Cranial Electrotherapy Stimulation for Anxiety

Overseen By Tad Brunye, Ph.D.

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Tufts University

Must not be taking: Prescription medications

Disqualifiers: Neurological, Psychological, Cardiac, Hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 23

Duration: 4-6 weeks

76 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this study is to quantify the effects of 20 sessions of Cranial Electrotherapy Stimulation (CES) on measures of acute stress responses in Soldiers. The main question it aims to answer is how 20 sessions of CES will affect Soldiers' biochemical (salivary alpha amylase and cortisol), physiological (e.g., heart rate, heart rate variability, respiration rate), emotional (state anxiety), and behavioral (i.e., cognitive task performance) responses. * On Day 1, participants will complete a baseline measure assessing their biochemical, physiological, emotional, and behavioral responses to a stressful lethal force decision making task. * In the next four to six weeks, participants will complete 20 CES sessions. * Within five days of completing the 20 CES sessions, participants will complete a follow-up measure assessing their biochemical, physiological, emotional, and behavioral responses to the same stressful lethal force decision making task they completed on Day 1. Researchers will compare the Active CES group to the Sham CES group to see how 20 sessions of Active CES will affect the participants responses to their biochemical, physiological, emotional and behavioral responses relative to the Sham CES group.

Do I have to stop taking my current medications for the trial?

Yes, you must stop taking prescription medications, except for oral contraceptives, to participate in the trial.

Will I have to stop taking my current medications?

Yes, you will need to stop taking prescription medications, except for oral contraceptives, to participate in this trial.

What data supports the idea that Cranial Electrotherapy Stimulation for Anxiety is an effective treatment?

The available research shows that Cranial Electrotherapy Stimulation (CES) is effective in treating anxiety. A meta-analysis of randomized controlled trials found CES to be significantly more effective than a placebo treatment for anxiety. This means that people who received CES experienced greater relief from anxiety symptoms compared to those who did not receive the actual treatment. Additionally, CES has been supported by over 40 years of research, including more than 100 clinical studies, indicating its effectiveness in treating anxiety, depression, and insomnia. While some studies have questioned its effectiveness, the overall evidence suggests that CES can be a helpful treatment for anxiety. ^{1 2 3 4 5}

What data supports the effectiveness of this treatment for anxiety?

Research shows that cranial electrotherapy stimulation (CES) is effective in treating anxiety, as demonstrated by a meta-analysis of multiple studies where CES was significantly more effective than a placebo treatment. ^{1 2 3 4 5}

What safety data exists for Cranial Electrotherapy Stimulation for Anxiety?

The provided research does not contain specific safety data for Cranial Electrotherapy Stimulation (CES) or its various names. The studies focus on epilepsy, antiepileptic drugs, and related conditions, not CES. For safety data on CES, it would be necessary to consult studies specifically evaluating CES or its alternative names like Alpha-Stim, P-Stim, or others. ^{6 7 8 9 10}

Is Cranial Electrotherapy Stimulation a promising treatment for anxiety?

Yes, Cranial Electrotherapy Stimulation (CES) is a promising treatment for anxiety. It has been supported by over 40 years of research and more than 100 clinical studies showing its effectiveness. CES is a non-invasive method that uses mild electrical stimulation to help reduce anxiety, and it is generally well-tolerated with rare side effects. ^{1 3 4 11 12}

How is cranial electrotherapy stimulation different from other anxiety treatments?

Cranial electrotherapy stimulation (CES) is unique because it uses a mild electrical current delivered through electrodes on the head to treat anxiety, unlike traditional treatments that often involve medication or talk therapy. It is non-invasive and has been shown to be effective in reducing anxiety, depression, and insomnia with minimal side effects. ^{1 3 4 11 12}

Research Team

Kana Okano, Ph.D.

Principal Investigator

Tufts University

Eligibility Criteria

This trial is for individuals aged 18-40 who have never used Cranial Electrotherapy Stimulation (CES) and can sit and stand freely. They must be willing to have their data stored for future research. People with hypertension, insomnia, brain conditions, pregnancy plans during the study, history of brain injury or illness, use of certain medications (excluding oral contraceptives), nursing mothers, or those with neurological/psychological disorders are excluded.

Inclusion Criteria

Agree to have their data stored in a repository (database) for future use

I can sit and stand without help.

I have never used or been treated with CES.

Exclusion Criteria

I am taking prescription medications other than birth control pills.

I have a history of neurological or psychological disorders.

I have a history of heart disease or irregular heartbeats.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline Assessment

Participants complete a baseline measure assessing their biochemical, physiological, emotional, and behavioral responses to a stressful lethal force decision making task

1 day

1 visit (in-person)

Treatment

Participants complete 20 sessions of Cranial Electrotherapy Stimulation (CES) over four to six weeks

4-6 weeks

20 visits (in-person)

Follow-up

Participants complete a follow-up measure assessing their biochemical, physiological, emotional, and behavioral responses to the same stressful lethal force decision making task

Within 5 days after treatment

1 visit (in-person)

Treatment Details

Interventions

• Active CES
• Sham CES

Trial Overview The study tests how 20 sessions of CES affect soldiers' stress responses by measuring biochemical markers like salivary alpha amylase and cortisol, physiological indicators such as heart rate variability, emotional state anxiety levels, and cognitive task performance before and after the treatment compared to a Sham CES group.

Participant Groups

Group I: Active CES Active Control 1 Intervention

Active Cranial Electrotherapy Stimulation (CES)

Group II: Sham CES Placebo Group 1 Intervention

Sham Cranial Electrotherapy Stimulation (CES)

Active CES is already approved in United States for the following indications:

Approved in United States as Cranial Electrotherapy Stimulation for:

• Anxiety
• Depression
• Insomnia
• Post-traumatic stress disorder
• Headache

Who Is Running the Clinical Trial?

Tufts University

Lead Sponsor

Trials

271

Recruited

595,000+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Findings from Research

Cranial electrotherapy stimulation (CES) significantly reduced depression scores in participants, improving from an average of 31.3 to 10.8 on the Beck depression inventory-II, indicating its efficacy in alleviating depressive symptoms.

CES also positively impacted stress response by flattening the cortisol slope and increasing bedtime cortisol levels, suggesting it may serve as an effective adjunctive therapy for stress management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cranial electrotherapy stimulation on improving depressive symptoms in people with stress: A randomized, double-blind controlled study. Lee, M., Kim, Y., Yoon, IY., et al.[2023]

The NEAT12 device, which uses cranial electrotherapy stimulation (CES) techniques, appears to positively influence brain activity in a 42-year-old male patient recovering from alcohol dependence, particularly by upregulating activity in the Cingulate Gyrus, a region associated with substance use disorders.

Pre- and post-treatment qEEG analysis showed significant changes in brain wave patterns, including a decrease in delta waves and an increase in alpha waves, suggesting that NEAT12 may help normalize electrical activity in the brain during protracted abstinence from alcohol, indicating potential as an anti-craving therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative Electroencephalography Analysis (qEEG) of Neuro-Electro-Adaptive Therapy 12™ [NEAT12] Up-Regulates Cortical Potentials in an Alcoholic during Protracted Abstinence: Putative Anti-Craving Implications. Waite, RL., Oscar-Berman, M., RBraverman, E., et al.[2019]

Cranial electrotherapy stimulation is an effective treatment for anxiety, depression, and insomnia, supported by over 40 years of research and more than 100 clinical studies.

The device has a very low incidence of adverse effects (less than 1%), which are generally mild and self-limiting, making it a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cranial electrotherapy stimulation for treatment of anxiety, depression, and insomnia. Kirsch, DL., Nichols, F.[2022]

Electrical cranial stimulation (CES) significantly reduces symptoms of anxiety, depression, and insomnia, with a strong effect size of -0.96 for anxiety based on a meta-analysis of 8 randomized controlled trials involving 337 participants.

The 'Alpha-Stim' device used for CES was particularly effective in alleviating anxiety compared to sham controls, and the treatment was well-accepted, showing no increased risk of dropout compared to control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of electrical cranial stimulation for treatment of psychiatric symptoms in patients with anxiety: A systematic review and meta-analysis. Chung, FC., Sun, CK., Chen, Y., et al.[2023]

Cranial electrostimulation (CES) was found to be significantly more effective than sham treatment for anxiety based on a meta-analysis of 14 randomized controlled trials, indicating its potential as a therapeutic intervention for anxiety disorders.

The review highlighted concerns about the quality of the studies, including a lack of complete data reporting and insufficient blinding of therapists, which could introduce bias in the results; thus, future research should address these issues to improve reliability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Meta-analysis of randomized controlled trials of cranial electrostimulation. Efficacy in treating selected psychological and physiological conditions. Klawansky, S., Yeung, A., Berkey, C., et al.[2019]

The Italian version of the Liverpool Adverse Events Profile (iLAEP) was validated as a reliable tool for monitoring adverse events of antiepileptic drugs (AEDs) in 204 patients, showing high internal consistency and a quick completion time of about 9 minutes.

The iLAEP effectively predicts treatment discontinuation, with a cutoff score of 36.5 indicating a significant risk of dropout, as patients scoring above this threshold had a 20.27-fold increased risk of stopping their AED treatment within 3 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liverpool Adverse Events Profile: Italian validation and predictive value for dropout from antiepileptic treatment in people with epilepsy. Romoli, M., Eusebi, P., Siliquini, S., et al.[2019]

The case of a 7-year-old girl with sleep electrical status epilepticus (SESE) revealed that SESE may be associated with hypersomnia and nocturnal enuresis, suggesting it could be an intrinsic sleep disorder rather than just an EEG finding.

Neuropsychological assessments indicated significant language deficits and potential limbic system involvement, highlighting the need for systematic testing for sleep disorders in children with SESE, as it may lead to neuropsychological consequences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Electrical status epilepticus during sleep]. Ortega, JJ., Belda, VJ., Tripiana, JL., et al.[2009]

This study is the first placebo-controlled double-blind cross-over trial assessing the efficacy of levetiracetam (LEV) in treating Electric Status Epilepticus during Sleep (ESES) in children, involving 18 patients.

Levetiracetam significantly reduced the mean spike index from 56 to 37, demonstrating a strong treatment effect (p<0.0002), indicating its potential effectiveness in managing ESES similar to its use in treating epileptic seizures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of levetiracetam on focal nocturnal epileptiform activity during sleep--a placebo-controlled double-blind cross-over study. Larsson, PG., Bakke, KA., Bjørnæs, H., et al.[2018]

In a study of 7973 patients requiring emergent sedation for behavioral emergencies, serious adverse events (SAEs) were rare, occurring in only 2.1% of cases, with cardiac arrest happening in just 0.1% of patients.

Ketamine was associated with a higher frequency of invasive airway placements and severe oxygen desaturation compared to benzodiazepines and antipsychotics, but it also resulted in fewer patients needing additional sedation, indicating a complex risk-benefit profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events following emergent prehospital sedation of patients with behavioral emergencies: A retrospective cohort study. Brown, LH., Crowe, RP., Pepe, PE., et al.[2023]

ESES/CSWS is a rare childhood epilepsy disorder characterized by continuous epileptiform activity during sleep, with an incidence of 0.2-0.5% among all childhood epilepsies, and it leads to neuropsychological regression and motor impairment.

There is currently no consensus on the best treatment for ESES/CSWS, as no controlled clinical trials exist; however, various treatment options like antiepileptic drugs, steroids, and dietary changes are reviewed, highlighting the need for a personalized therapeutic approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of encephalopathy with status epilepticus during sleep (ESES/CSWS syndrome): an update. Veggiotti, P., Pera, MC., Teutonico, F., et al.[2017]

Cranial electrotherapy stimulation (CES) significantly reduces anxiety symptoms in patients, showing a moderate effect size based on a systematic review of 11 randomized control trials involving 794 participants.

CES is well-tolerated with no severe side effects reported, making it a safe option for reducing both anxiety and depressive symptoms in patients with anxiety disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Cranial Electrotherapy Stimulation in the Treatment of Anxiety: A Systemic Review and Meta-Analysis. Ching, PY., Hsu, TW., Chen, GW., et al.[2022]

Cranial Electrotherapy Stimulation (CES) using novel in-ear electrodes significantly reduced state-anxiety symptoms in a 3-week study with nonclinical volunteers, compared to a sham treatment.

EEG analysis revealed that CES increased theta power in the left frontal region and high-beta activity in specific brain areas, suggesting that CES may positively influence brain activity related to anxiety management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of cranial electrotherapy stimulation with novel in-ear electrodes on anxiety and resting-state brain activity: A randomized double-blind placebo-controlled trial. Kim, J., Kim, H., Kim, DH., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of cranial electrotherapy stimulation on improving depressive symptoms in people with stress: A randomized, double-blind controlled study. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Quantitative Electroencephalography Analysis (qEEG) of Neuro-Electro-Adaptive Therapy 12™ [NEAT12] Up-Regulates Cortical Potentials in an Alcoholic during Protracted Abstinence: Putative Anti-Craving Implications. [2019]

3. United States pubmed.ncbi.nlm.nih.gov

Cranial electrotherapy stimulation for treatment of anxiety, depression, and insomnia. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy of electrical cranial stimulation for treatment of psychiatric symptoms in patients with anxiety: A systematic review and meta-analysis. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Meta-analysis of randomized controlled trials of cranial electrostimulation. Efficacy in treating selected psychological and physiological conditions. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Liverpool Adverse Events Profile: Italian validation and predictive value for dropout from antiepileptic treatment in people with epilepsy. [2019]

7. Spain pubmed.ncbi.nlm.nih.gov

[Electrical status epilepticus during sleep]. [2009]

8. United States pubmed.ncbi.nlm.nih.gov

The effect of levetiracetam on focal nocturnal epileptiform activity during sleep--a placebo-controlled double-blind cross-over study. [2018]

9. England pubmed.ncbi.nlm.nih.gov

Adverse events following emergent prehospital sedation of patients with behavioral emergencies: A retrospective cohort study. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Therapy of encephalopathy with status epilepticus during sleep (ESES/CSWS syndrome): an update. [2017]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Efficacy and Tolerability of Cranial Electrotherapy Stimulation in the Treatment of Anxiety: A Systemic Review and Meta-Analysis. [2022]

12. Netherlands pubmed.ncbi.nlm.nih.gov

Effects of cranial electrotherapy stimulation with novel in-ear electrodes on anxiety and resting-state brain activity: A randomized double-blind placebo-controlled trial. [2021]