CNS-related Subjective Symptoms During Treatment with Beta 1-adrenoceptor Antagonists (atenolol, Metoprolol): Two Double-blind Placebo Controlled Studies

1. Whilst a number of studies have investigated whether metoprolol and atenolol, the most widely used beta 1-adrenoceptor antagonists, differ with regard to CNS-related subjective symptoms, few placebo-controlled studies using standardised questionnaires have been performed. 2. In the present report, the findings of two randomised, double-blind, cross-over studies in healthy volunteers are presented. The subjects were treated with placebo and atenolol (100 mg once daily) (Study 1) and metoprolol (100 mg once daily) and placebo (Study 2). 3. Subjective experiences were evaluated using a standardised instrument, the Minor Symptoms Evaluation-profile (MSE-profile), which was filled in 4, 8 and 24 h after intake of the tablets. A Type A questionnaire was also completed by the subjects. 4. At 4 h both metoprolol and atenolol were found to affect negatively vitality and contentment, but these effects had declined after 8 h. A significant adverse effect on sleep was shown for atenolol compared with placebo, while no negative effect was observed for metoprolol. No significant differences were found in relation to Type A behaviour and beta-adrenoceptor blockade. The number of subjects with Type A personality was, however, low. 5. The results of the studies indicate that the subjective symptoms of the beta 1-adrenoceptor blockers are mild, and that the effects appear consistently with the recognised pharmacokinetic profiles of the two drugs.