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

J Clin Pharmacol. 1990 Feb;30(S2):S82-90. doi: 10.1002/j.1552-4604.1990.tb03502.x.


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.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Atenolol / administration & dosage
  • Atenolol / adverse effects
  • Atenolol / therapeutic use*
  • Blood Pressure / drug effects
  • Delayed-Action Preparations
  • Double-Blind Method
  • Exercise Test
  • Female
  • Heart Rate / drug effects
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Male
  • Metoprolol / administration & dosage
  • Metoprolol / adverse effects
  • Metoprolol / therapeutic use*
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • Surveys and Questionnaires
  • Tablets


  • Delayed-Action Preparations
  • Tablets
  • Atenolol
  • Metoprolol