Transcutaneous vagus nerve stimulation to enhance exposure efficacy in public speaking anxiety

Rationale: Social Anxiety Disorder (SAD) is a common and debilitating anxiety disorder. Exposure Therapy is a proven effective treatment strategy for SAD. Notwithstanding its efficacy, many patients remain symptomatic after treatment and remission rates tend to be low. Extinction learning is thought to be the most important mechanism of action of ET. Preclinical studies recently demonstrated that vagus nerve stimulation promotes extinction learning, compared to sham. As such, vagus nerve stimulation seems a promising enhancement strategy for exposure therapy. Here, we aim to examine for the first time if transcutaneous stimulation of the auricular branch of the vagus nerve (tVNS) enhances exposure in patients suffering from SAD, compared to sham.

Objective: To investigate whether augmentation of one standardized exposure session for SAD with tVNS results in lower fear compared to sham. We also aim to test if tVNS yields enhanced retention of extinction memory, during a second exposure session compared to sham. Secondary, we aim to test the effects of tVNS + exposure vs. sham + exposure on levels of self-reported social anxiety and cardiac activity, and explore if individual characteristics are related to changes in the primary outcome.

Study design: A single-blind placebo controlled intervention study

Study population: Fifty-two individuals (18-70 years) satisfying DSM-5 criteria for SAD

Intervention: All participants receive two standardized sessions of exposure for SAD, 26 randomly allocated participants will receive tVNS during the first session, 26 will receive sham stimulation during the first session.

Main study parameters/endpoints: Subjective Units of Distress (SUDs): participants will provide fear ratings (ranging from 0; no fear to 100 most anxiety imaginable) prior, during and after both exposure sessions. Main outcome is the change of the SUDs during the first exposure session.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Participants will visit the Leiden Universiteit Behandel en Expertise Centrum for two visits: 1) the baseline assessment and first exposure; 2) the second exposure session. After these sessions, follow-up assessments will be conducted online. Participation will take approximately 4 hours in total. Concerning the tVNS and sham stimulation: The stimulation frequency, intensity and duration are within safety limits established from prior work in humans (Kreuzer et al., 2012). Previous studies have used comparable or higher tVNS stimulation frequency, intensity and duration without reporting adverse side-effects (e.g. Dietrich et al., 2008; Kraus et al., 2007). The stimulation is not painful, only a typical short-lasting skin sensation (i.e., itching and/or tingling) can be experienced.

To investigate whether augmentation of one standardized exposure session for SAD with tVNS has beneficial effects compared to sham enhanced exposure by examining subjective anxiety during exposure. Subjective anxiety will be measured with ‘subjective units of distress’ (SUDs), which are commonly used to gauge extinction success (Lonsdorf et al., 2017. Specifically, we will examine:

Baseline, multiple assessments of SUDs during exposure

Transcutaneous vagus nerve stimulation at the cymbals concha with exposure; placebo stimulation of the earlobe with exposure