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

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.