Effect of Gabapentin on Heart Rate Variability in Patients with Painful Diabetic Peripheral Neuropathy: A Double-blinded Randomized Controlled Trial.

Background: Cardiac autonomic neuropathy (CAN) is one of the most significant complications of diabetes mellitus (DM) and is characterized by reduced heart rate variability (HRV). The CAN frequently coexists with peripheral neuropathy. Objectives: We attempted to determine whether gabapentin has any impact on HRV in individuals suffering from painful diabetic peripheral neuropathy (PDPN). Methods: In this double-blinded randomized controlled trial, 30 patients with painful peripheral neuropathy were enrolled. Fifteen patients in the intervention group were randomized to receive gabapentin capsules and capsaicin placebo cream, while 15 patients in the control group were randomized to receive gabapentin placebo capsules and capsaicin cream. The diagnosis of PDPN was established using the Neuropathy Symptom Scale (NSS), neuropathy disability score (NDS), and Visual Analogue Scale (VAS). The HRV was evaluated with the standard deviation of normal-normal beats (SDNN) via 24-hour Holter monitoring of heart rate. Results: Of the 30 randomized patients, 26 (86.7%) were included in the analysis (n = 15 intervention, n = 11 control). There were no statistically significant differences in age, sex, or Body Mass Index (BMI) between the two groups. Gabapentin increased the average level of SDNN by 11 ms in the intervention group and decreased by 6 ms in the control group. The between-group standardized mean difference (MD, Hedges' g) was 0.756 (95% CI = -0.04 - 1.5, P-value = 0.069), indicating a moderate effect that was marginally significant. Conclusions: Our findings in this small pilot trial suggest that gabapentin therapy may improve cardiovascular autonomic function and increase HRV in patients suffering from diabetic painful peripheral neuropathy. However, more studies with larger populations are needed to ultimately prove this.