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1
The Management of Anxiety, Insomnia and Depression with
Cranial Electrotherapy Stimulation (CES): Theory and Practice
Jeff Marksberry, MD, FAIS Science and Education Director
The application of low level current of <1 milliampere applied across the head for treatment of
anxiety (including PTSD), depression and insomnia with additional applications such as ADHD being studied.
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 One Hour
83%
78%
67%
70%
84%
81%
68%
56%
85%
90%
80%
84%
0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%
Alpha-‐S4m (N=311)
Alpha-‐S4m (N=89)
Wellbutrin (N=1168)
ZoloD (N=2028)
Alpha-‐S4m (N=163)
Alpha-‐S4m (N=98)
Sonata (N=62)
Lunesta (N=462)
Alpha-‐S4m (N=358)
Alpha-‐S4m (N=114)
A4van (N=838)
Xanax (N=2238)
2011 Military Service Member and Civilian Postmarke4ng Surveys: Alpha-‐S4m® CES Compared to WebMD Drug Surveys
Alpha-‐S(m Data from October 2011 Military Service Member Survey Analysis (N=152) and Alpha-‐S(m Pa(ent Survey (N=1,745) October 2011 Conducted by Larry Price PhD, Associate Dean of Research and Professor of Psychometrics and Sta(s(cs, Texas State University.
Pharmaceu(cal Survey Data from: www.WebMD.com/drugs. Accessed on October 28th, 2011.
Service Member Civilian
Anxiety
Depression
Insomnia
Percent of Pa4ents Repor4ng Improvement
2
Traditional View of Synaptic Activity
But only 2% of neuronal communication occurs at the chemical synapse.
Pert, Candace. Molecules of Emotion: Why You Feel The Way You Feel. Scribner, New York, 1997.
Models of Receptor Activation 21st
Century
The New Proposed
Theory: Physical/ Atomic
Electromagnetic Communication
19th & 20th Century
The Current Theory:
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
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 (like tuning in a radio).
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.
Alpha-Stim® Waveform On Oscilloscope It is the waveform that differentiates
devices.
Through periodic, but slow, reversal of the polarization of the DC current,
the Alpha-Stim waveform is able
to inject a spectrum of low frequencies into
the neuronal tissue to match
frequencies with different receptors,
thus activating them in a way
similar to chemical ligands.
3
Saul H. Rosenthal, MD, Psychiatrist and CES Researcher
Studied Medical Students at UT Austin Who Reported:
Relaxed
Alert
Tranquil
Not Worrying
Bright and Happy
Increased Energy
Improved Sleep
No Confusion, Memory Loss or Disorientation
Feelings Experienced During CES Treatment Stages
Dosage equals time inversely proportional to current level (i.e., less current requires longer treatment time per session)
SLEEPY
AWAKE
TIME
ALERT
20 minutes to 1 or more hours
HEAVY, GROGGY, EUPHORIC (never stop here)
No “brainfog”, vision is clear, and energetic as if the patient slept all night
LIGHT FEELING Some patients feel light rig
ht away
Putative Mechanism 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, James. Illustrating how CES works. Insert in Kirsch, Daniel L. Cranial electro-therapy
stimulation for the treatment of anxiety, depression, insomnia and other conditions. Natural Medicine,
23:118-120, 2006.
4
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, Texas
MNI x= 48 MNI x= 4
Regional deactivation associated with 0.5 Hz (blue) and 100 Hz (yellow)
Regions positively associated with current intensity for 0.5 Hz
Effects of Cranial Electrotherapy Stimulation on fMRI Brain Activity in the Resting State
Feusner , Jamie D., Madsen , Sarah, Moody, Teena D., Bohon , Cara, Hembacher, Emily, Bookheimer , Susan Y. and Bystritsky, Alexander. Effects of cranial electrotherapy stimulation on resting state brain activity. Brain and Behavior. Pp 1-10, 2012.
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 & 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
Effects of CES on Cerebralspinal Fluid and Plasma Neurochemicals
5
Safety Considerations
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
Adverse Effects from CES
From 144 human studies encompassing 10,556 people where 8,792 received active CES:
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 may persist for hours or even days.
6
Topics of Scientific Research on CES
Number of Pivotal Scientific Studies on Indicated Uses:
42 Anxiety
27 Insomnia
26 Depression
Research is done independently
Double blinding capabilities
Follow up studies show a durable effect
State (Situa4onal) Anxiety
State anxiety can be effectively treated in a single CES treatment session.
Results will vary based on initial anxiety level, length of treatment, comorbidities and overall patient health.
This is demonstrated in medical and dental studies and in mechanistic studies of EEG and fMRI changes from a single CES treatment.
Trait (Chronic) Anxiety
May require up to 6 weeks of CES treatments to see significant reduc(on in trait anxiety levels.
Treatment outcome may also depend on comorbidi(es such as depression and insomnia.
7
Generalized Anxiety Disorder
• RCT with an N of 115 at Liberty University
• 83.7% of the ac(ve group reported at least 50% improvement
• P=0.001, Cohen’s d=0.93
• The mean decrease on the HAM-‐A in the ac(ve group (32.8%) was more than 3 (mes the mean decrease of the sham group.
Barclay, Timothy H and Barclay, Raymond D., A Clinical Trial of cranial electrotherapy s(mula(on for anxiety disorders. In Process. Conducted at Liberty and Stetson Universi(es and presented at the American
Psychological Associa(on 121st annual conven(on, Honolulu, July 31 – Aug. 4, 2013.
19.89
13.37
21.98
19.98
12
14
16
18
20
22
24
Baseline Week 5
Mean Anxiety Scores
Ac4ve Sham
Barclay, Timothy H and Barclay, Raymond D., A Clinical Trial of cranial electrotherapy s(mula(on for anxiety disorders. In Process. Conducted at Liberty and Stetson Universi(es and presented at the American
Psychological Associa(on 121st annual conven(on, Honolulu, July 31 – Aug. 4, 2013.
P=0.001
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
PSS-I (Range: 0-51)
34
13
Re-experiencing (0-15)
7
2
Avoidance (0-21)
15
7
Increased Arousal (0-15)
12
4
Bracciano, Alfred G., Chang, Wen-Pin, Kokesh, Stephanie, Martinez, Abe, Meier , Melissa & Moore, Kathleen. Cranial Electrotherapy Stimulation in the Treatment of Posttraumatic Stress Disorder: A Pilot Study of Two Military
Veterans. Journal of Neurotherapy, 16(1): 60-69, 2012.
8
PTSD Symptom Scale – Interview (PSS-I)
PRE
POST
PSS-I (Range: 0-51)
29
10
Re-experiencing (0-15)
9
2
Avoidance (0-21)
9
5
Increased Arousal (0-15)
11
3
PTSD in a 38 Year Old Male Veteran Overall Decrease in Severity by 43% in One Month
Bracciano, Alfred G., Chang, Wen-Pin, Kokesh, Stephanie, Martinez, Abe, Meier , Melissa & Moore, Kathleen. Cranial Electrotherapy Stimulation in the Treatment of Posttraumatic Stress Disorder: A Pilot Study of Two Military
Veterans. Journal of Neurotherapy, 16(1): 60-69, 2012.
Mean HARS Score
21.17
15.36
10.44
0
5
10
15
20
25
1 3 6
Time (weeks)
Bystritsky et al, Journal of Clinical Psychiatry, 2008
CES Significantly Reduced the Symptom Burden of GAD with a Decrease in HARS Score (P=.01) Similar to that
Found in Clinical Psychopharmacology Trials – APA 2009
Bystritsky, Alexander, Kerwin, Lauren and Feusner, Jamie. A pilot study of cranial electrotherapy stimulation for generalized anxiety disorder. Journal of Clinical Psychiatry, 69:412-417, 2008
Situational Anxiety in Dentistry Following Real or Sham CES Treatment
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.
Treatment Phase
Visu
al A
nalo
gue
Scal
e A
nxie
ty S
core
P<.02 P<.02 P<.04 NS
9
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.
0
200
400
600
800
1000
1200
1400
Aggressiveepisodes
Seclusions Restraints PRN Meds
Incidents
Pre CES
Post CES
3 Month Trial with 48 Severe Aggressive Patients
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.
Insomnia Insomnia pa(ents usually see results aber one treatment.
Or it may take up to 4 weeks of treatment, especially if insomnia is associated with depression.
Recent study completed at Walter Reed showed an average increase of +46 minutes of sleep aber only 5 treatments.
3 Week RCT of CES for Insomnia in Fibromyalgia Patients
Lichtbroun, A.S., Raicer, M.M.C. and Smith, R.B. The treatment of fibromyalgia with cranial electrotherapy stimulation. Journal of Clinical Rheumatology. 7(2):72-78, 2001.
Presented at the 15th Annual International Symposium on Acupuncture and Electro Therapeutics, Columbia University, New York, October 1999.
0
10
20
30
40
50
60
70
P r e S t ud y S ham R x S ub s ens a t io n C E S S ens a t e C E S
G ro up R ep o r t ing
S leep P attern o f S tudy G ro ups
Little or No Sleep
Moderate Sleep
Good, Very Restful Sleep
P< .02
10
8 Week CES Fibromyalgia RCT Study
Taylor, Ann G., Anderson, Joel G., Riedel, Shannon L., Lewis, Janet E., Kinser, Patricia A., and Bourguignon, Cheryl. In Press, Pain Management Nursing, 2013.
(P<.001) (P<.071)
Depression
Expect a minimum of 3 weeks of daily CES treatment before results are seen.
A pa(ent who suffers from anxiety with a depression component will take up to 3 weeks to improve as well.
FDA Public Health Advisory March 22, 2004
WORSENING DEPRESSION AND SUICIDALITY IN PATIENTS BEING TREATED WITH
ANTIDEPRESSANT MEDICATIONS
Today the Food and Drug Administration (FDA) asked manufacturers of the following antidepressant drugs to
include in their labeling a Warning statement that recommends close observation of adult and pediatric
patients treated with these agents for worsening depression or the emergence of suicidality. The drugs
that are the focus of this new Warning are: Prozac (fluoxetine); Zoloft (sertraline); Paxil (paroxetine);
Effexor (venlafaxine); Serzone (nefazodone); and Remeron (mirtazapine)
11
Example of Side Effect Profile for the Popular Antidepressant Zoloft (sertaline)
Results from a placebo controlled clinical trial (n=2799) As cited by www.drugs.com/sfx/sertraline-side-effects.htm
6% Appe4te
>2% Abdominal Pain
>2% Paresthesia
21% Insomnia
8% Respiratory
13% Drowsiness
12% Fa4gue
14% Dry Mouth 12%
Dizziness
20% Diarrhea
21% Sexual
Dysfunc4on
7% Swea4ng
6% Libido
8% Tremor
6% Cons4pa4on
>2% Back Pain
25% Headache
>2% Malaise
>2% Flatulence
5% Nervousness
3% Rash
4% Vomi4ng
5% Agita4on
4% Anxiety
>2% Pain
25% Nausea
Depression Study
• RCT with an N of 115 at Liberty University
• 82.2% of the ac(ve group reported at least 50% improvement
• P=0.001, Cohen’s d=0.75
• The mean decrease on the HAM-‐A in the ac(ve group (32.9%) was more than 12 (mes the mean decrease of the sham group.
Barclay, Timothy H and Barclay, Raymond D., A Clinical Trial of cranial electrotherapy s(mula(on for anxiety disorders. In Process. Conducted at Liberty and Stetson Universi(es and presented at the American
Psychological Associa(on 121st annual conven(on, Honolulu, July 31 – Aug. 4, 2013.
9.64
6.47
10.22 9.96
6
7
8
9
10
11
Baseline Week 5
Mean Depression Scores
Ac4ve Sham
Barclay, Timothy H and Barclay, Raymond D., A Clinical Trial of cranial electrotherapy s(mula(on for anxiety disorders. In Process. Conducted at Liberty and Stetson Universi(es and presented at the American
Psychological Associa(on 121st annual conven(on, Honolulu, July 31 – Aug. 4, 2013.
P=0.001
12
Effects of 2 and 3 Weeks of CES on Depression 4 Studies that used the POMS Depression/Dejection Scale
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
Post CES Pre CES 0
2 4 6 8
10 12 14 16 18
Group Means
P< .05
P< .001 P< .03
P< .05
CES Induced Changes in Beck Depression Inventory Over 7 Months in Alcoholic Patients
1
Pre-test Mid-test Post-test
0
2
4
6
8
10
12
14
16
May, Brad & May, Carole. Pilot project using the Alpha-Stim 100 for drug and alcohol abuse. August, 1993
Usually results are seen from the first treatment.
There is no risk of accommoda(on or addic(on.
13
What is the first thing you think of when your computer breaks?
What is the first thing you think of treating when you have pain?
Tan, Gabriel, Dao, Tam K., Smith, Donna L., Robinson, Andrew and Jensen, Mark P. Incorporating Complementary and Alternative Medicine (CAM) Therapies to Expand Psychological Services to Veterans Suffering From Chronic Pain. Psychological Services, 7(3):148–161, 2010.
14
Percent Improvement in 32 Veterans Across 158 Treatment Sessions
Tan, Gabriel, Dao, Tam K., Smith, Donna L., Robinson, Andrew and Jensen, Mark P. Incorporating Complementary and Alternative Medicine (CAM) Therapies to Expand Psychological Services to Veterans
Suffering From Chronic Pain. Psychological Services, 7(3):148–161, 2010.
0% 10%
20%
30%
40%
50%
60%
70%
80%
Pain Anxiety Depression Sleep Well-‐being
Holubec, Jerry T. Cumulative Response from Cranial Electrotherapy Stimulation (CES) for Chronic Pain. Practical Pain Management, 9(9):80-83, 2009.
42%
50%
54%
64%
71%
40%
45%
50%
55%
60%
65%
70%
75%
1 2 3 4 5 CES Treatment Sessions
Percen
t Red
uc4o
n in Pain Levels
Cumula4ve Improvement in Pain ADer 1-‐5 CES Treatments
Example of the CES Response Over Time in a Patient with Severe Migraine
Courtesy of COL Michael Singer, Walter Reed Army Medical Center
Stay with it!
0
2
4
6
8
10
0 60 120 180
Pain Level
minutes
15
Migraine Headaches -- Frequency and Intensity CES Doubles Effects of Biofeedback
Following 8 Treatments 2/week for 1 month After 1 Month
After 2 Months After 3 Months
0
200
400
600
800
1000
1200
Acc
umul
ated
Per
cent
Impr
ovem
ent
Time After Treatment Began
Biofeedback PLUS CES Biofeedback Alone
Brotman, Philip. Low-intensity transcranial electrostimulation improves the efficacy of thermal biofeedback and quieting reflex training in the treatment of classical migraine headache. American Journal of Electromedicine, 6(5):120-123, 1989.
Doctoral dissertation, City University Los Angeles, 117 pages, 1986.
8 Week CES Fibromyalgia RCT Study
Taylor, Ann G., Anderson, Joel G., Riedel, Shannon L., Lewis, Janet E., Kinser, Patricia A., and Bourguignon, Cheryl. In Press Pain Management Nursing, 2013
(P<.023) (P<.028)
fMRI RCT on CES Activity in Brain Pain Processing Regions in Fibromyalgia Patients
Subjects using an ac(ve CES device had a decrease in ac(va(on in the pain processing regions of the brain compared to those using a sham device.
Taylor, Ann G., Anderson, Joel G., Riedel, Shannon L., Lewis, Janet E. and Bourguignon, Cheryl. Explore, 9(1):32-49, 2013
Figures 1, 2, and 3: Daily Pain Rating for Active CES and Sham CES Groups Tan, Gabriel, Rintala, Diana H., Thornby, John, Yang, June, Wade, Walter, and Vasilev, Christine.
Using cranial electrotherapy stimulation to treat pain associated with spinal cord injury. Journal of Rehabilitation Research and Development, 43(4):461-474, 2006.
Tan, Gabriel, Rintala, Diana, Jensen, Mark P., Richards, J. Scott, Holmes, Sally Ann, Parachuri, Rama, Lashgari-Saegh, Shamsi and Price, Larry R. Efficacy of cranial electrotherapy stimulation for neuropathic pain following spinal cord injury: a
multi-site randomized controlled trial with a secondary 6-month open-label phase. The Journal of Spinal Cord Medicine, 34(3):285-296, 2011
5.514.87 4.77
5.134.25 4.04 3.58
0
2
4
6
8
10
Baseline After Active 3 weeks
At 3-‐Month Follow-‐up
At 6-‐Month Follow-‐up
BPI Average Pa
in In
tensity
Participants in 3-‐Month Follow-‐up (n = 39)Participants in 6-‐Month Follow-‐up (n = 24)
3 Year, 5-Site Spinal Cord Injury Study
P<.01
P<.001
The Use of CES to Potentiate Anesthesia in Surgery
Fentanyl P<.05 N2O 50%
P<.05 N2O 62.5% P<.05 N2O 75%
P<.05
0 10 20 30 40 50 60 70 80 90
100
Am
ount
of A
nest
hetic
Req
uire
d
Anesthetic Used
Anesthesia Plus CES Anesthesia Alone
2 Studies
CES May Improve Efficacy of Meds, and May Warrant Reduced Dose
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
17
♦ Tail Flick Latency (TFL) studies
TFL as % of baseline
Drug Alone
Drug Plus CES
Revealed a significant increase in analgesic effect of opiates. (Stinus, 1990).
morphine fentanyl alfentanil dextromoramide
174% 176% 160% 267%
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 opiate- induced analgesia is centrally mediated.
♦ There was as much as a threefold increase in β-endorphin
concentration after just one CES treatment (Krupisky, 1991).
Experimental Rat Studies of CES CES May Improve Efficacy of Meds, May Warrant Reduced Dose
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
64% 60% 60% 53% 42% 45%
+ 9% + 12%
+ 26%
+ 9% + 20%
+ 55%
0%
20%
40%
60%
80%
100%
Anxiety PTSD Insomnia Depression Pain Headache
Percen
t Improvem
ent
Comparison of Service Members That Used Alpha-Stim With Or Without Medications
Alpha-‐S4m with Medica4ons Alpha-‐S4m Only
Alpha-‐S(m Data from October 2011 Military Service Member Survey Analysis (N=152) and Alpha-‐S(m Pa(ent Survey (N=1,745) October 2011 Conducted by Larry Price PhD, Associate Dean of Research and Professor of Psychometrics and Sta(s(cs, Texas State University.
Summary
• CES is safe • CES is easy to use • CES is proven effective • CES works quickly and lasts • CES is FDA, CE and ISO certified • DoD/VA is using and researching CES • CES is available to help you NOW!
18
Are Your Patients in Pain? Anxious? Depressed? Not Sleeping well?
Why Not Try Alpha-Stim?
Questions? Call 1-800-FOR-PAIN Email Dr. Jeff Marksberry: [email protected]