Impact of Vagus Nerve Stimulation on Suicidal Ideation in Markedly Treatment-Resistant Major Depression: A RECOVER...

Objective: To compare effects of adjunctive active versus sham vagus nerve stimulation (VNS) on suicidal ideation (SI) in markedly treatment-resistant depression (TRD).

Methods: RECOVER trial participants with nonpsychotic major depressive disorder and insufficient benefit from ≥4 adequate antidepressant trials in the current episode were randomized to adjunctive active or sham VNS plus treatment as usual over 12 months. SI was assessed at baseline and monthly (months 3-12) following VNS parameter titration/ pseudotitration. A composite suicidal ideation (CSI) score (range, 0-9) used SI items from 3 depressive symptom ratings to assess VNS effects on SI for those with (CSI ≥3) and without (CSI ≤2) significant baseline SI.

Results: This exploratory study involved a sample (N = 463) who averaged 13.3 failed lifetime antidepressant treatments, with 17.7 years in the current depressive episode; 40.4% had previously attempted suicide. Among individuals with baseline SI, the likelihood of meaningful improvement (CSI score change ≥3) was greater with active than sham VNS (odds ratio [OR] = 1.43; 95% CI, 1.004-2.021; P < .05) over 10 months of evaluation. Additionally, active VNS was superior to sham VNS for SI remission (CSI ≤2) in months 10-12 (OR = 1.67; 95% CI, 1.007-2.763; P < .05). VNS did not significantly worsen SI in participants.

Conclusions: This study suggests that, compared to sham VNS, active VNS reduces SI and potentially induces SI remission among participants with chronic TRD and baseline SI. Furthermore, VNS does not appear to worsen or induce SI in participants, regardless of their baseline SI status. Further research is warranted.

Trial Registration: ClinicalTrials.gov identifier: NCT03887715.