Clinical effectiveness of active Alpha-Stim AID versus sham Alpha-Stim AID in major depression in primary care in England (Alpha-Stim-D): a multicentre, parallel group, double-blind, randomised controlled trial.

BACKGROUND: Randomised sham-controlled trials of cranial electrostimulation with the Alpha-Stim Anxiety Insomnia and Depression (AID) device have reported improved anxiety and depression symptoms; however, no adequately powered sham-controlled trials in major depression are available. We investigated whether active Alpha-Stim AID is superior to sham Alpha-Stim AID in terms of clinical effectiveness for depression symptoms in major depression. METHODS: The Alpha-Stim-D trial was a multicentre, parallel group, double-blind, randomised controlled trial, recruiting participants from 25 primary care centres in two regions in England, UK. Eligible participants were aged 16 years or older with a current diagnosis of primary major depression, a score of 10-19 on the nine-item Patient Health Questionnaire, and had been offered or prescribed and reported taking antidepressant medication for at least 6 weeks in the previous 3 months. Main exclusion criteria were contraindications to Alpha-Stim AID device use, having persistent suicidal ideation or self-harm, neurological conditions, a substance use disorder or dependence, an eating disorder, bipolar disorder, or non-affective psychosis, or receiving psychological treatment in the past 3 months. Eligible participants were randomly assigned (1:1, minimised by region, anxiety disorder, and antidepressant use) to 1 h daily use of active (100 µA) or sham Alpha-Stim AID treatment for 8 weeks. Randomisation was via an independent web-based system, with participants, outcome assessors, and data analyst masked to treatment assignment. The primary outcome was change from baseline in score on the 17-item Hamilton Depression Rating Scale (HDRS-17, GRID version) at 16 weeks after randomisation, with participants analysed by intention to treat (ITT; all randomly assigned participants). Safety was assessed in all randomly assigned participants. The trial is registered with the ISRCTN registry (ISRCTN11853110); status completed. FINDINGS: Between Sept 8, 2020, and Jan 14, 2022, 236 eligible participants were randomly assigned to active or sham Alpha-Stim AID (n=118 each). 156 (66%) participants were women, 77 (33%) were men, and three (1%) self-reported as other gender; 200 (85%) were White British or Irish; and the mean age was 38·0 years (SD 15·3; range 16-83). 102 (86%) participants in the active Alpha-Stim AID group and 98 (83%) in the sham group were followed up 16 weeks after randomisation. In the ITT population, mean change in GRID-HDRS-17 at 16 weeks was -5·9 (95% CI -7·1 to -4·8) in the active Alpha-Stim AID group and -6·5 (-7·7 to -5·4) in the sham group (mean change difference -0·6 [95% CI -1·0 to 2·2], p=0·46). Among the 236 participants, 17 adverse events were reported in 17 (7%) participants (nine [8%] participants in the active Alpha-Stim AID group; and eight [7%] participants in the sham group). One serious adverse event of suicidal ideation leading to hospitalisation was reported in the sham group, which was judged to be unrelated to the device. INTERPRETATION: Active Alpha-Stim AID was safe and acceptable, but no more clinically effective than sham Alpha-Stim AID in major depression. FUNDING: National Institute for Health Research Applied Research Collaboration East Midlands and Electromedical Products International.

A randomised controlled trial investigating the clinical and cost-effectiveness of Alpha-Stim AID cranial electrotherapy stimulation (CES) in patients seeking treatment for moderate severity depression in primary care (Alpha-Stim-D Trial).

BACKGROUND: Major depression is the second leading cause of years lost to disability worldwide and is a leading contributor to suicide. However, first-line antidepressants are only fully effective for 33%, and only 40% of those offered psychological treatment attend for two sessions or more. Views gained from patients and primary care professionals are that greater treatment uptake might be achieved if people with depression could be offered alternative and more accessible treatment options. Although there is evidence that the Alpha-Stim Anxiety Insomnia and Depression (AID) device is safe and effective for anxiety and depression symptoms in people with anxiety disorders, there is much less evidence of efficacy in major depression without anxiety. This study investigates the effectiveness of the Alpha-Stim AID device, a cranial electrotherapy stimulation (CES) treatment that people can safely use independently at home. The device provides CES which has been shown to increase alpha oscillatory brain activity, associated with relaxation. METHODS: The aim of this study is to investigate the clinical and cost-effectiveness of Alpha-Stim AID in treatment-seeking patients (aged 16 years upwards) with moderate to moderately severe depressive symptoms in primary care. The study is a multi-centre parallel-group, double-blind, non-commercial, randomised controlled superiority trial. The primary objective of the study is to examine the clinical efficacy of active daily use of 8 weeks of Alpha-Stim AID versus sham Alpha-Stim AID on depression symptoms at 16 weeks (8 weeks after the end of treatment) in people with moderate severity depression. The primary outcome is the 17-item Hamilton Depression Rating Scale at 16 weeks. All trial and treatment procedures are carried out remotely using videoconferencing, telephone and postal delivery considering the COVID-19 pandemic restrictions. DISCUSSION: This study is investigating whether participants using the Alpha-Stim AID device display a reduction in depressive symptoms that can be maintained over 8 weeks post-treatment. The findings will help to determine whether Alpha-Stim AID should be recommended, including being made available in the NHS for patients with depressive symptoms. TRIAL REGISTRATION: ISRTCN ISRCTN11853110 . Registered on 14 August 2020.