pilot study. Journal of Neurotherapy. (8)2, 2004
Braverman E, et al.. Modification of P300 amplitude and other electrophysiological parameters of drug abuse
by cranial electrical stimulation. Current Therapeutic Research. 48(4):586-596, 1990
Empson JAC. Does electrosleep induce natural sleep? Electroencephalography and Clinical Neurophysiology.
35(6):663-664, 1973
Cox A and Heath RG. Neurotone therapy: A preliminary report of its effect on electrical activity of forebrain
structures. Diseases of the Nervous System. 36(5):245-247, 1975
Heffernan M. Comparative effects of microcurrent stimulation on EEG spectrum and correlation dimension.
Integrative Physiological and Behavioral Science. 31(3):202-209, 1996
Heffernan M. The effect of variable microcurrents on EEG spectrum and pain control. Canadian Journal of
Clinical Medicine. 4(10):4-11, 1997
Hozumi S, et al. Favorable effect of transcranial electrostimulation on behavior disorders in elderly patients with
dementia: a double-blind study. International Journal of Neuroscience. 88:1-10, 1996
Itil T, et al. Quantitative EEG analysis of electrosleep using frequency analyzer and digital computer methods.
Electroencephalography and Clinical Neurophysiology. 31:294, 1971
Krupitsky EM, et al. The administration of transcranial electric treatment for affective disturbances therapy in
alcoholic patients. Drug and Alcohol Dependence. 27:1-6, 1991
McKenzie R, et al. Some psycho-physiologic effects of electrical transcranial stimulation (electrosleep).
American Psychiatric Association, Scientific Proceedings Summary. 1971. Also in The Nervous System and
Electric Currents, Wulfsohn, N.L. & Sances, A. (Eds.) Plenum: New York, Pp. 163-167, 1976
Magora F, et al. Some aspects of electrical sleep and its therapeutic value. In Wageneder, F.M. and St. Schuy
(Eds). Electrotherapeutic Sleep and Electroanaesthesia. Excerpta Medica Foundation, International Congress
Series No. 136
Magora F, et al. Observations on electrically induced sleep in man. British Journal of Anesthesiology.
37:480-491, 1965
Schroeder MJ. Acquisition and quantitative analyses of EEG during CES and concurrent use of CES and
neurofeedback. Doctoral dissertation, The Graduate School of the University of Texas at Austin, Pp. 1 - 191,
1999
Singh B, et al. Sleep and consciousness mechanisms with special reference to electrosleep. Armed Forces
Medical Journal India (New Delhi). 27(3):292-297, 1971
Weiss MF. The treatment of insomnia through use of electrosleep: an EEG study. Journal of Nervous and
Mental Disease. 157(2):108-120, 1973
6
QEEG Changes in 30 Subjects Treated with 20 Minutes of CES
There is an increase in alpha activity with a simultaneous decrease in delta.
Blue = decrease Red = increase
Kennerly, Richard. QEEG analysis of cranial electrotherapy: a pilot study.
Journal of Neurotherapy, (8)2, 2004.
Presented at the International Society for Neuronal Regulation conference, September 18-21, 2003, Houston, TX
Relative p-value topographical EEG map for CES. Statistically significant changes
(P<.05 or better) after a single 0.5 Hz CES treatment are indicated by color;
white indicates no significant change. Arrows indicate direction of change.
Significant decreases were seen in delta & beta with significant increases in alpha.
.5 Hz CES
Kennerly, Richard C. Changes in quantitative EEG and low resolution tomography following cranial electrotherapy
stimulation. Ph.D. Dissertation, the University of North Texas. 529 pp., 81 tables, 233 figures, 171 references, 2006.
Low Resolution Tomography
Paired t-test for 8 Hz LORETA: Significant differences after 20 minutes of 0.5 Hz CES
Kennerly, Richard C. Changes in quantitative EEG and low resolution tomography following cranial electrotherapy stimulation.
Ph.D. Dissertation, the University of North Texas. 529 pp., 81 tables, 233 figures, 171 references, 2006.
7
Effects of Cranial Electrotherapy Stimulation
on fMRI Brain Activity in the Resting State
Regional deactivation associated with 0.5 Hz (blue) and 100 Hz (yellow)
MNI x= 4
MNI x= 48
Regions positively associated with current intensity for 0.5 Hz
Bystritsky A, Moody T, Hembacher E, Hoffman J, Moller H, Feusner J. Effects of cranial electrotherapy stimulation on brain
activity in the resting state. Presented at the American Society of Neuropsychopharmacology (ACNP), Hollywood, Florida,
December 8, 2009. From the Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry; Center for
Cognitive Neuroscience; Ahmanson-Lovelace Brain Mapping Center. University of California, Los Angeles.
Local maxima for significant between-groups activations
0.5 Hz. Deactivation:
Z score
Bilateral paracingulate cortex
Pre- and post-central gyrus
Bilateral precuneus
Middle frontal gyrus
Left frontal pole
3.34
3.30
3.13
2.86
2.85
100 Hz Deactivation:
x, y, z
6, 12, 50
40, -10, 52
-2, -74, -46
-30, 6, 54
-38, 52, 6
Z score
Postcentral gyrus
Precentral gyrus
Right superior parietal lobule
3.16
3.12
2.94
x, y, z
41, -34, 58
-22, -18, 70
12, -50, 70
Alexander Bystritsky et al 2009. From previous slide.
Research Methodology of
86 Pivotal (out of 126) Studies of CES
35 Double-Blind Placebo-Controlled RCT’s
9 Single-Blind
15 Controlled Study
6 Crossover
22 Open Clinical Trial
2 Retrospective Study
3 Case Study
13 Follow-up
8
How To Double-Blind
CES Devices for RCT Research
The current is locked in to a subsensory level of 100 µA by
oscilloscope.
The treatment time is locked at 1 hour to compensate for the
reduced current dose.
The frequency is locked to desired Hz.
Half the wires are non-conducting.
The controls are taped over so only the power-on button and
battery compartments are accessible.
Serial numbers are then randomized as per protocol
(researchers must record serial number for each subject).
Topics of Scientific Research on CES
Number of Pivotal Scientific Studies:
CES is FDA
cleared for
anxiety,
depression,
and insomnia
42 Anxiety + 1 Phobia
26 Depression
27 Insomnia
10 stress
Anxiety…
9
Two Meta-Analyses Reconfirmed
the Significance of CES Research
for Treating Anxiety:
♦ University of Tulsa
th
O’Connor, M.E. Presented at the 12 annual meeting
of the Bioelectromagnetics Society, 1991.
♦ Department of Health Policy and Management, Harvard
School of Public Health
Klawansky, S. et al, Journal of Nervous and Mental Disease 183(7):478485, 1995
Both Found CES
Significantly Effective
for Anxiety (P<.05)
Meta-Analysis of CES for Anxiety
40 Studies
r Effect Size = .58
17 Double Blind Studies
34 of 40 studies have P<.05
Effect sizes of r = .44 to r = .70 would be
expected to be found in the next 99 out of 100
meta-analyses (400 Studies) of CES for anxiety
R effect size = % improvement based on 100%
Scale: .10 is small, .30 is moderate, .50+ is considered high
Kirsch, Daniel L. and Gilula, Marshall. A review and meta-analysis of cranial electrotherapy stimulation
in the treatment of anxiety disorders – Part 1. Practical Pain Management, 7(2):40-47, 2007.
Kirsch, Daniel L. and Gilula, Marshall. Cranial electrotherapy stimulation in the treatment of anxiety disorders:
statistical considerations – Part 2. Practical Pain Management, 7(3):22-39, 2007.
Anxiety Scores Before and After CES
Based on 4 Studies Using Different Rating Scales
45
40
P< .001
35
30
Group
25
Means
20
P< .001
P< .05
P< .001
15
10
5
0
Pre
Profile of
Mood
States
Taylor
Manifest
Anxiety
State
Anxiety
Trait
Anxiety
Post
Smith R et al. Electrosleep in the management of alcoholism. Biological Psychiatry. 10(6):675-680, 1975.
Krupitsky EM et al. The administration of transcranial electric treatment for affective disturbances in alcoholic patients. Drug and
Alcohol Dependence. 27:1-6, 1991.
Matteson MT et al. An exploratory investigation of CES as an employee stress management technique.
Journal of Health and Human Resource Administration. 9:93-109, 1986.
Smith R. 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, 1999.
10
P<.05
4
3
2
1
0
-1
Stress Measure
Controls
Temperature
Temperature
CES Group
Pulse
Controls
Pulse
CES Group
Controls
Muscle Tension
-3
CES Group
-2
Muscle Tension
Number of Scale Points of Improvement
5
Change in Multiple Stress Measures
from a Single CES Treatment
Heffernan, Michael. The effect of a single cranial electrotherapy stimulation on multiple stress measures.
The Townsend Letter for Doctors. 147:60-64, 1995.
Presented at the Eighth International Montreux Congress on Stress, Montreux, Switzerland, February, 1996.
Situational Anxiety in Dentistry
Following One Real or Sham CES Treatment
Visual Analogue Scale Anxiety Score
60
50
40
30
CES Treated
Sham Treated
20
P<.02
P< .02
10
0
Pre
Post
Treatment Phase
Winick, Reid L. Cranial electrotherapy stimulation (CES): a safe and effective low cost
means of anxiety control in a dental practice. General Dentistry. 47(1):50-55, 1999.
Response of Anxious Impulse Control Parolees
70
Percent Improvement
60
CES Group
Sham Group
Placebo Controls
CES Group
Sham Group
Placebo Controls
CES Group
Sham Group
Placebo Controls
50
40
30
20
STAI
CES vs Sham and
Control P<.001
Sham vs Control
P<.3902
EMG
CES vs Sham and
Control P<.001
Sham vs Control
P<.6693
Temp
CES vs Sham
P<.0141
CES vs Control
P< .0011
Sham vs Control
P<.3109
10
0
-10
Anxiety Test
Electromyogram
Temperature
Stress Measure Used
Voris, Marshall, D. An investigation of the effectiveness of cranial electrotherapy stimulation in the treatment of
anxiety disorders among outpatient psychiatric patients, impulse control parolees and pedophiles.
Delos Mind/Body Institute, Dallas and Corpus Christi, TX, Pp. 1-19, 1995.
11
Hamilton Anxiety Scores
Changes from CES in Polysubstance Abusers
1 - 2 weeks of treatment
25
20
15
10
P<.05
5
Pre
0
Control
Post
Sham
CES
Bianco Jr., Faust. 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 Graduate School, Pp. 1-224, 1994.
CES Significantly Reduced the Symptom Burden of GAD
with a Decrease in HARS Score Similar to that Found in
Clinical Psychopharmacology Trials – APA 2009
Mean HARS Score
25
21.17
20
15.36
15
10.44
10
5
0
1
3
6
Time (weeks)
Bystritsky, Alexander, Kerwin, Lauren and Feusner, Jamie. A pilot study of cranial electrotherapy stimulation
Bystritsky
al, Journal
of Clinical
2008 Psychiatry, 69:412-417, 2008
for et
generalized
anxiety
disorder.Psychiatry,
Journal of Clinical
Improvement of Stress Measures in 182 Anxious Patients
Following 9, 25 Minute CES Treatments
80
Percent Improvement
70
60
P< .05
50
40
30
20
10
0
Temperature
Electrodermal
Anxiety Scale
Electromyogram
Stress Related Measure
Overcash, Stephen J. A retrospective study to determine the efficacy of cranial electrotherapy stimulation (CES) on
patients suffering from anxiety disorders. American Journal of Electromedicine. 16(1):49-51, 1999
12
Anxiety Scores Pre and Post CES and Sham CES
in Alcoholic Patients
20 treatments over 4 weeks
70
60
50
40
30
STAI
Reactive
P<.05
STAI
Personal
P<.05
20
10
Taylor
P<.01
0
Pre
Post
STAI
Reactive CES
STAI
Reactive
Sham
STAI
Personal
CES
STAI
Personal
Sham
Taylor CES
Taylor Sham
Krupitsky, E.M., Burakov, A.M., Karandashova, G.F., Katsnelson, J., Lebedev, V.P., Grinenko, A.J. & Borodkin, J.S. The
administration of transcranial electric treatment for affective disturbances therapy in alcoholic patients.
Drug and Alcohol Dependence. 27:1-6, 1991
Effect of CES on PTSD
in Burned Outpatients
US Army Institute of Surgical Research
COL Kathryn Gaylord
MAJ Elizabeth A. Mann
Alan Young, DO
Scott Dewey, PT, CHT, OCS
Larry Price, PhD
Completed
Outcomes of
Cranial Electrotherapy Stimulation
(CES) with Soldiers for
Combat-related Symptoms
Brooke Army Medical Center (BAMC)
LTC Mona O. Bingham
Alice Inman, PhD
Stacey Young-McCaughan, PhD
Completed
13
PTSD in a 54 Year Old Male Veteran
Overall Decrease in Severity by 39% in One Month
PTSD Symptom
Scale – Interview
(PSS-I)
PRE
POST
34
13
7
2
Avoidance
(0-21)
15
7
Increased Arousal
(0-15)
12
4
PSS-I
(Range: 0-51)
Re-experiencing
(0-15)
Bracciano, A. et al. Cranial Electrotherapy Stimulation in the Treatment of Posttraumatic Stress Disorder.
The American Journal of Occupational Therapy, In Press 2010.
PTSD in a 38 Year Old Male Veteran
Overall Decrease in Severity by 43% in One Month
PTSD Symptom
Scale – Interview
(PSS-I)
PSS-I
(Range: 0-51)
PRE
POST
29
10
Re-experiencing
(0-15)
9
2
Avoidance
(0-21)
9
5
Increased Arousal
(0-15)
11
3
Bracciano, A. et al. Cranial Electrotherapy Stimulation in the Treatment of Posttraumatic Stress Disorder.
The American Journal of Occupational Therapy, In Press 2010.
Mood Disorders in ADD with 18 Month Follow-up
35
Percent Improvement
30
25
P< .001
Depression
State Anxiety
Trait Anxiety
Verbal I.Q.
Performance I.Q.
Full Scale I.Q.
20
15
10
5
0
Mood and Cognitive Tests after 3 weeks and 18 months
Smith, R, Cranial electrotherapy stimulation in the treatment of stress related cognitive dysfunction,
with an 18 month follow up. Journal of Cognitive Rehabilitation. 17(6):14-18, 1999
14
3 Month Trial with 48 Severe Aggressive Patients
Incidents
1400
1200
Pre CES
1000
Post CES
800
600
400
200
0
Aggressive
episodes
Seclusions
Restraints
PRN Meds
41% reduction in episodes of violence (P<.001); 40% reduction in episodes requiring restraint (P<.001)
and seclusion (P<.05), and 42% fewer as-needed emergency medications (P<.01).
The decrease of 271 PRN med doses in 3 months saved >$12,000 for these med expenses alone.
Childs, Allen and Price, Larry. Cranial electrotherapy stimulation reduces aggression in violent neuropsychiatric patients.
Primary Psychiatry, 14(3):50-56, 2007; Presented at American Psychiatric Association annual meeting, 2007.
Depression…
15
Meta-Analysis of CES for Depression
20 Studies
r Effect Size = .50
9 Double Blind Studies
14 of 20 studies have P<.05
Effect sizes of r = .32 to r = .68 would be expected
to be found in the next 99 out of 100 meta-analyses
(200 Studies) of CES for depression
R effect size = % improvement based on 100%
Scale: .10 is small, .30 is moderate, .50+ is considered high
Kirsch, Daniel L. and Gilula, Marshall. Cranial electrotherapy stimulation in the treatment of depression – Part 1.
Practical Pain Management, 7(4):33-41, 2007.
Kirsch, Daniel L. and Gilula, Marshall. Cranial electrotherapy stimulation in the treatment of depression – Part 2.
Practical Pain Management, 7(5):32-40, 2007.
Effects of Antidepressant Treatments Above Placebo
Percent Improvement Over Placebo
70
60
50
40
30
20
10
0
Prozac
5 Studies
Paxil
12 Studies
Zoloft
3 Studies
Effexor
6 Studies
Serzone
8 Studies
CES
8 Studies
Treatment
Kirsch, I., Moore, T.J., Scorboria, A., and Nicholls, S.S. The emperor’s new drugs: An analysis of antidepressant
medication data submitted to the FDA. Prevention and Treatment, 5, 1-11, 2002.
Gilula, Marshall F., and Kirsch, Daniel L. Cranial electrotherapy stimulation review: a safer alternative to
psychopharmaceuticals in the treatment of depression. Journal of Neurotherapy, 9(2):7-26, 2005.
Effects of 1 and 2 Weeks of CES on Depression
80
60
Group
Means
2 Studies
that used
the Zung
Depression
Scale and 1
that used
the POMS
40
20
Pre
0
55% had
Marked
Improvement
Post
75% had
Marked
Improvement
P<.001
Rosenthal, Saul H. and Wulfsohn, Norman L. Electrosleep: A preliminary communication.
Journal of Nervous and Mental Disease. 151(2):146-151, 1970.
Rosenthal, Saul H. and Wulfsohn, Norman L. Studies of electrosleep with active and simulated treatment.
Current Therapeutic Research. 12(3):126-130, 1970.
Smith, Ray et al. Electrosleep in the management of alcoholism. Biological Psychiatry. 10(6):675-680, 1975
16
Effects of 2 and 3 Weeks of CES on Depression
4 Studies that used the POMS Depression/Dejection Scale
18
16
P< .03
P< .001
14
12
P< .05
Group
10
Means
8
6
4
2
0
Pre CES
Post CES
Matteson M et al. An exploratory investigation of CES as an employee stress management technique.
Journal of Health and Human Resource Administration. 9:93-109, 1986
Smith R et al. Electrosleep in the management of alcoholism. Biological Psychiatry. 10(6):675-680, 1975
Smith R et al. The use of cranial electrotherapy stimulation in the treatment of closed-head-injured patients.
Brain Injury, 8(4):357-361, 1994
Smith R et al. The use of transcranial electrical stimulation in the treatment of cocaine and/or polysubstance abuse, 2002
Hamilton Depression Scores
Changes in Polysubstance Abusers
1 - 2 weeks of treatment
25
20
15
10
P< .05
5
0
Pre
Controls
Post
Sham
CES
Bianco Jr., Faust. 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 Graduate School, Pp. 1-224, 1994
CES Induced Changes in Beck Depression
Inventory Over 7 Months in Alcoholic Patients
16
14
12
10
8
6
4
2
0
1
Pre-test
Mid-test
Post-test
May, Brad & May, Carole. Pilot project using the Alpha-Stim 100 for drug and alcohol abuse. August, 1993
17
Insomnia…
Meta-Analysis of CES for Insomnia
20 Studies
r Effect Size = .64
7 Double Blind Studies
15 of 20 studies have P<.05
Effect sizes of r = .41 to r = .87 would be expected
to be found in the next 99 out of 100 meta-analyses
(200 Studies) of CES for insomnia
R effect size = % improvement based on 100%
Scale: .10 is small, .30 is moderate, .50+ is considered high
Kirsch, Daniel L. and Gilula, Marshall F. CES in the treatment of insomnia: A review and meta-analysis.
Practical Pain Management, 7(8):30-43, 2007
CES for Insomnia With 2 Year Follow-up
90
CES Treatment
CES Follow-up
Sham Treated
Sham Follow-Up
80
Percent Improvement
70
60
CES P< .00077
Sham P< .367
50
40
30
20
10
0
-10
Seep Onset
Latency
% Bed Time
Awake
Stage One Sleep Delta, Stage IV Felt Very Rested
Sleep
in AM
Sleep Characteristic Measured
Weiss, Marc F. The treatment of insomnia through use of electrosleep: an EEG study.
Journal of Nervous and Mental Disease. 157(2):108-120, 1973
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3 Week RCT of CES for Insomnia
in Fibromyalgia Patients
Sleep Pattern of Study Groups
Little or No Sleep
Moderate Sleep
70
Good, Very Restf ul Sleep
Percent in Each Sleep
Category
60
P< .02
50
40
30
20
10
0
Pre Study
Sham Rx
Subsensation Sensate CES
CES
Group Reporting
Lichtbroun, A.S., Raicer, M.M.C. et al. The treatment of fibromyalgia with cranial electrotherapy stimulation.
Journal of Clinical Rheumatology. 7(2):72-78, 2001.
CES May Improve Efficacy of Meds,
and May Warrant Reduced Dose
The Use of CES to Potentiate Anesthesia in Surgery
Amount of Anesthetic Required
2 Studies
Anesthesia Plus CES
Anesthesia Alone
100
90
80
70
60
50
40
30
20
10
0
Fentanyl
P<.05
N2O 50%
P<.05
Anesthetic Used
N2O 62.5%
P<.05
N2O 75%
P<.05
Stanley, TH, Cazalaa, JA, et al. Transcutaneous cranial electrical stimulation decreases narcotic requirements during
neurolept anesthesia and operation in man. Anesthesia and Analgesia. 61(10):863-866, 1982
Stanley, TH, Cazalaa, JA, et al. Transcutaneous cranial electrical stimulation increases the potency of nitrous oxide
in humans. Anesthesiology. 57:293-297, 1982
CES May Improve Efficacy of Meds, May Warrant Reduced Dose
Experimental Rat Studies of CES
♦ There was as much as a threefold increase in β-endorphin
concentration after just one CES treatment (Krupisky, 1991).
♦ Tail Flick Latency
(TFL) studies
Revealed a significant
increase in analgesic
effect of opiates.
(Stinus, 1990).
TFL as % of baseline
morphine
fentanyl
alfentanil
dextromoramide
Drug
Alone
174%
176%
160%
267%
Drug Plus
CES
306%
336%
215%
392%
Results were also obtained after intracerebroventricular injection
of morphine (10 micrograms; analgesic effect increase from 152%
to 207% with CES) suggesting that CES potentiation of opiateinduced analgesia is centrally mediated.
Krupisky, EM, Katznelson, YaS, Lebedev, VP, et al. Transcranial electrostimulation (TES) of brain opioid structures (BOS):
experimental treatment of alcohol withdrawal syndrome (AWS) and clinical application.
Presented at the Society for Neuroscience Annual Meeting, New Orleans, November 10-15, 1991
Stinus, L, Auriacombe, M, et al. Transcranial electrical stimulation with high frequency intermittent current
(Limoge's) potentiates opiate-induced analgesia: blind studies. Pain. 42(3):351-363, 1990
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Comments on Follow-up from all
CES Research Studies
FROM PIVOTAL SCIENTIFIC STUDIES:
First Author
Year
N
Subject
Description
Authors’ Comments
on Follow-up
Brotman,
Philip
1986
36
classical
migraine pts
CES group responded significantly
better than the other 2 groups over the
3 month follow-up.
Brovar, A.
1984
25
cocaine
abusers
No CES patients had returned for
treatment, while 50% of the CES
refusers and 39% of the controls
recidivated in 6 to 8 months.
Flemenbaum,
A.
1974
28
anxiety,
depression,
insomnia
outpatients
unresponsive
to medication
Those who had beneficial results
maintained them throughout the
6 month follow-up.
Hearst, E.D.
1974
28
psychotherapy
outpatients
3 patients showed continued improvement for 2 weeks to 2 months.
Heffernan,
Michael
1995
20
generalized
stress pts
>1 year,
unresponsive
to medication
A: anxiety,
depression,
insomnia
hospitalized
polysubstance
B: abusers, and
9 B: asthmatic
children
unresponsive
to medication
32 CES
graduate
62
students,
22 controls
A:
20
Magora, F.
1967
Matteson,
Michael
1986
Moore, J.A.
1975
17
anxiety and
insomnia pts
1 week follow-up measures in the CES
group showed significant carryover
effects in EMG and HR
A: Follow-up has continued for
8-12 months after treatment and
has revealed no relapse.
B: The asthmatic attacks stopped
completely in 3 children and 4 months
later the children felt well without taking
any drugs.
A follow-up measure 2 weeks post
study found that 11 of the 13 variables
were still significantly improved in the
treatment group.
a remarkable improvement” in their
symptoms 2 - 3 weeks after CES.
197
anxiety
outpatients
On 6 - 8 month follow-up, 73% of the
patients were “well satisfied with their
treatment and had no significant
regression or other anxiety disorder.
186
hospitalized
alcohol and
polysubstance
abusers
78.5% were addiction-free (80.3% of
drug addicts) 1 to 8 years after CES,
with an average time in rehabilitation
of only 16 days.
Smith, Ray
1999
23
psychiatric
outpatients
with anxiety,
depression,
ADD
On 18 month follow-up the patients
performed as well or better than in the
original study.
Weiss, Marc
1973
10
insomnia
patients
All differences found were maintained
at the 2 week and 2 year follow-up.
Overcash,
Stephen
1999
Patterson, M.
1984
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Safety Considerations
Adverse Effects From CES
From 144 human studies encompassing 10,556 people
where 8,792 received active CES:
9 myogenic/cervicogenic headaches (0.10%, 1:977)
6 cases of skin irritation at electrode sites (0.07%, 1:1,465)
These are both mild and self-limiting
If the current is set too high headaches, vertigo or
nausea could develop and might endure for hours to
days in people with a history of vertigo
If the treatment is stopped too soon, a heavy feeling
accompanied by disorientation might persist for hours
or even days. Always continue treatment until at least 2
minutes after the patient feels “light”
CES may lower blood pressure in essential hypertension
Primary Contraindications
Interference with pre-1998 implants
(e.g., pacemakers and defibrillators)
– No longer applicable?
Pregnancy – possible
miscarriage and potential
unsubstantiated legal arguments
in case of developmental defects
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Embryofetal Effects of CES on Rats
844 fetal rats had 1 hour/daily CES throughout their pregnancy
at 10, 100, or 1,000 Hz, 1 volt, 125 µA via ear tag electrodes.
Autopsy revealed no congenital anomalies.
More pregnancy resorptions and fewer offspring in all groups, but only significant
in the 1,000 Hz group.
Average fetal weight and brain weight were inversely proportional to frequency.
Behavior resembled CES in humans, even in this aggressive species;
treated rats were not as active as the controls, so the decrease in fetal weights
may be due to lowered food intake.
Conclusion: CES may be embryolethal in the very early stages
of pregnancy and might cause some miscarriages,
but there is no evidence of fetotoxic effects.
Little, Bert and Patterson, Margaret A. Embryofetal effects of neuroelectric therapy. Electro and Magnetobiology. 15(1):1-8, 1996.
Cranial Electrotherapy
Stimulation (CES)
4-Step Procedure:
1. Wet Electrodes
2. Place on Ear Lobes
3. Turn on CES Device
4. Set to Comfortable Current
for 20 Minutes to 1 Hour
The application of low level current, (usually <1 mA)
applied across the head for medical or psychological conditions,
or just as an aid in relaxation
FDA cleared by Rx in the USA for anxiety, depression and insomnia
Approved for OTC sale worldwide outside of the USA
Feelings Experienced During CES
Treatment Stages
Dosage equals time inversely proportional to current level
(i.e., less current requires longer treatment time per session)
No “fibrofog”,
vision is clear,
and energetic as
if the patient
slept all night
ALERT
LIGHT FEELING
AWAKE
20 minutes to
1 or more hours
SLEEPY
HEAVY, GROGGY, EUPHORIC (never stop here)
TIME
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For Annotated Abstracts of All the CES Research
2nd Ed Out of Print
Now Available on CD Only
3rd Ed Coming in 2010
There are 146 Human
Studies as of April, 2010
Post Test Questions
1. If a patient reports feeling “heavy” during a CES treatment:
a) Stop the treatment immediately for that day
b) Continue until 2 minutes after the patient feels light
c) Continue for an additional 2 minutes after the heavy feeling then stop
d) Discontinue CES permanently because this patient is not a good candidate
for CES
Post Test Questions
2. CES treatments have been shown to:
a) Increase relaxation and increase alertness
b) Increased alpha brain waves and decreased delta brain waves on EEG
c) Reduce general anxiety disorder similar to clinical psychopharmacology
trials
d) All of the above
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Post Test Questions
3. Which of the following has not been shown to respond to CES:
a) Anxiety
b) Insomnia
c) Depression
d) Alzheimer's Disease
Are Your Patients Stressed? Anxious?
Depressed? Having Difficulty Sleeping?
Why Not Try CES?
Questions? email: [email protected]
www.drdaniellkirsch.com
Dr. Daniel L. Kirsch is a world renowned neurobiologist. He was board-certified by
the American Academy of Pain Management in 1990 and named a Fellow of the
American Institute of Stress in 1997. In 2008 he was awarded the Richard S.
Weiner Educator of the Year Award in Pain Management by AAPM. He is also a
Member of the American Board for Certification in Homeland Security, the
International Society for Neurotherapy and Research and Inter-Pain
(Switzerland/Germany). He is an Editor of the Journal of Neurotherapy and the
Electromedical Department Editor of the journal Practical Pain Management. He is
an expert research consultant at the Houston VAMC, Brooke Army Medical Center
and the US Army Institute for Surgical Research. He has presented at the San
Antonio Trauma Symposium, Force Health Protection, the American Veterinary
Medical Association, and many other civilian medical conferences including the
American Academy of Pain Management, American Academy of Orthopedic
Medicine, Inter-Pain, American Institute of Stress, International Society for
Neurotherapy and Research, American Association for Sensory Medicine, Nevada
Psychiatric Association Psychopharmacology Update, American Society for Pain
Management Nursing, American Academy of Anti-Aging Medicine. Southwest
Symposium, and he conducts Grand Rounds at military and civilian hospitals
worldwide. In May of 2008 he was in China working with the mental health teams for
the survivors of the great earthquake in Sichuan. He served as Clinical Director of
The Center for Pain and Stress Related Disorders at Columbia-Presbyterian
Medical Center, New York City, and of The Sports Medicine Group, Santa Monica,
California, and was the guest of the Minister of Health of Kuwait in 1992 where he
taught pain and stress management for physical and mental trauma from the
Persian Gulf War. Dr. Kirsch is the author of articles and books including The
Science Behind Cranial Electrotherapy Stimulation (2nd Ed., Medical Scope
Publishing, 2002) and Schmerzen lindern ohne Chemie CES, die Revolution in der
Schmerztherapie (Internationale Ärztegesellschaft für Energiemedizin, Austria 2000;
in German). In addition to his consulting and lecturing, Dr. Kirsch is Chairman of
Electromedical Products International, Inc. of Mineral Wells, Texas.
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