Metoprolol withdrawal phenomena: Mechanism and prevention

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Abstract
Patients (8) taking metoprolol (300 mg/day) for essential hypertension were studied after abrupt withdrawal and placebo replacement of the drug. A 52% average rebound increase in cardiac chronotropic sensitivity to isoproterenol and 15% rebound rise in resting heart rate occurred in all patients between 2-8 days after metoprolol withdrawal (P < 0.05). Holter monitoring showed no associated arrhythmia. A transient increase in blood pressure occurred in 1 patient and withdrawal-like symptoms were noted in 3 patients. There were no meaningful changes in plasma norepinephrine, epinephrine, thyroxine or triiodothyronine. Of 8 patients, 7 were again studied serially after the same metoprolol dosing, during a prolonged low-dose withdrawal schedule (50 mg/day for 10 days) and during placebo. Prolonged low dose before complete metoprolol withdrawal decreased but did not completely prevent the changes observed after abrupt withdrawal. The observed rebound of cardiac .beta.-adrenergic sensitivity may have application to the mechanism and prevention of the .beta.-blocker syndrome in patients with angina.

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