Effect of transcutaneous vagus nerve stimulation on stress‐reactive neuroendocrine measures in a sample of persons with temporal lobe epilepsy

OBJECTIVE: Dysregulation of stress‐reactive neuroendocrine measures, as well as subjective stress, have been found to worsen epilepsy. Transcutaneous vagus nerve stimulation (tVNS) is a relatively new treatment option for epilepsy. We were interested in its effect on the activity of the hypothalamic–pituitary–adrenal (HPA) axis and autonomic nervous system (ANS) as well as subjective stress and tiredness in patients with temporal lobe epilepsy (TLE). METHODS: Twenty patients (age 44 ± 11 years, 13 women) were enrolled in the study. They were free of seizures for more than 1 year. All took part in two sessions with 4 h of stimulation (tVNS vs. sham) in a randomized order. Saliva samples and subjective stress and tiredness levels were measured at five time points each session (before and after stimulation and three time points every hour in between). Data were analyzed using repeated measures analysis of variance as well as paired t‐tests. RESULTS: There was a dampened salivary cortisol (sCort) decrease during tVNS (time × condition effect: F ([2.38, 38.15]) = 6.50, P = 0.002, partial η (2) = 0.29). Furthermore, we detected a dampened increase in salivary flow rate during tVNS (time × condition effect: F ([3.28, 55.67]) = 2.82, P = 0.043, partial η (2) = 0.14). There was neither a difference in overall sCort or salivary alpha‐amylase (sAA) levels nor in subjective stress or tiredness levels between conditions. sAA levels at the last measurement point were slightly higher during tVNS (t ((19)) = 2.26, P = 0.035, d = 0.51), but this effect failed to reach significance when controlled for multiple comparisons. SIGNIFICANCE: Our results partially support that tVNS influences the regulation of stress‐reactive neuroendocrine systems (namely the HPA axis and ANS) in epilepsy. More research with larger samples is needed on the difference between short‐term and repeated long‐term stimulation.