Serotonin antagonism reduces the adverse symptoms of beta blockade

Summary

Beta-adrenoceptor antagonists (beta blockers) are a well-established first-line treatment for hypertension, but they have been associated with unwanted symptoms including cold extremities, lethargy, and nightmares. Ketanserin is a serotonin S₂-receptor antagonist that has previously been shown to reduce blood pressure in hypertensive patients by reducing systemic vascular resistance. Hypertensive patients whose sitting diastolic blood pressure was ≥95 mmHg, despite at least 4 weeks therapy with an optimal dose of beta blocker, were selected for the study. The beta-blocker dose remained constant throughout the study, but patients were randomly allocated to receive ketanserin 20 mg twice daily, ketanserin 40 mg twice daily, or bendrofluazide 5 mg each morning plus placebo at night in addition to the beta-blocker therapy. One hundred and forty two patients completed the symptom questionnaire at randomization and after 12 weeks treatment. The treatment groups were well matched for age, sex, weight, and blood pressure. Blood pressure was reduced significantly by all treatments, and there were no between-group differences. Bendrofluazide adversely affected alertness (p<0.05) and concentration (p<0.01) whereas ketanserin had no significant effect and the ketanserin 20 mg twice daily group had better concentration than the bendrofluazide group (p<0.05). Ketanserin treatment reduced the incidence of nightmares (p<0.05 for 20 mg twice daily and 40 mg twice daily) and was an improvement over bendrofluazide treatment in this respect (p<0.05).

Leg pain on walking (p<0.01) and at rest (p<0.05) was worse on bendrofluazide, whereas ketanserin treatment 20 mg twice daily improved incidence of leg pain on walking (p<0.05) and was an improvement over bendrofluazide treatment in this respect (p<0.05). Incidence of flushing was reduced by ketanserin 40 mg twice daily (p<0.01) more effectively than by bendrofluazide treatment (p<0.05).

The present study indicated that serotonin antagonism by ketanserin can reduce the nightmares and sleep disturbance and reverse the deterioration in peripheral circulation that may accompany treatment with beta blockers.