Morriss R, Xydopoulos G, Craven M, Price L and Fordham R. Clinical effectiveness and cost minimisation model of Alpha-Stim cranial electrotherapy stimulation in treatment seeking patients with moderate to severe generalised anxiety disorder. J Affect Disord, 2019 Apr 15;253: 426-437.

Device

Alpha-Stim^®

Key Variable

Anxiety

Objective

There were four aims in this current study to determine:

1. The proportion of anxiety patients treated with CES in IAPT services who reach the clinical threshold for remission (GAD-7 score of 7 or less, reliable improvement and recovery after treatment at 12 weeks.)
2. The proportion of anxiety patients treated with CES in IAPT services who maintain the clinical threshold for remission (GAD-7 score of 7 or less), reliable improvement and recovery at 24 weeks.
3. If there are significant changes over 24 weeks in generalized anxiety, depression, insomnia, social adjustment and quality of life.
4. If the cost of CES offsets the cost of psychological treatment and other treatment over 24 weeks.

Design

An open (ethical approved) consecutive patient cohort design with a 24 week follow up in National Health Service (NHS) mental health treatment settings in England was employed where all participants were offered Alpha-Stim cranial electrotherapy stimulation (CES) for 6–12 weeks if they had not reached remission with therapist or full guided self-help and were waiting to receive individual cognitive behavior therapy (iCBT).

Primary Effectiveness Endpoint

The primary outcome is the proportion of participants who reach remission (7 points or less) at 12 and 24 weeks on the GAD-7 since IAPT services are paid according to the proportion of patients who reach this threshold after treatment in their service.

Secondary Outcome Measures

• Personal Health Questionnaire is a 9-item self-rated measure of the severity of depression symptoms. Remission is a total score of 9 or less at 12 or 24 weeks in those who had scored 10 or more at baseline.
• Athens Insomnia Scale has 8 items with a maximum score of 24. A score of 6 indicates a possible sleep problem and 4 indicates recovery.
• Work and Social Adjustment Scale is an 8-item self-rated measure of work and social function. A total score of 20 or more indicates considerable impairment in function.
• EQ5D-5L is a 6-item self-rated measure of health utility and quality of life.

Key Inclusion Criteria

• A score of 8 or more on GAD-7 scale, a 7-item self-rated measure of symptoms of generalized anxiety disorder.
• A clinical diagnosis of generalized anxiety disorder alone or in combination with a comorbid depression or other anxiety disorder e.g. obsessive-compulsive disorder or physical health morbidity.
• On waiting list for individual CBT (high intensity psychological intervention).
• Does not require urgent clinical care.
• Gives informed written and oral consent to the study.
• Agrees to return Alpha-Stim equipment at the end of the study.

Key Exclusion Criteria

• Excluded was a diagnosis of any other mental disorder g., substance use disorder, eating disorder, bipolar disorder, non-affective psychosis.
• Pregnancy
• Implantation with a pacemaker or an implantable cardioverter device (ICD).

Protocol Summary

Consecutive treatment seeking patients who received low intensity IAPT interventions (therapist guided self-management on a computerized CBT program or bibliotherapy for GAD) but had not reached a total score of 8 or more, were unlikely to meet any exclusion criteria. All participants were offered 60 min per day of Alpha-Stim CES treatment at a current of one hundred microamperes per day 7 days per week for 6 consecutive weeks. The 60 min session starts when the ear clips are attached and stops automatically when the hour is finished. Participants could choose to continue with the same CES treatment for a further 6 weeks, thereby completing 12 weeks CES treatment in total. At the end of 12 weeks the participants could not receive any further CES treatment.

Results

Of 161 patients recruited, 72 (44.7%) and 77 (47.8%) achieved remission on the GAD-7 at 12 and 24 weeks respectively with 122 (75.8%) receiving at least 6 weeks CES. Mean (SD) GAD-7 score at baseline significantly improved from 15.77 (3.21) to 8.92 (5.42) and 8.99 (6.18) at 12 and 24 weeks respectively (p<0.001). 80 (49.7%) participants required further individual CBT. CES provided a saving of £540.88 ($684.68) per patient.

The proportions of participants achieving reliable improvement on the GAD-7 were 102 (63.4%) and 105 (65.2%) at 12 and 24 weeks respectively. No patient showed reliable deterioration at 12 or 24 weeks. The vast majority of the drop in GAD-7 is experienced in the first 6 weeks and there is no statistically significant difference between week 6 and any subsequent time point up to week 24.

Subjects

161 patients were recruited. All 161 participants started CES treatment and112 (69.6%) completed at least 6 weeks treatment.

Conclusion

This study shows that in moderate to severe treatment seeking patients with GAD, nearly 45% of patients achieved remission and 63% reliable improvement in their self-rated anxiety symptoms with Alpha-Stim CES treatment. These improvements were maintained for a further 12 weeks after CES was completed whether or not patients received iCBT in addition. Most of the improvement with CES was seen in the first 4 weeks. The study showed a moderate effect size. Remission rates are lower than reported for iCBT in routine IAPT services in the UK. The mean severity of GAD-7 symptoms decreased from severe to mild and below case threshold over 12 weeks and remained at that level for 24 weeks. There were similar drops in depression symptoms and insomnia symptoms as well as improvements in function and quality of life although all of these effects were smaller with some slippage between 12 and 24 weeks. There was a high degree of attrition of the study to follow up with the loss of 55.2% by 24 weeks despite financial incentive to provide data as opposed to 40% that we had anticipated. The study was adequately powered because CES was highly effective. As well as improvements in anxiety, there were improvements in depression and insomnia, which are also indications for CES. In conclusion, This study provides evidence that CES is clinically effective while reducing cost during administration and for three months afterwards in routine treatment settings offering psychological treatments for moderate to severe GAD. Alpha-Stim CES improves the efficiency of these services, a critical issue due to the shortage and high turnover of psychological treatment staff, allowing them to reach their targets for remission with fewer highly skilled staff.

Side Effects

Alpha-Stim CES was well tolerated with only six (4%) patients stopping it because of minor side effects and four (3%) because they were not making any progress.

Quality of the Research

The strengths of the study were that clinical and cost effectiveness was examined in a consecutive large sample of treatment seeking patients in universally available publicly funded services provided by the state irrespective of the ability to pay or health insurance. Inclusion criteria were set to reflect the criteria used by IAPT services to offer individual CBT. This criterion was set at 8 or more on the GAD-7 reflecting the upper end of mild severity compared to the usual clinical thresholds for mild, moderate and severe anxiety of 5,10 and 15 on the GAD-7. However, 95% of the sample had moderate or severe symptoms of GAD at baseline, well above the minimum threshold for entry to the study and the national NHSIAPT criteria for remission. They had already failed to improve with facilitated bibliotherapy or computerized psychological treatment for GAD, so spontaneous improvement was unlikely. Placebo responses are less frequent in research participants with less severe anxiety or depression and in those who have not responded to previous active treatment for their condition. Therefore, the study shows the effectiveness of CES in a clinical treatment seeking sample of patients with moderate to severe treatment resistant generalized anxiety disorder.

Limitations

There are important limitations of the study. There was no control group and the study was not a randomized controlled trial. However, metanalysis of previous RCTs of active CES versus sham CES already provides evidence that CES is effective in treating anxiety and depression symptoms.