Griffiths, C., Leathlean, C., Smart, D., Zafar, A., Hall, C-L., & Deeks, S. Alpha-Stim Cranial Electrotherapy Stimulation (CES) for Anxiety Treatment: Outcomes in a United Kingdom (UK) Primary Care Practice. Open Journal of Psychiatry. 2021; 11, 186-201.

Funding Source, Location of Study or Author’s Affiliation
National Institute for Health Research (NIHR) Clinical Research Network (CRN) East Midlands

Device
Alpha-Stim^® AID

Key Variable
Anxiety

Objective
To present outcomes on anxiety, depression, and quality of life of Alpha-Stim use in primary care patients in the United Kingdom’s (UK) National Health Service (NHS) who reported symptoms of anxiety.

Design
An open label patient cohort design.

Primary Outcome Measure

• GAD-7 is a 7-item self-rated measure of symptoms of Generalized Anxiety Disorder. Remission is a total score of 7 or less at the week 6 measurement, while reliable improvement is a reduction of 5 or more points from the baseline score. Recovery is defined as both reliable improvement and remission achievement.

Secondary Outcome Measure

• Personal Health Questionnaire (PHQ-9) is a 9-item self-rated measure of the severity of depression symptoms. Remission is a total score of 9 or less at the week 6 measurement, and recovery is defined as both reliable improvement and remission achievement.
• EQ5D-5L is a 6-item self-rated measure of health utility and quality of life that is widely used in national health surveys in the UK and clinical trials of mental health interventions.

Key Inclusion Criteria

• A score of 8 or more on the GAD-7.
• At least 18 years of age.
• Gives informed written and oral consent to the study.

Key Exclusion Criteria

• Lack of capacity to consent
• History of seizures
• Implantation with a pacemaker or an implanted electrical device.

Protocol Summary

Patients were given printed instructions on use of the Alpha-Stim and shown how it works. Support was provided if required. Patients remained on any physical or medical health medication they were currently taking. Measures were collected prior to the first treatment, mid-intervention at week 3, and shortly following the end of treatment at week 6.

Device Application Protocol
All participants were offered 60 minutes per day of Alpha-Stim CES treatment at a current of 100 uA per day 7 days per week for 6 consecutive weeks. However, devices were not locked at these settings.

Statistical Analysis Plan
Data were analyzed using SPSS software package. Apriori hypotheses were that Alpha-Stim treatment would significantly reduce levels of anxiety and depression while improving the patients’ quality of life.

Results

Subjects
Participants were referred to their Social Prescribing Link Worker (SPLW) by their GP, who in turn referred them to the lead SPLW for inclusion in this study. Thirty-six (36) participants were recruited. Prior to week 1, five declined to participate, one due to “extreme external pressure,” one due to “severe headache,” one due to “extreme anxiety,” and two declined for unknown reasons. Following baseline measurements, another four participants withdrew from the study, two due to anxiety about the device, one due to a concern over medical history, and one for unknown reasons. Prior to week 6, an additional four participants withdrew from the study; one stated extreme headaches, one felt unable to continue due to lack of coping following the bereavement of a family member, and the remaining two did not stipulate a reason for disengagement. Twenty-three (23) completed 6 weeks of treatment and post intervention mental health assessments. The participants were comprised of 29 (80.6%) females and seven (19.4%) males. Although the study does not state that participants were diagnosed with Generalized Anxiety Disorder or Major Depressive Disorder, the high baseline scores on the GAD-7 and PHQ-9 meet screening criteria for these disorders.

Data Analysis
At baseline, mean scores on the GAD-7 (17.93±3.41) and PHQ-9 (19.00±4.1) were in the severe ranges for both anxiety and depression. The table below shows the number of participants who achieved remission, reliable improvement, or recovery on the GAD-7, the PHQ-9, or on both measures at weeks 3 and 6. The reduction in GAD-7 scores from baseline to week 6 were significant (p<0.001). Similarly, the reduction in PHQ-9 scores were significant (p<0.001) at both week 3 and week 6. The effect sizes were found to be large for both the GAD-7 (partial n2=0.59) and for the PHQ-9 (partial n2=0.56).

*n=23

Remission, reliable improvement, and recovery

There were significant improvements on the EQ-5D-5L scores in the areas of self-care (p=0.015), ability to perform usual activities (p<0.001), and experience of depression and anxiety (p<0.001). There was also a significant improvement in the overall health index score (p=0.003). The overall health index score is used in research to calculate Quality-Life Adjusted Years (QALYs). From baseline to week 6, quality of life doubles with an improvement from 0.357 at baseline to .0721 at week 6. Measured across 10 years, this intervention adds 3.64 QALYs.

Conclusions
The results of this study indicate Alpha-Stim can be delivered in a primary care clinical setting and is effective in reducing anxiety and depression as well as improving patients’ quality of life. Although formal cost effectiveness measures were not evaluated in this study, the authors use thresholds stipulated by NICE for England and Wales and conclude Alpha-Stim is highly cost-effective, as the cost is well below the stipulated threshold.

Limitations
This was an open label study, so there was no control or comparator group. There were no follow up data collected beyond the end of the study to evaluate long-term effectiveness of Alpha-Stim treatment. The small sample size, which was predominately female, limits generalizability. However, the results of this study are consistent with other research on the effectiveness of Alpha-Stim in treating anxiety and depression.

Study Quality: FAIR