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. 2023 Jul 6;15:1173987. doi: 10.3389/fnagi.2023.1173987

Figure 2.

Figure 2

Clinical implications of VNS by different modalities and diseases. Traditional VNS is applied in the treatment of refractory epilepsy and depression and stroke, with FDA-approved indications. VNS is undergoing clinical trials for the treatment of epilepsy, tinnitus, generalized anxiety disorders, fibromyalgia, and rheumatic arthritis. Transcutaneous cervical VNS is FDA approved for cluster headache and migraine and is under clinical trials of COVID-19-related inflammation, stroke, atrial fibrillation, post-traumatic stress disorder, opioid use disorder, and painful chronic pancreatitis. Transcutaneous auricular VNS was applied in a broad spectrum of clinical studies. Most of the VNS studies have achieved the primary outcome, with significant effects, except for references 26, 29, and 33. VNS, vagus nerve stimulation; FDA, Food and Drug Administration; COVID-19, coronavirus disease 2019; ns, non-significant effect on study measure outcome. Reference number, 1 (Addorisio et al., 2019), 2 (Arsava et al., 2022), 3 (Badran et al., 2020), 4 (Chang et al., 2021), 5 (Courties et al., 2022), 6 (Dawson et al., 2021), 7 (De Ridder et al., 2015), 8 (Diener et al., 2019), 9 (Fisher et al., 2016), 10 (Garcia et al., 2021), 11 (Gaul et al., 2016), 12 (Gazi et al., 2022), 13 (Genovese et al., 2020), 14 (George et al., 2005), 15 (George et al., 2008), 16 (Goadsby et al., 2018), 17 (Gomolka et al., 2018), 18 (Grazzi et al., 2017), 19 (Kawai et al., 2017), 20 (Kozorosky et al., 2022), 21 (Kreuzer et al., 2014), 22 (Labar et al., 1999), 23 (Lange et al., 2011), 24 (Manning et al., 2019), 25 (Merchant et al., 2022), 26 (Mertens et al., 2022), 27 (Morris et al., 2013), 28 (Morris and Mueller, 1999), 29 (Muthulingam et al., 2021), 30 (Najib et al., 2022), 31 (Paccione et al., 2022), 32 (Redgrave et al., 2018), 33 (Rush et al., 2005a), 34 (Rush et al., 2005b), 35 (Salama et al., 2020), 36 (Shi et al., 2021), 37 (Silberstein et al., 2016a), 38 (Silberstein et al., 2016b), 39 (Stavrakis et al., 2020), 40 (Tassorelli et al., 2018), 41 (Tirado et al., 2022), 42 (Tornero et al., 2022), 43 (Tyler et al., 2017), 44 (Verrier et al., 2016), and 45 (Wittbrodt et al., 2021).