CNS-related side-effects with metoprolol and atenolol

Eur J Clin Pharmacol. 1985:28 Suppl:69-72. doi: 10.1007/BF00543713.


Vivid and bizarre dreams, hallucinations, sleep disturbance and psychosis have all been described following treatment with beta-blockers. It has been suggested that these central nervous system (CNS) side-effects are related to the degree of lipophilicity of the beta-blocker. A randomized double-blind crossover study was performed to compare the incidence of CNS side-effects with atenolol and metoprolol in hypertensive patients who had reported CNS side-effects with lipophilic beta-blockers. Eleven women and six men completed the study, in which a 30-item psychiatric questionnaire was used to detect changes in psychological status and possible CNS side-effects. Discontinuation of the original lipophilic beta-blocker produced a significant improvement in quality of sleep, dreams, concentration, memory, energy, and anxiety. No significant CNS side-effects were reported with atenolol, but introduction of metoprolol caused a significant increase in the incidence of sleep disturbance (p less than 0.01) and restless nights (p less than 0.05), as well as failure to achieve satisfactory sexual intercourse (p less than 0.05). When compared with atenolol, metoprolol was associated with a significantly higher incidence of restless disturbed nights (p less than 0.05). Blood pressure control was identical for both beta-blockers. This study appears to confirm the association between CNS-related side-effects and the lipophilicity of beta-blockers.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Anxiety
  • Atenolol / adverse effects*
  • Blood Pressure / drug effects
  • Central Nervous System / drug effects*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Metoprolol / adverse effects*
  • Middle Aged
  • Random Allocation
  • Sleep Wake Disorders / chemically induced


  • Atenolol
  • Metoprolol