Investigating Ultra-Short-Term Heart Rate Variability as an Indicator of Craving in Recently Treated Patients with Opioid Use Disorder.

Induced craving frequently leads to relapse in patients with a history of opioid use disorder (OUD). Quantifying the physiological manifestations of craving can enable caregivers of patients with OUD to continuously monitor craving and thus help inform treatment plans. Heart rate variability (HRV) is a promising candidate to capture the trends in such manifestations due to the ease of measuring changes in heartbeat intervals using the electrocardiogram. However, the relationship between craving and HRV measured over periods shorter than 5 minutes, i.e., ultra-short-term HRV, has not yet been investigated in detail. In this work, we present the first analysis on the relationship between 12 HRV features computed over ~2-minute periods and subjective craving reported on the visual analog scale (VAS-craving). Patients with OUD stable on medication (N = 12) went through an approximately 2-hour protocol involving audio/visual opioid cues to induce craving, alongside active transcutaneous vagus nerve stimulation or sham stimulation. Regardless of stimulation type, changes in VAS-craving scores over the course of the protocol were negatively correlated with changes in two ultra-short-term HRV features: the number of adjacent normal heartbeat intervals differing by more than 50 milliseconds (r = -0.63, p = 0.03) and the total power across all frequency bands (r = -0.69, p = 0.03).Clinical relevance-This preliminary study suggests that certain ultra-short-term HRV features can potentially serve as indicators of craving in patients with a history of OUD. Using such metrics computed over small data intervals can enable efficient clinical decision making and may help prevent opioid relapse.