Efficacy of transcutaneous vagus nerve stimulation as treatment for depression: A systematic review

Background Transcutaneous vagus nerve stimulation (tVNS) has been suggested as a treatment method for depression. Methods A systematic review to systematically evaluate the efficacy of tVNS for the treatment of depression was conducted according to PRISMA guidelines. Primary outcomes were mortality, self-harm, depressive symptoms, and health-related quality of life (HRQoL). Secondary outcomes were anxiety symptoms, medication use, everyday functioning, complications, and patients’ experiences of treatment. Five databases were searched systematically. The included articles were critically appraised and certainty of evidence was assessed using GRADE. Results Two studies evaluating efficacy and a case series collecting data on complications were included. One randomized trial (n = 37) and one cohort study (n = 160) comparing tVNS with sham-tVNS reported significant reduction in the tVNS group of self-rated (SMD = -0.82, 95%-CI = -1.50, -0.15) but not clinician-rated depressive symptoms, after two weeks, and of both self-rated (SMD = -0.99, 95%-CI = -1.32, -0.66) and clinician-rated (SMD = -0.89, 95%-CI = -1.22, -0.57) depressive symptoms, after four weeks, respectively. Furthermore, the cohort study found reduction of both self-rated (SMD = -0.66, 95%-CI = -0.98, -0.34) and clinician-rated (SMD = -0.14, 95%-CI = -0.46, 0.17) anxiety symptoms. One case series (n = 12), collecting data on complications, reported mild to moderate transient side effects. Limitations Available studies are few and heterogeneous, have major study limitations, problems with directness and imprecision. Conclusions It is uncertain whether tVNS reduces depressive symptoms and anxiety. Although existing studies show promising results, further studies are needed to increase the certainty of evidence.