Comparison of CNS-related subjective symptoms in hypertensive patients treated with either a new controlled release (CR/ZOK) formulation of metoprolol or atenolol.

The present study evaluated and compared subjective symptoms in hypertensive patients (N = 83) at therapeutically comparable dosages of a new controlled release (CR/ZOK) formulation of metoprolol (100 mg od) and atenolol (50 mg od). The trial was a 4-week randomized double-blind study preceded by a placebo run-in period. Blood pressure (BP) was recorded 24 hours after intake of last dose. In subpopulations, 24-hour ambulatory BP was recorded and exercise tests performed. Subjective symptoms were evaluated with a previously documented questionnaire (MSE-profile) which has been shown to be sensitive in detecting CNS-related symptoms caused by beta blockers. The MSE-profile includes three dimensions: Contentment, Vitality and Sleep. The results showed that there were no significant differences between the groups in BP reduction either at 24 hours or over the entire 24-hour dose interval. Furthermore, the degree of beta 1-blockade (reduction in exercise-induced tachycardia) 24 hours after last dose did not differ between the groups. There were no significant differences regarding subjective symptoms (Contentment, Vitality, Sleep) between the two treatment groups. An a posteriori power analysis showed that the power to detect a true difference was of an acceptable magnitude. In conclusion, there was no difference in CNS-related symptoms between metoprolol and atenolol at therapeutically comparable dosages indicating that the degree of lipophilicity may be of minor importance for the occurrence of such symptoms.