Depression affects millions of people worldwide, with limited effective treatment options. Antidepressant medications and psychological therapies have limitations, and patient preferences for treatment vary.
As a result, cranial electrostimulation (CES) therapy is being explored as a potential treatment option. The Alpha-Stim Anxiety Insomnia and Depression (AID) device, a CES device manufactured by Electromedical Products International, has received a CE-marking and is used for treating anxiety, insomnia, and depression.
While previous studies have shown promising results for using CES in reducing depressive symptoms, there is a lack of robust evidence on its clinical effectiveness versus sham treatment in people with primary major depression. The need for a broader range of practical and accessible treatments for depression is clear, and CES therapy may offer a promising solution.
A recent study published in The Lancet Psychiatry investigated the effectiveness of the Alpha-Stim Anxiety Insomnia and Depression (AID) device for treating depression symptoms in major depression. Randomized sham-controlled trials of cranial electrostimulation with the device had previously shown improvements in anxiety and depression symptoms.
However, there were no adequately powered trials in major depression. The study compared the clinical effectiveness of active Alpha-Stim AID to sham Alpha-Stim AID and aimed to determine whether the active device was superior in treating depression symptoms.
Alpha-Stim AID is a safe and acceptable treatment for primary major depression in individuals seeking help in primary care. However, a study showed no additional benefit when the active Alpha-Stim AID device delivered microcurrent, fixed-dose CES (100 μA) compared to sham treatment for primary significant depression symptoms that were unresponsive to antidepressant treatment. This study, known as the Alpha-Stim-D trial, was the first randomized controlled trial to assess the Alpha-Stim AID device for depression treatment in people seeking help for primary major depression.
The active and sham treatment groups showed clinically essential improvements in observer-rated depression symptoms and secondary outcomes after eight weeks. However, there was no significant difference between the active and sham groups regarding the change in depression symptoms at 16 weeks. Sham treatment was statistically superior to active treatment on the PHQ-9 at 4 and 16 weeks, on the GAD-7 at four weeks only, and on the EQ-5D-5L at 16 weeks only.
Nonetheless, the differences between treatment groups were slight and inconsistent across all time points, falling below clinically essential thresholds. The intervention was found to be well tolerated and safe for participants, with minor differences in adverse events between the groups. A high proportion of participants completed the recommended course of treatment.
Retention to the primary endpoint at 16 weeks after randomization was high (85%), with similar attrition between the groups, and the treatment completion at 73% was acceptable. The sample was representative of the age (including individuals aged 16–18) and gender characteristics of patients with depression in primary care. However, few people who were unemployed or with a disability were recruited into the study. The sample was broadly representative of the ethnicity of the population in England.
The study, which was an effectiveness trial rather than a test of efficacy, did not exclude all comorbidities, such as personality disorder or stable medical illness, to improve the generalizability of the results to patients seeking treatment for depression in primary care.
Although scores of 10–14 and 15–19 on the PHQ-9 were initially characterized as indicating moderate and moderately severe depression, more recent guidance published while the trial was recruiting suggests that these ranges should be regarded as mild and moderate severity.
The magnitude of mean clinical improvements met the minimum threshold for a clinically significant change at 16 weeks in both the active and sham Alpha-Stim AID groups on the GRID-HDRS-17 and in the sham group on the PHQ-9, GAD-7, and EQ-5D-5L. In the active Alpha-Stim AID group, clinically essential changes in PHQ-9, GAD-7, and EQ-5D-5L were observed at eight weeks.
However, the study found no evidence to support the clinical effectiveness of Alpha-Stim AID CES in patients with moderate to moderately severe primary major depression.