Seven of the eight patients 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. There were no meaningful changes in plasma norepinephrine, epinephrine, thyroxine, or triiodothyronine. A transient increase in blood pressure occurred in one patient and withdrawal-like symptoms were noted in three patients. Holter monitoring showed no associated arrhythmia. 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 to 8 days after metoprolol withdrawal (P less than 0.05). Eight patients taking metoprolol (300 mg/day) for essential hypertension were studied after abrupt withdrawal and placebo replacement of the drug.
