PMID- 36543841
OWN - NLM
STAT- MEDLINE
DCOM- 20221223
LR  - 20230122
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 12
IP  - 1
DP  - 2022 Dec 21
TI  - Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic 
      review and meta-analysis.
PG  - 22055
LID - 10.1038/s41598-022-25864-1 [doi]
LID - 22055
AB  - Transcutaneous auricular vagus nerve stimulation (taVNS) has been investigated as 
      a novel neuromodulation tool. Although taVNS is generally considered safe with 
      only mild and transient adverse effects (AEs), those specifically caused by taVNS 
      have not yet been investigated. This systematic review and meta-analysis on taVNS 
      aimed to (1) systematically analyze study characteristics and AE assessment, (2) 
      characterize and analyze possible AEs and their incidence, (3) search for 
      predictable risk factors, (4) analyze the severity of AE, and (5) suggest an 
      evidence-based taVNS adverse events questionnaire for safety monitoring. The 
      articles searched were published through April 7, 2022, in Medline, Embase, Web 
      of Science, Cochrane, and Lilacs databases. In general, we evaluated 177 studies 
      that assessed 6322 subjects. From these, 55.37% of studies did not mention the 
      presence or absence of any AEs; only 24.86% of the studies described that at 
      least one adverse event occurred. In the 35 studies reporting the number of 
      subjects with at least one adverse event, a meta-analytic approach to calculate 
      the risk differences of developing an adverse event between active taVNS and 
      controls was used. The meta-analytic overall adverse events incidence rate was 
      calculated for the total number of adverse events reported on a 100,000 
      person-minutes-days scale. There were no differences in risk of developing an 
      adverse event between active taVNS and controls. The incidence of AE, in general, 
      was 12.84/100,000 person-minutes-days of stimulation, and the most frequently 
      reported were ear pain, headache, and tingling. Almost half of the studies did 
      not report the presence or absence of any AEs. We attribute this to the absence 
      of AE in those studies. There was no causal relationship between taVNS and severe 
      adverse events. This is the first systematic review and meta-analysis of 
      transcutaneous auricular stimulation safety. Overall, taVNS is a safe and 
      feasible option for clinical intervention.
CI  - (c) 2022. The Author(s).
FAU - Kim, Angela Yun
AU  - Kim AY
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Medical 
      Center, Seoul, Republic of Korea.
FAU - Marduy, Anna
AU  - Marduy A
AD  - Uniao Metropolitana de Ensino e Cultura (UNIME) Salvador, Bahia, Brazil.
AD  - Neuromodulation Center and Center for Clinical Research Learning, Spaulding 
      Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical 
      School, 96 13th Street, Charlestown, Boston, MA, USA.
FAU - de Melo, Paulo S
AU  - de Melo PS
AD  - Neuromodulation Center and Center for Clinical Research Learning, Spaulding 
      Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical 
      School, 96 13th Street, Charlestown, Boston, MA, USA.
AD  - Department of Medicine, Escola Bahiana de Medicina e Saude Publica, Salvador, 
      Bahia, Brazil.
FAU - Gianlorenco, Anna Carolyna
AU  - Gianlorenco AC
AD  - Neuromodulation Center and Center for Clinical Research Learning, Spaulding 
      Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical 
      School, 96 13th Street, Charlestown, Boston, MA, USA.
AD  - Department of Physical Therapy, Federal University of Sao Carlos, Sao Carlos, 
      Brazil.
FAU - Kim, Chi Kyung
AU  - Kim CK
AD  - Department of Neurology, Korea University Guro Hospital, Seoul, Republic of 
      Korea.
FAU - Choi, Hyuk
AU  - Choi H
AD  - Department of Medical Sciences, Graduate School of Medicine, Korea University, 
      Seoul, Republic of Korea.
AD  - Neurive Co., Ltd., Gimhae, Republic of Korea.
FAU - Song, Jae-Jun
AU  - Song JJ
AD  - Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Medical 
      Center, Seoul, Republic of Korea.
AD  - Neurive Co., Ltd., Gimhae, Republic of Korea.
FAU - Fregni, Felipe
AU  - Fregni F
AD  - Neuromodulation Center and Center for Clinical Research Learning, Spaulding 
      Rehabilitation Hospital and Massachusetts General Hospital, Harvard Medical 
      School, 96 13th Street, Charlestown, Boston, MA, USA. 
      Fregni.Felipe@mgh.harvard.edu.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
PT  - Systematic Review
DEP - 20221221
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
SB  - IM
MH  - Humans
MH  - *Vagus Nerve Stimulation/adverse effects
MH  - *Transcutaneous Electric Nerve Stimulation/adverse effects
MH  - Vagus Nerve/physiology
MH  - Pain Management
MH  - Headache
PMC - PMC9772204
COIS- A.Y.K. has no conflicts of interest to declare. C.K.K., H.C. and J.S. are 
      directly associated with Neurive Co, a company developing neuromodulation 
      technologies, such as taVNS, to treat common brain diseases. A.C.G. is supported 
      by the Federal University Sao Carlos and is a consultant for Neurive. P.S.dM. and 
      A.M. are consultants for Neurive. F.F. is supported by NIH grants and is a 
      consultant for Neurive.
EDAT- 2022/12/22 06:00
MHDA- 2022/12/24 06:00
PMCR- 2022/12/21
CRDT- 2022/12/21 23:25
PHST- 2022/07/19 00:00 [received]
PHST- 2022/12/06 00:00 [accepted]
PHST- 2022/12/21 23:25 [entrez]
PHST- 2022/12/22 06:00 [pubmed]
PHST- 2022/12/24 06:00 [medline]
PHST- 2022/12/21 00:00 [pmc-release]
AID - 10.1038/s41598-022-25864-1 [pii]
AID - 25864 [pii]
AID - 10.1038/s41598-022-25864-1 [doi]
PST - epublish
SO  - Sci Rep. 2022 Dec 21;12(1):22055. doi: 10.1038/s41598-022-25864-1.