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, weight loss, and opioid withdrawal.

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 United 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 three 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: JXK.

Table 1. Cranial Electrotherapy Stimulation (CES) Devices Cleared by the US Food and Drug Administration

Device Name	Manufacturer	Date Cleared	510(k) No.	Indications
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

FDA: Food and Drug Administration.

Several devices for electroacupuncture designed to stimulate auricular acupuncture points have been cleared for marketing by 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 (CES) Devices Cleared by the US Food and Drug Administration

Device Name	Manufacturer	Date Cleared	510(k) No.	Indication
Drug Relief	DyAnsys Inc	05/02/2018	K173861	Reduce symptoms of opioid withdrawal
NSS-2 Bridge	Innovative Health Solutions	2017		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
Bridge Neurostimulation System	Innovative Health Solutions	2014		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
P-Stim™	Neuroscience Therapy Corp.	03/30/2006	K050123	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

FDA: Food and Drug Administration.

Related Policies

• Electrotherapies in Pain Management (Policy #025 in the Treatment Section)
• Repetitive Transcranial Magnetic Stimulation (Policy #104 in the Treatment Section)

FIDE-SNP Coverage:

For members enrolled in a Fully Integrated Dual Eligible Special Needs Plan (FIDE-SNP): (1) to the extent the service is covered under the Medicare portion of the member’s benefit package, the above Medicare Coverage statement applies; and (2) to the extent the service is not covered under the Medicare portion of the member’s benefit package, the above Medicaid Coverage statement applies.

[RATIONALE: This policy was created in 2011 and has been updated regularly with searches of the MEDLINE database. The most recent literature update was performed through January 11, 2019.

Evidence reviews assess the clinical evidence to determine whether the use of a technology improves the net health outcome. Broadly defined, health outcomes are 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 to 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 a technology, two domains are examined: the relevance and the quality and credibility. To be relevant, studies must represent one 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. RCTs 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 Test Purpose

The purpose of cranial electrotherapy stimulation 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 policy is: does cranial electrotherapy stimulation improve the net health outcome in patients with chronic pain?

The following PICOTS were used to select literature to inform this policy.

Patients

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

Interventions

The therapy being considered is cranial electrotherapy stimulation.

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.

Timing

The existing literature evaluating cranial electrotherapy stimulation as a treatment for acute or chronic pain has varying lengths of follow up. While studies described below all reported at least one outcome of interest, longer follow-up was necessary to fully observe outcomes.

Patients with acute or chronic pain are actively managed by occupational therapists, physical therapists and primary care providers in an outpatient clinical setting.

Study Selection Criteria

Methodologically credible studies were selected using the following principles: 

a.     To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

b.     In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

c.     To assess longer term outcomes and adverse events, single-arm studies that capture longer periods of follow-up and/or larger populations were sought.

d.     Studies with duplicative or overlapping populations were excluded.

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.^1, The literature search, conducted through 1991, identified 2 trials evaluating CES for the treatment of headache. Pooled analysis of the 2 trials (total 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.^2, 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.^3, 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 for chronic pain.

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.

Cranial electrotherapy stimulation Psychiatric, Behavioral, or Neurologic Conditions

Clinical Context and Test Purpose

The purpose of cranial electrotherapy stimulation 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 policy is: does cranial electrostimulation therapy improve the net health outcome in patients with psychiatric, behavioral, or neurological conditions?

The following PICOTS were used to select literature to inform this policy.

Patients

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

Interventions

The therapy being considered is cranial electrotherapy stimulation.

Comparators

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

Outcomes

The general outcomes of interest are symptoms, morbid events, functional outcomes, and treatment-related morbidity.

Timing

The existing literature evaluating cranial electrotherapy stimulation as a treatment for psychiatric, behavioral, or neurologic conditions has varying lengths of follow up. While studies described below all reported at least one outcome of interest, longer follow-up was necessary to fully observe outcomes.

Setting

Patients with psychiatric, behavioral, or neurologic conditions are actively managed by electrophysiologists and primary care providers in an outpatient clinical setting.

Study Selection Criteria

Methodologically credible studies were selected using the following principles: 

a.     To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

b.     In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

c.     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.

Anxiety and Depression

The Klawansky (1995) meta-analysis described in the Headache section above, analyzed 8 trials (n=228 patients) comparing CES with sham for the treatment of anxiety.¹ 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).

A Cochrane review by Kavirajan et al (2014), with a literature search through February 2014, found no high-quality RCTs assessing CES vs sham for the treatment of depression.^4, Several RCTs with sham controls have been subsequently published and are described below.

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) (see Table 3).⁵ Analysis of covariance showed a significant advantage of active CES over sham for both anxiety (p=0.001) and depression (p=0.001) over 5 weeks of treatment (see Table 4). 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.

In a smaller double-blind, sham-controlled randomized trial (N=30), Mischoulon et al (2015) found no significant benefit of CES as an adjunctive therapy in patients with treatment-resistant major depression (see Tables 3 and 4).⁶ Both active and sham groups showed improvements in depression over the 3 weeks of the study, suggesting a strong placebo effect.

A sham-controlled, double-blind randomized trial by Lyon et al (2015) 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 (see Tables 3 and 4).⁷This 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, 6-32 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 the low symptoms levels at baseline, resulting in a floor effect, and the low level of stimulation.

Table 3. Summary of RCT Characteristics Assessing CES for Anxiety and Depression

Study	Country	Sites	Dates	Participants	Interventions
					Active	Comparator
Barclay et al (2014)5,	U.S.	1	2012	Patients who met DSM-IV criteria for anxiety disorder as primary diagnosis	Alpha-Stim self-administered for 1 h/d for 5 wk (n=60)	Sham Alpha-Stim self-administered for 1 h/d for 5 wk (n=55)
Mischoulon et al (2015)6,	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 h/d for 3 wk (n=17)	·   Sham FW-100 ·   1 clinician-supervised and 4 self-administered for 1h/d for 3 wk (n=13)
Lyon et al (2015)7,	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 h/d for 2 wk after chemotherapy cessation (n=82)	Sham Alpha-Stim self-administered for 1 h/d for 2 wk after chemotherapy cessation (n=81)

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 4. 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 5a	Baseline	Week 1	Week 3	Week 5a
Barclayet al (2014)5,
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 3a
Mischoulon et al(2015)6,
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 3b		Timepoint	Timepoint 2	Timepoint 3b
Lyonet al (2015)7,
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)

CES: cranial electrotherapy stimulation; NR: not reported; RCT: randomized controlled trial; SD: standard deviation.

^a p=0.001.

^b p not significant.

The purpose of the gaps tables (see Tables X and X) is to display notable gaps identified in each study. This information is synthesized as a summary of the body of evidence following each table and provides the conclusions on the sufficiency of evidence supporting the position statement.  

Table 5. Relevance Gaps

Study	Populationa	Interventionb	Comparatorc	Outcomesd	Follow-Upe
Barclay et al (2014)5,	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.     1. Key health outcomes not addressed
Mischoulon et al (2015)6,
Lyon et al (2015)7,				1. Key health outcomes not addressed because despite the validated questionnaires being used, these are subjective and are subject to bias/

The evidence gaps 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.

The evidence gaps stated in this table are those notable in the current review; this is not a comprehensive gaps assessment.

^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.

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.^8,

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.^9,

Section Summary: Psychiatric, Behavioral, or Neurologic Conditions

The most direct evidence related to CES for anxiety and depression comes from sham-controlled randomized trials. Three trials with this design have reported inconsistent results. Additional evidence is needed to permit conclusions about whether CES improves outcomes for individuals with anxiety or depression. The evidence for acute or chronic pain, Parkinson disease, and smoking cessation does not support the use of CES.

Cranial electrotherapy stimulation for Functional Constipation

Clinical Context and Test Purpose

The purpose of cranial electrotherapy stimulation 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 policy is: does cranial electrostimulation therapy improve the net health outcome in patients with functional constipation?

The following PICOTS were used to select literature to inform this policy.

Patients

The relevant population of interest are individuals with functional constipation.

Interventions

The therapy being considered is cranial electrotherapy stimulation.

Comparators

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

Outcomes

The general outcomes of interest are symptoms, morbid events, functional outcomes, and treatment-related morbidity.

Timing

The existing literature evaluating cranial electrotherapy stimulation as a treatment for functional constipationhas varying lengths of follow up. While studies described below all reported at least one outcome of interest, longer follow-up was necessary to fully observe outcomes.

Setting

Patients with functional constipation are actively managed by nutritionists and primary care providers in an outpatient clinical setting.

Study Selection Criteria

Methodologically credible studies were selected using the following principles: 

a.     To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

b.     In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

c.     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.

Gong et al (2016) reported on a single-center, unblinded RCT comparing CES (Alpha-Stim) with biofeedback in 74 subjects with functional constipation.^10, 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<0.001); Self-Rating Depression Scale score (43.08 for CES patients vs 48.8 for controls; p<0.001) and the Wexner Constipation Score (10.0 for CES patients vs 12.6 for controls; p<0.001). 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 other studies is needed.

Auricular Electrostimulation FOR Acute or Chronic Pain

Clinical Context and Test 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 policy is: does electrical stimulation of auricular acupuncture points improve the net health outcome in patients with chronic pain?

The following PICOTS were used to select literature to inform this policy.

Patients

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

Interventions

The therapy being considered is auricular electrostimulation.

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.

Timing

The existing literature evaluating auricular electrostimulation as a treatment for acute or chronic pain has varying lengths of follow up, ranging from 3-months. While studies described below all reported at least one outcome of interest, longer follow-up was necessary to fully observe outcomes. Therefore, 3-months] of follow-up is considered necessary to demonstrate efficacy.

Setting

Patients with acute or chronic pain are actively managed by occupational therapists, physical therapists and primary care providers in an outpatient clinical setting.

Study Selection Criteria

Methodologically credible studies were selected using the following principles: 

a.     To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

b.     In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

c.     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.

 Acute Pain

In a review, Sator-Katzenschlager and Michalek-Sauberer (2007) found inconsistent results from studies assessing P-Stim use for the treatment of acute pain (eg, oocyte aspiration, molar tooth extraction).^11,

An RCT by Holzer et al (2011) tested the efficacy of the P-Stim on 40 women undergoing gynecologic surgery.^12, 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).^13, 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.^14, 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 the 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.^15, 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 three-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 (eg, 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 Test 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 policy is: does electrical stimulation of auricular acupuncture points improves the net health outcome in patients with obesity?

The following PICOTS were used to select literature to inform this policy.

Patients

The relevant population of interest are 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.

Outcomes

The general outcomes of interest are symptoms, morbid events, functional outcomes, and treatment-related morbidity.

Timing

The existing literature evaluating auricular electrostimulation as a treatment for obesity has varying lengths of follow up. While studies described below all reported at least one outcome of interest, longer follow-up was necessary to fully observe outcomes.

Setting

Patients with obesity are actively managed by nutritionists and primary care providers in an outpatient clinical setting.

Study Selection Criteria

Methodologically credible studies were selected using the following principles: 

a.     To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

b.     In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

c.     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.

 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.^16, 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 (LM) was more effective than LM alone (Hedges’ g = 1.104, 95% CI = 0.531–1.678) and sham acupuncture plus LM (Hedges’ g = 0.324, 95% CI = 0.177–0.471), whereas acupuncture alone was not more effective than sham acupuncture alone and no treatment. Interestingly, acupuncture treatment was effective only in subjects with overweight (25 ≤ body massindex < 30, Hedges’ g = 0.528, 95% CI = 0.279–0.776), not in subjects with obesity (body mass index ≥30). Auricular acupuncture (Hedges’ g = 0.522, 95% CI = 0.152–0.893), manual acupuncture, (Hedges’ g = 0445, 95% CI = 0.044–0.846) and pharmacopuncture (Hedges’ g = 0.411, 95% CI = 0.026–0.796) also were aligned with weight loss.

Schukro et al (2014) reported on a double-blinded RCT evaluating the effects of the P-Stim on weight loss in 56 obese patients.¹⁷ 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<0.001). Four weeks after treatment, body weight was reduced by 5.1% in the active stimulation group and 0.2% in the sham group (p<0.001). 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.^18, 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

RCTs that have assessed the use of auricular electrostimulation to treat obesity have had small sample sizes and evaluated different treatment protocols. Additionally, the RCTs reported inconsistent results.

Auricular electrostimulation for Opioid Withdrawal Symptoms

Clinical Context and Test 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 policy is: does electrical stimulation of auricular acupuncture points improves the net health outcome in patients with opioid withdrawal?

The following PICOTS were used to select literature to inform this policy.

Patients

The relevant population of interest are individuals with opioid withdrawal symptoms.

Interventions

The therapy being considered is auricular electrostimulation.

Comparators

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

Outcomes

The general outcomes of interest are symptoms, morbid events, functional outcomes, and treatment-related morbidity.

Timing

The existing literature evaluating auricular electrostimulation as a treatment for opioid withdrawal symptoms has varying lengths of follow up, ranging from 1-year] While studies described below all reported at least one outcome of interest, longer follow-up was necessary to fully observe outcomes. Therefore, 1-year of follow-up is considered necessary to demonstrate efficacy.

Setting

Patients with opioid withdrawal symptoms are actively managed by emergency care providers and primary care providers in an outpatient clinical setting.

Study Selection Criteria

Methodologically credible studies were selected using the following principles: 

a.     To assess efficacy outcomes, comparative controlled prospective trials were sought, with a preference for RCTs;

b.     In the absence of such trials, comparative observational studies were sought, with a preference for prospective studies.

c.     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.

 Kroening and Oleson (1985) published a case series assessing 14 patients with chronic pain who were scheduled for withdrawal from their opiate medications.^19, 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.^20, 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. Mean baseline COWS score was 20.1. At 20 minutes, mean COWS score decreased to 7.5; at 30 minutes, mean COWS was 4.0; and at 60 minutes, mean COWS was 3.1. At 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 case series with different protocols. Both studies reported successful alleviation of opioid withdrawal symptoms, though, without comparators, conclusions to be drawnfrom 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 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 (eg, depression and anxiety, Parkinson 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 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 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 (eg, 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.

SUPPLEMENTAL INFORMATION

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.

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

No guidelines or statements were identified.

U.S. Preventive Services Task Force Recommendations

Not applicable.

Ongoing and Unpublished Clinical Trials

Table 5 provides a summary of ongoing trials that may influence this policy.

Table 7. Summary of Key Trials

NCT No.	Trial Name	Planned Enrollment	Completion Date
Ongoing
NCT03222752a	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	Jun 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	150	Aug 2018
NCT02851186	Combined Electroacupuncture and Auricular Acupuncture for Postoperative Pain after Abdominal Surgery for Gynecological Diseases: a Randomized Sham-Controlled Trial	72	Jan 2019
NCT03210155	Effects of Cranial Electrotherapy Stimulation on Psychological Distress and Maternal Functioning in New Mothers During the Postpartum Period	50	Jan 2020
NCT03060122	The Clinical Feasibility of Combining Cranial Electrotherapy Stimulation (CES Alpha-Stim) and Non-invasive Interactive Neurostimulation (InterX) for Optimized Rehabilitation Following Extremity Immobilization	94	May 2020

NCT: national clinical trial.

^a Denotes industry sponsorship]
________________________________________________________________________________________

Horizon BCBSNJ Medical Policy Development Process:

This Horizon BCBSNJ Medical Policy (the “Medical Policy”) has been developed by Horizon BCBSNJ’s Medical Policy Committee (the “Committee”) consistent with generally accepted standards of medical practice, and reflects Horizon BCBSNJ’s view of the subject health care services, supplies or procedures, and in what circumstances they are deemed to be medically necessary or experimental/ investigational in nature. This Medical Policy also considers whether and to what degree the subject health care services, supplies or procedures are clinically appropriate, in terms of type, frequency, extent, site and duration and if they are considered effective for the illnesses, injuries or diseases discussed. Where relevant, this Medical Policy considers whether the subject health care services, supplies or procedures are being requested primarily for the convenience of the covered person or the health care provider. It may also consider whether the services, supplies or procedures are more costly than an alternative service or sequence of services, supplies or procedures that are at least as likely to produce equivalent therapeutic or diagnostic results as to the diagnosis or treatment of the relevant illness, injury or disease. In reaching its conclusion regarding what it considers to be the generally accepted standards of medical practice, the Committee reviews and considers the following: all credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, physician and health care provider specialty society recommendations, the views of physicians and health care providers practicing in relevant clinical areas (including, but not limited to, the prevailing opinion within the appropriate specialty) and any other relevant factor as determined by applicable State and Federal laws and regulations.

___________________________________________________________________________________________________________________________

Index:
Cranial Electrotherapy Stimulation and Auricular Electrostimulation
Auricular Electrostimulation
Cranioelectrotherapy Stimulation
Electrostimulation, Auricular
Electrotherapy Stimulation, Cranial
Stimulation, Cranial Electrotherapy
P-Stim™
P Stim
E-Pulse
E Pulse
Alpha-Stim® CES Device
Cranial Electrical Nerve Stimulator
Elexoma Medic
CES Ultra
Net-2000 Microcurrent Stimulator
Transcranial Electrotherapy Stimulator-A, Model TESA-1
Model TESA-1, Trancranial Electrotherapy Stimulator-A
Drug Relief
NSS-2 Bridge
Stivax System
ANSiStim
AcuStim

References:
1. 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):478-484. PMID 7623022

2. Bronfort G, Nilsson N, Haas M, et al. Non-invasive physical treatments for chronic/recurrent headache. Cochrane Database Syst Rev. Jul 2004(3):CD001878. PMID 15266458

3. 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(4):CD008208. PMID 24729198

4. Kavirajan HC, Lueck K, Chuang K. Alternating current cranial electrotherapy stimulation (CES) for depression. Cochrane Database Syst Rev. Jul 8 2014;7:CD010521. PMID 25000907

5. Barclay TH, Barclay RD. A clinical trial of cranial electrotherapy stimulation for anxiety and comorbid depression. J Affect Disord. Aug 2014;164:171-177. PMID 24856571

6. 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

7. 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. Oct 2015;4:369. PMID 26435889

8. 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):1477-1480. PMID 21538515

9. 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):116-121. PMID 9209728

10. 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

11. 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

12. 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

13. 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):1359-1364, table of contents. PMID 15105215

14. 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

15. 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):187-193. PMID 18787327

16. 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

17. 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):21-25. PMID 24559812

18. 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):1517-1530. PMID 25183702

19. Kroening RJ, Oleson TD. Rapid narcotic detoxification in chronic pain patients treated with auricular electroacupuncture and naloxone. Int J Addict. Sep 1985;20(9):1347-1360. PMID 2867052

20. 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

Codes:
(The list of codes is not intended to be all-inclusive and is included below for informational purposes only. Inclusion or exclusion of a procedure, diagnosis, drug or device code(s) does not constitute or imply authorization, certification, approval, offer of coverage or guarantee of payment.)

CPT*

99199

S8930