A novel home-based, combined occipital and trigeminal afferent stimulation therapy for major depressive disorder: Efficacy and safety results from a double-blind multicenter randomized sham-controlled study

Abstract

Objective

Patients with Major Depressive Disorder (MDD) who fail to achieve satisfactory benefits with existing antidepressants have limited treatment options. This study assessed the safety and efficacy of a novel non-invasive brain neuromodulation therapy which delivers external Combined Occipital and Trigeminal Afferent Stimulation (eCOT-AS) as a therapeutic option for MDD.

Methods

124 adults with MDD who failed to respond to antidepressants and with a baseline Hamilton Depression Rating Scale (HDRS21) score ≥20 were enrolled in a randomized, double-blind, sham-controlled, multicenter study of self-administered daily active or sham eCOT-AS (n = 62 per arm) for eight weeks. The double-blind phase was followed by an 8-week active open label phase. HDRS17 was used to assess outcomes.

Results

Baseline depression scores were similar for both groups and reflected moderate to very severe depression. After 8 weeks of treatment, the adjusted mean HDRS17 improvement in the active treatment group was 8.62 points versus 6.01 for sham (p = 0.0196). Compared to sham treatment, participants receiving active treatment had significantly higher remission rates (21.3 % vs 6.0 %, p = 0.027) and achieved significantly more shifts to lower HDRS17 depression severity categories. Participants further improved during the subsequent eight weeks of open-label active stimulation with a mean reduction of almost 10 points from baseline and achieved a remission rate of 32 %. The treatment was well-tolerated with generally mild and transient adverse events.

Conclusion

This home-based brain neuromodulation system is safe and effective in treating depression. These findings support eCOT-AS as a promising new adjunct therapy for MDD patients with nonresponse to antidepressants.