Noninvasive indices of autonomic regulation after alprazolam and lorazepam: effects on sympathovagal balance

Abstract

Skin conductance level (SCL) and spectral analysis of variations in heart rate (HR) and blood pressure (BP), in relation to plasma catecholamine concentrations, were used to evaluate autonomic nervous system activity during situations of supine rest within a period of 4 h after oral administration of 1 mg alprazolam and 2 mg lorazepam. Twelve healthy men received in a double-blind, randomized crossover design, either 1 mg alprazolam, or 2 mg lorazepam, or a placebo on different days. ECG, BP, respiration, and SCL were monitored continuously during each session. For HR, systolic and diastolic BP (SBP, DBP) time series, power spectra were calculated per 5 min for three 15-min periods at 30 min, 1 h and 45 min, and 3 h after dosing. Spectral power was assessed for three frequency bands: low (0.02-0.06 Hz), mid (0.07-0.14 Hz), and high (0.15-0.50 Hz). Per time segment, the gain in the mid-frequency band between the systolic BP values and the RR interval times was computed as index of baroreflex sensitivity (BRS). Blood samples for assay of plasma catecholamines were obtained after each 15-min period. Alprazolam reduced DBP during the whole recording period; the effect was accompanied by an initial increase of mid-frequency band fluctuations of BP at 30 min, which subsequently decreased at 1 h 45 min and 3 h after dose administration, in comparison with placebo (suggesting an initial reflectory increase, followed by an attenuation of sympathetic tone). The BP effects were accompanied by a reduction of plasma noradrenaline concentrations. HR showed a time-dependent decrease after alprazolam and an increase in high-frequency band fluctuations of HR and BRS (suggesting a time-dependent increase in cardiac vagal tone). SCL was decreased after alprazolam administration. Lorazepam did not show a time-dependent reduction of HR and had no effect on BP, but increased low-frequency band power of HR and DBP and mildly reduced SCL. Alprazolam and lorazepam had no effect on respiratory frequency. Noninvasive indices of autonomic regulation revealed several small, but significant, time-dependent effects of 1 mg alprazolam on sympathetic and parasympathetic processes, whereas for 2 mg lorazepam, these effects were less clear. The reduction in noninvasive indices of sympathetic tone after alprazolam administration corresponded with the attenuation of plasma noradrenaline concentrations by alprazolam.