Predictors of response for vagus nerve stimulation in treatment-resistant depression

The past 20 years have witnessed the emergence of several new and effective neurostimulation treatments for depression. Stimulation of the left cervical vagus, or Vagus Nerve Stimulation (VNS), originally employed in treatment refractory seizure disorders, is emerging as a hopeful option to treat patients with highly treatment-resistant depression (TRD). Several clinical trials have demonstrated that a significant subset of highly refractory TRD patients experience an antidepressant response to VNS; one that is typically sustained. Although VNS in TRD is relatively new, existing studies support that certain TRD patient characteristics, as well as treatment delivery, can influence the likelihood of an antidepressant outcome. Existing data supports that VNS is effective: equally for bipolar versus unipolar TRD, in highly resistant patients (studies suggest antidepressant efficacy even in patients who have failed as many as 8 or more medications), as well as for patients suffering from prolonged depression. Failure to respond to electroconvulsive therapy (ECT) likely decreases the likelihood of response to VNS; however, many patients failing ECT do still respond. Clinical trial data to date also support that higher electrical current/charge delivered over time likely contributes to sustained antidepressant response. Brain imaging studies support that overactive insular cortical activity, as well as hypoactive orbitofrontal cortical activity, decreases likelihood of response. Finally, although concomitant personality disorder has not been studied in VNS antidepressant effectiveness trials, existing consensus indicates that severe concomitant personality disorder likely diminishes response. Additional studies need to be done to assess predictors of response of VNS in TRD.