A patient-level meta-analysis of studies evaluating vagus nerve stimulation therapy for treatment-resistant depression

Abstract

Objective: To compare response and remission rates in depressed patients with chronic treatment-resistant depression (TRD) treated with vagus nerve stimulation (VNS) Therapy ® plus treatment as usual (VNS + TAU) or TAU alone in a meta-analysis using Bayesian hierarchical models. Data sources and study selection: Six outpatient, multicenter, clinical trials that have evaluated VNS + TAU or TAU in TRD, including two single-arm studies of VNS + TAU (n = 60 and n = 74), a randomized study of VNS + TAU versus TAU (n = 235), a randomized study of VNS + TAU comparing different VNS stimulation intensities (n = 331), a nonrandomized registry of VNS + TAU versus TAU (n = 636), and a single-arm study of TAU (n = 124) to provide longer-term, control data for comparison with VNS-treated patients. Data extraction: A systematic review of individual patient-level data based on the intent-to-treat principle, including all patients who contributed more than one post-baseline visit. Response was based on the Montgomery-Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions scale's Improvement subscale (CGI-I), as these were the two clinician-rated measures common across all or most studies. Remission was based on the MADRS. Results: Outcomes were compared from baseline up to 96 weeks of treatment with VNS + TAU (n = 1035) versus TAU (n = 425). The MADRS response rate for VNS + TAU at 12, 24, 48, and 96 weeks were 12%, 18%, 28%, and 32% versus 4%, 7%, 12%, and 14% for TAU. The MADRS remission rate for VNS + TAU at 12, 24, 48, and 96 weeks were 3%, 5%, 10%, and 14% versus 1%, 1%, 2%, and 4%, for TAU. Adjunctive VNS Therapy was associated with a greater likelihood of response (odds ratio [OR] = 3.19, 95% confidence interval [CI]: 2.12, 4.66) and remission (OR = 4.99, CI: 2.93, 7.76), compared with TAU. For patients who had responded to VNS + TAU at 24 weeks, sustained response was more likely at 48 weeks (OR = 1.98, CI: 1.34, 3.01) and at 96 weeks (OR = 3.42, CI: 1.78, 7.31). Similar results were observed for CGI-I response. Conclusion: For patients with chronic TRD, VNS + TAU has greater response and remission rates that are more likely to persist than TAU. Keywords: Bayesian meta-analysis, remission rate, response rate, treatment-resistant depression, vagus nerve stimulation, VNS Therapy IntroductionDepression is a prevalent, disabling, and often chronic or recurrent psychiatric condition affecting about 350 million people worldwide.1 Among the general adult population in the US, the lifetime prevalence of major depressive disorder (MDD) is about 29.9% and the 12-month prevalence is about 8.6%.2 MDD imposes significant costs on patients, their families, caregivers, employers, and insurance payers, with an estimated Dovepress submit your manuscript | www.dovepress.com 54.191.190.102 on 11-May-2018 For personal use only. direct cost of more than US$80 billion per year to the US economy, which includes costs associated with health care, suicide mortality, and lost workplace productivity. 3,4 While several modal...

Interoceptive dysfunction: Toward an integrated framework for understanding somatic and affective disturbance in depression.

“…A number of studies have established the efficacy of VNS for TRD (see Table 2). For example, in a meta-analysis of six prospective studies including over 1,000 patients receiving VNS plus standard treatment and 400 patients receiving standard treatment, VNS significantly improved treatment response and remission rates for TRD (Berry et al, 2013). In rodent models, VNS similarly has antidepressant-like effects (Krahl, Senanayake, Pekary, & Sattin, 2004) and has been shown to increase neurogenesis and hippocampal plasticity (e.g., Biggio et al, 2009).…”

“…Studies on the efficacy of Vagal Nerve Stimulation (VNS) in depression. Only studies including Treatment as Usual (TAU) or Sham VNS controls are included (see Berry et al, 2013; for a broader meta-analysis). That is, case studies (e.g., Borckardt et al, 2006; Critchley et al, 2007), studies of VNS efficacy without controls (e.g., Christmas et al, 2013; Cristancho et al, 2011), studies comparing only various levels of VNS intensity (e.g., Aaronson et al, 2013), and studies focused solely on specific biological and cognitive consequences of VNS in depression, such as effects on pain perception, cravings, and flavor perception (e.g., Borckardt et al, 2005; Sperling et al, 2011) are not included.…”

Parametric characterization of neural activity in the locus coeruleus in response to vagus nerve stimulation

“…More than 75,000 patients have received vagus nerve stimulation (VNS) therapy for the treatment of epilepsy and depression (Schlaepfer et al, 2008, Englot, Chang and Auguste., 2011, Berry et al, 2013, Ben-Menachem et al, 2015). Emerging studies provide evidence that VNS paired with rehabilitative training may be useful in the treatment of additional neurological disorders, including tinnitus and stroke (Dawson et al, 2016, De Ridder et al, 2014, Hays., 2016).…”

Combining electroencephalographic activity and instantaneous heart rate for assessing brain–heart dynamics during visual emotional elicitation in healthy subjects

“…Dysfunctions of the ANS were found in acute and chronic stressful conditions [10][11][12], insomnia [13,14], epilepsy [15,16], parkinsonisms [17,18], psychosomatic disorders [19] and schizophrenia, anxiety and mood disorders [6,[20][21][22][23][24], which are typically considered CNS-related conditions. Moreover, vagal nerve stimulation has been shown as an effective treatment for major depression [25,26], while relaxation techniques based on cardio-feedback are used for managing negative emotions and psychological symptoms [27,28].…”