Vagus Nerve Stimulation (VNS) vs. Deep Brain Stimulation (DBS) Treatment for Major Depressive Disorder and Bipolar Depression: A Comparative Meta-analytic Review Article View

Abstract

Background: Patients who suffer from major depressive episodes and bipolar disorder often exhibit pharmaco-resistance. Therefore, novel treatment methodologies are being proposed to treat the disease or provide symptomatic relief. VNS and DBS are two such techniques, both of which utilize neurostimulation to achieve therapeutic relief. However, it is necessary to establish the comparative efficacies of these methods in treating MDD in patients. Objective: To assess the relative difference in the efficacy of VNS versus DBS for treatment of Major Depressive Disorder and bipolar depression and to provide evidence for the superior technique. Methods: To compare the efficacy of VNS versus DBS for the reduction of depressive symptoms in patients who meet the criteria for a major depressive episode, we conducted a meta-analysis of studies of the subject. Twenty-six studies were selected, consisting of 1160 patients who were treated with either VNS (Mean age = 47.75 years old, mean duration of illness = 22.86 years) or DBS (Mean age = 33.11 years old, mean duration of illness = 9.9 years) treatment arms and analyzed them to determine the amount of improvement in mood. The primary outcome measures were evaluated in terms of change between pre-test and post-test scores over a period of three months, as measured by HDRS and MADRS rating scales. Results: A comparison of the summary effect size produced by VNS (HDRS = 1.247, MADRS = 1.110) to that produced by DBS (HDRS = 2.063, MADRS = 1.996) seems to demonstrate that DBS is the more effective treatment. The effect size for VNS was lower than that of DBS groups, indicating that DBS is more effective than VNS. The finding is corroborated by the tests of heterogeneity; while the VNS group of studies indicated a high level of heterogeneity Vs. DBS group indicated insignificant level of heterogeneity. Conclusion: Current meta-analysis demonstrates that Deep Brain Stimulation (DBS) is a better treatment modality for Major Depressive Disorder and Bipolar Depression than Vagus Nerve Stimulation (VNS). However, as the VNS and DBS groups differed concerning the clinical profiles of the patients (both in terms of age and regarding the duration of the illness. Research studies with larger, synchronous sample sizes and control groups are required for a meta-analysis to draw a steadfast conclusion.

Can Deep Brain Stimulation Be a Promising Treatment for Treatment-Resistant Depression?

“…The main disadvantages of VNS therapy can be as: i) Antidepressant effects of VNS in short-term (10-12 weeks) sham study demonstrated to be statistically nonsignificant, albeit, open-label long-term response and remission rates were high (27% response rate and 16% remission rate after 12 months of stimulation) and statistically significant [46], the average response time in VNS is 9 months after stimulation onset [47]; ii) In the longer-term study, 21%-50% of responders to VNS failed to maintain at least a 40% reduction in baseline depression severity over 1-2 years [39]; iii) VNS has no acute efficacy in the treatment of TRD but has shown to be effective in the treatment of chronic depression [48,49]; iv) Its high cost, lack of Medicare or Commercial coverage, and inadequacy in treating acute depression caused the number of patients benefitting from this treatment modality is low despite 15 years of commercial availability [16]; v) Although most of the VNS side effects are generally reversible, the most frequent acute complications include temporary salivation, coughing, paralysis of the vocal cords, lower facial weakness, rarely bradycardia, and, very rarely, asystole.…”

An Overview of the Heterogeneity of Major Depressive Disorder: Current Knowledge and Future Prospective

“…These can aid in developing multitargeted therapies with more promise as compared to the standard treatment. In addition, brain stimulation therapies like deep brain stimulation and vagal nerve stimulation along with new classes of antidepressant-like vortioxetine, a multimodal antidepressant that acts as 5-HT transporter inhibitor, a 5-HT 3 , 5-HT 1D and 5-HT 7 receptor antagonist, 5-HT 1B receptor partial agonist and 5-HT 1A receptor agonist, may hold better assurance than the conventional antidepressants [ 260 - 262 ]. As a breakthrough in decades, esketamine, the S-enantiomer of racemic ketamine was recently approved by the FDA to use in conjunction with an oral antidepressant, for the treatment of treatment-resistant depression in adults [ 263 ].…”

A retrospective, naturalistic study of deep brain stimulation and vagal nerve stimulation in young patients*

“…Additionally, a meta-analysis comparing VNS and DBS for treatment of unipolar and bipolar depression showed that patients receiving DBS had greater improvement (Khan et al, 2018). Wong et al (2019) examined the results of five clinical trials and showed that VNS was less efficacious than DBS over time.…”

“…At every 3‐month follow‐up assessment, the efficacy of anterior thalamic DBS was higher than that of VNS. Additionally, a meta‐analysis comparing VNS and DBS for treatment of unipolar and bipolar depression showed that patients receiving DBS had greater improvement (Khan et al., 2018 ). Wong et al.…”