CNS side effects of centrally-active antihypertensive agents: a prospective, placebo-controlled study of sleep, mood state, and cognitive and sexual function in hypertensive males

Abstract

A prospective, placebo-controlled, comparative evaluation was conducted on two widely prescribed, sympatholytic antihypertensive agents with known CNS effects. In order to separately assess these effects in younger and older male hypertensives, patients were assigned to either of two treatment studies based on age. For study I, 24 males aged 31-59 (mean = 49.8; SD = 7.4) with mild hypertension (mean DBP = 100.2 mm Hg; SD = 8.0) received 3 months of treatment with propranolol (20-80 mg bid), clonidine (0.1-0.3 mg bid), or double-blind placebo in a counterbalanced, crossover design. For study II, 23 elderly hypertensive males (mean DBP = 102.6 mm Hg; SD = 8.2) aged 60-78 years (mean = 65.1; SD = 4.6) were randomized to propranolol (20-40 mg bid) or double-blind placebo therapy. Patients received cognitive testing, mood assessments, and all-night polysomnographic evaluations before and after each treatment period. Multivariate analysis of EEG sleep data was statistically significant for study I, with significant univariate effects on four of the six primary sleep variables: total sleep time was reduced, sleep maintenance decreased, REM latency increased, and percent total REM time was reduced. A similar MANOVA analysis for the effects of treatment on the sleep of older patients (study II) was not significant. However, propranolol administration was found to be associated with a significant decline in cognitive performance in these patients. Significant mood effects were observed with each of the study drugs, and nocturnal penile tumescence (NPT) was significantly decreased in both younger and older patients. Overall, this research suggests that distinct patterns of CNS effects are associated with each of the antihypertensive agents studied.