Cranial Electrotherapy Stimulation (CES) and Auricular Electrostimulation - CAM 80158

Description
Cranial electrotherapy stimulation (CES), also known as cranial electrical stimulation, transcranial electrical stimulation, or electrical stimulation therapy, delivers weak pulses of electrical current to the earlobes, mastoid processes, or scalp with devices such as the Alpha-Stim. Auricular electrostimulation involves stimulation of acupuncture points on the ear. Devices, including the P-Stim and E-pulse, provide ambulatory auricular electrical stimulation over a period of several days. CES is being evaluated for a variety of conditions, including pain, insomnia, depression, anxiety, and functional constipation. Auricular electrical stimulation is being evaluated for pain, weight loss, and opioid withdrawal.

Cranial Electrotherapy Stimulation
For individuals who have acute or chronic pain who receive CES, the evidence includes a number of small sham-controlled randomized trials, and pooled analyses. Relevant outcomes are symptoms, morbid events, functional outcomes, and treatment-related morbidity. Three trials studied headache and CES, and 5 trials studied chronic pain and CES. Pooled analyses found marginal benefits for a headache with CES and no benefits for chronic pain with CES. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have psychiatric, behavioral, or neurologic conditions (e.g., depression and anxiety, Parkinson's disease, addiction) who receive CES, the evidence includes a number of small sham-controlled randomized trials. Relevant outcomes are symptoms, morbid events, functional outcomes, and treatment-related morbidity. Three randomized controlled trials (RCTs) evaluated CES for depression and anxiety and reported inconsistent outcomes. Comparisons between these trials cannot be made due to the heterogeneity in study populations and treatment protocols. Studies evaluating CES for Parkinson's disease and smoking cessation do not support the use of CES for these conditions. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have functional constipation who receive CES, the evidence includes an RCT. Relevant outcomes are symptoms, morbid events, functional outcomes, and treatment-related morbidity. The single RCT reported positive results for the treatment of constipation with CES. However, the trial was unblinded, and most outcomes were self-reported. The evidence is insufficient to determine the effects of the technology on health outcomes.

Auricular Electrostimulation
For individuals who have acute or chronic pain (e.g., acute pain from surgical procedures, chronic back pain, chronic pain from osteoarthritis or rheumatoid arthritis) who receive auricular electrostimulation, the evidence includes a limited number of trials. Relevant outcomes are symptoms, morbid events, functional outcomes, and treatment-related morbidity. Studies evaluating the effect of electrostimulation technology on acute pain are inconsistent, and the small amount of evidence on chronic pain has methodologic limitations. For example, a comparison of auricular electrostimulation with manual acupuncture for chronic low back pain did not include a sham-control group, and, in a study of rheumatoid arthritis, auricular electrostimulation was compared with autogenic training and resulted in a small improvement in visual analog scale pain scores of unclear clinical significance. Overall, the few published studies have small sample sizes and methodologic limitations. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have obesity who receive auricular electrostimulation, the evidence includes small RCTs. Relevant outcomes are symptoms, morbid events, functional outcomes, and treatment-related morbidity. The RCTs reported inconsistent results and used different treatment protocols. The evidence is insufficient to determine the effects of the technology on health outcomes.

For individuals who have opioid withdrawal symptoms who receive auricular electrostimulation, the evidence includes 2 case series. Relevant outcomes are symptoms, morbid events, functional outcomes, and treatment-related morbidity. Both case series report positive outcomes for the use of CES to treat opioid withdrawal symptoms. The studies used different treatment protocols and no comparators, limiting conclusions drawn from the results. The evidence is insufficient to determine the effects of the technology on health outcomes.

Background
Cranial electrotherapy stimulation (CES), also known as cranial electrical stimulation, transcranial electrical stimulation, or electrical stimulation therapy, delivers weak pulses of electrical current to the earlobes, mastoid processes, or scalp with devices such as the Alpha-Stim. Auricular electrostimulation involves stimulation of acupuncture points on the ear. Devices, including the P-Stim and E-pulse, provide ambulatory auricular electrical stimulation over a period of several days. CES and auricular electrostimulation are being evaluated for a variety of conditions, including pain, insomnia, depression, anxiety, and weight loss.

Interest in CES began in the early 1900s on the theory that weak pulses of electrical current have a calming effect on the central nervous system. The technique was further developed in the U.S.S.R. and Eastern Europe in the 1950s as a treatment for anxiety and depression, and use of CES later spread to Western Europe and the United States as a treatment for various psychological and physiological conditions. Presently, the mechanism of action is thought to be the modulation of activity in brain networks by direct action in the hypothalamus, limbic system, and/or the reticular activating system. One device used in the Unites States is the Alpha-Stim CES, which provides pulsed, low-intensity current via clip electrodes that attach to the earlobes. Other devices place the electrodes on the eyelids, frontal scalp, mastoid processes, or behind the ears. Treatments may be administered once or twice daily for several days to several weeks.

Other devices provide electrical stimulation to auricular acupuncture sites over several days. One device, the P-Stim, is a single-use miniature electrical stimulator for auricular acupuncture points that is worn behind the ear with a self-adhesive electrode patch. A selection stylus that measures electrical resistance is used to identify 3 auricular acupuncture points. The P-Stim device connects to 3 inserted acupuncture needles with caps and wires. The device is preprogrammed to be on for 180 minutes, then off for 180 minutes. The maximum battery life of this single-use device is 96 hours.

Regulatory Status
A number of devices for CES have been cleared for marketing by the U.S. Food and Drug Administration (FDA) through the 510(k) process. In 1992, the Alpha-Stim® CES device (Electromedical Products International) received marketing clearance for the treatment of anxiety, insomnia, and depression. Devices cleared since 2000 are summarized in Table 1.

FDA product code: QJQ.

Table 1. Cranial Electrotherapy Stimulation Devices Cleared by the U.S. Food and Drug Administration

Device Name	Manufacturer	Date Cleared	510(k) No.	Indications
Cervella	Innovative Neurological Devices	03/07/2019	K182311	Insomnia, depression, anxiety
Cranial Electrical Nerve Stimulator	Johari Digital Healthcare	05/29/2009	K090052	Insomnia, depression, anxiety
Elexoma Medic™	Redplane AG	05/21/2008	K070412	Insomnia, depression, anxiety
CES Ultra™	Neuro-Fitness	04/05/2007	K062284	Insomnia, depression, anxiety
Net-2000 Microcurrent Stimulator	Auri-Stim Medical	10/13/2006	K060158	Insomnia, depression, anxiety
Transcranial Electrotherapy Stimulator-A, Model TESA-1	Kalaco Scientific	07/21/2003	K024377	Insomnia, depression, anxiety

Several devices for electroacupuncture designed to stimulate auricular acupuncture points have been cleared for marketing by the FDA through the 510(k) process. Devices cleared since 2000 are summarized in Table 2.

FDA product codes: BWK, PZR.

Table 2. Cranial Electrotherapy Stimulation Devices Cleared by the U.S. Food and Drug Administration

Device Name	Manufacturer	Date Cleared	510(k) No.	Indication
AXUS ES-5 Electro-Acupuncture Device	Lhasa OMS, INC.	02/03/2021	K200636	Practice of acupuncture by qualified practitioners of acupuncture as determined by the states
Drug Relief V1	DyAnsys Inc	11/05/2021	K211971	Reduce symptoms of opioid withdrawal
Sparrow Therapy System	Spark Biomedical, Inc.	01/02/2021	K201873	Reduce symptoms of opioid withdrawal
Drug Relief	DyAnsys Inc	05/02/2018	K173861	Reduce symptoms of opioid withdrawal
Ansistem-Pp	DyAnsys Inc	03/09/2017	K170391	Practice of acupuncture by qualified practitioners of acupuncture as determined by the states
NSS-2 Bridge	Innovative Health Solutions	2017	N/A^a	Substance use disorders
Stivax System	Biegler Gmbh	05/26/2016	K152571	Practice of acupuncture by qualified practitioners as determined by the states
ANSiStim^®	DyAnsys Inc	05/15/2015	K141168	Practice of acupuncture by qualified practitioners as determined by the states
Pantheon Electrostimulator	Pantheon Research	11/07/2014	K133980	Practice of acupuncture by qualified practitioners as determined by the states
Electro Auricular Device	Navigant Consulting, Inc.	10/02/2014	K140530	Practice of acupuncture by qualified practitioners as determined by the states
P-Stim	Biegler GMBH	06/27/2014	K140788	Practice of acupuncture by qualified practitioners as determined by the states
Jiajian Cmn Stimulator	Wuxi Jiajian Medical Instrument Co., Ltd.	08/16/2013	K130768	Practice of acupuncture by qualified practitioners as determined by the states
JiaJian Electro-Acupuncture Stimulators	Wuxi Jiajian Medical Instrument Co., Ltd.	04/11/2013	K122812	Practice of acupuncture by qualified practitioners as determined by the states
Multi-Purpose Health Device	UPC Medical Supplies, Inc. DBA United Pacific Co.	08/05/2010	K093322	Unknown - Summary not provided
Electro-Acupuncture: Aculife/Model ADOC-01	Inno-Health Technology, Inc.	04/02/2010	K091933	Practice of acupuncture by qualified practitioners as determined by the states
e-Pulse^®	Medevice Corporation	12/07/2009	K091875	Practice of acupuncture by qualified practitioners as determined by the states
Model ES-130	Ito Co., Ltd.	11/24/2008	K081943	Practice of acupuncture by qualified practitioners as determined by the states
P-Stim™	Neuroscience Therapy Corp.	03/30/2006	K050123	Practice of acupuncture by qualified practitioners as determined by the states
Aculife	Inno-Health Technology, Inc.	03/28/2006	K051197	Practice of acupuncture by qualified practitioners as determined by the states
AcuStim	S.H.P. Intl. Pty., Ltd.	06/12/2002	K014273	As an electroacupuncture device

a "FDA cleared the NSS-2 Bridge Device for Substance Use Disorders through the de novo premarket review pathway, a regulatory pathway for some low- to moderate-risk devices that are novel and for which there is no legally marketed predicate device to which the device can claim substantial equivalence"¹
N/A: Not applicable

Related Policies
10109 Transcutaneous Electrical Nerve Stimulation (TENS)

Policy
Cranial electrotherapy stimulation (also known as cranial electrostimulation therapy or CES) is investigational and/or unproven and therefore considered NOT MEDICALLY NECESSARY.

Electrical stimulation of auricular acupuncture points is investigational and/or unproven and therefore considered NOT MEDICALLY NECESSARY.

Policy Guidelines
Please see the Codes table for details..

Benefit Application
BlueCard/National Account Issues
State or federal mandates (e.g., FEP) may dictate that all devices approved by the U.S. Food and Drug Administration (FDA) may not be considered investigational. Therefore, FDA-approved devices may only be assessed on the basis of their medical necessity.

Rationale
This evidence review was created in September 2011 with searches of the PubMed database. The most recent literature update was performed through Dec. 10, 2021.

Evidence reviews assess the clinical evidence to determine whether the use of technology improves the net health outcome. Broadly defined, health outcomes are the length of life, quality of life, and ability to function including benefits and harms. Every clinical condition has specific outcomes that are important to patients and managing the course of that condition. Validated outcome measures are necessary to ascertain whether a condition improves or worsens; and whether the magnitude of that change is clinically significant. The net health outcome is a balance of benefits and harms.

To assess whether the evidence is sufficient to draw conclusions about the net health outcome of technology, 2 domains are examined: the relevance, and quality and credibility. To be relevant, studies must represent 1 or more intended clinical use of the technology in the intended population and compare an effective and appropriate alternative at a comparable intensity. For some conditions, the alternative will be supportive care or surveillance. The quality and credibility of the evidence depend on study design and conduct, minimizing bias and confounding that can generate incorrect findings. The randomized controlled trial (RCT) is preferred to assess efficacy; however, in some circumstances, nonrandomized studies may be adequate. Randomized controlled trials are rarely large enough or long enough to capture less common adverse events and long-term effects. Other types of studies can be used for these purposes and to assess generalizability to broader clinical populations and settings of clinical practice.

Cranial Electrotherapy Stimulation for Acute or Chronic Pain
Clinical Context and Therapy Purpose
The purpose of cranial electrotherapy stimulation (CES) is to provide a treatment option that is an alternative to or an improvement on existing therapies, such as medical management and other conservative therapies, in patients with acute or chronic pain.

The question addressed in this evidence review is: Does CES improve the net health outcome in patients with acute or chronic pain?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with acute or chronic pain.

Interventions
The therapy being considered is CES.

Comparators
Comparators of interest include medical management and other conservative therapies. Treatments include physical exercise, stress management, and analgesic and narcotic medication therapy.

Outcomes
The general outcomes of interest are symptoms, morbid events, functional outcomes, and treatment-related morbidity. While studies described below have varying lengths of follow-up, longer follow-up is necessary to fully observe outcomes.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess longer-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Headache
Klawansky et al. (1995) published a meta-analysis of 14 RCTs comparing CES with sham for the treatment of various psychological and physiological conditions.² The literature search, conducted through 1991, identified 2 trials evaluating CES for the treatment of headache. Pooled analysis of the 2 trials (N = 102 patients) favored CES over placebo (0.68; 95% confidence interval [CI], 0.09 to 1.28).

A Cochrane review by Bronfort et al. (2004) assessed noninvasive treatments for headaches; reviewers conducted a literature search through November 2002. They identified 1 poor quality, placebo-controlled, randomized trial (N = 100) of CES for a migraine or a tension-type headache.³ Results from the trial showed greater reductions in pain intensity in the CES group than in the placebo group (0.4; 95% CI, 0.0 to 0.8).

Chronic Pain
A Cochrane review by O’Connell et al. (2014) evaluated noninvasive brain stimulation techniques for chronic pain and conducted a literature search through July 2013.⁴ Reviewers identified 11 randomized trials of CES for chronic pain. A meta-analysis of 5 trials (N=270 participants) found no significant difference in pain scores between active and sham stimulation (-0.24; 95% CI, -0.48 to 0.01) for the treatment of chronic pain.

Subsequent to the Cochrane review by O’Connell et al. (2014),⁴ Ahn et al. (2020) published a double-blind, randomized, sham-controlled pilot study of the feasibility and efficacy of remotely supervised CES via secure videoconferencing in 30 older adults with chronic pain due to knee osteoarthritis.⁵ Mean age was 59.43 years. Cranial electrotherapy stimulation was delivered via the Alpha-Stim M Stimulator, which was preset at 0.1 mA at a frequency of 0.5 Hz, and applied for 1 hour daily on weekdays for 2 weeks. The sham electrodes were identical in appearance and placement, but the stimulator did not deliver electrical current. The study was conducted in a single center in Houston. All 30 participants completed the study and were included in the outcome analyses. For the primary outcome of clinical pain at 2 weeks as assessed by a Numeric Rating Scale, a significantly greater reduction occurred in the active CES group (-17.00 vs. +5.73; p < .01). No patients reported any adverse effects. Important relevancy limitations include lack of assessment of important health outcomes or long-term efficacy. An important conduct and design limitation is that it is unclear how convincing the sham procedure was as it did not involve any feature designed to simulate a tingling sensation and give the patient the feeling of being treated (i.e., subtherapeutic amplitude, initial current slowly turned to zero). Thus, findings may be subject to the placebo effect. This trial was also limited by the small number of participants. These limitations preclude drawing conclusions based on these findings.

Section Summary: Acute or Chronic Pain
Three trials were identified testing CES for the treatment of headache, with analyses marginally favoring CES over placebo. A meta-analysis of 5 trials comparing CES with sham for the treatment of chronic pain found no difference between the treatment and sham groups. A sham-controlled trial of remotely supervised CES via secure videoconferencing found a significant benefit with CES for pain reduction, but it had important relevance and design and conduct limitations. Additional evidence is needed to permit conclusions about whether CES improves outcomes for individuals with chronic pain.

Cranial Electrotherapy Stimulation for Psychiatric, Behavioral, or Neurologic Conditions
Clinical Context and Therapy Purpose
The purpose of CES is to provide a treatment option that is an alternative to or an improvement on existing therapies, such as standard therapy, in patients with psychiatric, behavioral, or neurologic conditions.

The question addressed in this evidence review is: Does CES improve the net health outcome in patients with psychiatric, behavioral, or neurological conditions?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with psychiatric, behavioral, or neurologic conditions.

Interventions
The therapy being considered is CES.

Comparators
Comparators of interest include standard therapy. Treatment includes psychiatric counseling.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess longer-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Anxiety and Depression
Systematic Reviews
An older meta-analysis by Klawansky et al. (1995) described in the Headache section above, analyzed 8 trials (N = 228 patients) comparing CES with sham for the treatment of anxiety.² While only 2 studies independently reported CES to be more effective than sham, the pooled estimate found CES to be significantly more effective than sham (-0.59; 95% CI, -0.95 to -0.23). More recently, Price et al. (2021) published a meta-analysis evaluating CES for the treatment of depression and/or anxiety and depression (Tables 3, 4, and 5).⁶ Five RCTs and 12 open-label, non-randomized studies that utilized Alpha-Stim were included. When considering pooled data from RCTs, results demonstrated that the mean depression level at post-test for the CES group was -0.69 standard deviations lower than the mean depression level for the sham stimulation group, which corresponds to a medium effect size. Pooled data from nonrandomized studies showed a smaller effect of -0.43 standard deviations in favor of CES.

Table 3. Comparison of Trials/Studies Included in SR and M-As

Study	Prince et al. (2021)⁶
Amr (2013)	⚫
Barclay and Barclay (2014)	⚫
Bystritsky (2008)	⚫
Chen (2007)	⚫
Gong (2016)	⚫
Kirsch (2019)	⚫
Libretto (2015)	⚫
Lu (2005)	⚫
Mellen and Mackey (2009)	⚫
Mellen and Mackey (2008)	⚫
Morriss and Price (2020)	⚫
Morrow (2019)	⚫
Platoni (2019)	⚫
Rickabaugh (2016)	⚫
Royal (2020)	⚫
Tillisch (2020)	⚫
Yennurajalingam (2018)	⚫

M-A: meta-analysis; NR: not reported; RCT: randomized controlled trial; SR: systematic review.

Table 4. SR & M-A Characteristics

Study	Dates	Trials	Participants	N (Range)	Duration
Price et al. (2021)⁶	NR	5 RCTs; 12 nonrandomized	Patients exhibiting symptoms of depression and/or anxiety and depression.	RCTs: 242; nonrandomized studies: 1173	RCTs: 3 to 8 weeks; nonrandomized studies: 2 to 24 weeks

M-A: meta-analysis; NR: not reported; RCT: randomized controlled trial; SR: systematic review.

Table 5. SR & M-A Results

Study	Effect size using RCT data	Effect size using nonrandomized study data
Price et al. (2021)^6,
Total N	242	1173
Effect	-0.69	-0.43
SE	0.14	0.03
I² (p)	0 (.85)	81.66 (NR)

M-A: meta-analysis; NR: not reported; RCT: randomized controlled trial; SE: standard error; SR: systematic review.

Randomized Controlled Trials
Kim et al. (2021) reported on a 3-week randomized, double-blind, sham-controlled trial evaluating the effectiveness of home-based CES (n = 25) versus sham treatment (n = 29) in nonclinical patients with daily anxiety.⁷ Novel, headphone-like in-ear electrodes were used in this study. Results demonstrated a significant reduction in anxiety scores using the State Anxiety Inventory (SAI) with CES versus sham stimulation treatment. Depression inventory scores did not significantly differ between groups. Limitations of this study included the use of a small sample of nonclinical patients, short follow-up, post-randomization withdrawals that did not contribute data to the analysis, and the unclear clinical significance of a decreased anxiety inventory score.

Barclay and Barclay (2014) reported on a randomized, double-blind, sham-controlled trial evaluating the effectiveness of 1 hour of daily CES for patients with anxiety (n = 115) and comorbid depression (n = 23) (Table 6).⁸ Analysis of covariance showed a significant advantage of active CES over sham for both anxiety (p = .001) and depression (p = .001) over 5 weeks of treatment (Table 7). The mean decrease in the Hamilton Rating Scale for Anxiety score was 32.8% for active CES and 9.1% for sham. The mean decrease in the Hamilton Rating Scale for Depression score was 32.9% for active CES and 2.6% for sham. However, because key health outcomes were not addressed and, as noted in a Veterans Affairs Evidence Synthesis Program review in 2018 by Shekelle et al.,⁹ due to the serious methodological limitations of this study (i.e., unclear sham credibility), the strength of this evidence is low.

In a smaller, double-blind, sham-controlled randomized trial (N = 30), Mischoulon et al. (2015) found no significant benefit of CES as adjunctive therapy in patients with treatment-resistant major depression (Tables 6 and 7).¹⁰ Both active and sham groups showed improvements in depression over the 3 weeks of the study, suggesting a strong placebo effect.

In 2015, a sham-controlled, double-blind randomized trial by Lyon et al. found no significant benefit of CES with the Alpha-Stim device for symptoms of depression, anxiety, pain, fatigue, and sleep disturbances in women receiving chemotherapy for breast cancer (Tables 6 and 7).¹¹ This phase 3 trial randomized 167 women with early-stage breast cancer to 1 hour of daily CES or to sham stimulation beginning within 48 hours of the first chemotherapy session and continuing until 2 weeks after chemotherapy ended (range, 6 to 32 weeks). Stimulation intensity was below the level of sensation. Active and sham devices were factory preset, and neither evaluators nor patients were aware of the treatment assignment. Outcomes were measured using validated questionnaires that assessed pain, anxiety, and depression, fatigue, and sleep disturbance. There were no significant differences between the active and sham CES groups during treatment. However, the trial might have been limited by low symptoms levels at baseline, resulting in a floor effect, and the low level of stimulation.

Table 6. Summary of RCT Characteristics Assessing CES for Anxiety and Depression

Study	Country	Sites	Dates	Participants	Interventions
					Active	Comparator
Barclay et al. (2014)⁸	U.S.	1	2012	Patients who met DSM-IV criteria for anxiety disorder as a primary diagnosis	Alpha-Stim self-administered for 1 hour/day for 5 wk (n = 60)	Sham Alpha-Stim self-administered for 1 hour/day for 5 wk (n = 55)
Mischoulon et al. (2015)¹⁰	U.S.	1	NR	Patients with major depressive disorder with inadequate response to standard antidepressants	FW-100 1 clinician-supervised and 4 self-administered 1 hour/day for 3 wk (n = 17)	Sham FW-100 1 clinician-supervised and 4 self-administered for 1 hour/day for 3 wk (n = 13)
Lyon et al. (2015)¹¹	U.S.	1	2009 – 2012	Women with newly diagnosed stages I-IIIA breast cancer scheduled for ≥4 cycles of chemotherapy	Alpha-Stim self-administered for 1 hour/day for 2 wk after chemotherapy cessation (n = 82)	Sham Alpha-Stim self-administered for 1 hour/day for 2 wk after chemotherapy cessation (n = 81)
Kim et al. (2021)⁷	Korea	1	NR	Nonclinical volunteers experiencing daily anxiety.	Home-based CES for 3 wk using novel, headphone-like in-ear electrodes delivering an alternating current at a frequency of 10 Hz and an intensity of 500 μA (N = 25)	Sham ear devices without flowing current for 3 wk (n = 29)

CES: cranial electrotherapy stimulation; DSM-IV: Diagnostic and Statistical Manual of Mental Health Disorders, 4th edition; FW-100: Fisher Wallace Cranial Stimulator; NR: not reported; RCT: randomized controlled trial.

Table 7. Summary of RCT Results Assessing CES for Anxiety and Depression

Study					Mean Hamilton Scale for Anxiety Score (SD)						Mean Hamilton Scale for Depression Score (SD)
					Baseline	Week 1		Week 3		Week 5^a	Baseline		Week 1		Week 3		Week 5^a
Barclay et al. (2014)⁸
CES (n = 57)					29.5	19.9		16.1		13.4	14.5		9.6		8.1		6.5
Sham (n = 51)					27.6	22.0		19.9		20.0	13.2		10.2		9.9		10.0
											Baseline		Week 1		Week 2		Week 3^a
Mischoulon et al. (2015)¹⁰
CES (n = 15)											18.1 (1.5)		15.8 (4.2)		14.6 (6.1)		14.8 (6.3)
Sham (n = 13)											18.7 (3.9)		14.5 (4.1)		15.3 (5.5)		13.6 (5.8)
					Mean Hospital Anxiety and Depression Scale Score (SD)
					Timepoint 1		Timepoint 2		Timepoint 3^b			Timepoint 1		Timepoint 2		Timepoint 3^b
Lyon et al. (2015)¹¹
CES (n = 82)					7.1 (4.1)		4.4 (3.2)		4.1 (3.5)			3.0 (2.5)		4.2 (3.2)		4.5 (3.4)
Sham (n = 81)					7.6 (4.1)		5.0 (3.7)		4.5 (4.0)			3.1 (2.8)		4.0 (3.1)		4.6 (3.7)
	Mean State Anxiety Inventory Score (SD)		Mean Beck Depression Inventory Score (SD)
	*Baseline*	*Week 3^c*	*Baseline*	*Week 3^b*
Kim et al. (2021)⁷
CES (n = 25)	39.1 (4.3)	36.3 (5.9)	16.0 (8.5)	9.9 (6.6)
Sham (n = 29)	38.4 (5.8)	38.9 (5.4)	17.8 (7.9)	9.6 (7.9)

CES: cranial electrotherapy stimulation; RCT: randomized controlled trial; SD: standard deviation.
a p=.001.
b p not significant.
c p=.039

Tables 8 and 9 summarize the important relevance and design and conduct limitations of the RCTs discussed above.

Table 8. Study Relevance Limitations

Study	Population^a	Intervention^b	Comparator^c	Outcomes^d	Follow-Up^e
Barclay et al. (2014)⁸	1. Intended use population unclear as the population targeted, those suffering from mental health issues, may be more likely to experience a placebo effect from the sham procedure despite blinding			1. Key health outcomes not addressed
Mischoulon et al. (2015)¹⁰
Lyon et al. (2015)¹¹				1. Key health outcomes not addressed because despite the validated questionnaires being used, these are subjective and are subject to bias
Kim et al. (2021)⁷	4. Study population not representative of intended use; international, nonclinical participants	4. Not the intervention of interest; novel device used		5. Clinical significant difference not prespecified	1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
a Population key: 1. Intended use population unclear; 2. Clinical context is unclear; 3. Study population is unclear; 4. Study population not representative of intended use.
b Intervention key: 1. Not clearly defined; 2. Version used unclear; 3. Delivery not similar intensity as comparator; 4. Not the intervention of interest.
c Comparator key: 1. Not clearly defined; 2. Not standard or optimal; 3. Delivery not similar intensity as intervention; 4. Not delivered effectively.
d Outcomes key: 1. Key health outcomes not addressed; 2. Physiologic measures, not validated surrogates; 3. No CONSORT reporting of harms; 4. Not establish and validated measurements; 5. Clinical significant difference not prespecified; 6. Clinical significant difference not supported.
e Follow-Up key: 1. Not sufficient duration for benefit; 2. Not sufficient duration for harms.

Table 9. Study Design and Conduct Limitations

Study	Allocation^a	Blinding^b	Selective Reporting^c	Follow-Up^d	Power^e	Statistical^f
Barclay et al. (2014)⁸
Mischoulon et al. (2015)¹⁰		1. Patients were not blinded to treatment assignment
Lyon et al. (2015)¹¹
Kim et al. (2021)⁷			2. Inadequate handling of missing data; post-randomization withdrawals were excluded from the data analysis		2. Power not calculated for primary outcome

The study limitations stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.
ITT: intention to treat
a Allocation key: 1. Participants not randomly allocated; 2. Allocation not concealed; 3. Allocation concealment unclear; 4. Inadequate control for selection bias.
b Blinding key: 1. Not blinded to treatment assignment; 2. Not blinded outcome assessment; 3. Outcome assessed by treating physician.
c Selective Reporting key: 1. Not registered; 2. Evidence of selective reporting; 3. Evidence of selective publication.
d Follow-Up key: 1. High loss to follow-up or missing data; 2. Inadequate handling of missing data; 3. High number of crossovers; 4. Inadequate handling of crossovers; 5. Inappropriate exclusions; 6. Not intent to treat analysis (per protocol for noninferiority trials).
e Power key: 1. Power calculations not reported; 2. Power not calculated for primary outcome; 3. Power not based on clinically important difference.
f Statistical key: 1. Intervention is not appropriate for outcome type: (a) continuous; (b) binary; (c) time to event; 2. Intervention is not appropriate for multiple observations per patient; 3. Confidence intervals and/or p values not reported; 4.Comparative treatment effects not calculated.

Parkinson Disease
Shill et al. (2011) found no benefit of CES with the Nexalin device for motor or psychological symptoms in a crossover study of 23 patients with early Parkinson disease.¹²

Smoking Cessation
Pickworth et al. (1997) reported that 5 days of CES was ineffective for reducing withdrawal symptoms or facilitating smoking cessation in a double-blind RCT of 101 cigarette smokers who wanted to stop smoking.¹³

Tic Disorders
Wu et al. (2020) published a double-blind, randomized, sham-controlled trial of the efficacy and safety of CES as an add-on treatment for tic disorders in 62 children and adolescents who lacked a clinical response to prior treatment of 4 weeks of pharmacotherapy.¹⁴ Cranial electrotherapy stimulation was delivered via the CES ultra stimulator (American Neuro Fitness LLC) at 500 μA-mA and applied for 30 minutes daily on weekdays for 40 days. The sham CES was delivered at lower than 100 μA. The study was conducted at a single academic medical center in China. A total of 9 participants (14.5%) discontinued the intervention early and were excluded from the analyses. There was no significant difference between the active CES and sham groups in the change in Yale Global Tic Severity Scale (YGTSS) score (-31.66% vs. 23.96%; p = .13).

Section Summary: Psychiatric, Behavioral, or Neurologic Conditions
The most direct evidence related to CES for anxiety and depression comes from 4 sham-controlled randomized trials and systematic reviews. One RCT each found a significant benefit with CES for anxiety or depression, but both had important relevance limitations. Additional evidence is needed to permit conclusions about whether CES improves outcomes for individuals with anxiety or depression. The evidence for depression, anxiety, Parkinson disease, smoking cessation, and tic disorders does not support the use of CES.

Cranial Electrotherapy Stimulation for Functional Constipation
Clinical Context and Therapy Purpose
The purpose of CES is to provide a treatment option that is an alternative to or an improvement on existing therapies, such as medication, biofeedback, and behavior modification in patients with functional constipation.

The question addressed in this evidence review is: Does CES improve the net health outcome in patients with functional constipation?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with functional constipation.

Interventions
The therapy being considered is CES.

Comparators
Comparators of interest include medication, biofeedback, and behavior modification. Treatment includes dietary modifications and a maintenance regimen of laxatives.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess longer-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Gong et al. (2016) reported on a single-center, unblinded RCT comparing CES (Alpha-Stim) with biofeedback in 74 subjects with functional constipation.¹⁵ Eligible patients met Rome III criteria for functional constipation and had been recommended by their physicians for biofeedback therapy. Patients were randomized to biofeedback with CES (n = 38) or biofeedback alone (n = 36) and followed at 4 time points (baseline and 3 follow-up visits); however, the duration of time between each follow-up visit was not specified. In a repeated-measures analysis of variance model for change from baseline, at the second and third follow-up visits, there were significant differences between groups in: Self-Rating Anxiety Scale score (41.8 for CES patients vs. 46.8 for controls; p < .001); Self-Rating Depression Scale score (43.08 for CES patients vs. 48.8 for controls; p < .001) and the Wexner Constipation Score (10.0 for CES patients vs. 12.6 for controls; p < .001). A subset of patients underwent anorectal manometry, with no between-group differences in pressure before or after treatment.

Section Summary: Functional Constipation
One RCT was identified evaluating CES for functional constipation. Although this trial demonstrated improvements in several self-reported outcomes, given its unblinded design, there was a high risk of bias. Additional confirmation with stronger studies is needed.

Auricular Electrostimulation for Acute or Chronic Pain
Clinical Context and Therapy Purpose
The purpose of auricular electrostimulation is to provide a treatment option that is an alternative to or an improvement on existing therapies, such as medical management and other conservative therapies, in patients with acute or chronic pain.

The question addressed in this evidence review is: Does electrical stimulation of auricular acupuncture points improve the net health outcome in patients with acute or chronic pain?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with acute or chronic pain.

Interventions
The therapy being considered is auricular electrostimulation.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess longer-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Acute Pain
In a 2007 review, Sator-Katzenschlager and Michalek-Sauberer found inconsistent results from studies assessing P-Stim use for the treatment of acute pain (eg, oocyte aspiration, molar tooth extraction).¹⁶

An RCT by Holzer et al. (2011) tested the efficacy of the P-Stim on 40 women undergoing gynecologic surgery.¹⁷ Patients were randomized to auricular acupuncture or sham stimulation. Patients in the control group received electrodes without needles, and the P-Stim devices were applied without electrical stimulation. The P-Stim device was placed behind the ear at the end of surgery on all patients while they were still under general anesthesia, and the dominant ear was completely covered with identical dressing in both groups to maintain blinding. Postoperatively, patients received paracetamol 1000 mg every 6 hours, with additional piritramide given on demand. Needles and devices were removed 72 hours postoperatively. A blinded observer found no significant difference between the 2 groups in consumption of piritramide during the first 72 hours postoperatively (acupuncture, 15.3 mg vs. placebo, 13.9 mg) or in visual analog scale (VAS) scores taken at 0, 2, 24, 48, and 72 hours (average VAS score: acupuncture, 2.32 vs. placebo, 2.62).

Chronic Low Back Pain
Sator-Katzenschlager et al. (2004) reported on a double-blind RCT that compared auricular electroacupuncture with conventional auricular acupuncture in 61 patients with chronic low back pain (at least 6 months).¹⁸ All needles were connected to the P-Stim device. In the control group, devices were applied without electrical stimulation. Treatment was performed once weekly for 6 weeks, with needles withdrawn 48 hours after insertion. Patients received questionnaires assessing pain intensity and quality, psychological well-being, activity level, and quality of sleep using VAS. There was a significant reduction in pain at up to the 18-week follow-up. Auricular electroacupuncture resulted in greater improvements in the outcome measures than the control procedure. For example, VAS pain intensity was less than 5 in the control group and less than 2 in the electroacupuncture group. This trial was limited by the small number of participants.

Chronic Cervical Pain
Sator-Katzenschlager et al. (2003) presented results from a small double-blind, randomized trial of 21 patients with chronic cervical pain.¹⁹ In 10 patients, needles were stimulated with a P-Stim device, and in 11 patients, no stimulation was administered. Treatment was administered once a week for 6 weeks. Patients receiving electrical stimulation experienced significant reductions in pain scores and improvements in psychological well-being, activity, and sleep.

Rheumatoid Arthritis
Bernateck et al. (2008) reported on P-Stim use in an RCT of 44 patients with rheumatoid arthritis.²⁰ The control group received autogenic training, a psychological intervention in which participants learned to relax their limbs, breathing, and heart rate. Electroacupuncture (continuous stimulation for 48 hours at home) and lessons in autogenic training were performed once weekly for 6 weeks. Also, the control patients were encouraged to use an audiotape to practice autogenic training every day. The needles and devices were removed after 48 hours. Seven patients withdrew from the study before beginning the intervention; the 37 remaining patients completed the trial through the 3-month follow-up. The primary outcome measures were the mean weekly pain intensity and the Disease Activity Score. At the end of treatment and 3-month follow-up, statistically significant improvements were observed in all outcome measures for both groups. There was greater improvement in the electroacupuncture group (VAS pain score, 2.79) than in the control group (VAS pain score, 3.95) during treatment. This level of improvement did not persist at the 3-month follow-up. The clinical significance of a 1-point difference in VAS score from this small trial is unclear.

Section Summary: Acute or Chronic Pain
One trial of P-Stim for women undergoing gynecologic surgery found no significant reductions in pain outcomes. Trials in chronic low back pain, chronic cervical pain, and rheumatoid arthritis showed small improvements but had methodologic limitations (e.g., small sample sizes, large loss to follow-up). Additional studies are needed to determine whether auricular electrostimulation improves outcomes for acute or chronic pain.

Auricular Electrostimulation for Obesity
Clinical Context and Therapy Purpose
The purpose of auricular electrostimulation is to provide a treatment option that is an alternative to or an improvement on existing therapies, such as standard therapy, in patients with obesity.

The question addressed in this evidence review is: Does electrical stimulation of auricular acupuncture points improve the net health outcome in patients with obesity?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with obesity.

Interventions
The therapy being considered is auricular electrostimulation.

Comparators
Comparators of interest include standard therapy. Treatments include physical exercise, low-carbohydrate dieting, and low-fat dieting.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess longer-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Systematic Reviews
The results of a systematic review and meta-analysis were published by Kim et al. (2018). The purpose of this review was to evaluate the effect of acupuncture and other intervention types on weight loss.²¹ In total, 27 RCTs were deemed to meet inclusion criteria. These RCTs had 32 intervention arms and 2219 patients. The meta-analysis results indicate that acupuncture plus lifestyle modification was more effective than lifestyle modification alone (Hedges’ g = 1.104, 95% CI, 0.531 to 1.678) and sham acupuncture plus lifestyle modification (Hedges’ g = 0.324, 95% CI, 0.177 to 0.471), whereas acupuncture alone, was not more effective than sham acupuncture alone and no treatment. Interestingly, acupuncture treatment was effective only in subjects who were overweight (25 ≤ body mass index < 30, Hedges’ g = 0.528, 95% CI, 0.279 to 0.776), not in subjects with obesity (body mass index ≥ 30). Auricular acupuncture (Hedges’ g = 0.522, 95% CI, 0.152 to 0.893), manual acupuncture, (Hedges’ g = 0445, 95% CI, 0.044 to 0.846) and pharmacopuncture (Hedges’ g = 0.411, 95% CI, 0.026 to 0.796) also were aligned with weight loss. The authors noted significant heterogeneity across studies with respect to the interventions used, participants, and treatment period.

A systematic review was published by Yeh et al. (2017), which included the RCTs by Schukro et al. (2014) and Yeh et al. (2015) that are summarized in the section below.²² Although their meta-analysis of 13 RCTs with a total of 1775 participants found that auricular acupoint stimulation improves physical anthropometric parameters, including body weight (mean difference of -1.21 kg; 95% CI, -1.94 to -0.47; I2 = 88%), body mass index (mean difference -0.57 kg/m2; 95% CI, -0.82 to -0.33; I2 = 78%), body fat (mean difference -0.83%; 95% CI, -1.43 to -0.24; I2 = 0%), and waist circumference (-1.75 cm; 95% CI, -2.95 to -0.55; I2 = 87%) in overweight and obese adults, key limitations of these findings include high heterogeneity for most of the measures and unclear clinical importance of the differences. Although subgroup analyses based on treatment length (shorter = less than 6 weeks vs. longer = more than or equal to 6 weeks) improved consistency of findings somewhat for the longer subgroup, heterogeneity was still moderate (e.g., I2 = 59% for body weight; I2 = 52% for body mass index).

Randomized Controlled Trials
Schukro et al. (2014) reported on a double-blind RCT evaluating the effects of the P-Stim on weight loss in 56 obese patients.²³ The auricular acupuncture points for hunger, stomach, and colon were stimulated 4 days a week over 6 weeks with the P-Stim in the active group (n = 28), and the placebo group received treatment with a sham P-Stim device (n = 28). At the end of treatment, body weight was reduced by 3.7% in the active stimulation group and 0.7% in the sham group (p < .001). Four weeks after treatment, body weight was reduced by 5.1% in the active stimulation group and 0.2% in the sham group (p < .001). Similar improvements were observed for body mass index and body fat.

Yeh et al. (2015) randomized 70 patients to electrical stimulation on true acupressure points or sham acupressure points.²⁴ As part of the 10-week treatment program, all patients received auricular acupressure and nutrition counseling following the electrical stimulation sessions. Both groups experienced significant improvements in body mass index, blood pressure, and cholesterol levels from baseline. However, there was no significant difference between groups.

Section Summary: Obesity
Randomized controlled trials and systematic reviews that have assessed the use of auricular electrostimulation to treat obesity have had small sample sizes, evaluated different treatment protocols, and have reported inconsistent results.

Auricular Electrostimulation for Opioid Withdrawal Symptoms
Clinical Context and Therapy Purpose
The purpose of auricular electrostimulation is to provide a treatment option that is an alternative to or an improvement on existing therapies, such as standard therapy in patients with opioid withdrawal symptoms.

The question addressed in this evidence review is: Does electrical stimulation of auricular acupuncture points improve the net health outcome in patients with opioid withdrawal?

The following PICO was used to select literature to inform this review.

Populations
The relevant population of interest is individuals with opioid withdrawal symptoms.

Interventions
The therapy being considered is auricular electrostimulation.

Comparators
Comparators of interest include standard therapy. Treatment includes opioid analgesics.

Study Selection Criteria
Methodologically credible studies were selected using the following principles:

To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs.
In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.
To assess longer-term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.
Studies with duplicative or overlapping populations were excluded.

Review of Evidence
Observational Studies
Kroening and Oleson (1985) published a case series assessing 14 patients with chronic pain who were scheduled for withdrawal from their opiate medications.²⁵ During the withdrawal process, patients were given oral methadone, followed by bilateral auricular electroacupuncture for 2 to 6 hours, and periodic intravenous injections of low dose naloxone. On successive days, the methadone doses were halved. By day 7, 12 of 14 patients were completely withdrawn from methadone. Through at least 1-year follow-up, the 12 patients experienced minimal or no withdrawal symptoms and remained off narcotic medications.

Miranda and Taca (2018) conducted an open-label, uncontrolled, retrospective pilot study to evaluate the effect of neuromodulation with percutaneous electrical field stimulation on opioid withdrawal symptoms.²⁶ Eight participating clinics provided data on 73 patients who met Diagnostic and Statistical Manual of Mental Health Disorders, 4th edition, criteria for opioid dependence and voluntarily agreed to be treated with the NSS-2 Bridge device. All providers were trained to use the Bridge through online modules. Patients were monitored during the first hour following implantation of the device and sent home with instructions to return for follow-up within 1 to 5 days, depending on the clinic, and to keep the device on for the entire 5-day period. The primary outcome of withdrawal symptom improvement was measured using the Clinical Opioid Withdrawal Scale (COWS), which ranges from 0 to 48 (5 to 12 = mild; 13 to 24 = moderate, 25 to 36 = moderately severe, > 36 = severe). Another outcome was a successful transition, defined as receiving first maintenance medication on day 5 of the study. The mean baseline COWS score was 20.1. At 20 minutes, the mean COWS score decreased to 7.5; at 30 minutes, the mean COWS was 4.0; and at 60 minutes, the mean COWS was 3.1. At a 5-day follow-up, 89% of patients successfully transitioned to maintenance medication.

Section Summary: Opioid Withdrawal Symptoms
Evidence on the use of auricular electrostimulation to treat patients with opioid withdrawal symptoms consists of 2 observational studies with different protocols. Both studies reported successful alleviation of opioid withdrawal symptoms, though, without comparators, conclusions to be drawn from this evidence are limited.

Summary of Evidence
Cranial Electrotherapy Stimulation
For individuals who have acute or chronic pain who receive CES, the evidence includes a number of small sham-controlled randomized trials and pooled analyses. Relevant outcomes are symptoms, morbid events, functional outcomes, and treatment-related morbidity. Three trials studied headache and CES, and 6 trials studied chronic pain and CES. Pooled analyses found marginal benefits for headache with CES and no benefits for chronic pain with CES. A subsequent sham-controlled trial of remotely supervised CES via secure videoconferencing found a significant benefit with CES for pain reduction, but it had important relevance and conduct and design limitations. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have psychiatric, behavioral, or neurologic conditions (e.g., depression and anxiety, Parkinson disease, addiction) who receive CES, the evidence includes a number of small sham-controlled randomized trials and systematic reviews. Relevant outcomes are symptoms, morbid events, functional outcomes, and treatment-related morbidity. Four RCTs evaluated CES for depression and anxiety. One RCT each found a significant benefit with CES for anxiety or depression, but both had important relevance limitations. Comparisons between these trials cannot be made due to the heterogeneity in study populations and treatment protocols. Studies evaluating CES for Parkinson disease, smoking cessation, and tic disorders do not support the use of CES for these conditions. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Auricular Electrostimulation
For individuals who have acute or chronic pain (e.g., acute pain from surgical procedures, chronic back pain, chronic pain from osteoarthritis or rheumatoid arthritis) who receive auricular electrostimulation, the evidence includes a limited number of trials. Relevant outcomes are symptoms, morbid events, functional outcomes, and treatment-related morbidity. Studies evaluating the effect of electrostimulation technology on acute pain are inconsistent, and the small amount of evidence on chronic pain has methodologic limitations. For example, a comparison of auricular electrostimulation with manual acupuncture for chronic low back pain did not include a sham control group, and, in a study of rheumatoid arthritis, auricular electrostimulation was compared with autogenic training and resulted in a small improvement in visual analog scale pain scores of unclear clinical significance. Overall, the few published studies have small sample sizes and methodologic limitations. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have obesity who receive auricular electrostimulation, the evidence includes small RCTs and systematic reviews. Relevant outcomes are symptoms, morbid events, functional outcomes, and treatment-related morbidity. The RCTs reported inconsistent results and used different treatment protocols. The systematic reviews are limited by high heterogeneity with respect to the interventions used, participants included, treatment period, and outcome measures. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

For individuals who have opioid withdrawal symptoms who receive auricular electrostimulation, the evidence includes 2 observational studies. Relevant outcomes are symptoms, morbid events, functional outcomes, and treatment-related morbidity. Both studies report positive outcomes for the use of CES to treat opioid withdrawal symptoms. The studies used different treatment protocols and no comparators, limiting conclusions drawn from the results. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

The purpose of the following information is to provide reference material. Inclusion does not imply endorsement or alignment with the evidence review conclusions.

Clinical Input From Physician Specialty Societies and Academic Medical Centers
While the various physician specialty societies and academic medical centers may collaborate with and make recommendations during this process, through the provision of appropriate reviewers, input received does not represent an endorsement or position statement by the physician specialty societies or academic medical centers, unless otherwise noted.

2011 Input
In response to requests, input on auricular electrostimulation was received from 3 physician specialty societies and 5 academic medical centers while this policy was under review in 2011. There was a consensus that auricular electrostimulation is investigational.

Practice Guidelines and Position Statements
Guidelines or position statements will be considered for inclusion in Supplemental Information if they were issued by, or jointly by, a U.S. professional society, an international society with U.S. representation, or National Institute for Health and Care Excellence (NICE). Priority will be given to guidelines that are informed by a systematic review, include strength of evidence ratings, and include a description of management of conflict of interest.

No guidelines or statements were identified.

U.S. Preventive Services Task Force Recommendations
Not applicable

Ongoing and Unpublished Clinical Trials
Table 10 provides a summary of ongoing and unpublished trials that may influence this review.

Table 10. Summary of Key Trials

NCT No.	Trial Name	Planned Enrollment	Completion Date
Ongoing
NCT04963907	Randomised Controlled Trial of the Clinical and Cost Effectiveness of Alpha-Stim AID Cranial Electrotherapy Stimulation (CES) in Treatment Seeking Patients With Moderate Severity Depressive Episodes in Primary Care	230	December 2022
NCT03825471	Effects of Cranial Electrotherapy Stimulation on Anesthetics Consumption, Perioperative Cytokines Response, and Postoperative Pain in Patients Undergoing Colonic Surgery	80	December 2020
NCT03909217	Effectiveness and Safety of Transcutaneous Electrical Cranial-auricular Acupoint Stimulation (TECAS) for Patients With Mild-to-moderate Depression	470	December 2021
NCT03896438	Increased Thalamocortical Connectivity in Tdcs-potentiated Generalization of Cognitive Training	90	April 2024
NCT04189354	Study of the Synergistic Effects of Biofeedback and Transcranial Electrical Stimulation in Anxio-depressive Disorders	50	November 2021
NCT04061577	Transcranial Electrical Stimulation in Stroke EaRly After Onset Clinical Trial_ Bridging and Adjunctive Neuroprotection	24	September 2025
NCT04171804	Efficacy of Prefrontal Transcranial Direct Current Stimulation On Cognitive Functions and Electrophysiological Measures In Parkinson's Disease Mild Cognitive Impairment	20	June 2021
NCT04160806	The Effect Of Prefrontal Transcranial Direct Current Stimulation On Clinical Severity, Attentional Bias and Interoceptive Accuracy In Panic Disorder	30	November 2020
NCT03222752^a	A 6-Week Randomized, Double-Blind, Placebo-Controlled Evaluation of Efficacy and Tolerability of Cranial Electrotherapy (CES) for the Treatment of Adults from 18-65 Years of Age with Treatment Resistant Major Depressive Disorder (MDD) with a 2-Week Open Label Extension Phase	141	December 2021
Unpublished
NCT03815253	Electro-acupuncture for Central Obesity	168	March 2021
NCT02851186	Combined Electroacupuncture and Auricular Acupuncture for Postoperative Pain after Abdominal Surgery for Gynecological Diseases: a Randomized Sham-Controlled Trial	72	November 2018
NCT03277846	A Randomized, Double-Blind, Placebo-Controlled Parallel Group Study of the Safety and Efficacy of Nexalin Electrical Brain Stimulation for the Treatment of Depression in Patients Referred to Electro-Convulsive Therapy	101	May 2018
NCT03210155	Effects of Cranial Electrotherapy Stimulation on Psychological Distress and Maternal Functioning in New Mothers During the Postpartum Period	1	Terminated August 2019
NCT03060122	The Clinical Feasibility of Combining Cranial Electrotherapy Stimulation (CES Alpha-Stim) and Non-invasive Interactive Neurostimulation (InterX) for Optimized Rehabilitation Following Extremity Immobilization	35	August 20

NCT: national clinical trial.
a Denotes industry sponsorship.

References

U.S. Food & Drug Administration. FDA News Release: FDA grants marketing authorization of the first device for use in helping to reduce the symptoms of opioid withdrawal. https://www.fda.gov/news-events/press-announcements/fda-grants-marketing-authorization-first-device-use-helping-reduce-symptoms-opioid-withdrawal. November 15, 2017. Accessed December 10, 2021.
Klawansky S, Yeung A, Berkey C, et al. Meta-analysis of randomized controlled trials of cranial electrostimulation. Efficacy in treating selected psychological and physiological conditions. J Nerv Ment Dis. Jul 1995; 183(7): 478-84. PMID 7623022
Bronfort G, Nilsson N, Haas M, et al. Non-invasive physical treatments for chronic/recurrent headache. Cochrane Database Syst Rev. 2004; (3): CD001878. PMID 15266458
O'Connell NE, Wand BM, Marston L, et al. Non-invasive brain stimulation techniques for chronic pain. Cochrane Database Syst Rev. Apr 11 2014; (4): CD008208. PMID 24729198
Ahn H, Galle K, Mathis KB, et al. Feasibility and efficacy of remotely supervised cranial electrical stimulation for pain in older adults with knee osteoarthritis: A randomized controlled pilot study. J Clin Neurosci. Jul 2020; 77: 128-133. PMID 32402609
Price L, Briley J, Haltiwanger S, et al. A meta-analysis of cranial electrotherapy stimulation in the treatment of depression. J Psychiatr Res. Mar 2021; 135: 119-134. PMID 33477056
Kim J, Kim H, Kim DH, et al. Effects of cranial electrotherapy stimulation with novel in-ear electrodes on anxiety and resting-state brain activity: A randomized double-blind placebo-controlled trial. J Affect Disord. Dec 01 2021; 295: 856-864. PMID 34706456
Barclay TH, Barclay RD. A clinical trial of cranial electrotherapy stimulation for anxiety and comorbid depression. J Affect Disord. Aug 2014; 164: 171-7. PMID 24856571
Shekelle PG, Cook IA, Miake-Lye IM, et al. Benefits and Harms of Cranial Electrical Stimulation for Chronic Painful Conditions, Depression, Anxiety, and Insomnia: A Systematic Review. Ann Intern Med. Mar 20 2018; 168(6): 414-421. PMID 29435567
Mischoulon D, De Jong MF, Vitolo OV, et al. Efficacy and safety of a form of cranial electrical stimulation (CES) as an add-on intervention for treatment-resistant major depressive disorder: A three week double blind pilot study. J Psychiatr Res. Nov 2015; 70: 98-105. PMID 26424428
Lyon D, Kelly D, Walter J, et al. Randomized sham controlled trial of cranial microcurrent stimulation for symptoms of depression, anxiety, pain, fatigue and sleep disturbances in women receiving chemotherapy for early-stage breast cancer. Springerplus. 2015; 4: 369. PMID 26435889
Shill HA, Obradov S, Katsnelson Y, et al. A randomized, double-blind trial of transcranial electrostimulation in early Parkinson's disease. Mov Disord. Jul 2011; 26(8): 1477-80. PMID 21538515
Pickworth WB, Fant RV, Butschky MF, et al. Evaluation of cranial electrostimulation therapy on short-term smoking cessation. Biol Psychiatry. Jul 15 1997; 42(2): 116-21. PMID 9209728
Wu WJ, Wang Y, Cai M, et al. A double-blind, randomized, sham-controlled study of cranial electrotherapy stimulation as an add-on treatment for tic disorders in children and adolescents. Asian J Psychiatr. Jun 2020; 51: 101992. PMID 32145674
Gong BY, Ma HM, Zang XY, et al. Efficacy of Cranial Electrotherapy Stimulation Combined with Biofeedback Therapy in Patients with Functional Constipation. J Neurogastroenterol Motil. Jul 30 2016; 22(3): 497-508. PMID 26932836
Sator-Katzenschlager SM, Michalek-Sauberer A. P-Stim auricular electroacupuncture stimulation device for pain relief. Expert Rev Med Devices. Jan 2007; 4(1): 23-32. PMID 17187468
Holzer A, Leitgeb U, Spacek A, et al. Auricular acupuncture for postoperative pain after gynecological surgery: a randomized controlled trail. Minerva Anestesiol. Mar 2011; 77(3): 298-304. PMID 21441884
Sator-Katzenschlager SM, Scharbert G, Kozek-Langenecker SA, et al. The short- and long-term benefit in chronic low back pain through adjuvant electrical versus manual auricular acupuncture. Anesth Analg. May 2004; 98(5): 1359-64, table of contents. PMID 15105215
Sator-Katzenschlager SM, Szeles JC, Scharbert G, et al. Electrical stimulation of auricular acupuncture points is more effective than conventional manual auricular acupuncture in chronic cervical pain: a pilot study. Anesth Analg. Nov 2003; 97(5): 1469-1473. PMID 14570667
Bernateck M, Becker M, Schwake C, et al. Adjuvant auricular electroacupuncture and autogenic training in rheumatoid arthritis: a randomized controlled trial. Auricular acupuncture and autogenic training in rheumatoid arthritis. Forsch Komplementmed. Aug 2008; 15(4): 187-93. PMID 18787327
Kim SY, Shin IS, Park YJ. Effect of acupuncture and intervention types on weight loss: a systematic review and meta-analysis. Obes Rev. Nov 2018; 19(11): 1585-1596. PMID 30180304
Yeh TL, Chen HH, Pai TP, et. al. The Effect of Auricular Acupoint Stimulation in Overweight and Obese Adults: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Evidence-Based Complementary and Alternative Medicine. 2017; vol. 2017, Article ID 3080547, 16 pages, 2017. https://doi.org/10.1155/2017/3080547.
Schukro RP, Heiserer C, Michalek-Sauberer A, et al. The effects of auricular electroacupuncture on obesity in female patients--a prospective randomized placebo-controlled pilot study. Complement Ther Med. Feb 2014; 22(1): 21-5. PMID 24559812
Yeh ML, Chu NF, Hsu MY, et al. Acupoint Stimulation on Weight Reduction for Obesity: A Randomized Sham-Controlled Study. West J Nurs Res. Dec 2015; 37(12): 1517-30. PMID 25183702
Kroening RJ, Oleson TD. Rapid narcotic detoxification in chronic pain patients treated with auricular electroacupuncture and naloxone. Int J Addict. Sep 1985; 20(9): 1347-60. PMID 2867052
Miranda A, Taca A. Neuromodulation with percutaneous electrical nerve field stimulation is associated with reduction in signs and symptoms of opioid withdrawal: a multisite, retrospective assessment. Am J Drug Alcohol Abuse. 2018; 44(1): 56-63. PMID 28301217

Coding Section

Codes	Number	Description
CPT		No specific codes: see below
	63650	Percutaneous implantation of neurostimulator electrode array, epidural
	64555	Percutaneous implantation of neurostimulator electrode array; peripheral nerve (excludes sacral nerve)
	97813	Acupuncture, 1 or more needles; with electrical stimulation, initial 15 minutes of personal one-on-one contact with the patient
	97814	; with electrical stimulation, each additional 15 minutes of personal one-on-one contact with the patient, with re-insertion of needle(s) (List separately in addition to code for primary procedure)
HCPCS	K1002	Cranial electrotherapy stimulation (ces) system, includes all supplies and accessories, any type (eff 1/1/20)
	L8680	Implantable neurostimulator electrode, each
	S8930	Electrical stimulation of auricular acupuncture points; each 15 minutes of personal one-on-one contact with the patient
ICD-10-CM		Investigational for all diagnoses
ICD-10-PCS		ICD-10-PCS codes are only used for inpatient services. There is no specific ICD-10-PCS code for this therapy.
	8E0H300, 8E0H30Z	Other procedures, integumentary system, percutaneous, acupuncture code list
Type of service	Medical
Place of service	Outpatient, Inpatient, Professional

Procedure and diagnosis codes on Medical Policy documents are included only as a general reference tool for each policy. They may not be all-inclusive.

This medical policy was developed through consideration of peer-reviewed medical literature generally recognized by the relevant medical community, U.S. FDA approval status, nationally accepted standards of medical practice and accepted standards of medical practice in this community, Blue Cross Blue Shield Association technology assessment program (TEC) and other non-affiliated technology evaluation centers, reference to federal regulations, other plan medical policies and accredited national guidelines.

History From 2014 Forward

09/09/2022	Annual review, no change to policy intent. Updating rationale and references.
09/01/2021	Annual review, no change to policy intent. Updating rationale and references.
09/01/2020	Annual review, no change to policy intent. Updating regulatory status, guidelines, coding, rationale and references.
11/20/2019	Removed related policies CAM 20150 and CAM 70129. They have been archived
09/01/2019	Annual review, no change to policy intent. Updating rationale and references.
09/06/2018	Annual review, no change to policy intent. Updating description, rationale and references.
09/19/2017	Annual review, no change to policy intent. Updating background, description, regulatory status, rationale and references.
09/01/2016	Annual review, no change to policy intent. Updating rationale and references.
09/01/2015	Annual reivew, no change to policy intent. Updated background, description, rationale, references and coding. Added guidelines.
08/21/2014	Annual review. Updated rationale and references. Added ICD 9 and 10 coding and supplemental information section. No change to policy intent.
08/19/2014	Annual review. Updated rationale and references. Adding ICD 9 and 10 coding. No change to policy intent.

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Cranial Electrotherapy Stimulation (CES) and Auricular Electrostimulation - CAM 80158