Transcutaneous vagus nerve stimulation enhances reward-effort efficiency in severe major depressive disorder.

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder with changes in motivation to work for rewards being a core symptom. Transcutaneous vagus nerve stimulation (tVNS) has emerged as a promising therapy but its effects on the core features of MDD, such as changes in motivation, remained relatively unexplored. In this randomised, single-blind, cross-over, controlled trial, we used a grip strength effort task to investigate how tVNS impacted choices to exert different levels of physical effort for varying monetary rewards in MDD patients (n = 53) and a non-depressed control group (n = 45). The primary analyses showed no interaction between condition (sham versus tVNS) and group (control versus MDD). However, secondary analyses showed that tVNS effects were dependent on symptom severity. Compared to sham stimulation, tVNS enhanced the efficiency with which participants with severe depressive symptoms allocated physical effort for rewards (reward-effort efficiency). These effects were not seen in healthy participants or MDD patients with less severe symptoms. The effect of tVNS on reward-effort efficiency was driven by reduced unnecessary effort in those with severe MDD symptoms - a reduction in choices to exert additional effort when this was not required to gain a larger reward. This suggests a motivational mechanism by which tVNS exerts its therapeutic effects in severe MDD but these remain secondary findings which should be interpreted with caution. Determining whether the effects of tVNS are linked to broader changes in executive functioning, such as improvements in cognitive flexibility in MDD, should be a key aim for future work.