Comparison of CNS‐Related Subjective Symptoms in Hypertensive Patients Treated with Either a New Controlled Release (CR/ZOK) Formulation of Metoprolol or Atenolol

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Abstract
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 beta1‐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.