<p>Durability of symptomatic responses obtained with adjunctive vagus nerve stimulation in treatment-resistant depression</p>

Abstract

Objective To compare the durations of response achieved with adjunctive vagus nerve stimulation (VNS + TAU) vs treatment as usual (TAU) alone in treatment-resistant depression (TRD) over a 5-year period in the TRD registry. Materials and methods Data from 271 participants on TAU and 328 participants on VNS + TAU were analyzed. Response was defined as ≥50% decrease in baseline Montgomery–Åsberg Depression Rating Scale (MADRS) score at postbaseline visit and was considered retained until the decrease was <40%. MADRS was obtained quarterly in year 1 and biannually thereafter. Time-to-events were estimated using Kaplan–Meier method and compared using log-rank test. HR was estimated using Cox proportion hazard model. Results In the VNS + TAU arm, 62.5% (205/328) of participants had a first response over 5 years compared with 39.9% (108/271) in TAU. The time to first response was significantly shorter for VNS + TAU than for TAU ( P <0.01). For responders in the first year, median time to relapse from first response was 10.1 months (Q1=4.2, Q3=31.5) for VNS + TAU vs 7.3 months (Q1=3.1, Q3=17.6) for TAU ( P <0.01). HR=0.6 (95% CI: 0.4, 0.9) revealed a significantly lower chance for relapse in VNS + TAU. Probability of retaining first response for a year was 0.39 (0.27, 0.51) for TAU and 0.47 (0.38, 0.56) for VNS + TAU. Timing of the onset of the response did not impact the durability of the response. Conclusion VNS therapy added to TAU in severe TRD leads to rapid onset and higher likelihood of response, and a greater durability of the response as compared to TAU alone.

<p>The Long and Winding Road of Vagus Nerve Stimulation: Challenges in Developing an Intervention for Difficult-to-Treat Mood Disorders</p>

“…Rather, in the VNS trials to date patients who achieved either response or remission showed strong durability of benefit. 18,22,24 In these patients there was also evidence that degrees of symptomatic improvement less than the traditional threshold of 50% were associated with meaningful improvement in quality of life. 13 It is noteworthy that the 50% criterion for declaring response is traditionally applied across all types of antidepressant treatment and depressed patient populations.…”

“…[15][16][17][18][19][20][21] Furthermore, those patients who show clinical benefit are likely to maintain it over long periods of time. 18,[21][22][23][24] These characteristics of VNS, slow onset and strong durability, pose challenges in designing clinical trials that adequately quantify its beneficial and adverse effects. Early studies of VNS in TRD used trial designs mainly based on acute treatment phase studies of antidepressant medications, applying the same pharmacological rationale to neuromodulation but without insight into the "electrodynamics" and "electrokinetics" of VNS or neuromodulation in general.…”

A prospective, multi-center randomized, controlled, blinded trial of vagus nerve stimulation for difficult to treat depression: A novel design for a novel treatment

“…For example, some interventions in MDD, like sleep deprivation, have little clinical utility despite marked immediate benefit, since virtually all patients who benefit relapse quickly [20]. Prior research has suggested that among antidepressant treatments, the durability of benefit following improvement with VNS is strong [30].…”

“…Recently, several new TRD treatment modalities have emerged, including ketamine [29], neurosteroids [32], and novel forms of neurostimulation [35]. Among neurostimulation interventions, vagus nerve stimulation (VNS) alone has undergone considerable study in more severe presentations of TRD [1,2,4,30].…”

Vagus Nerve Stimulation in Rodent Models: An Overview of Technical Considerations

“…Vagus nerve stimulation (VNS) is an FDA-approved treatment for select neurological and psychiatric conditions including epilepsy, treatment-resistant depression, and cluster headache (Heck et al, 2002; Ruffoli et al, 2011; Conway et al, 2016; Pisapia and Baltuch, 2016; Lainez and Guillamon, 2017; Kumar et al, 2019). There is also growing interest in using VNS to treat other conditions, such as heart failure, rheumatoid arthritis, inflammatory bowel disease, ischemic stroke, and traumatic brain injury (Zhang et al, 2009; Bonaz et al, 2013; Cai et al, 2014; Levine et al, 2014a,b, Levine et al, 2018a,b; Dawson et al, 2016; Guiraud et al, 2016; Koopman et al, 2016; Pruitt et al, 2016; Kanashiro et al, 2018), many of which are characterized by inflammation.…”